Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy that can present as a pulmonary or pleural mass. In most cases, pleuropulmonary blastoma is associated with germline pathogenic variants of the DICER1 gene. The International Pleuropulmonary Blastoma/DICER1 Registry is a valuable resource for information about this rare malignancy.[1,2]

The following subtypes of pleuropulmonary blastoma have been identified:

The International Pleuropulmonary Blastoma Registry reported on 350 centrally reviewed and confirmed cases of pleuropulmonary blastoma over a 50-year period (see Table 1).[2]

References

1. The International Pleuropulmonary Blastoma/DICER1 Registry. Minneapolis, Minn: Children’s Minnesota. Available online. Last accessed August 23, 2024.
2. Messinger YH, Stewart DR, Priest JR, et al.: Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer 121 (2): 276-85, 2015. [PUBMED Abstract]
3. Nelson AT, Harris AK, Watson D, et al.: Type I and Ir pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry. Cancer 129 (4): 600-613, 2023. [PUBMED Abstract]
4. Hill DA, Jarzembowski JA, Priest JR, et al.: Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol 32 (2): 282-95, 2008. [PUBMED Abstract]
5. Nelson AT, Vasta LM, Watson D, et al.: Prevalence of lung cysts in adolescents and adults with a germline DICER1 pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/DICER1 Registry. Thorax 79 (7): 644-651, 2024. [PUBMED Abstract]
6. Priest JR, McDermott MB, Bhatia S, et al.: Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 80 (1): 147-61, 1997. [PUBMED Abstract]
7. Dehner LP, Messinger YH, Schultz KA, et al.: Pleuropulmonary Blastoma: Evolution of an Entity as an Entry into a Familial Tumor Predisposition Syndrome. Pediatr Dev Pathol 18 (6): 504-11, 2015 Nov-Dec. [PUBMED Abstract]
8. Priest JR, Hill DA, Williams GM, et al.: Type I pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. J Clin Oncol 24 (27): 4492-8, 2006. [PUBMED Abstract]
9. Miniati DN, Chintagumpala M, Langston C, et al.: Prenatal presentation and outcome of children with pleuropulmonary blastoma. J Pediatr Surg 41 (1): 66-71, 2006. [PUBMED Abstract]
10. Vokuhl C, de Leon-Escapini L, Leuschner I: Strong Expression and Amplification of IGF1R in Pleuropulmonary Blastomas. Pediatr Dev Pathol 20 (6): 475-481, 2017 Nov-Dec. [PUBMED Abstract]

References

1. Hill DA, Ivanovich J, Priest JR, et al.: DICER1 mutations in familial pleuropulmonary blastoma. Science 325 (5943): 965, 2009. [PUBMED Abstract]
2. Slade I, Bacchelli C, Davies H, et al.: DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48 (4): 273-8, 2011. [PUBMED Abstract]
3. Foulkes WD, Bahubeshi A, Hamel N, et al.: Extending the phenotypes associated with DICER1 mutations. Hum Mutat 32 (12): 1381-4, 2011. [PUBMED Abstract]
4. Schultz KA, Pacheco MC, Yang J, et al.: Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the International Pleuropulmonary Blastoma Registry. Gynecol Oncol 122 (2): 246-50, 2011. [PUBMED Abstract]
5. Schultz KAP, Williams GM, Kamihara J, et al.: DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies. Clin Cancer Res 24 (10): 2251-2261, 2018. [PUBMED Abstract]
6. Boman F, Hill DA, Williams GM, et al.: Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry. J Pediatr 149 (6): 850-854, 2006. [PUBMED Abstract]
7. Chernock RD, Rivera B, Borrelli N, et al.: Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations. Mod Pathol 33 (7): 1264-1274, 2020. [PUBMED Abstract]
8. Stewart DR, Best AF, Williams GM, et al.: Neoplasm Risk Among Individuals With a Pathogenic Germline Variant in DICER1. J Clin Oncol 37 (8): 668-676, 2019. [PUBMED Abstract]

Presenting symptoms for children with pleuropulmonary blastoma are not specific. They commonly include the following:

The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the heart/great vessels, mediastinum, diaphragm, and/or pleura.[1,2] Tumor embolism is a known risk, and radiographic evaluation of the central circulation is performed to identify potentially fatal embolic complications.[3]

Imaging evaluation may include chest radiography, computed tomography, magnetic resonance imaging, and echocardiography. Primary, recurrent, and/or extracranial metastatic pleuropulmonary blastoma presents with an fluorine F 18-fludeoxyglucose–avid lesion on positron emission tomography imaging.[4]

References

1. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007. [PUBMED Abstract]
2. Bisogno G, Brennan B, Orbach D, et al.: Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report. Eur J Cancer 50 (1): 178-84, 2014. [PUBMED Abstract]
3. Priest JR, Andic D, Arbuckle S, et al.: Great vessel/cardiac extension and tumor embolism in pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. Pediatr Blood Cancer 56 (4): 604-9, 2011. [PUBMED Abstract]
4. Hagedorn KN, Nelson AT, Towbin AJ, et al.: Assessing the role of positron emission tomography and bone scintigraphy in imaging of pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry. Pediatr Blood Cancer 70 (11): e30628, 2023. [PUBMED Abstract]

In a comprehensive analysis of 350 patients reported by the International Pleuropulmonary Blastoma Registry, only two prognostic factors were identified: the type of pleuropulmonary blastoma and the presence of metastatic disease at diagnosis.[1] In three additional small cohort series, the ability to perform a complete surgical resection was also identified as a prognostic factor.[2–4]

The presence of a germline DICER1 pathogenic variant is not a prognostic factor.[1]

A retrospective study analyzed TP53 expression by immunohistochemistry (IHC) in patients with pleuropulmonary blastoma.[5] A total of 143 cases were included in the study, with the following distribution of pleuropulmonary blastoma types: Type I, 23%; Type Ir, 14%; Type II, 32%; and Type III, 31%. TP53 expression was determined by IHC and grouped as follows: 0%, 1% to 25%, 26% to 75%, and 76% to 100%. All Type I pleuropulmonary blastomas showed TP53 expressions of 0% to 25%, compared with Type III pleuropulmonary blastomas, which had higher TP53 expressions (>25%) (P < .0001). High TP53 expression (staining observed in >25% of the tumor cells) was significantly associated with age older than 1 year (P = .0033), neoadjuvant therapy (P = .0009), positive resection margin (P = .0008), and anaplasia (P < .0001). TP53 expression was significantly associated with recurrence-free survival (P < .0001) and overall survival (P = .0350). Higher TP53 expression was associated with a worse prognosis. Comparisons of concordance statistics showed no significant difference in prognostication when using morphological types compared with TP53 expression groups (P = .647).[5]

References

1. Messinger YH, Stewart DR, Priest JR, et al.: Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer 121 (2): 276-85, 2015. [PUBMED Abstract]
2. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007. [PUBMED Abstract]
3. Bisogno G, Brennan B, Orbach D, et al.: Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report. Eur J Cancer 50 (1): 178-84, 2014. [PUBMED Abstract]
4. Sparber-Sauer M, Seitz G, Kirsch S, et al.: The impact of local control in the treatment of type II/III pleuropulmonary blastoma. Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS). J Surg Oncol 115 (2): 164-172, 2017. [PUBMED Abstract]
5. González IA, Mallinger P, Watson D, et al.: Expression of p53 is significantly associated with recurrence-free survival and overall survival in pleuropulmonary blastoma (PPB): a report from the International Pleuropulmonary Blastoma/DICER1 Registry. Mod Pathol 34 (6): 1104-1115, 2021. [PUBMED Abstract]

There are no standard treatment options for childhood pleuropulmonary blastoma. Current treatment regimens for these rare tumors have been informed by consensus opinion. The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network–European Registry) published comprehensive recommendations for the diagnosis and treatment of pleuropulmonary blastoma in children and adolescents.[1]

Treatment options for childhood pleuropulmonary blastoma include the following:

A complete surgical resection is required for cure.[2]

Data from the International Pleuropulmonary Blastoma Registry and the European Cooperative Study Group for Pediatric Rare Tumors suggest that adjuvant chemotherapy may reduce the risk of recurrence.[3]; [4][Level of evidence C1] Responses to chemotherapy have been reported with agents similar to those used for the treatment of rhabdomyosarcoma.[3–5]

Some general treatment considerations from the International Pleuropulmonary Blastoma Registry, according to subtype, are discussed below.[3,6]

References

1. Bisogno G, Sarnacki S, Stachowicz-Stencel T, et al.: Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer 68 (Suppl 4): e29045, 2021. [PUBMED Abstract]
2. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007. [PUBMED Abstract]
3. Messinger YH, Stewart DR, Priest JR, et al.: Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer 121 (2): 276-85, 2015. [PUBMED Abstract]
4. Bisogno G, Brennan B, Orbach D, et al.: Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report. Eur J Cancer 50 (1): 178-84, 2014. [PUBMED Abstract]
5. Venkatramani R, Malogolowkin MH, Wang L, et al.: Pleuropulmonary blastoma: a single-institution experience. J Pediatr Hematol Oncol 34 (5): e182-5, 2012. [PUBMED Abstract]
6. The International Pleuropulmonary Blastoma/DICER1 Registry. Minneapolis, Minn: Children’s Minnesota. Available online. Last accessed August 23, 2024.
7. Nelson AT, Harris AK, Watson D, et al.: Type I and Ir pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry. Cancer 129 (4): 600-613, 2023. [PUBMED Abstract]
8. Sparber-Sauer M, Seitz G, Kirsch S, et al.: The impact of local control in the treatment of type II/III pleuropulmonary blastoma. Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS). J Surg Oncol 115 (2): 164-172, 2017. [PUBMED Abstract]
9. Schultz KAP, Harris AK, Nelson AT, et al.: Outcomes for Children With Type II and Type III Pleuropulmonary Blastoma Following Chemotherapy: A Report From the International PPB/DICER1 Registry. J Clin Oncol 41 (4): 778-789, 2023. [PUBMED Abstract]

A retrospective review included 35 children with Type II or Type III pleuropulmonary blastoma and progressive or recurrent disease who were registered in national and European databases and trials (2000–2018).[1] Patients had a median age of 3.9 years (range, 0.5–17.8 years).

References

1. Sparber-Sauer M, Tagarelli A, Seitz G, et al.: Children with progressive and relapsed pleuropulmonary blastoma: A European collaborative analysis. Pediatr Blood Cancer 68 (12): e29268, 2021. [PUBMED Abstract]

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Types of Pleuropulmonary Blastoma

Added text to state that in the National Cancer Institute Natural History of DICER1 Syndrome study and the International Pleuropulmonary Blastoma/DICER1 Registry, people with germline DICER1 pathogenic or likely pathogenic variants who did not have computed tomography (CT) scans before age 12 years were screened with chest CT. Cystic lesions were identified in 38% of individuals. Five cysts were resected, four of which were classified as Type Ir. The other cysts were not biopsied to confirm the Type Ir diagnosis (cited Nelson et al. as reference 5).

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

Esophageal cancer is rare in children and adolescents, although it is relatively common in older adults.[1,2]

Most of these tumors are squamous cell carcinomas, although sarcomas can also arise in the esophagus. The most common benign tumor is leiomyoma.

Risk factors include caustic ingestion, gastroesophageal reflux, and Barrett esophagus.[2]

Symptoms are related to difficulty in swallowing and associated weight loss. Diagnosis is made by histological examination of biopsy tissue.

Prognosis is generally poor for children with esophageal cancer.

References

1. Gangopadhyay AN, Mohanty PK, Gopal SC, et al.: Adenocarcinoma of the esophagus in an 8-year-old boy. J Pediatr Surg 32 (8): 1259-60, 1997. [PUBMED Abstract]
2. Issaivanan M, Redner A, Weinstein T, et al.: Esophageal carcinoma in children and adolescents. J Pediatr Hematol Oncol 34 (1): 63-7, 2012. [PUBMED Abstract]

Treatment options for childhood esophageal carcinoma include the following:[1]

Esophageal cancer in children can rarely be completely resected.

For more information, see Esophageal Cancer Treatment.

References

1. Issaivanan M, Redner A, Weinstein T, et al.: Esophageal carcinoma in children and adolescents. J Pediatr Hematol Oncol 34 (1): 63-7, 2012. [PUBMED Abstract]

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Esophageal Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

Inflammatory myofibroblastic tumors (IMTs) occur throughout the body, but the lungs are the most commonly involved organs. IMTs are one of the most frequent lung tumors in children, accounting for between 16% and 38% of cases in various series.[1–3]

The biology of IMT is variable, with the potential for local recurrences and rare distant metastases.[4] The ALK locus (located on chromosome 2p23) is rearranged in approximately 50% of IMT cases. ALK rearrangements can involve various different genes.[5,6] Other potentially targetable fusions have been reported in a smaller fraction of IMTs, including ROS1, NTRK3, RET, and PDGFRB fusions.[6,7]

References

1. Yu DC, Grabowski MJ, Kozakewich HP, et al.: Primary lung tumors in children and adolescents: a 90-year experience. J Pediatr Surg 45 (6): 1090-5, 2010. [PUBMED Abstract]
2. Weldon CB, Shamberger RC: Pediatric pulmonary tumors: primary and metastatic. Semin Pediatr Surg 17 (1): 17-29, 2008. [PUBMED Abstract]
3. Siemion K, Reszec-Gielazyn J, Kisluk J, et al.: What do we know about inflammatory myofibroblastic tumors? – A systematic review. Adv Med Sci 67 (1): 129-138, 2022. [PUBMED Abstract]
4. Lichtenberger JP, Biko DM, Carter BW, et al.: Primary Lung Tumors in Children: Radiologic-Pathologic Correlation From the Radiologic Pathology Archives. Radiographics 38 (7): 2151-2172, 2018 Nov-Dec. [PUBMED Abstract]
5. Coffin CM, Hornick JL, Fletcher CD: Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 31 (4): 509-20, 2007. [PUBMED Abstract]
6. Lovly CM, Gupta A, Lipson D, et al.: Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions. Cancer Discov 4 (8): 889-95, 2014. [PUBMED Abstract]
7. Antonescu CR, Suurmeijer AJ, Zhang L, et al.: Molecular characterization of inflammatory myofibroblastic tumors with frequent ALK and ROS1 gene fusions and rare novel RET rearrangement. Am J Surg Pathol 39 (7): 957-67, 2015. [PUBMED Abstract]

Inflammatory myofibroblastic tumors (IMTs) present with a large, peripherally located lobulated mass with a lower lobe predominance. Chest wall, vascular, and mediastinal invasion may be seen. Calcification is occasionally present. Enhancement is heterogeneous on contrast-enhanced computed tomography. Magnetic resonance imaging findings are variable, but IMTs may be isointense relative to skeletal muscle.

Treatment options for pulmonary inflammatory myofibroblastic tumors (IMTs) include the following:[1–3]

For more information about the treatment of this tumor, see the Inflammatory myofibroblastic tumor and epithelioid inflammatory myofibroblastic sarcoma section in Childhood Soft Tissue Sarcoma Treatment.

References

1. Coffin CM, Hornick JL, Fletcher CD: Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 31 (4): 509-20, 2007. [PUBMED Abstract]
2. Butrynski JE, D’Adamo DR, Hornick JL, et al.: Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 363 (18): 1727-33, 2010. [PUBMED Abstract]
3. Chavez C, Hoffman MA: Complete remission of ALK-negative plasma cell granuloma (inflammatory myofibroblastic tumor) of the lung induced by celecoxib: A case report and review of the literature. Oncol Lett 5 (5): 1672-1676, 2013. [PUBMED Abstract]
4. Mossé YP, Voss SD, Lim MS, et al.: Targeting ALK With Crizotinib in Pediatric Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumor: A Children’s Oncology Group Study. J Clin Oncol 35 (28): 3215-3221, 2017. [PUBMED Abstract]
5. Nakano K: Inflammatory myofibroblastic tumors: recent progress and future of targeted therapy. Jpn J Clin Oncol 53 (10): 885-892, 2023. [PUBMED Abstract]
6. Fischer M, Moreno L, Ziegler DS, et al.: Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol 22 (12): 1764-1776, 2021. [PUBMED Abstract]
7. Desai AV, Robinson GW, Gauvain K, et al.: Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro Oncol 24 (10): 1776-1789, 2022. [PUBMED Abstract]
8. Fujiki T, Sakai Y, Ikawa Y, et al.: Pediatric inflammatory myofibroblastic tumor of the bladder with ALK-FN1 fusion successfully treated by alectinib. Pediatr Blood Cancer 70 (4): e30172, 2023. [PUBMED Abstract]
9. Schoot RA, Orbach D, Minard Colin V, et al.: Inflammatory Myofibroblastic Tumor With ROS1 Gene Fusions in Children and Young Adolescents. JCO Precis Oncol 7: e2300323, 2023. [PUBMED Abstract]

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Treatment of Childhood Pulmonary Inflammatory Myofibroblastic Tumors (IMTs)

Added alectinib to the list of targeted therapies used for patients with IMTs. Also added text to state that a case report described the successful treatment of a patient with an IMT and a FN1::ALK gene fusion using alectinib, a second-generation ALK inhibitor (cited Fujiki et al. as reference 8).

Added text about the results of a retrospective, international, multicenter study that analyzed patients younger than 21 years with ROS1-altered IMTs who were enrolled in either the European paediatric Soft Tissue Sarcoma Study Group NRSTS-2005 study or the Soft Tissue Sarcoma Registry (cited Schoot et al. as reference 9).

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

References

1. Jayasinghe Y, Simmons PS: Fibroadenomas in adolescence. Curr Opin Obstet Gynecol 21 (5): 402-6, 2009. [PUBMED Abstract]
2. Lee M, Soltanian HT: Breast fibroadenomas in adolescents: current perspectives. Adolesc Health Med Ther 6: 159-63, 2015. [PUBMED Abstract]
3. Sun C, Zhang W, Ma H, et al.: Main Traits of Breast Fibroadenoma Among Adolescent Girls. Cancer Biother Radiopharm 35 (4): 271-276, 2020. [PUBMED Abstract]
4. McLaughlin CM, Gonzalez-Hernandez J, Bennett M, et al.: Pediatric breast masses: an argument for observation. J Surg Res 228: 247-252, 2018. [PUBMED Abstract]
5. Zmora O, Klin B, Iacob C, et al.: Characterizing excised breast masses in children and adolescents-Can a more aggressive pathology be predicted? J Pediatr Surg 55 (10): 2197-2200, 2020. [PUBMED Abstract]
6. Yin Lee JP, Thomas AJ, Lum SK, et al.: Gene expression profiling of giant fibroadenomas of the breast. Surg Oncol 37: 101536, 2021. [PUBMED Abstract]
7. Neinstein LS, Atkinson J, Diament M: Prevalence and longitudinal study of breast masses in adolescents. J Adolesc Health 14 (4): 277-81, 1993. [PUBMED Abstract]
8. Javed A, Jenkins SM, Labow B, et al.: Intermediate and long-term outcomes of fibroadenoma excision in adolescent and young adult patients. Breast J 25 (1): 91-95, 2019. [PUBMED Abstract]
9. Valdes EK, Boolbol SK, Cohen JM, et al.: Malignant transformation of a breast fibroadenoma to cystosarcoma phyllodes: case report and review of the literature. Am Surg 71 (4): 348-53, 2005. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Breast Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

References

1. Rivera-Hueto F, Hevia-Vázquez A, Utrilla-Alcolea JC, et al.: Long-term prognosis of teenagers with breast cancer. Int J Surg Pathol 10 (4): 273-9, 2002. [PUBMED Abstract]
2. Costa NM, Rodrigues H, Pereira H, et al.: Secretory breast carcinoma–case report and review of the medical literature. Breast 13 (4): 353-5, 2004. [PUBMED Abstract]
3. Flaherty DC, Bawa R, Burton C, et al.: Breast Cancer in Male Adolescents and Young Adults. Ann Surg Oncol 24 (1): 84-90, 2017. [PUBMED Abstract]
4. Richards MK, Goldin AB, Beierle EA, et al.: Breast Malignancies in Children: Presentation, Management, and Survival. Ann Surg Oncol 24 (6): 1482-1491, 2017. [PUBMED Abstract]
5. Veiga LH, Curtis RE, Morton LM, et al.: Association of Breast Cancer Risk After Childhood Cancer With Radiation Dose to the Breast and Anthracycline Use: A Report From the Childhood Cancer Survivor Study. JAMA Pediatr 173 (12): 1171-1179, 2019. [PUBMED Abstract]
6. Murthy V, Pawar S, Chamberlain RS: Disease Severity, Presentation, and Clinical Outcomes Among Adolescents With Malignant Breast Neoplasms: A 20-Year Population-Based Outcomes Study From the SEER Database (1973-2009). Clin Breast Cancer 17 (5): 392-398, 2017. [PUBMED Abstract]
7. Gutierrez JC, Housri N, Koniaris LG, et al.: Malignant breast cancer in children: a review of 75 patients. J Surg Res 147 (2): 182-8, 2008. [PUBMED Abstract]
8. Sadler C, Goldfarb M: Comparison of primary and secondary breast cancers in adolescents and young adults. Cancer 121 (8): 1295-302, 2015. [PUBMED Abstract]
9. Kaste SC, Hudson MM, Jones DJ, et al.: Breast masses in women treated for childhood cancer: incidence and screening guidelines. Cancer 82 (4): 784-92, 1998. [PUBMED Abstract]
10. Metayer C, Lynch CF, Clarke EA, et al.: Second cancers among long-term survivors of Hodgkin’s disease diagnosed in childhood and adolescence. J Clin Oncol 18 (12): 2435-43, 2000. [PUBMED Abstract]
11. Swerdlow AJ, Barber JA, Hudson GV, et al.: Risk of second malignancy after Hodgkin’s disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol 18 (3): 498-509, 2000. [PUBMED Abstract]
12. van Leeuwen FE, Klokman WJ, Veer MB, et al.: Long-term risk of second malignancy in survivors of Hodgkin’s disease treated during adolescence or young adulthood. J Clin Oncol 18 (3): 487-97, 2000. [PUBMED Abstract]
13. Henderson TO, Amsterdam A, Bhatia S, et al.: Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152 (7): 444-55; W144-54, 2010. [PUBMED Abstract]
14. Watanabe T, Honda T, Totsuka H, et al.: Simple prediction model for homologous recombination deficiency in breast cancers in adolescents and young adults. Breast Cancer Res Treat 182 (2): 491-502, 2020. [PUBMED Abstract]
15. Kataoka A, Tokunaga E, Masuda N, et al.: Clinicopathological features of young patients (<35 years of age) with breast cancer in a Japanese Breast Cancer Society supported study. Breast Cancer 21 (6): 643-50, 2014. [PUBMED Abstract]
16. Keegan TH, DeRouen MC, Press DJ, et al.: Occurrence of breast cancer subtypes in adolescent and young adult women. Breast Cancer Res 14 (2): R55, 2012. [PUBMED Abstract]
17. Anders CK, Hsu DS, Broadwater G, et al.: Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 26 (20): 3324-30, 2008. [PUBMED Abstract]
18. Murphy BL, Day CN, Hoskin TL, et al.: Adolescents and Young Adults with Breast Cancer have More Aggressive Disease and Treatment Than Patients in Their Forties. Ann Surg Oncol 26 (12): 3920-3930, 2019. [PUBMED Abstract]
19. Gabriel CA, Domchek SM: Breast cancer in young women. Breast Cancer Res 12 (5): 212, 2010. [PUBMED Abstract]
20. Tichy JR, Lim E, Anders CK: Breast cancer in adolescents and young adults: a review with a focus on biology. J Natl Compr Canc Netw 11 (9): 1060-9, 2013. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

Childhood nuclear protein of the testis (NUT) carcinomas (also known as midline tract carcinomas) arise in midline epithelial structures, typically the mediastinum and upper aerodigestive tract. These tumors present as very aggressive, undifferentiated carcinomas, with or without squamous differentiation.[1,2]

Although the original description of this neoplasm was reported in children and young adults, individuals of all ages can be affected.[3] A retrospective series with clinicopathological correlation of 54 patients found that the median age at diagnosis was 16 years (range, 0.1–78 years).[4] One study identified 11 patients younger than 18 years with NUT carcinoma in a German registry.[5] The median age was 13.2 years (range, 6.6–17.8 years). Thoracic and mediastinal tumors were found to be the primary site in six patients, head and neck tumors were the primary site in four patients, and one patient had a multifocal tumor with an unknown primary. All patients presented with regional lymph node involvement, and eight patients (72.7%) had distant metastases. Despite treatment with multiple therapies, the median event-free survival was 1.5 months, and the overall survival was 6.5 months.

References

1. French CA, Kutok JL, Faquin WC, et al.: Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22 (20): 4135-9, 2004. [PUBMED Abstract]
2. Chau NG, Hurwitz S, Mitchell CM, et al.: Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck. Cancer 122 (23): 3632-3640, 2016. [PUBMED Abstract]
3. French CA: NUT midline carcinoma. Cancer Genet Cytogenet 203 (1): 16-20, 2010. [PUBMED Abstract]
4. Bauer DE, Mitchell CM, Strait KM, et al.: Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clin Cancer Res 18 (20): 5773-9, 2012. [PUBMED Abstract]
5. Flaadt T, Wild H, Abele M, et al.: NUT carcinoma in pediatric patients: Characteristics, therapeutic regimens, and outcomes of 11 cases registered with the German Registry for Rare Pediatric Tumors (STEP). Pediatr Blood Cancer 71 (3): e30821, 2024. [PUBMED Abstract]

NUT carcinoma is a very rare and aggressive malignancy that is genetically defined by rearrangements of the NUTM1 gene. In most cases (75%), the NUTM1 gene on chromosome 15q14 is fused with the BRD4 gene on chromosome 19p13, creating chimeric genes that encode BRD4::NUT fusion proteins. In the remaining cases, NUTM1 is fused to other partners, most commonly BRD3 on chromosome 9q34 or NSD3 on chromosome 8p11.[1]

References

1. French CA, Rahman S, Walsh EM, et al.: NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism. Cancer Discov 4 (8): 928-41, 2014. [PUBMED Abstract]

The outcomes of patients with NUT carcinomas are very poor, with a median survival of less than 1 year. Preliminary studies suggested that patients with NUT carcinomas without the typical BRD4::NUTM1 fusion gene may have a better prognosis than patients with other NUT carcinomas.[1,2] A retrospective analysis of 124 patients (including 47 patients younger than 18 years) reported that NUT carcinomas could be divided into three risk groups based on the anatomical location and specific NUTM1 fusion partner. The group with the best prognosis (median overall survival, 36.5 months) consisted of 12 patients (9.7%) with nonthoracic primary tumors and NUTM1 fusions with genes other than BRD4.[3]

References

1. French CA, Kutok JL, Faquin WC, et al.: Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22 (20): 4135-9, 2004. [PUBMED Abstract]
2. French CA: NUT midline carcinoma. Cancer Genet Cytogenet 203 (1): 16-20, 2010. [PUBMED Abstract]
3. Chau NG, Ma C, Danga K, et al.: An Anatomical Site and Genetic-Based Prognostic Model for Patients With Nuclear Protein in Testis (NUT) Midline Carcinoma: Analysis of 124 Patients. JNCI Cancer Spectr 4 (2): pkz094, 2020. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Treatment options for childhood NUT carcinoma include the following:

Treatment of childhood NUT carcinoma includes a multimodal approach with systemic chemotherapy, surgery, and radiation therapy. Cisplatin, taxanes, and alkylating agents have been used with some success. While early response to these agents is common, tumor progression occurs early in the course of the disease.[1]; [2][Level of evidence C1]

In a report from the NUT Midline Carcinoma Registry, 40 patients with primary tumors in the head and neck were evaluable. The 2-year overall survival rate was 30%. The three long-term survivors (with survivals of 35, 72, and 78 months) underwent primary gross-total resection and received adjuvant therapy.[3]; [4][Level of evidence C1]

Because of the presence of the BRD4::NUTM1 gene fusion in NUT carcinomas, there has been increased interest in evaluating BET bromodomain inhibitors for adults and children with this malignancy.[5] Unfortunately, activity for this class of agents has been limited in reported clinical trials:

References

1. Lemelle L, Pierron G, Fréneaux P, et al.: NUT carcinoma in children and adults: A multicenter retrospective study. Pediatr Blood Cancer 64 (12): , 2017. [PUBMED Abstract]
2. Bauer DE, Mitchell CM, Strait KM, et al.: Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clin Cancer Res 18 (20): 5773-9, 2012. [PUBMED Abstract]
3. Sopfe J, Greffe B, Treece AL: Metastatic NUT Midline Carcinoma Treated With Aggressive Neoadjuvant Chemotherapy, Radiation, and Resection: A Case Report and Review of the Literature. J Pediatr Hematol Oncol 43 (1): e73-e75, 2021. [PUBMED Abstract]
4. Chau NG, Hurwitz S, Mitchell CM, et al.: Intensive treatment and survival outcomes in NUT midline carcinoma of the head and neck. Cancer 122 (23): 3632-3640, 2016. [PUBMED Abstract]
5. Pearson AD, DuBois SG, Buenger V, et al.: Bromodomain and extra-terminal inhibitors-A consensus prioritisation after the Paediatric Strategy Forum for medicinal product development of epigenetic modifiers in children-ACCELERATE. Eur J Cancer 146: 115-124, 2021. [PUBMED Abstract]
6. Piha-Paul SA, Hann CL, French CA, et al.: Phase 1 Study of Molibresib (GSK525762), a Bromodomain and Extra-Terminal Domain Protein Inhibitor, in NUT Carcinoma and Other Solid Tumors. JNCI Cancer Spectr 4 (2): pkz093, 2020. [PUBMED Abstract]
7. Cousin S, Blay JY, Garcia IB, et al.: Safety, pharmacokinetic, pharmacodynamic and clinical activity of molibresib for the treatment of nuclear protein in testis carcinoma and other cancers: Results of a Phase I/II open-label, dose escalation study. Int J Cancer 150 (6): 993-1006, 2022. [PUBMED Abstract]
8. Lewin J, Soria JC, Stathis A, et al.: Phase Ib Trial With Birabresib, a Small-Molecule Inhibitor of Bromodomain and Extraterminal Proteins, in Patients With Selected Advanced Solid Tumors. J Clin Oncol 36 (30): 3007-3014, 2018. [PUBMED Abstract]

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

The following are examples of national and/or institutional clinical trials that are currently being conducted:

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

References

1. Bitar MA, Moukarbel RV, Zalzal GH: Management of congenital subglottic hemangioma: trends and success over the past 17 years. Otolaryngol Head Neck Surg 132 (2): 226-31, 2005. [PUBMED Abstract]
2. McGuirt WF, Little JP: Laryngeal cancer in children and adolescents. Otolaryngol Clin North Am 30 (2): 207-14, 1997. [PUBMED Abstract]
3. Bauman NM, Smith RJ: Recurrent respiratory papillomatosis. Pediatr Clin North Am 43 (6): 1385-401, 1996. [PUBMED Abstract]
4. Forsyth AM, Camilon PR, Tracy L, et al.: Pediatric laryngeal tumors and demographics, management, and survival in laryngeal squamous cell carcinoma. Int J Pediatr Otorhinolaryngol 140: 110507, 2021. [PUBMED Abstract]
5. Siddiqui F, Sarin R, Agarwal JP, et al.: Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med Pediatr Oncol 40 (5): 322-4, 2003. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Laryngeal Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

References

1. Fortes HR, von Ranke FM, Escuissato DL, et al.: Recurrent respiratory papillomatosis: A state-of-the-art review. Respir Med 126: 116-121, 2017. [PUBMED Abstract]
2. Derkay CS, Wiatrak B: Recurrent respiratory papillomatosis: a review. Laryngoscope 118 (7): 1236-47, 2008. [PUBMED Abstract]
3. Maloney EM, Unger ER, Tucker RA, et al.: Longitudinal measures of human papillomavirus 6 and 11 viral loads and antibody response in children with recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 132 (7): 711-5, 2006. [PUBMED Abstract]
4. Novakovic D, Cheng ATL, Zurynski Y, et al.: A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program. J Infect Dis 217 (2): 208-212, 2018. [PUBMED Abstract]
5. Meites E, Stone L, Amiling R, et al.: Significant Declines in Juvenile-onset Recurrent Respiratory Papillomatosis Following Human Papillomavirus (HPV) Vaccine Introduction in the United States. Clin Infect Dis 73 (5): 885-890, 2021. [PUBMED Abstract]
6. Gélinas JF, Manoukian J, Côté A: Lung involvement in juvenile onset recurrent respiratory papillomatosis: a systematic review of the literature. Int J Pediatr Otorhinolaryngol 72 (4): 433-52, 2008. [PUBMED Abstract]
7. Karatayli-Ozgursoy S, Bishop JA, Hillel A, et al.: Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population. Ann Otol Rhinol Laryngol 125 (3): 235-41, 2016. [PUBMED Abstract]
8. Amiling R, Meites E, Querec TD, et al.: Juvenile-Onset Recurrent Respiratory Papillomatosis in the United States, Epidemiology and HPV Types-2015-2020. J Pediatric Infect Dis Soc 10 (7): 774-781, 2021. [PUBMED Abstract]
9. Andrus JG, Shapshay SM: Contemporary management of laryngeal papilloma in adults and children. Otolaryngol Clin North Am 39 (1): 135-58, 2006. [PUBMED Abstract]
10. Xiao Y, Zhang X, Ma L, et al.: Long-term outcomes of juvenile-onset recurrent respiratory papillomatosis. Clin Otolaryngol 46 (1): 161-167, 2021. [PUBMED Abstract]
11. Carnevale C, Ferrán-De la Cierva L, Til-Pérez G, et al.: Safe use of systemic bevacizumab for respiratory recurrent papillomatosis in two children. Laryngoscope 129 (4): 1001-1004, 2019. [PUBMED Abstract]
12. Ruiz R, Balamuth N, Javia LR, et al.: Systemic Bevacizumab Treatment for Recurrent Respiratory Papillomatosis: Long-Term Follow-Up. Laryngoscope 132 (10): 2071-2075, 2022. [PUBMED Abstract]
13. Zhao X, Wang J, Chen Q, et al.: Systemic bevacizumab for treatment of recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol 281 (4): 1865-1875, 2024. [PUBMED Abstract]
14. So RJ, Rayle C, Joo HH, et al.: Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Institution’s Experience. Laryngoscope 134 (7): 3253-3259, 2024. [PUBMED Abstract]
15. Avidano MA, Singleton GT: Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 112 (2): 197-202, 1995. [PUBMED Abstract]
16. Derkay CS, Smith RJ, McClay J, et al.: HspE7 treatment of pediatric recurrent respiratory papillomatosis: final results of an open-label trial. Ann Otol Rhinol Laryngol 114 (9): 730-7, 2005. [PUBMED Abstract]
17. Sidell DR, Nassar M, Cotton RT, et al.: High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 123 (3): 214-21, 2014. [PUBMED Abstract]
18. Chadha NK, James A: Adjuvant antiviral therapy for recurrent respiratory papillomatosis. Cochrane Database Syst Rev 12: CD005053, 2012. [PUBMED Abstract]
19. Ivancic R, Iqbal H, deSilva B, et al.: Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol 3 (1): 22-34, 2018. [PUBMED Abstract]
20. Young DL, Moore MM, Halstead LA: The use of the quadrivalent human papillomavirus vaccine (gardasil) as adjuvant therapy in the treatment of recurrent respiratory papilloma. J Voice 29 (2): 223-9, 2015. [PUBMED Abstract]
21. Mészner Z, Jankovics I, Nagy A, et al.: Recurrent laryngeal papillomatosis with oesophageal involvement in a 2 year old boy: successful treatment with the quadrivalent human papillomatosis vaccine. Int J Pediatr Otorhinolaryngol 79 (2): 262-6, 2015. [PUBMED Abstract]
22. Katsuta T, Miyaji Y, Offit PA, et al.: Treatment With Quadrivalent Human Papillomavirus Vaccine for Juvenile-Onset Recurrent Respiratory Papillomatosis: Case Report and Review of the Literature. J Pediatric Infect Dis Soc 6 (4): 380-385, 2017. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was reformatted.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

References

1. Sultan I, Rodriguez-Galindo C, Al-Sharabati S, et al.: Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck 33 (10): 1476-81, 2011. [PUBMED Abstract]
2. Cesmebasi A, Gabriel A, Niku D, et al.: Pediatric head and neck tumors: an intra-demographic analysis using the SEER* database. Med Sci Monit 20: 2536-42, 2014. [PUBMED Abstract]
3. Chowdhry AK, McHugh C, Fung C, et al.: Second primary head and neck cancer after Hodgkin lymphoma: a population-based study of 44,879 survivors of Hodgkin lymphoma. Cancer 121 (9): 1436-45, 2015. [PUBMED Abstract]
4. Boukheris H, Stovall M, Gilbert ES, et al.: Risk of salivary gland cancer after childhood cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys 85 (3): 776-83, 2013. [PUBMED Abstract]
5. da Cruz Perez DE, Pires FR, Alves FA, et al.: Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases. Int J Pediatr Otorhinolaryngol 68 (7): 895-902, 2004. [PUBMED Abstract]
6. Muenscher A, Diegel T, Jaehne M, et al.: Benign and malignant salivary gland diseases in children A retrospective study of 549 cases from the Salivary Gland Registry, Hamburg. Auris Nasus Larynx 36 (3): 326-31, 2009. [PUBMED Abstract]
7. Fu H, Wang J, Wang L, et al.: Pleomorphic adenoma of the salivary glands in children and adolescents. J Pediatr Surg 47 (4): 715-9, 2012. [PUBMED Abstract]
8. Galer C, Santillan AA, Chelius D, et al.: Minor salivary gland malignancies in the pediatric population. Head Neck 34 (11): 1648-51, 2012. [PUBMED Abstract]
9. Thariat J, Vedrine PO, Temam S, et al.: The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands. J Pediatr 162 (4): 839-43, 2013. [PUBMED Abstract]
10. Chiaravalli S, Guzzo M, Bisogno G, et al.: Salivary gland carcinomas in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer 61 (11): 1961-8, 2014. [PUBMED Abstract]
11. Laikui L, Hongwei L, Hongbing J, et al.: Epithelial salivary gland tumors of children and adolescents in west China population: a clinicopathologic study of 79 cases. J Oral Pathol Med 37 (4): 201-5, 2008. [PUBMED Abstract]
12. Louredo BVR, Santos-Silva AR, Vargas PA, et al.: Clinicopathological analysis and survival outcomes of primary salivary gland tumors in pediatric patients: A systematic review. J Oral Pathol Med 50 (5): 435-443, 2021. [PUBMED Abstract]
13. Rahbar R, Grimmer JF, Vargas SO, et al.: Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience. Arch Otolaryngol Head Neck Surg 132 (4): 375-80, 2006. [PUBMED Abstract]
14. Kupferman ME, de la Garza GO, Santillan AA, et al.: Outcomes of pediatric patients with malignancies of the major salivary glands. Ann Surg Oncol 17 (12): 3301-7, 2010. [PUBMED Abstract]
15. Aro K, Leivo I, Mäkitie A: Management of salivary gland malignancies in the pediatric population. Curr Opin Otolaryngol Head Neck Surg 22 (2): 116-20, 2014. [PUBMED Abstract]
16. Locati LD, Collini P, Imbimbo M, et al.: Immunohistochemical and molecular profile of salivary gland cancer in children. Pediatr Blood Cancer 64 (9): , 2017. [PUBMED Abstract]
17. Techavichit P, Hicks MJ, López-Terrada DH, et al.: Mucoepidermoid Carcinoma in Children: A Single Institutional Experience. Pediatr Blood Cancer 63 (1): 27-31, 2016. [PUBMED Abstract]
18. Baněčková M, Thompson LDR, Hyrcza MD, et al.: Salivary Gland Secretory Carcinoma: Clinicopathologic and Genetic Characteristics of 215 Cases and Proposal for a Grading System. Am J Surg Pathol 47 (6): 661-677, 2023. [PUBMED Abstract]
19. Simon CT, McHugh JB, Rabah R, et al.: Secretory Carcinoma in Children and Young Adults: A Case Series. Pediatr Dev Pathol 25 (2): 155-161, 2022 Mar-Apr. [PUBMED Abstract]
20. Ngouajio AL, Drejet SM, Phillips DR, et al.: A systematic review including an additional pediatric case report: Pediatric cases of mammary analogue secretory carcinoma. Int J Pediatr Otorhinolaryngol 100: 187-193, 2017. [PUBMED Abstract]
21. Khalele BA: Systematic review of mammary analog secretory carcinoma of salivary glands at 7 years after description. Head Neck 39 (6): 1243-1248, 2017. [PUBMED Abstract]
22. Skálová A, Vanecek T, Sima R, et al.: Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 34 (5): 599-608, 2010. [PUBMED Abstract]
23. Othman BK, Steiner P, Leivo I, et al.: Rearrangement of KMT2A Characterizes a Subset of Pediatric Parotid Mucoepidermoid Carcinomas Arising Metachronous to Acute Lymphoblastic Leukemia. Fetal Pediatr Pathol 42 (5): 796-807, 2023. [PUBMED Abstract]
24. Rutt AL, Hawkshaw MJ, Lurie D, et al.: Salivary gland cancer in patients younger than 30 years. Ear Nose Throat J 90 (4): 174-84, 2011. [PUBMED Abstract]
25. Allan BJ, Tashiro J, Diaz S, et al.: Malignant tumors of the parotid gland in children: incidence and outcomes. J Craniofac Surg 24 (5): 1660-4, 2013. [PUBMED Abstract]
26. Seng D, Fang Q, Liu F, et al.: Intraparotid Lymph Node Metastasis Decreases Survival in Pediatric Patients With Parotid Cancer. J Oral Maxillofac Surg 78 (5): 852.e1-852.e6, 2020. [PUBMED Abstract]
27. Verma J, Teh BS, Paulino AC: Characteristics and outcome of radiation and chemotherapy-related mucoepidermoid carcinoma of the salivary glands. Pediatr Blood Cancer 57 (7): 1137-41, 2011. [PUBMED Abstract]
28. Védrine PO, Coffinet L, Temam S, et al.: Mucoepidermoid carcinoma of salivary glands in the pediatric age group: 18 clinical cases, including 11 second malignant neoplasms. Head Neck 28 (9): 827-33, 2006. [PUBMED Abstract]
29. Dublin JC, Oliver JR, Tam MM, et al.: Nodal Metastases in Pediatric and Adult Acinic Cell Carcinoma of the Major Salivary Glands. Otolaryngol Head Neck Surg 167 (6): 941-951, 2022. [PUBMED Abstract]
30. Phillips AL, Li C, Liang J, et al.: Adenoid cystic carcinoma of the parotid and submandibular glands in children and young adults: A population-based study. Pediatr Blood Cancer 71 (5): e30928, 2024. [PUBMED Abstract]
31. Surun A, Schneider DT, Ferrari A, et al.: Salivary gland carcinoma in children and adolescents: The EXPeRT/PARTNER diagnosis and treatment recommendations. Pediatr Blood Cancer 68 (Suppl 4): e29058, 2021. [PUBMED Abstract]
32. Ryan JT, El-Naggar AK, Huh W, et al.: Primacy of surgery in the management of mucoepidermoid carcinoma in children. Head Neck 33 (12): 1769-73, 2011. [PUBMED Abstract]
33. Morse E, Fujiwara RJT, Husain Z, et al.: Pediatric Salivary Cancer: Epidemiology, Treatment Trends, and Association of Treatment Modality with Survival. Otolaryngol Head Neck Surg 159 (3): 553-563, 2018. [PUBMED Abstract]
34. Grant SR, Grosshans DR, Bilton SD, et al.: Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics. Radiother Oncol 116 (2): 309-15, 2015. [PUBMED Abstract]
35. Mao MH, Zheng L, Wang XM, et al.: Surgery combined with postoperative (125) I seed brachytherapy for the treatment of mucoepidermoid carcinoma of the parotid gland in pediatric patients. Pediatr Blood Cancer 64 (1): 57-63, 2017. [PUBMED Abstract]
36. Drilon A, Siena S, Ou SI, et al.: Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7 (4): 400-409, 2017. [PUBMED Abstract]
37. Drilon A, Laetsch TW, Kummar S, et al.: Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378 (8): 731-739, 2018. [PUBMED Abstract]

Sialoblastoma is usually a benign tumor presenting in the neonatal period, but it has been reported to present as late as age 15 years. Sialoblastoma rarely metastasizes to the lungs, lymph nodes, or bones.[1]

The main treatment for patients with sialoblastoma is surgical resection. However, it has been suggested that neoadjuvant chemotherapy may be indicated as an alternative to mutilating surgery. Chemotherapy regimens with carboplatin, epirubicin, vincristine, etoposide, dactinomycin, doxorubicin, and ifosfamide have produced responses in two children with sialoblastoma.[2]; [3][Level of evidence C3]

References

1. Irace AL, Adil EA, Archer NM, et al.: Pediatric sialoblastoma: Evaluation and management. Int J Pediatr Otorhinolaryngol 87: 44-9, 2016. [PUBMED Abstract]
2. Prigent M, Teissier N, Peuchmaur M, et al.: Sialoblastoma of salivary glands in children: chemotherapy should be discussed as an alternative to mutilating surgery. Int J Pediatr Otorhinolaryngol 74 (8): 942-5, 2010. [PUBMED Abstract]
3. Scott JX, Krishnan S, Bourne AJ, et al.: Treatment of metastatic sialoblastoma with chemotherapy and surgery. Pediatr Blood Cancer 50 (1): 134-7, 2008. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Salivary Gland Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

More than 90% of tumors and tumor-like lesions in the oral cavity are benign.[1–4] Oral cavity cancer is extremely rare in children and adolescents.[5,6] According to the Surveillance, Epidemiology, and End Results Program Stat Fact Sheets, only 0.4% of all cases are diagnosed in patients younger than 20 years. From 2017 to 2021, the age-adjusted incidence rate for this population was 0.2 cases per 100,000.[7]

The incidence of oral cavity and pharynx cancers has increased in adolescent and young adult females. This pattern is consistent with the national increase in orogenital sexual intercourse in younger females and human papillomavirus (HPV) infection.[8] It is currently estimated that the prevalence of oral HPV infection in the United States is 6.9% in people aged 14 to 69 years and that HPV causes about 30,000 oropharyngeal cancers. Furthermore, from 1999 to 2008, the incidence rates for HPV-related oropharyngeal cancer increased by 4.4% per year in White men and 1.9% in White women.[9–11] Current practices to increase HPV immunization rates in both boys and girls may reduce the burden of HPV-related cancers.[12,13] For more information about HPV vaccines and oral cavity cancer prevention, see Oral Cavity, Oropharyngeal, Hypopharyngeal, and Laryngeal Cancers Prevention.

References

1. Das S, Das AK: A review of pediatric oral biopsies from a surgical pathology service in a dental school. Pediatr Dent 15 (3): 208-11, 1993 May-Jun. [PUBMED Abstract]
2. Ulmansky M, Lustmann J, Balkin N: Tumors and tumor-like lesions of the oral cavity and related structures in Israeli children. Int J Oral Maxillofac Surg 28 (4): 291-4, 1999. [PUBMED Abstract]
3. Tröbs RB, Mader E, Friedrich T, et al.: Oral tumors and tumor-like lesions in infants and children. Pediatr Surg Int 19 (9-10): 639-45, 2003. [PUBMED Abstract]
4. Tanaka N, Murata A, Yamaguchi A, et al.: Clinical features and management of oral and maxillofacial tumors in children. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88 (1): 11-5, 1999. [PUBMED Abstract]
5. Young JL, Miller RW: Incidence of malignant tumors in U. S. children. J Pediatr 86 (2): 254-8, 1975. [PUBMED Abstract]
6. Berstein L, Gurney JG: Carcinomas and other malignant epithelial neoplasms. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649, Chapter 11, pp 139-148. Also available online. Last accessed August 23, 2022.
7. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
8. Bleyer A: Cancer of the oral cavity and pharynx in young females: increasing incidence, role of human papilloma virus, and lack of survival improvement. Semin Oncol 36 (5): 451-9, 2009. [PUBMED Abstract]
9. D’Souza G, Dempsey A: The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med 53 (Suppl 1): S5-S11, 2011. [PUBMED Abstract]
10. Gillison ML, Broutian T, Pickard RK, et al.: Prevalence of oral HPV infection in the United States, 2009-2010. JAMA 307 (7): 693-703, 2012. [PUBMED Abstract]
11. Simard EP, Ward EM, Siegel R, et al.: Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin 62 (2): 118-28, 2012 Mar-Apr. [PUBMED Abstract]
12. Gillison ML, Chaturvedi AK, Lowy DR: HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women. Cancer 113 (10 Suppl): 3036-46, 2008. [PUBMED Abstract]
13. Guo T, Eisele DW, Fakhry C: The potential impact of prophylactic human papillomavirus vaccination on oropharyngeal cancer. Cancer 122 (15): 2313-23, 2016. [PUBMED Abstract]

Acquired conditions and genetic syndromes associated with the development of oral cavity and/or head and neck squamous cell carcinoma include the following:[1–8]

References

1. Oksüzoğlu B, Yalçin S: Squamous cell carcinoma of the tongue in a patient with Fanconi’s anemia: a case report and review of the literature. Ann Hematol 81 (5): 294-8, 2002. [PUBMED Abstract]
2. Reinhard H, Peters I, Gottschling S, et al.: Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia. J Pediatr Hematol Oncol 29 (7): 488-91, 2007. [PUBMED Abstract]
3. Ragin CC, Modugno F, Gollin SM: The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J Dent Res 86 (2): 104-14, 2007. [PUBMED Abstract]
4. Fine JD, Johnson LB, Weiner M, et al.: Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol 60 (2): 203-11, 2009. [PUBMED Abstract]
5. Kraemer KH, Lee MM, Scotto J: Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol 123 (2): 241-50, 1987. [PUBMED Abstract]
6. Alter BP: Cancer in Fanconi anemia, 1927-2001. Cancer 97 (2): 425-40, 2003. [PUBMED Abstract]
7. Mazereeuw-Hautier J, Bitoun E, Chevrant-Breton J, et al.: Keratitis-ichthyosis-deafness syndrome: disease expression and spectrum of connexin 26 (GJB2) mutations in 14 patients. Br J Dermatol 156 (5): 1015-9, 2007. [PUBMED Abstract]
8. Alter BP, Giri N, Savage SA, et al.: Cancer in dyskeratosis congenita. Blood 113 (26): 6549-57, 2009. [PUBMED Abstract]

Benign odontogenic neoplasms of the oral cavity include odontoma and ameloblastoma. The most common nonodontogenic neoplasms of the oral cavity are fibromas, hemangiomas, vascular malformations, and papillomas. Tumor-like lesions of the oral cavity include granulomas and Langerhans cell histiocytosis.[1–4] For more information about Langerhans cell histiocytosis of the oral cavity, see the Oral cavity section in Langerhans Cell Histiocytosis Treatment.

Malignant lesions of the oral cavity were found in 0.1% to 2% of a series of oral biopsies performed in children and 3% to 13% of oral tumor biopsies.[3–7] Malignant tumor types include lymphomas (especially Burkitt), sarcomas (including rhabdomyosarcoma and fibrosarcoma), and oral cavity squamous cell carcinoma. Mucoepidermoid carcinomas of the oral cavity have also been reported in the pediatric and adolescent age groups.[5–8]

References

1. Das S, Das AK: A review of pediatric oral biopsies from a surgical pathology service in a dental school. Pediatr Dent 15 (3): 208-11, 1993 May-Jun. [PUBMED Abstract]
2. Ulmansky M, Lustmann J, Balkin N: Tumors and tumor-like lesions of the oral cavity and related structures in Israeli children. Int J Oral Maxillofac Surg 28 (4): 291-4, 1999. [PUBMED Abstract]
3. Tröbs RB, Mader E, Friedrich T, et al.: Oral tumors and tumor-like lesions in infants and children. Pediatr Surg Int 19 (9-10): 639-45, 2003. [PUBMED Abstract]
4. Tanaka N, Murata A, Yamaguchi A, et al.: Clinical features and management of oral and maxillofacial tumors in children. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88 (1): 11-5, 1999. [PUBMED Abstract]
5. da Silva Barros CC, da Silva LP, Gonzaga AKG, et al.: Neoplasms and non-neoplastic pathologies in the oral and maxillofacial regions in children and adolescents of a Brazilian population. Clin Oral Investig 23 (4): 1587-1593, 2019. [PUBMED Abstract]
6. Zhang JL, Liu Y, Shan XF, et al.: Clinical Characterization of Oral and Maxillofacial Tumors and Tumor-Like Lesions in Children and Adolescents. J Craniofac Surg 34 (5): 1496-1502, 2023 Jul-Aug 01. [PUBMED Abstract]
7. Park SH, Kim H, Song JS, et al.: A 20-year retrospective study of pediatric oral lesion biopsy. J Korean Acad Pediatr Dent 48(4): 425-6, 2021. Also available online. Last accessed July 11, 2024.
8. Perez DE, Pires FR, Alves Fde A, et al.: Juvenile intraoral mucoepidermoid carcinoma. J Oral Maxillofac Surg 66 (2): 308-11, 2008. [PUBMED Abstract]

The prognosis for patients with oral cavity tumors varies based on histology and disease staging.

Review of the Surveillance, Epidemiology, and End Results (SEER) Program database identified 54 patients younger than 20 years with oral cavity squamous cell carcinoma (SCC) between 1973 and 2006. Pediatric patients with oral cavity SCC were more often female and had better survival than adult patients. When differences in patient, tumor, and treatment-related characteristics were adjusted for, the pediatric and adult groups experienced equivalent survival rates.[1][Level of evidence C1] Most tumors have a low or intermediate grade and are often cured with surgery alone.[1]; [2][Level of evidence C1] A retrospective study of the National Cancer Database identified 159 patients younger than 20 years with SCC of the head and neck. Of these tumors, 55% originated in the oral cavity, and patients with laryngeal tumors had a better survival rate than did those who presented with oral cavity primary tumors.[3]

A review of 102 intraoral mucoepidermoid carcinomas identified nine patients younger than 18 years. All patients were treated with surgical resection, and eight patients were disease free after a mean follow-up of 98.4 months. One patient died after developing recurrent disease 15 years after their initial treatment.[2]

References

1. Morris LG, Ganly I: Outcomes of oral cavity squamous cell carcinoma in pediatric patients. Oral Oncol 46 (4): 292-6, 2010. [PUBMED Abstract]
2. Perez DE, Pires FR, Alves Fde A, et al.: Juvenile intraoral mucoepidermoid carcinoma. J Oral Maxillofac Surg 66 (2): 308-11, 2008. [PUBMED Abstract]
3. Modh A, Gayar OH, Elshaikh MA, et al.: Pediatric head and neck squamous cell carcinoma: Patient demographics, treatment trends and outcomes. Int J Pediatr Otorhinolaryngol 106: 21-25, 2018. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Lip and Oral Cavity Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

Treatment options for childhood oral cavity cancer include the following:

The management of malignant tumors of the oral cavity depends on histology.[1] Most patients with oral cavity squamous cell carcinoma and intraoral mucoepidermoid carcinoma who were managed with surgery alone have a good prognosis and do not experience recurrences.[2–4] For more information, see Lip and Oral Cavity Cancer Treatment.

Langerhans cell histiocytosis of the oral cavity may require treatment in addition to surgery. For more information, see Langerhans Cell Histiocytosis Treatment.

Surgery is the primary treatment modality for benign oral cavity tumors.

References

1. Sturgis EM, Moore BA, Glisson BS, et al.: Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young adults: a case series. Head Neck 27 (9): 748-56, 2005. [PUBMED Abstract]
2. Woo VL, Kelsch RD, Su L, et al.: Gingival squamous cell carcinoma in adolescence. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107 (1): 92-9, 2009. [PUBMED Abstract]
3. Morris LG, Ganly I: Outcomes of oral cavity squamous cell carcinoma in pediatric patients. Oral Oncol 46 (4): 292-6, 2010. [PUBMED Abstract]
4. Ryan JT, El-Naggar AK, Huh W, et al.: Primacy of surgery in the management of mucoepidermoid carcinoma in children. Head Neck 33 (12): 1769-73, 2011. [PUBMED Abstract]

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

Esthesioneuroblastoma (also called olfactory neuroblastoma) is a very rare small round cell tumor arising from the nasal neuroepithelium. Less than 10% of cases occur in children and adolescents.[1,2] The estimated incidence of esthesioneuroblastoma is 0.1 cases per 100,000 people per year in children younger than 15 years.[3] In the pediatric population, the median age is 10 years, and there are no gender or racial predilections.[2]

Despite its rarity, esthesioneuroblastoma is the most common cancer of the nasal cavity in pediatric patients, accounting for 28% of cases in a Surveillance, Epidemiology, and End Results (SEER) Program study.[1]

References

1. Benoit MM, Bhattacharyya N, Faquin W, et al.: Cancer of the nasal cavity in the pediatric population. Pediatrics 121 (1): e141-5, 2008. [PUBMED Abstract]
2. Berger MH, Lehrich BM, Yasaka TM, et al.: Characteristics and overall survival in pediatric versus adult esthesioneuroblastoma: A population-based study. Int J Pediatr Otorhinolaryngol 144: 110696, 2021. [PUBMED Abstract]
3. Bisogno G, Soloni P, Conte M, et al.: Esthesioneuroblastoma in pediatric and adolescent age. A report from the TREP project in cooperation with the Italian Neuroblastoma and Soft Tissue Sarcoma Committees. BMC Cancer 12: 117, 2012. [PUBMED Abstract]

Figure 1 depicts the areas of the body where esthesioneuroblastoma tumors may form, including the olfactory nerve endings, olfactory bulb, nasal cavity, nasal sinuses, and brain.

Enlarge

Most children present with symptoms that may include the following:[1]

References

1. Venkatramani R, Pan H, Furman WL, et al.: Multimodality Treatment of Pediatric Esthesioneuroblastoma. Pediatr Blood Cancer 63 (3): 465-70, 2016. [PUBMED Abstract]

Esthesioneuroblastoma can be histologically confused with other small round cell tumors of the nasal cavity, including sinonasal undifferentiated carcinoma, small cell carcinoma, melanoma, and rhabdomyosarcoma. Esthesioneuroblastoma typically shows diffuse staining with neuron-specific enolase, synaptophysin, and chromogranins, with variable cytokeratin expression.[1]

Nine medical centers obtained 66 samples of olfactory neuroblastoma and tumor samples from other cancers, including alveolar rhabdomyosarcoma and sinonasal adenocarcinoma. The tumor samples were analyzed by genome-wide DNA methylation profiling, copy number analysis, immunohistochemistry, and next-generation panel sequencing. Unsupervised hierarchal clustering analysis of DNA methylation data identified the following four distinct clusters:[2]

Using this information, the authors developed an algorithm that incorporates methylation analysis to improve the diagnostic accuracy of this entity.[2]

References

1. Su SY, Bell D, Hanna EY: Esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma: differentiation in diagnosis and treatment. Int Arch Otorhinolaryngol 18 (Suppl 2): S149-56, 2014. [PUBMED Abstract]
2. Capper D, Engel NW, Stichel D, et al.: DNA methylation-based reclassification of olfactory neuroblastoma. Acta Neuropathol 136 (2): 255-271, 2018. [PUBMED Abstract]

Review of multiple case series of mainly adult patients indicates that the following may correlate with adverse prognosis:[1–3]

References

1. Dulguerov P, Allal AS, Calcaterra TC: Esthesioneuroblastoma: a meta-analysis and review. Lancet Oncol 2 (11): 683-90, 2001. [PUBMED Abstract]
2. Patel SG, Singh B, Stambuk HE, et al.: Craniofacial surgery for esthesioneuroblastoma: report of an international collaborative study. J Neurol Surg B Skull Base 73 (3): 208-20, 2012. [PUBMED Abstract]
3. Herr MW, Sethi RK, Meier JC, et al.: Esthesioneuroblastoma: an update on the massachusetts eye and ear infirmary and massachusetts general hospital experience with craniofacial resection, proton beam radiation, and chemotherapy. J Neurol Surg B Skull Base 75 (1): 58-64, 2014. [PUBMED Abstract]

Tumors are staged according to the Kadish system (see Table 1). Correlated with Kadish stage, survival rates range from 90% (stage A) to less than 40% (stage D). Most patients present with locally advanced–stage disease (Kadish stages B and C). Reports of metastatic disease (Kadish stage D) vary among studies and is described at rates of 20% to 30%.[1–6]

Reports suggest that positron emission tomography–computed tomography (PET-CT) may aid in staging the disease.[7]

References

1. Bisogno G, Soloni P, Conte M, et al.: Esthesioneuroblastoma in pediatric and adolescent age. A report from the TREP project in cooperation with the Italian Neuroblastoma and Soft Tissue Sarcoma Committees. BMC Cancer 12: 117, 2012. [PUBMED Abstract]
2. Benoit MM, Bhattacharyya N, Faquin W, et al.: Cancer of the nasal cavity in the pediatric population. Pediatrics 121 (1): e141-5, 2008. [PUBMED Abstract]
3. Venkatramani R, Pan H, Furman WL, et al.: Multimodality Treatment of Pediatric Esthesioneuroblastoma. Pediatr Blood Cancer 63 (3): 465-70, 2016. [PUBMED Abstract]
4. Berger MH, Lehrich BM, Yasaka TM, et al.: Characteristics and overall survival in pediatric versus adult esthesioneuroblastoma: A population-based study. Int J Pediatr Otorhinolaryngol 144: 110696, 2021. [PUBMED Abstract]
5. Dumont B, Fresneau B, Claude L, et al.: Pattern of loco-regional relapses and treatment in pediatric esthesioneuroblastoma: The French very rare tumors group (Fracture) contribution. Pediatr Blood Cancer 67 (4): e28154, 2020. [PUBMED Abstract]
6. Safi C, Spielman D, Otten M, et al.: Treatment Strategies and Outcomes of Pediatric Esthesioneuroblastoma: A Systematic Review. Front Oncol 10: 1247, 2020. [PUBMED Abstract]
7. Broski SM, Hunt CH, Johnson GB, et al.: The added value of 18F-FDG PET/CT for evaluation of patients with esthesioneuroblastoma. J Nucl Med 53 (8): 1200-6, 2012. [PUBMED Abstract]

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

The use of multimodal therapy optimizes the chances for survival, with more than 70% of children expected to survive 5 or more years after initial diagnosis.[1–5] Neuromeningeal progression is the most common type of treatment failure.[5,6][Level of evidence C1]

Treatment options according to Kadish stage include the following:[7]

The mainstay of treatment is surgery and radiation therapy. However, esthesioneuroblastoma is a chemosensitive neoplasm, and the use of neoadjuvant chemotherapy can facilitate resection.[5,7–9] Endoscopic sinus surgery offers short-term outcomes similar to open craniofacial resection.[10]; [11][Level of evidence C2] Other techniques such as stereotactic radiosurgery and proton-beam therapy (charged-particle radiation therapy) may also play a role in the management of this tumor.[3,12,13]

Routine neck dissection and nodal exploration are not indicated in the absence of clinical or radiological evidence of disease.[14] Management of cervical lymph node metastases has been addressed in a review article.[14]

Reports have indicated promising results with the increased use of resection and neoadjuvant or adjuvant chemotherapy in patients with advanced-stage disease.[2,5,15–17]; [18][Level of evidence C1] Chemotherapy regimens that have been used with efficacy include the following:

References

1. Bisogno G, Soloni P, Conte M, et al.: Esthesioneuroblastoma in pediatric and adolescent age. A report from the TREP project in cooperation with the Italian Neuroblastoma and Soft Tissue Sarcoma Committees. BMC Cancer 12: 117, 2012. [PUBMED Abstract]
2. Eich HT, Müller RP, Micke O, et al.: Esthesioneuroblastoma in childhood and adolescence. Better prognosis with multimodal treatment? Strahlenther Onkol 181 (6): 378-84, 2005. [PUBMED Abstract]
3. Lucas JT, Ladra MM, MacDonald SM, et al.: Proton therapy for pediatric and adolescent esthesioneuroblastoma. Pediatr Blood Cancer 62 (9): 1523-8, 2015. [PUBMED Abstract]
4. Berger MH, Lehrich BM, Yasaka TM, et al.: Characteristics and overall survival in pediatric versus adult esthesioneuroblastoma: A population-based study. Int J Pediatr Otorhinolaryngol 144: 110696, 2021. [PUBMED Abstract]
5. Venkatramani R, Pan H, Furman WL, et al.: Multimodality Treatment of Pediatric Esthesioneuroblastoma. Pediatr Blood Cancer 63 (3): 465-70, 2016. [PUBMED Abstract]
6. Dumont B, Fresneau B, Claude L, et al.: Pattern of loco-regional relapses and treatment in pediatric esthesioneuroblastoma: The French very rare tumors group (Fracture) contribution. Pediatr Blood Cancer 67 (4): e28154, 2020. [PUBMED Abstract]
7. Safi C, Spielman D, Otten M, et al.: Treatment Strategies and Outcomes of Pediatric Esthesioneuroblastoma: A Systematic Review. Front Oncol 10: 1247, 2020. [PUBMED Abstract]
8. Ozsahin M, Gruber G, Olszyk O, et al.: Outcome and prognostic factors in olfactory neuroblastoma: a rare cancer network study. Int J Radiat Oncol Biol Phys 78 (4): 992-7, 2010. [PUBMED Abstract]
9. Di Carlo D, Fichera G, Dumont B, et al.: Olfactory neuroblastoma in children and adolescents: The EXPeRT recommendations for diagnosis and management. EJC Paediatr Oncol 3: 100136, 2024. Also available online. Last accessed July 11, 2024.
10. Soler ZM, Smith TL: Endoscopic versus open craniofacial resection of esthesioneuroblastoma: what is the evidence? Laryngoscope 122 (2): 244-5, 2012. [PUBMED Abstract]
11. Gallia GL, Reh DD, Lane AP, et al.: Endoscopic resection of esthesioneuroblastoma. J Clin Neurosci 19 (11): 1478-82, 2012. [PUBMED Abstract]
12. Unger F, Haselsberger K, Walch C, et al.: Combined endoscopic surgery and radiosurgery as treatment modality for olfactory neuroblastoma (esthesioneuroblastoma). Acta Neurochir (Wien) 147 (6): 595-601; discussion 601-2, 2005. [PUBMED Abstract]
13. Drescher NR, Indelicato DJ, Dagan R, et al.: Outcomes following proton therapy for pediatric esthesioneuroblastoma. Pediatr Blood Cancer 71 (2): e30793, 2024. [PUBMED Abstract]
14. Zanation AM, Ferlito A, Rinaldo A, et al.: When, how and why to treat the neck in patients with esthesioneuroblastoma: a review. Eur Arch Otorhinolaryngol 267 (11): 1667-71, 2010. [PUBMED Abstract]
15. Kumar M, Fallon RJ, Hill JS, et al.: Esthesioneuroblastoma in children. J Pediatr Hematol Oncol 24 (6): 482-7, 2002 Aug-Sep. [PUBMED Abstract]
16. Loy AH, Reibel JF, Read PW, et al.: Esthesioneuroblastoma: continued follow-up of a single institution’s experience. Arch Otolaryngol Head Neck Surg 132 (2): 134-8, 2006. [PUBMED Abstract]
17. Porter AB, Bernold DM, Giannini C, et al.: Retrospective review of adjuvant chemotherapy for esthesioneuroblastoma. J Neurooncol 90 (2): 201-4, 2008. [PUBMED Abstract]
18. Benfari G, Fusconi M, Ciofalo A, et al.: Radiotherapy alone for local tumour control in esthesioneuroblastoma. Acta Otorhinolaryngol Ital 28 (6): 292-7, 2008. [PUBMED Abstract]
19. Kim DW, Jo YH, Kim JH, et al.: Neoadjuvant etoposide, ifosfamide, and cisplatin for the treatment of olfactory neuroblastoma. Cancer 101 (10): 2257-60, 2004. [PUBMED Abstract]
20. Kumar R: Esthesioneuroblastoma: Multimodal management and review of literature. World J Clin Cases 3 (9): 774-8, 2015. [PUBMED Abstract]
21. El Kababri M, Habrand JL, Valteau-Couanet D, et al.: Esthesioneuroblastoma in children and adolescent: experience on 11 cases with literature review. J Pediatr Hematol Oncol 36 (2): 91-5, 2014. [PUBMED Abstract]
22. Kiyota N, Tahara M, Fujii S, et al.: Nonplatinum-based chemotherapy with irinotecan plus docetaxel for advanced or metastatic olfactory neuroblastoma: a retrospective analysis of 12 cases. Cancer 112 (4): 885-91, 2008. [PUBMED Abstract]

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

Incidence

In the United States, the annual incidence of thyroid cancers is 10.7 cases per 1 million in people aged 0 to 19 years. The incidence is higher in females than in males (17.6 vs. 4.1 cases per 1 million people, respectively) and lower in Black people than in White people (3.9 vs. 11.8 cases per 1 million people, respectively). It accounts for approximately 6% of all cancers in this age group.[1] Thyroid cancer incidence is higher in children aged 15 to 19 years (34.4 cases per 1 million people), and it accounts for approximately 14% of all cancers arising in this older age group.[1] The trend toward larger tumors suggests that diagnostic scrutiny is not the only explanation for the observed results.[2]

Two time-trend studies using the Surveillance, Epidemiology, and End Results (SEER) Program database have shown a 2% and 3.8% annual increase in the incidence of differentiated thyroid carcinoma in the United States among children, adolescents, and young adults in the 1973 to 2011 and 1984 to 2010 periods, respectively.[2,3] Newer data from the National Childhood Cancer Registry show an average annual increase in incidence rates of 1.2% between 2012 and 2021, without changes in survival.[1] A similar trend has been documented in other countries.[4,5]

The papillary subtype is the most common subtype of childhood thyroid cancer, accounting for approximately 60% of cases, followed by the papillary follicular variant subtype (20%–25%), the follicular subtype (10%), and the medullary subtype (<10%). The anaplastic subtype occurs in less than 1% of pediatric thyroid carcinomas. The incidence of the papillary subtype and its follicular variant peaks between the ages of 15 and 19 years. The incidence of medullary thyroid cancer is the highest in children aged 0 to 4 years and declines at older ages (see Figure 1).[6]

Enlarge

Diagnostic Evaluation

The prevalence of benign thyroid nodules in childhood has been estimated at about 0.5% to 2%.[7] However, thyroid nodules in children have a higher risk of malignancy (22%–26%) than thyroid nodules in adults (5%–15%).[8] Initial evaluation of a child or adolescent with a thyroid nodule includes the following:

• Ultrasonography of the thyroid and neck. Common ultrasonographic features of malignancy include hypoechogenicity, invasive margins, increased intranodular blood flow, microcalcifications, and abnormal cervical lymph nodes. Based on ultrasonographic characteristics, scoring systems have been developed to facilitate selection of nodules that require fine-needle aspiration (FNA) in adults. The most popular of these scoring systems is the Thyroid Imaging Reporting and Data System. However, the higher incidence of differentiated thyroid carcinoma in pediatric thyroid nodules and the lack of validation in the pediatric population limits the extrapolation of these criteria to children.[7,8]
• Serum thyroid-stimulating hormone (TSH) level. Thyroid function is usually normal. Hyperfunctioning nodules have a very low risk of malignancy (2%–6%).[8]
• Serum thyroglobulin level, which is usually elevated in differentiated thyroid carcinoma.
• FNA. The sensitivity, specificity, and accuracy of FNA in children are similar to those in adults, but there is a greater risk of false-negative findings in nodules larger than 4 cm.[8]

  FNA results are categorized according to the six tiers of The Bethesda System for Reporting Thyroid Cytopathology (see Table 1).[8]

  Table 1. Bethesda System for Reporting Thyroid Cytopathologya

  Bethesda Category	Cytopathological Category	Malignancy Rate	Suggested Treatment
  FNA = fine-needle aspiration; US = ultrasonography.
  aReprinted from Journal of Pediatric Surgery, Volume 55, Issue 11, Emily R. Christison-Lagay, Reto M. Baertschiger, Catherine Dinauer, Gary L. Francis, Marcus M. Malek, Timothy B Lautz, Jennifer H. Aldrink, Christa Grant, Daniel S. Rhee, Peter Ehrlich, Roshni Dasgupta, Shahab Abdessalam, Pediatric differentiated thyroid carcinoma: An update from the APSA Cancer Committee, Pages 2273–2283, Copyright (2020), with permission from Elsevier.[8]
  I	Nondiagnostic/inadequate	1%–5%	Repeat FNA (other options: continued US surveillance, lobectomy)
  II	Benign	0%–10%	Serial US if small, lobectomy if >4 cm
  III	Atypia/follicular lesion of undetermined significance	0%–44%	Molecular genetics, lobectomy if no concerning mutation, thyroidectomy if BRAF or fusion mutation
  IV	Follicular neoplasm	60%–71%	Molecular genetics, lobectomy if no concerning mutation, thyroidectomy if BRAF or fusion mutation
  V	Suspicious for malignancy	70%–86%	Total thyroidectomy +/− central neck dissection
  VI	Malignant	97%–100%	Total thyroidectomy +/− central neck dissection

  While molecular testing of thyroid nodules could be helpful in the diagnosis of papillary thyroid carcinoma, there is no evidence to support its use.[7]

• Lymph node evaluation. Examination of the cervical lymph nodes is critically important in stratifying risk and determining operative strategies. Architecturally concerning features found on ultrasound in adults include round shape, irregular margins, calcifications, cystic change, peripheral vascularity, loss of fatty hilum, and heterogeneous echotexture. FNA should be performed on any suspicious lymph nodes in the lateral neck as confirmation of metastatic involvement before lateral neck dissection.[8]

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References

1. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
2. Vergamini LB, Frazier AL, Abrantes FL, et al.: Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study. J Pediatr 164 (6): 1481-5, 2014. [PUBMED Abstract]
3. Golpanian S, Perez EA, Tashiro J, et al.: Pediatric papillary thyroid carcinoma: outcomes and survival predictors in 2504 surgical patients. Pediatr Surg Int 32 (3): 201-8, 2016. [PUBMED Abstract]
4. Pole JD, Zuk AM, Wasserman JD: Diagnostic and Treatment Patterns Among Children, Adolescents, and Young Adults with Thyroid Cancer in Ontario: 1992-2010. Thyroid 27 (8): 1025-1033, 2017. [PUBMED Abstract]
5. Schmidt Jensen J, Grønhøj C, Mirian C, et al.: Incidence and Survival of Thyroid Cancer in Children, Adolescents, and Young Adults in Denmark: A Nationwide Study from 1980 to 2014. Thyroid 28 (9): 1128-1133, 2018. [PUBMED Abstract]
6. Dermody S, Walls A, Harley EH: Pediatric thyroid cancer: An update from the SEER database 2007-2012. Int J Pediatr Otorhinolaryngol 89: 121-6, 2016. [PUBMED Abstract]
7. Lebbink CA, Links TP, Czarniecka A, et al.: 2022 European Thyroid Association Guidelines for the management of pediatric thyroid nodules and differentiated thyroid carcinoma. Eur Thyroid J 11 (6): , 2022. [PUBMED Abstract]
8. Christison-Lagay ER, Baertschiger RM, Dinauer C, et al.: Pediatric differentiated thyroid carcinoma: An update from the APSA Cancer Committee. J Pediatr Surg 55 (11): 2273-2283, 2020. [PUBMED Abstract]

Treatment of Papillary and Follicular Thyroid Carcinoma

Treatment options for papillary and follicular (differentiated) thyroid carcinoma include the following:

1. Surgery.
2. Radioactive iodine ablation (RAI).

Because differentiated thyroid cancer is rare in children, centralization of care to expert centers is highly encouraged.[6,9,24]

In 2015, the American Thyroid Association (ATA) Task Force on Pediatric Thyroid Cancer published guidelines for the management of thyroid nodules and differentiated thyroid cancer in children and adolescents. These guidelines are based on scientific evidence and expert panel opinion, with a careful assessment of the level of evidence.[9] In 2020 and 2022, the Cancer Committee of the American Pediatric Surgery Association and the European Thyroid Association (ETA) reviewed and expanded the ATA guidelines by incorporating more recent evidence.[24] The following sections of this summary provide an overview of the ATA guidelines and the proposed revisions, which are presented here without a specific endorsement by the National Cancer Institute (NCI).

Preoperative evaluation

Preoperative evaluation factors to consider include the following:

• Neck palpation and a comprehensive ultrasonography of all regions of the neck using a high-resolution probe and Doppler technique should be obtained by an experienced ultrasonographer. A complete ultrasonography examination should be performed before surgery.[6,9]
• The addition of cross-sectional imaging (contrast-enhanced computed tomography [CT] or magnetic resonance imaging) should be considered when there is concern about invasion of the aerodigestive tract. Importantly, if iodinated contrast agents are used, further evaluation and treatment with radioactive iodine may need to be delayed for 2 to 3 months until total body iodine burden decreases.[9]
• Chest imaging (x-ray or CT) may be considered for patients with substantial cervical lymph node disease.[9]
• Thyroid nuclear scintigraphy should be pursued only if the patient presents with suppressed thyroid-stimulating hormone (TSH).[9]
• The routine use of bone scan or fluorine F 18-fludeoxyglucose positron emission tomography (PET) is not recommended.[9]
• Further genetic or imaging diagnostics should be considered in cases of suspected familiar or extensive disease.[6]

Surgery

Total thyroidectomy is the cornerstone of the management of differentiated thyroid carcinoma. Pediatric thyroid surgery is ideally completed by a surgeon who has experience performing endocrine procedures in children and in a hospital with the full spectrum of pediatric specialty care. The ATA recommends that the thyroidectomy be performed by an experienced thyroid surgeon (>30 cases/year) or as a multidisciplinary approach between a pediatric surgeon and an adult endocrine or head and neck surgeon.[6,9]

Thyroidectomy

For patients with papillary or follicular carcinoma, total thyroidectomy is the recommended treatment. The ATA expert panel recommendation is based on data showing an increased incidence of bilateral (30%) and multifocal (65%) disease.[6,9]

In patients with a small unilateral tumor confined to the gland, a near-total thyroidectomy—in which a small amount of thyroid tissue (<1%–2%) is left in place at the entry point of the recurrent laryngeal nerve or superior parathyroid glands—might be considered to decrease permanent damage to those structures.[40]

A retrospective analysis identified factors associated with bilateral thyroid involvement in 115 pediatric patients with well-differentiated thyroid cancer.[41] Bilateral disease was present in 47 of 115 participants (41%). In multivariable analysis, only multifocality in the primary lobe was independently associated with bilateral disease (OR, 7.61; 95% CI, 2.44–23.8; P < .001). Among clinically node-negative patients with papillary carcinoma who did not have tumor multifocality in the primary lobe, bilateral disease was present in 5 of 32 patients (16%). The authors concluded that in children with differentiated thyroid cancer, tumor multifocality in the primary lobe is associated with bilateral disease, and they recommended prompt consideration of complete thyroidectomy after initial lobectomy.

Another multicenter retrospective analysis evaluated the prevalence of and risk factors for multifocal disease in 212 pediatric patients with papillary thyroid carcinoma.[42] The mean age at diagnosis was 14.1 years, and 23 patients were aged 10 years or younger. A total of 173 patients (82%) were female. Any amount of multifocal disease was present in 98 cases (46%), with bilateral multifocal disease present in 73 cases (34%). Predictors for multifocal and bilateral multifocal disease included age 10 years or younger, T3 tumor stage, and N1b nodal stage. The authors concluded that these risk factors and the high prevalence of multifocal disease should be considered when assessing the risks and benefits of surgical management options in pediatric patients with papillary thyroid carcinoma.

Thyroid resections that are less than a total thyroidectomy are associated with up to tenfold greater recurrence rates. Total thyroidectomy also optimizes the use of radioactive iodine for imaging and treatment.

Central neck dissection

A therapeutic central neck lymph node dissection (level VI nodes) should be done in the presence of clinical evidence of central or lateral neck metastases.[13]

For patients without clinical evidence of gross extrathyroidal invasion or locoregional metastasis, a prophylactic central neck dissection may be considered based on tumor focality and primary tumor size. However, because of the increased morbidity associated with central lymph node dissection, it is important to consider the risks and benefits of the extent of dissection on a case-by-case basis.[43]

Lateral neck dissection

Modified radical neck dissection is reserved for biopsy-proven metastatic disease in the lateral compartment (levels II, III, IV, and V). Cytological confirmation of metastatic disease to lymph nodes in the lateral neck is recommended before surgery.

Routine prophylactic lateral neck dissection is not recommended.

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Classification and risk assignment

Despite the limited data in pediatrics, the ATA Task Force recommends the use of the tumor-node-metastasis (TNM) classification system to categorize patients into one of three risk groups.[9] This categorization strategy is meant to define the risk of persistent cervical disease and help determine which patients should undergo postoperative staging for the presence of distant metastasis.

• ATA pediatric low risk: Disease confined to the thyroid with N0 or NX disease or patients with incidental N1a (microscopic metastasis to a small number of central neck nodes). These patients are at lowest risk of distant disease but may still be at risk of residual cervical disease, especially if the initial surgery did not include central neck dissection.
• ATA pediatric intermediate risk: Extensive N1a or minimal N1b disease. These patients are at low risk of distant metastasis but are at an increased risk of incomplete lymph node resection and persistent cervical disease.
• ATA pediatric high risk: Regionally extensive disease (N1b) or locally invasive disease (T4), with or without distant metastasis. Patients in this group are at the highest risk of incomplete resection, persistent disease, and distant metastasis.

For more information about the TNM system, see the Stage Information for Thyroid Cancer section in Thyroid Cancer Treatment.

Postoperative staging and long-term surveillance

After surgical resection, disease is staged based on the operative findings to identify patients with persistent disease and those at intermediate or high risk of recurrence. Initial staging should be performed within 12 weeks after surgery to assess for evidence of persistent locoregional disease and to identify patients who are likely to benefit from additional therapy with 131I. The ATA pediatric risk level helps determine the extent of postoperative testing.[9] The standard imaging study for the follow-up of patients who have been treated for differentiated thyroid carcinoma is neck ultrasonography. It should be performed by a professional with experience using this procedure in children. The sensitivity and specificity of neck ultrasonography for recurrent differentiated thyroid carcinoma in follow-up for children who have been treated with total thyroidectomy are 85.7% and 89.4%, respectively.[6]

ATA pediatric low risk

• Initial postoperative staging includes a TSH-suppressed thyroglobulin. A diagnostic iodine I 123 (123I) scan is not required.
• TSH suppression should be targeted to serum levels of 0.5 to 1.0 mIU/L.
• In patients with no evidence of disease, surveillance should include ultrasonography at 6 months postoperatively and then annually for 5 years, as well as TSH-suppressed thyroglobulin levels every 3 to 6 months for 2 years and then annually.
• In children with positive thyroglobulin antibodies (common in patients with Hashimoto thyroiditis), trending thyroglobulin is less reliable, and a diagnostic 123I scan may be required.

ATA pediatric intermediate risk

• Initial postoperative staging includes a TSH-stimulated thyroglobulin and diagnostic 123I whole-body scan for further stratification and determination with 131I.
• TSH suppression should be targeted to serum levels of 0.1 to 0.5 mIU/L.
• In patients with no evidence of disease, surveillance should include ultrasonography at 6 months postoperatively and then every 6 to 12 months for 5 years (and then less frequently), as well as thyroglobulin levels (on hormone replacement therapy) every 3 to 6 months for 3 years and then annually.
• TSH-stimulated thyroglobulin and diagnostic 123I scan should be considered in 1 to 2 years for patients treated with 131I.

ATA pediatric high risk

• Initial postoperative staging includes a TSH-stimulated thyroglobulin and diagnostic 123I whole-body scan for further stratification and determination with 131I.
• TSH suppression should be targeted to serum levels of less than 0.1 mIU/L.
• In patients with no evidence of disease, surveillance should include ultrasonography at 6 months postoperatively and then every 6 to 12 months for 5 years (and then less frequently), as well as thyroglobulin levels (on hormone replacement therapy) every 3 to 6 months for 3 years and then annually.
• TSH-stimulated thyroglobulin and, possibly, a diagnostic 123I scan in 1 to 2 years in patients treated with 131I.

For patients with antithyroglobulin antibodies, deferred postoperative staging to allow time for antibody clearance, except in patients with T4 or M1 disease.

Radioactive iodine ablation (RAI)

The goal of 131I therapy is to decrease recurrence and mortality by eliminating iodine-avid disease.[6,9]

• The ATA Task Force recommends the use of 131I for the treatment of iodine-avid, persistent locoregional, or nodal disease that cannot be resected, and for known or presumed iodine-avid distant metastases. For patients with persistent disease after administration of 131I, the decision to pursue additional 131I therapy should be individualized based on clinical data and previous response. For patients without lymph node or distant metastases, there is no evidence that 131I can improve survival or reduce recurrence rates.[6]
• To facilitate 131I uptake by residual iodine-avid disease, the TSH level should be above 30 mIU/L. This level can be achieved by withdrawing levothyroxine for at least 14 days. A low-iodine diet should also be followed for 2 weeks before therapy. RAI should be deferred for 2 to 3 months after exposure to iodinated CT contrast, and urine iodine excretion should be confirmed to be less than 75 µ/L. In patients who cannot mount an adequate TSH response or cannot tolerate profound hypothyroidism, recombinant human TSH may be used.
• Therapeutic 131I administration is commonly based on either empiric dosing or whole-body dosimetry. Based on the lack of data comparing empiric treatment and treatment informed by dosimetry, the ATA Task Force was unable to recommend one specific approach. However, because of the differences in body size and iodine clearance in children compared with adults, all activities of 131I should be calculated by experts with experience in dosing children.
• A posttreatment whole-body scan is recommended for all children 4 to 7 days after 131I therapy. The addition of single-photon emission CT with integrated conventional CT (SPECT/CT) may help to distinguish the anatomic location of focal uptake.

  While rare, late effects of 131I treatment include salivary gland dysfunction, bone marrow suppression, pulmonary fibrosis, and second malignancies.[44]

• Because response to 131I may be observed up to 15 to 18 months after therapy, long intervals of at least 12 months are suggested before re-treatment.[6]

Evidence (RAI):

1. In a multicenter study of children and adolescents with differentiated thyroid carcinoma, 285 consecutive patients were treated with total thyroidectomy and RAI according to the ATA guidelines.[45]
   • 87% of the patients had no evidence of active disease at a median follow-up of 133 months.
2. In a single-center study of ATA pediatric low-risk differentiated thyroid cancer diagnosed between 2010 and 2020, 95 patients underwent total thyroidectomy followed by 131I therapy in 53% of patients.[46]
   • There was no statistical difference in remission rates between patients treated with or without 131I therapy at 1 year (70% vs. 68.9%, respectively; P = .089) or last clinical evaluation (82% vs. 75.6%; P = .534).
   • Over the study period, use of 131I in the patient population declined steadily, as the 2015 ATA Pediatric Differentiated Thyroid Cancer Guidelines recommended withholding 131I therapy in patients with low-risk disease. Accordingly, patients who received 131I therapy had longer follow-up (median, 5.8 years) than those who did not receive 131I therapy (median, 3.6 years).

The ETA has proposed a simplified follow-up plan based on thyroglobulin levels and neck ultrasonography (see Figure 4).[6]

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Medullary thyroid carcinoma is a rare form of thyroid carcinoma that originates from calcitonin-secreting parafollicular C cells and accounts for less than 10% of all cases of thyroid carcinoma in children.[1]

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6. Acquaviva G, Visani M, Repaci A, et al.: Molecular pathology of thyroid tumours of follicular cells: a review of genetic alterations and their clinicopathological relevance. Histopathology 72 (1): 6-31, 2018. [PUBMED Abstract]
7. Francis GL, Waguespack SG, Bauer AJ, et al.: Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 25 (7): 716-59, 2015. [PUBMED Abstract]
8. Waguespack SG, Rich TA, Perrier ND, et al.: Management of medullary thyroid carcinoma and MEN2 syndromes in childhood. Nat Rev Endocrinol 7 (10): 596-607, 2011. [PUBMED Abstract]
9. Raval MV, Sturgeon C, Bentrem DJ, et al.: Influence of lymph node metastases on survival in pediatric medullary thyroid cancer. J Pediatr Surg 45 (10): 1947-54, 2010. [PUBMED Abstract]
10. Kuhlen M, Frühwald MC, Dunstheimer DPA, et al.: Revisiting the genotype-phenotype correlation in children with medullary thyroid carcinoma: A report from the GPOH-MET registry. Pediatr Blood Cancer 67 (4): e28171, 2020. [PUBMED Abstract]
11. Wells SA, Asa SL, Dralle H, et al.: Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25 (6): 567-610, 2015. [PUBMED Abstract]
12. Dinauer C, Francis GL: Thyroid cancer in children. Endocrinol Metab Clin North Am 36 (3): 779-806, vii, 2007. [PUBMED Abstract]
13. Vasko V, Bauer AJ, Tuttle RM, et al.: Papillary and follicular thyroid cancers in children. Endocr Dev 10: 140-72, 2007. [PUBMED Abstract]
14. Halac I, Zimmerman D: Thyroid nodules and cancers in children. Endocrinol Metab Clin North Am 34 (3): 725-44, x, 2005. [PUBMED Abstract]
15. Machens A, Elwerr M, Thanh PN, et al.: Impact of central node dissection on postoperative morbidity in pediatric patients with suspected or proven thyroid cancer. Surgery 160 (2): 484-92, 2016. [PUBMED Abstract]
16. Machens A, Elwerr M, Lorenz K, et al.: Long-term outcome of prophylactic thyroidectomy in children carrying RET germline mutations. Br J Surg 105 (2): e150-e157, 2018. [PUBMED Abstract]
17. Wells SA, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012. [PUBMED Abstract]
18. Thornton K, Kim G, Maher VE, et al.: Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res 18 (14): 3722-30, 2012. [PUBMED Abstract]
19. Fox E, Widemann BC, Chuk MK, et al.: Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma. Clin Cancer Res 19 (15): 4239-48, 2013. [PUBMED Abstract]
20. Kraft IL, Akshintala S, Zhu Y, et al.: Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib. Clin Cancer Res 24 (4): 753-765, 2018. [PUBMED Abstract]
21. Kurzrock R, Sherman SI, Ball DW, et al.: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 29 (19): 2660-6, 2011. [PUBMED Abstract]
22. Elisei R, Schlumberger MJ, Müller SP, et al.: Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 31 (29): 3639-46, 2013. [PUBMED Abstract]
23. Wirth LJ, Sherman E, Robinson B, et al.: Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med 383 (9): 825-835, 2020. [PUBMED Abstract]
24. Shankar A, Kurzawinski T, Ross E, et al.: Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma. Eur J Cancer 158: 38-46, 2021. [PUBMED Abstract]
25. Eli Lilly and Company: RETEVMO (selpercatinib): Prescribing Information. Indianapolis, Ind: Lilly USA, LLC, 2024. Available online. Last accessed November 29, 2024.

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life:

For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3–5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Thyroid Cancer Treatment.

References

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010. [PUBMED Abstract]
2. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed February 25, 2025.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed December 30, 2024.
6. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr. [PUBMED Abstract]
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017. [PUBMED Abstract]
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017. [PUBMED Abstract]
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019. [PUBMED Abstract]
10. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children’s Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010. [PUBMED Abstract]

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Differentiated Thyroid Cancer (Papillary/Follicular)

Added text to state that some sections of this summary provide an overview of the American Thyroid Association guidelines and the proposed revisions, which are presented here without a specific endorsement by the National Cancer Institute.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.