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.

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]

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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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References

1. Cahoon EK, Nadyrov EA, Polyanskaya ON, et al.: Risk of Thyroid Nodules in Residents of Belarus Exposed to Chernobyl Fallout as Children and Adolescents. J Clin Endocrinol Metab 102 (7): 2207-2217, 2017. [PUBMED Abstract]
2. Rose J, Wertheim BC, Guerrero MA: Radiation treatment of patients with primary pediatric malignancies: risk of developing thyroid cancer as a secondary malignancy. Am J Surg 204 (6): 881-6; discussion 886-7, 2012. [PUBMED Abstract]
3. Lal G, Groff M, Howe JR, et al.: Risk of subsequent primary thyroid cancer after another malignancy: latency trends in a population-based study. Ann Surg Oncol 19 (6): 1887-96, 2012. [PUBMED Abstract]
4. Lubin JH, Adams MJ, Shore R, et al.: Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts. J Clin Endocrinol Metab 102 (7): 2575-2583, 2017. [PUBMED Abstract]
5. Iglesias ML, Schmidt A, Ghuzlan AA, et al.: Radiation exposure and thyroid cancer: a review. Arch Endocrinol Metab 61 (2): 180-187, 2017 Mar-Apr. [PUBMED Abstract]
6. 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]
7. Keefe G, Culbreath K, Cherella CE, et al.: Autoimmune Thyroiditis and Risk of Malignancy in Children with Thyroid Nodules. Thyroid 32 (9): 1109-1117, 2022. [PUBMED Abstract]
8. 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]
9. 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]
10. Al-Qurayshi Z, Hauch A, Srivastav S, et al.: A National Perspective of the Risk, Presentation, and Outcomes of Pediatric Thyroid Cancer. JAMA Otolaryngol Head Neck Surg 142 (5): 472-8, 2016. [PUBMED Abstract]
11. Shayota BJ, Pawar SC, Chamberlain RS: MeSS: A novel prognostic scale specific for pediatric well-differentiated thyroid cancer: a population-based, SEER outcomes study. Surgery 154 (3): 429-35, 2013. [PUBMED Abstract]
12. Ye B, Shi J, Shen C, et al.: Comparison of differentiated thyroid carcinoma recurrence and its clinical features in children of different ages. Oncotarget 8 (29): 48051-48059, 2017. [PUBMED Abstract]
13. Kim J, Sun Z, Adam MA, et al.: Predictors of nodal metastasis in pediatric differentiated thyroid cancer. J Pediatr Surg 52 (1): 120-123, 2017. [PUBMED Abstract]
14. Lazar L, Lebenthal Y, Steinmetz A, et al.: Differentiated thyroid carcinoma in pediatric patients: comparison of presentation and course between pre-pubertal children and adolescents. J Pediatr 154 (5): 708-14, 2009. [PUBMED Abstract]
15. Redlich A, Luster M, Lorenz K, et al.: Age, American Thyroid Association Risk Group, and Response to Therapy Are Prognostic Factors in Children With Differentiated Thyroid Cancer. J Clin Endocrinol Metab 107 (1): e165-e177, 2022. [PUBMED Abstract]
16. Chesover AD, Vali R, Hemmati SH, et al.: Lung Metastasis in Children with Differentiated Thyroid Cancer: Factors Associated with Diagnosis and Outcomes of Therapy. Thyroid 31 (1): 50-60, 2021. [PUBMED Abstract]
17. Sassolas G, Hafdi-Nejjari Z, Casagranda L, et al.: Thyroid cancers in children, adolescents, and young adults with and without a history of childhood exposure to therapeutic radiation for other cancers. Thyroid 23 (7): 805-10, 2013. [PUBMED Abstract]
18. Lee YA, Lee H, Im SW, et al.: NTRK and RET fusion-directed therapy in pediatric thyroid cancer yields a tumor response and radioiodine uptake. J Clin Invest 131 (18): , 2021. [PUBMED Abstract]
19. Franco AT, Ricarte-Filho JC, Isaza A, et al.: Fusion Oncogenes Are Associated With Increased Metastatic Capacity and Persistent Disease in Pediatric Thyroid Cancers. J Clin Oncol 40 (10): 1081-1090, 2022. [PUBMED Abstract]
20. Tian T, Huang S, Dai H, et al.: Radioactive Iodine-Refractory Pulmonary Metastases of Papillary Thyroid Cancer in Children, Adolescents, and Young Adults. J Clin Endocrinol Metab 108 (2): 306-314, 2023. [PUBMED Abstract]
21. Garner EF, Maizlin II, Dellinger MB, et al.: Effects of socioeconomic status on children with well-differentiated thyroid cancer. Surgery 162 (3): 662-669, 2017. [PUBMED Abstract]
22. Scholfield DW, Lopez J, Eagan A, et al.: Is Multifocality a Predictor of Poor Outcome in Childhood and Adolescent Papillary Thyroid Carcinoma? J Clin Endocrinol Metab 108 (12): 3135-3144, 2023. [PUBMED Abstract]
23. Garcia Alves-Junior PA, de Andrade Barreto MC, de Andrade FA, et al.: Stimulated thyroglobulin and diagnostic 131-iodine whole-body scan as a predictor of distant metastasis and association with response to treatment in pediatric thyroid cancer patients. Endocrine 84 (3): 1081-1087, 2024. [PUBMED Abstract]
24. 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]
25. 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]
26. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
27. Brady C, Manning SC, Rudzinski E, et al.: Clinical Outcomes of Diffuse Sclerosing Variant Papillary Thyroid Carcinoma in Pediatric Patients. Laryngoscope 132 (5): 1132-1138, 2022. [PUBMED Abstract]
28. Sugino K, Nagahama M, Kitagawa W, et al.: Distant Metastasis in Pediatric and Adolescent Differentiated Thyroid Cancer: Clinical Outcomes and Risk Factor Analyses. J Clin Endocrinol Metab 105 (11): , 2020. [PUBMED Abstract]
29. Stosic A, Fuligni F, Anderson ND, et al.: Diverse Oncogenic Fusions and Distinct Gene Expression Patterns Define the Genomic Landscape of Pediatric Papillary Thyroid Carcinoma. Cancer Res 81 (22): 5625-5637, 2021. [PUBMED Abstract]
30. Bauer AJ: Molecular Genetics of Thyroid Cancer in Children and Adolescents. Endocrinol Metab Clin North Am 46 (2): 389-403, 2017. [PUBMED Abstract]
31. Cancer Genome Atlas Research Network: Integrated genomic characterization of papillary thyroid carcinoma. Cell 159 (3): 676-90, 2014. [PUBMED Abstract]
32. Sisdelli L, Cordioli MICV, Vaisman F, et al.: AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma. Pediatr Blood Cancer 66 (7): e27707, 2019. [PUBMED Abstract]
33. Bulanova Pekova B, Sykorova V, Mastnikova K, et al.: RET fusion genes in pediatric and adult thyroid carcinomas: cohort characteristics and prognosis. Endocr Relat Cancer 30 (12): , 2023. [PUBMED Abstract]
34. Wasserman JD, Sabbaghian N, Fahiminiya S, et al.: DICER1 Mutations Are Frequent in Adolescent-Onset Papillary Thyroid Carcinoma. J Clin Endocrinol Metab 103 (5): 2009-2015, 2018. [PUBMED Abstract]
35. 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]
36. Onder S, Mete O, Yilmaz I, et al.: DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection. Endocr Pathol 33 (4): 437-445, 2022. [PUBMED Abstract]
37. Ricarte-Filho JC, Casado-Medrano V, Reichenberger E, et al.: DICER1 RNase IIIb domain mutations trigger widespread miRNA dysregulation and MAPK activation in pediatric thyroid cancer. Front Endocrinol (Lausanne) 14: 1083382, 2023. [PUBMED Abstract]
38. Potter SL, Reuther J, Chandramohan R, et al.: Integrated DNA and RNA sequencing reveals targetable alterations in metastatic pediatric papillary thyroid carcinoma. Pediatr Blood Cancer 68 (1): e28741, 2021. [PUBMED Abstract]
39. Pekova B, Sykorova V, Dvorakova S, et al.: RET, NTRK, ALK, BRAF, and MET Fusions in a Large Cohort of Pediatric Papillary Thyroid Carcinomas. Thyroid 30 (12): 1771-1780, 2020. [PUBMED Abstract]
40. Spinelli C, Strambi S, Rossi L, et al.: Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients. J Endocrinol Invest 39 (9): 1055-9, 2016. [PUBMED Abstract]
41. Cherella CE, Richman DM, Liu E, et al.: Predictors of Bilateral Disease in Pediatric Differentiated Thyroid Cancer. J Clin Endocrinol Metab 106 (10): e4242-e4250, 2021. [PUBMED Abstract]
42. Banik GL, Shindo ML, Kraimer KL, et al.: Prevalence and Risk Factors for Multifocality in Pediatric Thyroid Cancer. JAMA Otolaryngol Head Neck Surg 147 (12): 1100-1106, 2021. [PUBMED Abstract]
43. 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]
44. Albano D, Bertagna F, Panarotto MB, et al.: Early and late adverse effects of radioiodine for pediatric differentiated thyroid cancer. Pediatr Blood Cancer 64 (11): , 2017. [PUBMED Abstract]
45. Cistaro A, Quartuccio N, Garganese MC, et al.: Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study. Eur J Nucl Med Mol Imaging 49 (4): 1374-1385, 2022. [PUBMED Abstract]
46. Bojarsky M, Baran JA, Halada S, et al.: Outcomes of ATA Low-Risk Pediatric Thyroid Cancer Patients Not Treated With Radioactive Iodine Therapy. J Clin Endocrinol Metab 108 (12): 3338-3344, 2023. [PUBMED Abstract]
47. 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]
48. 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]
49. Powers PA, Dinauer CA, Tuttle RM, et al.: Treatment of recurrent papillary thyroid carcinoma in children and adolescents. J Pediatr Endocrinol Metab 16 (7): 1033-40, 2003. [PUBMED Abstract]
50. Brose MS, Nutting CM, Jarzab B, et al.: Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 384 (9940): 319-28, 2014. [PUBMED Abstract]
51. Iyer P, Mayer JL, Ewig JM: Response to sorafenib in a pediatric patient with papillary thyroid carcinoma with diffuse nodular pulmonary disease requiring mechanical ventilation. Thyroid 24 (1): 169-74, 2014. [PUBMED Abstract]
52. Schlumberger M, Tahara M, Wirth LJ, et al.: Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 372 (7): 621-30, 2015. [PUBMED Abstract]
53. Mahajan P, Dawrant J, Kheradpour A, et al.: Response to Lenvatinib in Children with Papillary Thyroid Carcinoma. Thyroid 28 (11): 1450-1454, 2018. [PUBMED Abstract]
54. Brose MS, Cabanillas ME, Cohen EE, et al.: Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol 17 (9): 1272-82, 2016. [PUBMED Abstract]
55. Subbiah V, Kreitman RJ, Wainberg ZA, et al.: Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol 36 (1): 7-13, 2018. [PUBMED Abstract]
56. 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]
57. Chu YH, Dias-Santagata D, Farahani AA, et al.: Clinicopathologic and molecular characterization of NTRK-rearranged thyroid carcinoma (NRTC). Mod Pathol 33 (11): 2186-2197, 2020. [PUBMED Abstract]
58. Bayer HealthCare Pharmaceuticals: VITRAKVI (larotrectinib): Prescribing Information. Stamford, Conn: Loxo Oncology, Inc., 2018. Available online. Last accessed November 29, 2024.
59. 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]
60. Eli Lilly and Company: RETEVMO (selpercatinib): Prescribing Information. Indianapolis, Ind: Lilly USA, LLC, 2024. Available online. Last accessed November 29, 2024.
61. Brose MS, Robinson B, Sherman SI, et al.: Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 22 (8): 1126-1138, 2021. [PUBMED Abstract]
62. Duke ES, Barone AK, Chatterjee S, et al.: FDA Approval Summary: Cabozantinib for Differentiated Thyroid Cancer. Clin Cancer Res 28 (19): 4173-4177, 2022. [PUBMED Abstract]

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]

References

1. 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]
2. Viola D, Romei C, Elisei R: Medullary thyroid carcinoma in children. Endocr Dev 26: 202-13, 2014. [PUBMED Abstract]
3. Bauer AJ: Molecular Genetics of Thyroid Cancer in Children and Adolescents. Endocrinol Metab Clin North Am 46 (2): 389-403, 2017. [PUBMED Abstract]
4. Hensley SG, Hu MI, Bassett RL, et al.: Pediatric Medullary Thyroid Carcinoma: Clinical Presentations and Long-Term Outcomes in 144 Patients Over 6 Decades. J Clin Endocrinol Metab 109 (9): 2256-2268, 2024. [PUBMED Abstract]
5. Al-Qurayshi Z, Hauch A, Srivastav S, et al.: A National Perspective of the Risk, Presentation, and Outcomes of Pediatric Thyroid Cancer. JAMA Otolaryngol Head Neck Surg 142 (5): 472-8, 2016. [PUBMED Abstract]
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.

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.

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]
11. Brecht IB, Graf N, Schweinitz D, et al.: Networking for children and adolescents with very rare tumors: foundation of the GPOH Pediatric Rare Tumor Group. Klin Padiatr 221 (3): 181-5, 2009 May-Jun. [PUBMED Abstract]
12. Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007. [PUBMED Abstract]
13. Balcerska A, Godziński J, Bień E, et al.: [Rare tumours–are they really rare in the Polish children population?]. Przegl Lek 61 (Suppl 2): 57-61, 2004. [PUBMED Abstract]
14. Bisogno G, Ferrari A, Bien E, et al.: Rare cancers in children – The EXPeRT Initiative: a report from the European Cooperative Study Group on Pediatric Rare Tumors. Klin Padiatr 224 (6): 416-20, 2012. [PUBMED Abstract]
15. Musselman JR, Spector LG, Krailo MD, et al.: The Children’s Oncology Group Childhood Cancer Research Network (CCRN): case catchment in the United States. Cancer 120 (19): 3007-15, 2014. [PUBMED Abstract]
16. Pappo AS, Furman WL, Schultz KA, et al.: Rare Tumors in Children: Progress Through Collaboration. J Clin Oncol 33 (27): 3047-54, 2015. [PUBMED Abstract]

These cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from small case series or cohorts combining pediatric and adult patients.

Childhood sarcomas often occur in the head and neck area and they are described in other summaries. Rare pediatric head and neck cancers include the following:

The prognosis, diagnosis, classification, and treatment of pediatric thoracic cancers are discussed below. These cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Rare pediatric thoracic cancers include the following:

References

1. Weldon CB, Shamberger RC: Pediatric pulmonary tumors: primary and metastatic. Semin Pediatr Surg 17 (1): 17-29, 2008. [PUBMED Abstract]

The prognosis, diagnosis, classification, and treatment of pediatric abdominal cancers are discussed below. These cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series. For information about kidney tumors, see Wilms Tumor and Other Childhood Kidney Tumors Treatment.

Rare pediatric abdominal cancers include the following:

The prognosis, diagnosis, classification, and treatment of pediatric genital/urinary tumors are discussed below. These tumors are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Rare pediatric genital/urinary tumors include the following:

The prognosis, diagnosis, classification, and treatment of other rare childhood cancers are discussed below. These cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Other rare childhood cancers include the following:

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.

Nasopharyngeal carcinoma arises in the lining of the nasal cavity and pharynx, and it accounts for about one-third of all cancers of the upper airways in children.[1,2]

Nasopharyngeal carcinoma is exceedingly rare in children younger than 10 years.[3] The age-adjusted incidence rates (2016–2020) for both sexes and all races of children younger than 20 years in the United States are shown in Table 1.[3]

The incidence of nasopharyngeal carcinoma is characterized by racial and geographic variations, with an endemic distribution among well-defined ethnic groups. These groups include inhabitants of some areas in North Africa, the Mediterranean basin, and, particularly, Southeast Asia. In the United States, the incidence of nasopharyngeal carcinoma is markedly higher in Black children than in other racial or ethnic groups (see Table 2).[3–5]

References

1. Ayan I, Kaytan E, Ayan N: Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol 4 (1): 13-21, 2003. [PUBMED Abstract]
2. Yan Z, Xia L, Huang Y, et al.: Nasopharyngeal carcinoma in children and adolescents in an endemic area: a report of 185 cases. Int J Pediatr Otorhinolaryngol 77 (9): 1454-60, 2013. [PUBMED Abstract]
3. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.
4. Sultan I, Casanova M, Ferrari A, et al.: Differential features of nasopharyngeal carcinoma in children and adults: a SEER study. Pediatr Blood Cancer 55 (2): 279-84, 2010. [PUBMED Abstract]
5. Richards MK, Dahl JP, Gow K, et al.: Factors Associated With Mortality in Pediatric vs Adult Nasopharyngeal Carcinoma. JAMA Otolaryngol Head Neck Surg 142 (3): 217-22, 2016. [PUBMED Abstract]

Epstein-Barr virus (EBV). Nasopharyngeal carcinoma is strongly associated with EBV infection. In addition to the serological evidence of infection in more than 98% of patients, EBV DNA is present as a monoclonal episome in the nasopharyngeal carcinoma cells, and tumor cells can have EBV antigens on their cell surface.[1] The circulating levels of EBV DNA and serological documentation of EBV infection may help with the diagnosis.[1]

HLA subtypes. Specific HLA subtypes, such as the HLA A2 Bsin2 haplotype, are associated with a higher risk of nasopharyngeal carcinoma.[1,2]

References

1. Chen YP, Chan ATC, Le QT, et al.: Nasopharyngeal carcinoma. Lancet 394 (10192): 64-80, 2019. [PUBMED Abstract]
2. Ayan I, Kaytan E, Ayan N: Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol 4 (1): 13-21, 2003. [PUBMED Abstract]

Given the rich lymphatic drainage of the nasopharynx, bilateral cervical lymphadenopathy is often the first sign of nasopharyngeal carcinoma. Other signs and symptoms include the following:[1,2]

The tumor spreads locally to adjacent areas of the oropharynx and may invade the skull base, resulting in cranial nerve palsy or difficulty with movements of the jaw (trismus). Distant metastatic sites may include the bones, lungs, and liver.

References

1. Yan Z, Xia L, Huang Y, et al.: Nasopharyngeal carcinoma in children and adolescents in an endemic area: a report of 185 cases. Int J Pediatr Otorhinolaryngol 77 (9): 1454-60, 2013. [PUBMED Abstract]
2. Hu S, Xu X, Xu J, et al.: Prognostic factors and long-term outcomes of nasopharyngeal carcinoma in children and adolescents. Pediatr Blood Cancer 60 (7): 1122-7, 2013. [PUBMED Abstract]

Diagnostic tests determine the extent of the primary tumor and the presence of metastases. Visualization of the nasopharynx, by an otolaryngologist using nasal endoscopy and magnetic resonance imaging of the head and neck, can determine the extent of the primary tumor.

A diagnosis can be made from a biopsy of the primary tumor or enlarged lymph nodes of the neck. Nasopharyngeal carcinomas must be distinguished from all other cancers that can present with enlarged lymph nodes and from other types of cancer in the head and neck area. Thus, diseases such as thyroid cancer, rhabdomyosarcoma, non-Hodgkin lymphoma (including Burkitt lymphoma), and Hodgkin lymphoma must be considered, as well as benign conditions such as nasal angiofibroma, which usually presents with epistaxis in adolescent males, infectious lymphadenitis, and Rosai-Dorfman disease.

Evaluation of the chest and abdomen by computed tomography (CT) and bone scan is performed to determine whether there is metastatic disease. Fluorine F 18-fludeoxyglucose positron emission tomography (PET)–CT may also be helpful in the evaluation of potential metastatic lesions.[1]

References

1. Cheuk DK, Sabin ND, Hossain M, et al.: PET/CT for staging and follow-up of pediatric nasopharyngeal carcinoma. Eur J Nucl Med Mol Imaging 39 (7): 1097-106, 2012. [PUBMED Abstract]

The World Health Organization (WHO) recognizes the following three histological subtypes of nasopharyngeal carcinoma:

Children with nasopharyngeal carcinoma are more likely to have WHO type II or type III disease.[1,2]

References

1. Sultan I, Casanova M, Ferrari A, et al.: Differential features of nasopharyngeal carcinoma in children and adults: a SEER study. Pediatr Blood Cancer 55 (2): 279-84, 2010. [PUBMED Abstract]
2. Richards MK, Dahl JP, Gow K, et al.: Factors Associated With Mortality in Pediatric vs Adult Nasopharyngeal Carcinoma. JAMA Otolaryngol Head Neck Surg 142 (3): 217-22, 2016. [PUBMED Abstract]

Four tertiary academic medical centers in China studied 30 patients (25 male and 5 female) with pathologically confirmed nasopharyngeal carcinoma who were younger than 20 years.[1] Nasopharyngeal primary tumors with paired blood samples were collected and sequenced using whole-exome sequencing. Several genes such as SHOC1 (formerly known as C9orf84) (20%), ZFHX4 (16.7%), ZC3H6 (16.7%), and RBM38 (16.7%) were frequently altered in nasopharyngeal carcinoma. Copy number analysis revealed highly recurring gain/amplification of the HLA class II genes at 6p21.32 (63.3%) and losses of TOLLIP at 11p15.5 (20%).

In another analysis, homozygous deletion of the CDKN2A locus on 9p21.3 was confirmed in 7 of 15 nasopharyngeal carcinoma specimens (46.7%) and in 3 of 5 cell lines/patient-derived xenografts (60%). CCND1 amplification was found in 3 of 20 nasopharyngeal tumors (15%).[2] Whole-genome sequencing of nasopharyngeal carcinoma revealed that TP53 was the most significantly altered gene (n = 10), followed by TRAF3, NFKBIA, AEBP1, and NLRC5. All of these genes have been reported to regulate nuclear factor kappa B.[3] In addition, significant somatic aberrations detected in HLA-A and NLRC5 suggest the impairment of antigen presentation, while PTEN variants may activate the PI3K pathway. This study found four coding genes that were significantly altered, namely PLIN4, MUC21, SLC35G5, and ERVW-1.

References

1. Wu B, Shen L, Peng G, et al.: Molecular characteristics of pediatric nasopharyngeal carcinoma using whole-exome sequencing. Oral Oncol 135: 106218, 2022. [PUBMED Abstract]
2. Tsang CM, Lui VWY, Bruce JP, et al.: Translational genomics of nasopharyngeal cancer. Semin Cancer Biol 61: 84-100, 2020. [PUBMED Abstract]
3. Bruce JP, To KF, Lui VWY, et al.: Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape. Nat Commun 12 (1): 4193, 2021. [PUBMED Abstract]

The overall survival of children and adolescents with nasopharyngeal carcinoma has improved over the last four decades through the use of state-of-the-art multimodal treatment.[1–8] The 5-year relative survival rate was 91% for children younger than 20 years who were diagnosed with nasopharyngeal carcinoma in the United States between 2013 and 2019.[9] After controlling for stage, children with nasopharyngeal carcinoma have significantly better outcomes than adults.[1,7] However, the intensive use of chemotherapy and radiation therapy results in significant acute and long-term morbidities, including subsequent neoplasms.[1–3,6]

References

1. Sultan I, Casanova M, Ferrari A, et al.: Differential features of nasopharyngeal carcinoma in children and adults: a SEER study. Pediatr Blood Cancer 55 (2): 279-84, 2010. [PUBMED Abstract]
2. Cheuk DK, Billups CA, Martin MG, et al.: Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. Cancer 117 (1): 197-206, 2011. [PUBMED Abstract]
3. Casanova M, Bisogno G, Gandola L, et al.: A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project. Cancer 118 (10): 2718-25, 2012. [PUBMED Abstract]
4. Buehrlen M, Zwaan CM, Granzen B, et al.: Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in children and young adults: preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG. Cancer 118 (19): 4892-900, 2012. [PUBMED Abstract]
5. Hu S, Xu X, Xu J, et al.: Prognostic factors and long-term outcomes of nasopharyngeal carcinoma in children and adolescents. Pediatr Blood Cancer 60 (7): 1122-7, 2013. [PUBMED Abstract]
6. Sahai P, Mohanti BK, Sharma A, et al.: Clinical outcome and morbidity in pediatric patients with nasopharyngeal cancer treated with chemoradiotherapy. Pediatr Blood Cancer 64 (2): 259-266, 2017. [PUBMED Abstract]
7. Richards MK, Dahl JP, Gow K, et al.: Factors Associated With Mortality in Pediatric vs Adult Nasopharyngeal Carcinoma. JAMA Otolaryngol Head Neck Surg 142 (3): 217-22, 2016. [PUBMED Abstract]
8. Gioacchini FM, Tulli M, Kaleci S, et al.: Prognostic aspects in the treatment of juvenile nasopharyngeal carcinoma: a systematic review. Eur Arch Otorhinolaryngol 274 (3): 1205-1214, 2017. [PUBMED Abstract]
9. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed February 25, 2025.

Tumor staging is performed using the tumor-node-metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC).[1,2]

The AJCC has designated staging by TNM classification to define nasopharyngeal carcinoma.[3]

More than 90% of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4).[4,5] Population-based studies have reported that patients younger than 20 years had a higher incidence of advanced-stage disease than did adult patients.[6,7] However, less than 10% of children and adolescents with nasopharyngeal carcinoma presented with distant metastases at diagnosis.[4,5,8]

References

1. Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017.
2. Lee AWM, Lydiatt WM, Colevas AD, et al.: Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 103-11.
3. Nasopharynx. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 103–11.
4. Cheuk DK, Billups CA, Martin MG, et al.: Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. Cancer 117 (1): 197-206, 2011. [PUBMED Abstract]
5. Casanova M, Bisogno G, Gandola L, et al.: A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project. Cancer 118 (10): 2718-25, 2012. [PUBMED Abstract]
6. Sultan I, Casanova M, Ferrari A, et al.: Differential features of nasopharyngeal carcinoma in children and adults: a SEER study. Pediatr Blood Cancer 55 (2): 279-84, 2010. [PUBMED Abstract]
7. Richards MK, Dahl JP, Gow K, et al.: Factors Associated With Mortality in Pediatric vs Adult Nasopharyngeal Carcinoma. JAMA Otolaryngol Head Neck Surg 142 (3): 217-22, 2016. [PUBMED Abstract]
8. Buehrlen M, Zwaan CM, Granzen B, et al.: Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in children and young adults: preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG. Cancer 118 (19): 4892-900, 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.

Information about these tumors may also be found in sources relevant to adults with cancer, such as Nasopharyngeal Carcinoma 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 European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network–European Registry) have published comprehensive recommendations for the diagnosis and treatment of nasopharyngeal carcinoma in children and adolescents.[1]

Treatment options for newly diagnosed nasopharyngeal carcinoma include the following:

References

1. Ben-Ami T, Kontny U, Surun A, et al.: Nasopharyngeal carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer 68 (Suppl 4): e29018, 2021. [PUBMED Abstract]
2. Chen YP, Chan ATC, Le QT, et al.: Nasopharyngeal carcinoma. Lancet 394 (10192): 64-80, 2019. [PUBMED Abstract]
3. Blanchard P, Lee AWM, Carmel A, et al.: Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7080 patients. Clin Transl Radiat Oncol 32: 59-68, 2022. [PUBMED Abstract]
4. Zhang Y, Chen L, Hu GQ, et al.: Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med 381 (12): 1124-1135, 2019. [PUBMED Abstract]
5. Zhang Y, Chen L, Hu GQ, et al.: Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial. J Clin Oncol 40 (22): 2420-2425, 2022. [PUBMED Abstract]
6. Casanova M, Bisogno G, Gandola L, et al.: A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project. Cancer 118 (10): 2718-25, 2012. [PUBMED Abstract]
7. Buehrlen M, Zwaan CM, Granzen B, et al.: Multimodal treatment, including interferon beta, of nasopharyngeal carcinoma in children and young adults: preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG. Cancer 118 (19): 4892-900, 2012. [PUBMED Abstract]
8. Casanova M, Özyar E, Patte C, et al.: International randomized phase 2 study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents. Cancer Chemother Pharmacol 77 (2): 289-98, 2016. [PUBMED Abstract]
9. Rodriguez-Galindo C, Krailo MD, Krasin MJ, et al.: Treatment of Childhood Nasopharyngeal Carcinoma With Induction Chemotherapy and Concurrent Chemoradiotherapy: Results of the Children’s Oncology Group ARAR0331 Study. J Clin Oncol 37 (35): 3369-3376, 2019. [PUBMED Abstract]
10. Zhang L, Huang Y, Hong S, et al.: Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet 388 (10054): 1883-1892, 2016. [PUBMED Abstract]
11. Liu LT, Liu H, Huang Y, et al.: Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol 24 (7): 798-810, 2023. [PUBMED Abstract]
12. Langendijk JA, Leemans ChR, Buter J, et al.: The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol 22 (22): 4604-12, 2004. [PUBMED Abstract]
13. Yan M, Kumachev A, Siu LL, et al.: Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis. Eur J Cancer 51 (12): 1570-9, 2015. [PUBMED Abstract]
14. Ribassin-Majed L, Marguet S, Lee AWM, et al.: What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis. J Clin Oncol 35 (5): 498-505, 2017. [PUBMED Abstract]
15. Yao JJ, Jin YN, Lin YJ, et al.: The feasibility of reduced-dose radiotherapy in childhood nasopharyngeal carcinoma with favorable response to neoadjuvant chemotherapy. Radiother Oncol 178: 109414, 2023. [PUBMED Abstract]
16. Römer T, Franzen S, Kravets H, et al.: Multimodal Treatment of Nasopharyngeal Carcinoma in Children, Adolescents and Young Adults-Extended Follow-Up of the NPC-2003-GPOH Study Cohort and Patients of the Interim Cohort. Cancers (Basel) 14 (5): , 2022. [PUBMED Abstract]
17. Cheuk DK, Billups CA, Martin MG, et al.: Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. Cancer 117 (1): 197-206, 2011. [PUBMED Abstract]
18. Sahai P, Mohanti BK, Sharma A, et al.: Clinical outcome and morbidity in pediatric patients with nasopharyngeal cancer treated with chemoradiotherapy. Pediatr Blood Cancer 64 (2): 259-266, 2017. [PUBMED Abstract]
19. Hu S, Xu X, Xu J, et al.: Prognostic factors and long-term outcomes of nasopharyngeal carcinoma in children and adolescents. Pediatr Blood Cancer 60 (7): 1122-7, 2013. [PUBMED Abstract]
20. Uezono H, Indelicato DJ, Rotondo RL, et al.: Proton therapy following induction chemotherapy for pediatric and adolescent nasopharyngeal carcinoma. Pediatr Blood Cancer 66 (12): e27990, 2019. [PUBMED Abstract]
21. Liang YJ, Wen DX, Luo MJ, et al.: Induction or adjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in paediatric nasopharyngeal carcinoma in the IMRT era: A recursive partitioning risk stratification analysis based on EBV DNA. Eur J Cancer 159: 133-143, 2021. [PUBMED Abstract]
22. Mai HQ, Chen QY, Chen D, et al.: Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med 27 (9): 1536-1543, 2021. [PUBMED Abstract]

The outcome is poor for patients with relapsed or refractory nasopharyngeal carcinoma, and most patients present with distant metastases.

Treatment options for relapsed or refractory nasopharyngeal carcinoma include the following:

References

1. DeRenzo C, Lam C, Rodriguez-Galindo C, et al.: Salvage regimens for pediatric patients with relapsed nasopharyngeal carcinoma. Pediatr Blood Cancer 66 (1): e27469, 2019. [PUBMED Abstract]
2. Straathof KC, Bollard CM, Popat U, et al.: Treatment of nasopharyngeal carcinoma with Epstein-Barr virus–specific T lymphocytes. Blood 105 (5): 1898-904, 2005. [PUBMED Abstract]
3. Louis CU, Straathof K, Bollard CM, et al.: Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother 33 (9): 983-90, 2010 Nov-Dec. [PUBMED Abstract]
4. Luo J, Xiao W, Hua F, et al.: Efficacy and safety of PD-1 inhibitors in recurrent or metastatic nasopharyngeal carcinoma patients after failure of platinum-containing regimens: a systematic review and meta-analysis. BMC Cancer 23 (1): 1172, 2023. [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.

For more information from the National Cancer Institute about rare cancers of childhood, visit:

For more childhood cancer information and other general cancer resources, visit: