Thymoma and thymic carcinoma, collectively termed thymic epithelial tumors (TETs), are relatively rare tumors arising from the thymus. Although infrequent, TETs are the most common tumors of the anterior mediastinum in adults. TETs, particularly thymomas, have unique biological properties and are associated with autoimmune paraneoplastic diseases. TETs have the lowest tumor mutational burden of all solid tumors in adults. All TETs have malignant potential and the ability to metastasize. The clinical behavior of TETs can vary from relatively indolent to aggressive, resulting in a range of clinical outcomes.

Surgery is the main treatment, especially for early-stage disease. Multimodality therapy, including chemotherapy and radiation therapy, is used to treat locally advanced disease, and systemic therapy alone is indicated for metastatic TETs.[1]

References

1. Kelly RJ, Petrini I, Rajan A, et al.: Thymic malignancies: from clinical management to targeted therapies. J Clin Oncol 29 (36): 4820-7, 2011. [PUBMED Abstract]
2. Fornasiero A, Daniele O, Ghiotto C, et al.: Chemotherapy of invasive thymoma. J Clin Oncol 8 (8): 1419-23, 1990. [PUBMED Abstract]
3. Engels EA: Epidemiology of thymoma and associated malignancies. J Thorac Oncol 5 (10 Suppl 4): S260-5, 2010. [PUBMED Abstract]
4. Carter BW, Benveniste MF, Madan R, et al.: IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms. Radiographics 37 (3): 758-776, 2017 May-Jun. [PUBMED Abstract]
5. Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003. [PUBMED Abstract]
6. Levy Y, Afek A, Sherer Y, et al.: Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 28 (2): 73-9, 1998. [PUBMED Abstract]
7. Marx A, Willcox N, Leite MI, et al.: Thymoma and paraneoplastic myasthenia gravis. Autoimmunity 43 (5-6): 413-27, 2010. [PUBMED Abstract]
8. Bernard C, Frih H, Pasquet F, et al.: Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev 15 (1): 82-92, 2016. [PUBMED Abstract]
9. Padda SK, Yao X, Antonicelli A, et al.: Paraneoplastic Syndromes and Thymic Malignancies: An Examination of the International Thymic Malignancy Interest Group Retrospective Database. J Thorac Oncol 13 (3): 436-446, 2018. [PUBMED Abstract]
10. Kisand K, Lilic D, Casanova JL, et al.: Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications. Eur J Immunol 41 (6): 1517-27, 2011. [PUBMED Abstract]
11. Hoffacker V, Schultz A, Tiesinga JJ, et al.: Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 96 (12): 3872-9, 2000. [PUBMED Abstract]
12. Buckley C, Douek D, Newsom-Davis J, et al.: Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann Neurol 50 (1): 64-72, 2001. [PUBMED Abstract]
13. Ströbel P, Helmreich M, Menioudakis G, et al.: Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas. Blood 100 (1): 159-66, 2002. [PUBMED Abstract]
14. Martinez B, Browne SK: Good syndrome, bad problem. Front Oncol 4: 307, 2014. [PUBMED Abstract]
15. Burbelo PD, Browne SK, Sampaio EP, et al.: Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia. Blood 116 (23): 4848-58, 2010. [PUBMED Abstract]
16. Morgenthaler TI, Brown LR, Colby TV, et al.: Thymoma. Mayo Clin Proc 68 (11): 1110-23, 1993. [PUBMED Abstract]
17. Souadjian JV, Enriquez P, Silverstein MN, et al.: The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med 134 (2): 374-9, 1974. [PUBMED Abstract]
18. Voltz RD, Albrich WC, Nägele A, et al.: Paraneoplastic myasthenia gravis: detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor. Neurology 49 (5): 1454-7, 1997. [PUBMED Abstract]
19. Gautel M, Lakey A, Barlow DP, et al.: Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin. Neurology 43 (8): 1581-5, 1993. [PUBMED Abstract]
20. Kondo K, Monden Y: Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan. Ann Thorac Surg 79 (1): 219-24, 2005. [PUBMED Abstract]
21. Budde JM, Morris CD, Gal AA, et al.: Predictors of outcome in thymectomy for myasthenia gravis. Ann Thorac Surg 72 (1): 197-202, 2001. [PUBMED Abstract]
22. Evoli A, Minisci C, Di Schino C, et al.: Thymoma in patients with MG: characteristics and long-term outcome. Neurology 59 (12): 1844-50, 2002. [PUBMED Abstract]
23. Schmidt-Wolf IG, Rockstroh JK, Schüller H, et al.: Malignant thymoma: current status of classification and multimodality treatment. Ann Hematol 82 (2): 69-76, 2003. [PUBMED Abstract]
24. Rajan A, Giaccone G: Treatment of advanced thymoma and thymic carcinoma. Curr Treat Options Oncol 9 (4-6): 277-87, 2008. [PUBMED Abstract]
25. Rosai J: Histological Typing of Tumours of the Thymus. Springer-Verlag, 2nd ed., 1999.
26. Strollo DC, Rosado-de-Christenson ML: Tumors of the thymus. J Thorac Imaging 14 (3): 152-71, 1999. [PUBMED Abstract]
27. Sperling B, Marschall J, Kennedy R, et al.: Thymoma: a review of the clinical and pathological findings in 65 cases. Can J Surg 46 (1): 37-42, 2003. [PUBMED Abstract]
28. Rendina EA, Venuta F, Ceroni L, et al.: Computed tomographic staging of anterior mediastinal neoplasms. Thorax 43 (6): 441-5, 1988. [PUBMED Abstract]
29. Tomiyama N, Johkoh T, Mihara N, et al.: Using the World Health Organization Classification of thymic epithelial neoplasms to describe CT findings. AJR Am J Roentgenol 179 (4): 881-6, 2002. [PUBMED Abstract]
30. Sasaki M, Kuwabara Y, Ichiya Y, et al.: Differential diagnosis of thymic tumors using a combination of 11C-methionine PET and FDG PET. J Nucl Med 40 (10): 1595-601, 1999. [PUBMED Abstract]
31. Kageyama M, Seto H, Shimizu M, et al.: Thallium-201 single photon emission computed tomography in the evaluation of thymic carcinoma. Radiat Med 12 (5): 237-9, 1994 Sep-Oct. [PUBMED Abstract]
32. Adams S, Baum RP, Hertel A, et al.: Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumours: comparison with the expression of the Ki-67 antigen. Nucl Med Commun 19 (7): 641-7, 1998. [PUBMED Abstract]
33. Kubota K, Yamada S, Kondo T, et al.: PET imaging of primary mediastinal tumours. Br J Cancer 73 (7): 882-6, 1996. [PUBMED Abstract]
34. Carter BW, Lichtenberger JP, Benveniste MF: MR Imaging of Thymic Epithelial Neoplasms. Top Magn Reson Imaging 27 (2): 65-71, 2018. [PUBMED Abstract]
35. Okumura M, Ohta M, Tateyama H, et al.: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 94 (3): 624-32, 2002. [PUBMED Abstract]
36. Chen G, Marx A, Wen-Hu C, et al.: New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 95 (2): 420-9, 2002. [PUBMED Abstract]
37. Kondo K, Yoshizawa K, Tsuyuguchi M, et al.: WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 77 (4): 1183-8, 2004. [PUBMED Abstract]
38. Rena O, Papalia E, Maggi G, et al.: World Health Organization histologic classification: an independent prognostic factor in resected thymomas. Lung Cancer 50 (1): 59-66, 2005. [PUBMED Abstract]
39. Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002. [PUBMED Abstract]
40. Blumberg D, Burt ME, Bains MS, et al.: Thymic carcinoma: current staging does not predict prognosis. J Thorac Cardiovasc Surg 115 (2): 303-8; discussion 308-9, 1998. [PUBMED Abstract]
41. Eng TY, Fuller CD, Jagirdar J, et al.: Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys 59 (3): 654-64, 2004. [PUBMED Abstract]
42. Buckley C, Newsom-Davis J, Willcox N, et al.: Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence? Neurology 57 (9): 1579-82, 2001. [PUBMED Abstract]
43. Engels EA, Pfeiffer RM: Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer 105 (4): 546-51, 2003. [PUBMED Abstract]
44. Pan CC, Chen PC, Wang LS, et al.: Thymoma is associated with an increased risk of second malignancy. Cancer 92 (9): 2406-11, 2001. [PUBMED Abstract]

The histological classification of thymic epithelial tumors (TETs) is largely based on the third edition of the World Health Organization (WHO) classification of tumors of the lung, pleura, thymus, and heart, published in 2004. The fourth edition of the WHO classification, published in 2015, contains refined histological and immunohistochemical diagnostic criteria and is the most widely accepted cellular classification of TETs.[1,2] Thymomas arise from the thymic epithelium and consist of epithelial cells mixed with varying proportions of immature T cells. Thymic carcinomas are epithelial tumors with overt cytological atypia and without organotypic (i.e., thymus-like) features.

References

1. Travis WD, Brambilla E, Burke E, et al.: WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. International Agency for Research on Cancer, 2015.
2. Marx A, Chan JK, Coindre JM, et al.: The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes. J Thorac Oncol 10 (10): 1383-95, 2015. [PUBMED Abstract]
3. Hirabayashi H, Fujii Y, Sakaguchi M, et al.: p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma. Int J Cancer 73 (5): 639-44, 1997. [PUBMED Abstract]
4. Sasaki H, Kobayashi Y, Tanahashi M, et al.: Ets-1 gene expression in patients with thymoma. Jpn J Thorac Cardiovasc Surg 50 (12): 503-7, 2002. [PUBMED Abstract]
5. Rajan A, Girard N, Marx A: State of the art of genetic alterations in thymic epithelial tumors. J Thorac Oncol 9 (9 Suppl 2): S131-6, 2014. [PUBMED Abstract]
6. Radovich M, Pickering CR, Felau I, et al.: The Integrated Genomic Landscape of Thymic Epithelial Tumors. Cancer Cell 33 (2): 244-258.e10, 2018. [PUBMED Abstract]
7. Travis W, Brambilla E, Müller-Hermelink H, et al., eds.: Pathology and Genetics of Tumours of the Lung, Pleura, and Thymus. IARC Press, 2004. World Health Organization Classification of Tumours.
8. Marx A, Chan J, Coindre J-M, et al.: The 2015 WHO classification of tumors of the thymus: continuity and changes. J Thorac Oncol 10 (10): 1383–95, 2015.

Evaluating the invasiveness of a thymoma involves the use of staging criteria that indicate the presence and degree of contiguous invasion, the presence of tumor implants, and lymph node or distant metastases regardless of histological type. The staging system, proposed by Masaoka in 1981 and modified by Koga in 1994, is most commonly used, with the modified system being recommended by the International Thymic Malignancies Interest Group (ITMIG) (see Table 8).[1,2] To establish consistency in the staging of thymic epithelial tumors (TETs), the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) adopted a new TNM (tumor, node, metastasis) classification system developed by the International Association for the Study of Lung Cancer (IASLC) and ITMIG.[3–5]

AJCC Stage Groupings and TNM Definitions

References

1. Masaoka A, Monden Y, Nakahara K, et al.: Follow-up study of thymomas with special reference to their clinical stages. Cancer 48 (11): 2485-92, 1981. [PUBMED Abstract]
2. Koga K, Matsuno Y, Noguchi M, et al.: A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int 44 (5): 359-67, 1994. [PUBMED Abstract]
3. Thymus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 423–9.
4. Carter BW, Benveniste MF, Madan R, et al.: IASLC/ITMIG Staging System and Lymph Node Map for Thymic Epithelial Neoplasms. Radiographics 37 (3): 758-776, 2017 May-Jun. [PUBMED Abstract]
5. Detterbeck FC, Stratton K, Giroux D, et al.: The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: proposal for an evidence-based stage classification system for the forthcoming (8th) edition of the TNM classification of malignant tumors. J Thorac Oncol 9 (9 Suppl 2): S65-72, 2014. [PUBMED Abstract]
6. Okumura M, Ohta M, Tateyama H, et al.: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 94 (3): 624-32, 2002. [PUBMED Abstract]

The primary treatment for patients with thymoma or thymic carcinoma is surgical resection with en bloc resection for invasive tumors, if possible.[1–3] Depending on tumor stage, multimodality treatment options—including the use of radiation therapy and chemotherapy with or without surgery—may be used.[4,5] The optimal strategy for induction therapy, which minimizes operative morbidity and mortality and optimizes resectability rates and ultimately survival, remains unknown. A review of the management of thymic epithelial tumors has been published.[1]

References

1. Girard N, Ruffini E, Marx A, et al.: Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26 (Suppl 5): v40-55, 2015. [PUBMED Abstract]
2. Ruffini E, Filosso PL, Guerrera F, et al.: Optimal surgical approach to thymic malignancies: New trends challenging old dogmas. Lung Cancer 118: 161-170, 2018. [PUBMED Abstract]
3. Cameron RB, Loehrer Sr, Marx A: Neoplasms of the mediastinum. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, et al., eds.: DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer, 2019, pp 700-12.
4. Rimner A, Yao X, Huang J, et al.: Postoperative Radiation Therapy Is Associated with Longer Overall Survival in Completely Resected Stage II and III Thymoma-An Analysis of the International Thymic Malignancies Interest Group Retrospective Database. J Thorac Oncol 11 (10): 1785-92, 2016. [PUBMED Abstract]
5. Rajan A, Giaccone G: Chemotherapy for thymic tumors: induction, consolidation, palliation. Thorac Surg Clin 21 (1): 107-14, viii, 2011. [PUBMED Abstract]
6. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [PUBMED Abstract]
7. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
8. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
9. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
10. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
11. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
12. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
13. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [PUBMED Abstract]

For patients presenting with a mediastinal mass that is highly suspicious for an early-stage thymic epithelial tumor (TET) and is potentially completely resectable, surgical resection is the preferred initial treatment.[1] Under these circumstances, surgical resection serves as a diagnostic and therapeutic procedure. Complete resection of the tumor can be achieved in nearly all patients with stage I and stage II TETs.

Postoperative radiation therapy (PORT) is associated with survival benefit and is generally recommended for patients with stage II or stage III disease.[2] Patients with stage IVA disease are usually offered multimodality therapy consisting of induction chemotherapy followed by surgery (if the disease is considered resectable) and PORT.[3–6] Patients with stage IVB disease are treated with definitive chemotherapy.[7–9,9,10] Surgery and radiation therapy usually do not have a role as primary treatment modalities for advanced disease.

References

1. Maggi G, Casadio C, Cavallo A, et al.: Thymoma: results of 241 operated cases. Ann Thorac Surg 51 (1): 152-6, 1991. [PUBMED Abstract]
2. Rimner A, Yao X, Huang J, et al.: Postoperative Radiation Therapy Is Associated with Longer Overall Survival in Completely Resected Stage II and III Thymoma-An Analysis of the International Thymic Malignancies Interest Group Retrospective Database. J Thorac Oncol 11 (10): 1785-92, 2016. [PUBMED Abstract]
3. Macchiarini P, Chella A, Ducci F, et al.: Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 68 (4): 706-13, 1991. [PUBMED Abstract]
4. Rea F, Sartori F, Loy M, et al.: Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg 106 (3): 543-9, 1993. [PUBMED Abstract]
5. Kim ES, Putnam JB, Komaki R, et al.: Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer 44 (3): 369-79, 2004. [PUBMED Abstract]
6. Yokoi K, Matsuguma H, Nakahara R, et al.: Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol 2 (1): 73-8, 2007. [PUBMED Abstract]
7. Loehrer PJ, Kim K, Aisner SC, et al.: Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol 12 (6): 1164-8, 1994. [PUBMED Abstract]
8. Fornasiero A, Daniele O, Ghiotto C, et al.: Chemotherapy for invasive thymoma. A 13-year experience. Cancer 68 (1): 30-3, 1991. [PUBMED Abstract]
9. Loehrer PJ, Jiroutek M, Aisner S, et al.: Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 91 (11): 2010-5, 2001. [PUBMED Abstract]
10. Lemma GL, Lee JW, Aisner SC, et al.: Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol 29 (15): 2060-5, 2011. [PUBMED Abstract]
11. Masaoka A, Monden Y, Nakahara K, et al.: Follow-up study of thymomas with special reference to their clinical stages. Cancer 48 (11): 2485-92, 1981. [PUBMED Abstract]
12. Pollack A, Komaki R, Cox JD, et al.: Thymoma: treatment and prognosis. Int J Radiat Oncol Biol Phys 23 (5): 1037-43, 1992. [PUBMED Abstract]
13. Ogawa K, Uno T, Toita T, et al.: Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer 94 (5): 1405-13, 2002. [PUBMED Abstract]
14. Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003. [PUBMED Abstract]
15. Ariaratnam LS, Kalnicki S, Mincer F, et al.: The management of malignant thymoma with radiation therapy. Int J Radiat Oncol Biol Phys 5 (1): 77-80, 1979. [PUBMED Abstract]
16. Penn CR, Hope-Stone HF: The role of radiotherapy in the management of malignant thymoma. Br J Surg 59 (7): 533-9, 1972. [PUBMED Abstract]
17. Curran WJ, Kornstein MJ, Brooks JJ, et al.: Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol 6 (11): 1722-7, 1988. [PUBMED Abstract]
18. Mangi AA, Wright CD, Allan JS, et al.: Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 74 (4): 1033-7, 2002. [PUBMED Abstract]
19. Singhal S, Shrager JB, Rosenthal DI, et al.: Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg 76 (5): 1635-41; discussion 1641-2, 2003. [PUBMED Abstract]
20. Thomas CR, Wright CD, Loehrer PJ: Thymoma: state of the art. J Clin Oncol 17 (7): 2280-9, 1999. [PUBMED Abstract]
21. Berman AT, Litzky L, Livolsi V, et al.: Adjuvant radiotherapy for completely resected stage 2 thymoma. Cancer 117 (15): 3502-8, 2011. [PUBMED Abstract]
22. Berruti A, Borasio P, Gerbino A, et al.: Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience. Br J Cancer 81 (5): 841-5, 1999. [PUBMED Abstract]
23. Shin DM, Walsh GL, Komaki R, et al.: A multidisciplinary approach to therapy for unresectable malignant thymoma. Ann Intern Med 129 (2): 100-4, 1998. [PUBMED Abstract]
24. Loehrer PJ, Chen M, Kim K, et al.: Cisplatin, doxorubicin, and cyclophosphamide plus thoracic radiation therapy for limited-stage unresectable thymoma: an intergroup trial. J Clin Oncol 15 (9): 3093-9, 1997. [PUBMED Abstract]
25. Fernandes AT, Shinohara ET, Guo M, et al.: The role of radiation therapy in malignant thymoma: a Surveillance, Epidemiology, and End Results database analysis. J Thorac Oncol 5 (9): 1454-60, 2010. [PUBMED Abstract]
26. Weksler B, Shende M, Nason KS, et al.: The role of adjuvant radiation therapy for resected stage III thymoma: a population-based study. Ann Thorac Surg 93 (6): 1822-8; discussion 1828-9, 2012. [PUBMED Abstract]
27. Lucchi M, Melfi F, Dini P, et al.: Neoadjuvant chemotherapy for stage III and IVA thymomas: a single-institution experience with a long follow-up. J Thorac Oncol 1 (4): 308-13, 2006. [PUBMED Abstract]
28. Yagi K, Hirata T, Fukuse T, et al.: Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded. Ann Thorac Surg 61 (2): 521-4, 1996. [PUBMED Abstract]
29. Akaogi E, Ohara K, Mitsui K, et al.: Preoperative radiotherapy and surgery for advanced thymoma with invasion to the great vessels. J Surg Oncol 63 (1): 17-22, 1996. [PUBMED Abstract]
30. Giaccone G, Ardizzoni A, Kirkpatrick A, et al.: Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 14 (3): 814-20, 1996. [PUBMED Abstract]

Thymic carcinoma is rare, and the optimal treatment is undefined. For patients with clearly resectable well-defined disease, surgical resection is often the initial therapeutic intervention. For patients with clinically borderline or frankly unresectable lesions, neoadjuvant (preoperative) chemotherapy, thoracic radiation therapy, or both have been given.[1] Patients presenting with locally advanced disease are carefully evaluated and undergo multimodality therapy. Patients with poor performance status and high associated operative risks are generally not candidates for these aggressive treatments. Patients with metastatic disease may respond to combination chemotherapy.

References

1. Koizumi T, Takabayashi Y, Yamagishi S, et al.: Chemotherapy for advanced thymic carcinoma: clinical response to cisplatin, doxorubicin, vincristine, and cyclophosphamide (ADOC chemotherapy). Am J Clin Oncol 25 (3): 266-8, 2002. [PUBMED Abstract]
2. Hsu HC, Huang EY, Wang CJ, et al.: Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors. Int J Radiat Oncol Biol Phys 52 (3): 801-5, 2002. [PUBMED Abstract]
3. Omasa M, Date H, Sozu T, et al.: Postoperative radiotherapy is effective for thymic carcinoma but not for thymoma in stage II and III thymic epithelial tumors: the Japanese Association for Research on the Thymus Database Study. Cancer 121 (7): 1008-16, 2015. [PUBMED Abstract]
4. Ahmad U, Yao X, Detterbeck F, et al.: Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg 149 (1): 95-100, 101.e1-2, 2015. [PUBMED Abstract]
5. Kondo K, Monden Y: Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 76 (3): 878-84; discussion 884-5, 2003. [PUBMED Abstract]
6. Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002. [PUBMED Abstract]
7. Greene MA, Malias MA: Aggressive multimodality treatment of invasive thymic carcinoma. J Thorac Cardiovasc Surg 125 (2): 434-6, 2003. [PUBMED Abstract]
8. Lucchi M, Mussi A, Ambrogi M, et al.: Thymic carcinoma: a report of 13 cases. Eur J Surg Oncol 27 (7): 636-40, 2001. [PUBMED Abstract]
9. Weide LG, Ulbright TM, Loehrer PJ, et al.: Thymic carcinoma. A distinct clinical entity responsive to chemotherapy. Cancer 71 (4): 1219-23, 1993. [PUBMED Abstract]
10. Loehrer PJ, Kim K, Aisner SC, et al.: Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group. J Clin Oncol 12 (6): 1164-8, 1994. [PUBMED Abstract]
11. Loehrer PJ, Jiroutek M, Aisner S, et al.: Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 91 (11): 2010-5, 2001. [PUBMED Abstract]
12. Fornasiero A, Daniele O, Ghiotto C, et al.: Chemotherapy for invasive thymoma. A 13-year experience. Cancer 68 (1): 30-3, 1991. [PUBMED Abstract]
13. Giaccone G, Ardizzoni A, Kirkpatrick A, et al.: Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 14 (3): 814-20, 1996. [PUBMED Abstract]
14. Lemma GL, Lee JW, Aisner SC, et al.: Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol 29 (15): 2060-5, 2011. [PUBMED Abstract]

References

1. Girard N, Ruffini E, Marx A, et al.: Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26 (Suppl 5): v40-55, 2015. [PUBMED Abstract]
2. Gbolahan OB, Porter RF, Salter JT, et al.: A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma. J Thorac Oncol 13 (12): 1940-1948, 2018. [PUBMED Abstract]
3. Palmieri G, Montella L, Martignetti A, et al.: Somatostatin analogs and prednisone in advanced refractory thymic tumors. Cancer 94 (5): 1414-20, 2002. [PUBMED Abstract]
4. Palmieri G, Buonerba C, Ottaviano M, et al.: Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial. Future Oncol 10 (14): 2141-7, 2014. [PUBMED Abstract]
5. Loehrer PJ, Wang W, Johnson DH, et al.: Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group phase II trial. J Clin Oncol 22 (2): 293-9, 2004. [PUBMED Abstract]
6. Thomas A, Rajan A, Berman A, et al.: Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol 16 (2): 177-86, 2015. [PUBMED Abstract]
7. Zucali PA, De Pas T, Palmieri G, et al.: Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Cisplatin-Based Chemotherapy. J Clin Oncol 36 (4): 342-349, 2018. [PUBMED Abstract]
8. Sato J, Satouchi M, Itoh S, et al.: Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial. Lancet Oncol 21 (6): 843-850, 2020. [PUBMED Abstract]
9. Urgesi A, Monetti U, Rossi G, et al.: Aggressive treatment of intrathoracic recurrences of thymoma. Radiother Oncol 24 (4): 221-5, 1992. [PUBMED Abstract]
10. Okumura M, Shiono H, Inoue M, et al.: Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to world health organization histologic classification system. J Surg Oncol 95 (1): 40-4, 2007. [PUBMED Abstract]
11. Ruffini E, Mancuso M, Oliaro A, et al.: Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome. J Thorac Cardiovasc Surg 113 (1): 55-63, 1997. [PUBMED Abstract]
12. Cho J, Kim HS, Ku BM, et al.: Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. J Clin Oncol 37 (24): 2162-2170, 2019. [PUBMED Abstract]
13. Giaccone G, Kim C, Thompson J, et al.: Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol 19 (3): 347-355, 2018. [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.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Adult 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.

Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.

Other PDQ summaries on Testicular Cancer Treatment and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

It is estimated that 9,720 new cases of testicular cancer will be diagnosed in men, and 600 men will die of this disease in the United States in 2025.[1] Testicular cancer is the most common malignancy in men aged 15 to 34 years.[2,3] It accounts for approximately 1% of all cancers in men. Worldwide, testicular cancer has more than doubled in the last 40 years. Incidence varies considerably in different geographical areas, being highest in Scandinavia and Switzerland; intermediate in the United States, Australia, and the United Kingdom; and lowest in Asia and Africa. It also varies according to ethnic groups, with a much higher rate among White men than Black men in the American population.[4] An annual increase of 3% is reported for White populations.[5] Despite the increase in observed incidence, there has been a dramatic decrease in mortality as a result of effective treatments.

Unlike most other cancers, testicular cancer is generally found in young men and has the highest incidence rate among men aged 25 to 34 years at approximately 15 cases per 100,000 men. Men in the surrounding age groups (20–24 years and 35–39 years) have a slightly lower incidence at approximately 12 cases per 100,000 men. The racial and ethnic groups with the highest incidence rates include non-Hispanic White men and non-Hispanic American Indian or Alaskan Native men, both at approximately 7 cases per 100,000 men. Testicular cancer is the most commonly diagnosed cancer among men aged 20 to 39 years.[6]

Approximately 66% of testicular cancers are localized, 19% are regional, and 12% are distant stage at diagnosis.[6] Although there has been no appreciable change in the stage distribution at diagnosis, advances in treatment have been associated with a 60% decrease in mortality. Most testicular cancers are curable even at advanced stages, and it would be impractical to document a further decrease in mortality associated with screening.

Germ cell tumors (GCTs) of the testis constitute 94% of testicular tumors and include five basic cell types:[7]

Sixty percent of GCTs are seminomas; the remainder are nonseminomatous GCTs. Almost half of all GCTs contain more than one of the five cell types.[7]

Three subtypes of pure seminomas have been described: classic, anaplastic, and spermatocytic. Classic seminoma accounts for 80% to 85% of all seminomas and occurs most commonly in men aged 30 to 50 years. Anaplastic seminoma accounts for 5% to 10% of all seminomas and has an age distribution similar to that of the typical subtype. A number of features suggest that anaplastic seminoma is a more aggressive and potentially more lethal variant of typical seminoma. These characteristics include greater mitotic activity, higher rate of local invasion, increased rate of metastatic spread, and higher rate of tumor marker (human chorionic gonadotropin [hCG] beta, or beta hCG) production. Spermatocytic seminoma accounts for 2% to 12% of all seminomas, and nearly half occur in men older than 50 years. The cells closely resemble different phases of maturing spermatogonia. The metastatic potential of this tumor is extremely low, and the prognosis is favorable.[8]

References

1. American Cancer Society: Cancer Facts and Figures 2025. American Cancer Society, 2025. Available online. Last accessed January 16, 2025.
2. McGlynn KA, Devesa SS, Sigurdson AJ, et al.: Trends in the incidence of testicular germ cell tumors in the United States. Cancer 97 (1): 63-70, 2003. [PUBMED Abstract]
3. Garner MJ, Turner MC, Ghadirian P, et al.: Epidemiology of testicular cancer: an overview. Int J Cancer 116 (3): 331-9, 2005. [PUBMED Abstract]
4. Huyghe E, Matsuda T, Thonneau P: Increasing incidence of testicular cancer worldwide: a review. J Urol 170 (1): 5-11, 2003. [PUBMED Abstract]
5. Horwich A, Shipley J, Huddart R: Testicular germ-cell cancer. Lancet 367 (9512): 754-65, 2006. [PUBMED Abstract]
6. 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.
7. Dieckmann KP, Pichlmeier U: Clinical epidemiology of testicular germ cell tumors. World J Urol 22 (1): 2-14, 2004. [PUBMED Abstract]
8. Richie JP, Steele GS: Neoplasms of the testis. In: Campbell MF, Wein AJ, Kavoussi LR: Campbell-Walsh Urology. 9th ed. Saunders Elsevier, 2007, pp 893-935.

Testicular cancer is more than four times more common among White men than Black men,[1,2] with intermediate incidence rates for Hispanic, American Indian, and Asian men. High-risk groups exist. Males with cryptorchidism have 3 to 17 times the average risk. Approximately 7% to 10% of patients with testicular tumors have a history of cryptorchidism.[2,3] Although the association is established, the biological mechanism underlying the association remains uncertain; testicular cancer and cryptorchidism may share environmental and/or genetic risk factors; or, it is the ectopic position per se that is a postnatal risk factor for testicular cancer, or it is a combination of the two.[3] Orchiopexy may not prevent cancer in these children but allows clinical surveillance of patients with a previously impalpable gonad.

There is also an increased risk in males with gonadal dysgenesis and Klinefelter syndrome.[4] Men with a family history of testicular cancer may be at a higher risk of this disease.[5] A history of testicular cancer is associated with a higher risk of a contralateral tumor.[3,2] Although not consistently found, infertility, testicular atrophy, twinship, or abnormal semen parameters have been associated with a higher risk of testicular cancer, but the evidence is weak.[3,6–8]

There is a low cumulative risk of metachronous contralateral testicular cancer and a favorable overall survival of patients diagnosed with metachronous contralateral testicular cancer.[9] Future research is necessary to delineate the genetic and environmental risk factors for testicular cancer.[10]

References

1. Moul JW, Schanne FJ, Thompson IM, et al.: Testicular cancer in blacks. A multicenter experience. Cancer 73 (2): 388-93, 1994. [PUBMED Abstract]
2. Richie JP, Steele GS: Neoplasms of the testis. In: Campbell MF, Wein AJ, Kavoussi LR: Campbell-Walsh Urology. 9th ed. Saunders Elsevier, 2007, pp 893-935.
3. Dieckmann KP, Pichlmeier U: Clinical epidemiology of testicular germ cell tumors. World J Urol 22 (1): 2-14, 2004. [PUBMED Abstract]
4. Henderson BE, Benton B, Jing J, et al.: Risk factors for cancer of the testis in young men. Int J Cancer 23 (5): 598-602, 1979. [PUBMED Abstract]
5. Dieckmann KP, Pichlmeier U: The prevalence of familial testicular cancer: an analysis of two patient populations and a review of the literature. Cancer 80 (10): 1954-60, 1997. [PUBMED Abstract]
6. Jacobsen R, Bostofte E, Engholm G, et al.: Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ 321 (7264): 789-92, 2000. [PUBMED Abstract]
7. Walsh TJ, Croughan MS, Schembri M, et al.: Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 169 (4): 351-6, 2009. [PUBMED Abstract]
8. Hotaling JM, Walsh TJ: Male infertility: a risk factor for testicular cancer. Nat Rev Urol 6 (10): 550-6, 2009. [PUBMED Abstract]
9. Fosså SD, Chen J, Schonfeld SJ, et al.: Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 97 (14): 1056-66, 2005. [PUBMED Abstract]
10. Richiardi L, Pettersson A, Akre O: Genetic and environmental risk factors for testicular cancer. Int J Androl 30 (4): 230-40; discussion 240-1, 2007. [PUBMED Abstract]
11. Olesen IA, Hoei-Hansen CE, Skakkebaek NE, et al.: Testicular carcinoma in situ in subfertile Danish men. Int J Androl 30 (4): 406-11; discussion 412, 2007. [PUBMED Abstract]
12. Jørgensen N, Müller J, Giwercman A, et al.: Clinical and biological significance of carcinoma in situ of the testis. Cancer Surv 9 (2): 287-302, 1990. [PUBMED Abstract]
13. Dieckmann KP, Loy V: Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms. J Clin Oncol 14 (12): 3126-32, 1996. [PUBMED Abstract]

The sensitivity, specificity, and positive predictive value of routine screening of asymptomatic men for testicular cancer are not known.[1,2] In a report of a single-center case series of men being evaluated for infertility, testicular symptoms, or erectile dysfunction, 1,320 men underwent testicular ultrasonography.[3] Focal lesions were found in 27 (2%) men, 17 of the lesions were palpable, and 10 were nonpalpable. Eighty percent of the lesions were ultimately shown to have benign histologies, for a positive predictive value of about 0.2. It is not clear if early discovery of the cancers resulted in clinical benefit, and the positive predictive value is likely to be lower in the target population of asymptomatic men in the screening setting.

Most testicular cancers are first detected by the patient, either unintentionally or by self-examination. Some are discovered by routine physical examination. However, no studies have been done to determine the effectiveness of testicular self-examination or clinical testicular examination in reducing mortality from testicular cancer. An updated systematic review performed on behalf of the U.S. Preventive Services Task Force, published in 2010, found no randomized trials, cohort studies, or case-control studies that examined benefits of testicular cancer screening (whether by physical examination, self-examination, or other screening tests) in an asymptomatic population.[2] Likewise, a systematic Cochrane Collaboration review found no randomized or quasi-randomized controlled trials that evaluated the effectiveness of screening by a health professional or patient self-examination.[4]

Screening would be very unlikely to decrease mortality substantially because therapy is so effective at virtually all stages of disease.[5] For more information, see Testicular Cancer Treatment. However, early detection may affect therapy. There is an increase in both the number of courses of chemotherapy and the extent of surgery required for treatment of advanced disease that results in higher morbidity. Patients diagnosed with localized disease require less treatment and have lower morbidity.[6]

References

1. U.S. Preventive Services Task Force: Screening for testicular cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med 154 (7): 483-6, 2011. [PUBMED Abstract]
2. Lin K, Sharangpani R: Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 153 (6): 396-9, 2010. [PUBMED Abstract]
3. Carmignani L, Gadda F, Gazzano G, et al.: High incidence of benign testicular neoplasms diagnosed by ultrasound. J Urol 170 (5): 1783-6, 2003. [PUBMED Abstract]
4. Ilic D, Misso ML: Screening for testicular cancer. Cochrane Database Syst Rev (2): CD007853, 2011. [PUBMED Abstract]
5. Feldman DR, Bosl GJ, Sheinfeld J, et al.: Medical treatment of advanced testicular cancer. JAMA 299 (6): 672-84, 2008. [PUBMED Abstract]
6. Sagalowsky AI: Expectant management of stage A nonseminomatous testicular tumors. In: Ratiff TL, Catalona WJ, eds.: Genitourinary Cancer. Martinus Nijhoff, 1987, pp 225-237.

Harms of screening for testicular cancer are poorly quantified. They may include false positive tests [1] and resulting anxiety as well as subsequent unwarranted invasive diagnostic procedures. Two systematic reviews found no studies that provided a quantitative assessment of the harms of screening.[2,3]

References

1. Carmignani L, Gadda F, Gazzano G, et al.: High incidence of benign testicular neoplasms diagnosed by ultrasound. J Urol 170 (5): 1783-6, 2003. [PUBMED Abstract]
2. Lin K, Sharangpani R: Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 153 (6): 396-9, 2010. [PUBMED Abstract]
3. Ilic D, Misso ML: Screening for testicular cancer. Cochrane Database Syst Rev (2): CD007853, 2011. [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.

Incidence and Mortality

Updated statistics with estimated new cases and deaths for 2025 (cited American Cancer Society as reference 1).

This summary is written and maintained by the PDQ Screening and Prevention 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.

Screening is looking for cancer before a person has any symptoms. This can help find cancer at an early stage. When abnormal tissue or cancer is found early, it may be easier to treat. By the time symptoms appear, cancer may have begun to spread.

Scientists are trying to better understand which people are more likely to get certain types of cancer. They also study the things we do and the things around us to see if they cause cancer. This information helps doctors recommend who should be screened for cancer, which screening tests should be used, and how often the tests should be done.

It is important to remember that your doctor does not necessarily think you have cancer if he or she suggests a screening test. Screening tests are given when you have no cancer symptoms.

If a screening test result is abnormal, you may need to have more tests done to find out if you have cancer. These are called diagnostic tests.

Surgery is the standard treatment for early stage ovarian borderline tumors. The type of surgery usually depends on whether a patient plans to have children.

For patients who plan to have children, surgery is either:

To prevent recurrence of disease, most doctors recommend surgery to remove the remaining ovarian tissue when a patient no longer plans to have children.

For patients who do not plan to have children, treatment may be hysterectomy and bilateral salpingo-oophorectomy.

Learn more about these treatments in the Treatment Option Overview.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Treatment for advanced stage ovarian borderline tumors may be hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. A lymph node dissection may also be done. Patients with advanced disease should undergo a total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, node sampling, and aggressive cytoreductive surgery.

Learn more about these treatments in the Treatment Option Overview.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Treatment for recurrent ovarian borderline tumors may include:

Learn more about these treatments in the Treatment Option Overview.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For general cancer information and other resources from the National Cancer Institute, visit:

Childhood nasopharyngeal cancer is a rare type of cancer that forms in the tissue lining the nasopharynx. The nasopharynx is the upper part of the throat behind the nose. The nostrils allow air into the nasopharynx. Air and food pass through the pharynx on the way to the trachea or esophagus.

Nasopharyngeal cancer is more common in children aged 10 to 19 years than in children younger than 10 years.

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Childhood nasopharyngeal cancer is caused by certain changes in the way the cells in the nasal cavity and top part of the throat function, especially how they grow and divide into new cells. Often, the exact cause of these changes is unknown. Learn more about how cancer develops at What Is Cancer?

A risk factor is anything that increases the chance of getting a disease. A known risk factor for childhood nasopharyngeal cancer is infection from the Epstein-Barr virus (EBV). Not every child with this risk factor will develop nasopharyngeal cancer. And it will develop in some children who don’t have a known risk factor. Talk with your child’s doctor if you think your child may be at risk.

Children may not have symptoms of nasopharyngeal cancer until the tumor has grown bigger. It’s important to check with your child’s doctor if your child has:

These symptoms may be caused by problems other than nasopharyngeal cancer. The only way to know is for your child to see a doctor.

If your child has symptoms that suggest nasopharyngeal cancer, the doctor will need to find out if these are due to cancer or another problem. The doctor will ask when the symptoms started and how often your child has been having them. They will also ask about your child’s personal and family medical history and do a physical exam. Depending on these results, the doctor may recommend other tests. If your child is diagnosed with nasopharyngeal cancer, the results of these tests will help plan treatment.

You may want to get a second opinion to confirm your child’s cancer diagnosis and treatment plan. If you seek a second opinion, you will need to get medical test results and reports from the first doctor to share with the second doctor. The second doctor will review the pathology report, slides, and scans. This doctor may agree with the first doctor, suggest changes to the treatment plan, or provide more information about your child’s cancer.

To learn more about choosing a doctor and getting a second opinion, visit Finding Cancer Care. You can contact NCI’s Cancer Information Service via chat, email, or phone (both in English and Spanish) for help finding a doctor or hospital that can provide a second opinion. For questions you might want to ask at your child’s appointments, visit Questions to Ask Your Doctor about Cancer.

The cancer stage describes the extent of cancer in the body, such as the size of the tumor, whether it has spread, and how far it has spread from where it first formed. It is important to know the stage of nasopharyngeal cancer to plan the best treatment.

There are several staging systems for cancer. Nasopharyngeal cancer staging usually uses the TNM staging system. You may see your child’s cancer described by this staging system in the pathology report. Based on the TNM results, a stage (I, II, III, or IV, also written as 1, 2, 3, or 4) is assigned to your child’s cancer. When talking with you about your child’s cancer, your child’s doctor may describe it as one of these stages.

Learn more about Cancer Staging.

Learn about the tests and procedures used to determine the stage of nasopharyngeal cancer. 

Stage I nasopharyngeal cancer

In stage I, nasopharyngeal cancer has formed and is found in the nasopharynx only or has spread from the nasopharynx to the oropharynx and/or nasal cavity.

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If your child has been diagnosed with nasopharyngeal cancer, you likely have questions about how serious the cancer is and your child’s chances of survival. The likely outcome or course of a disease is called prognosis. The prognosis can be affected by whether the cancer has spread to other parts of the body at the time of diagnosis and whether the cancer has just been diagnosed or has recurred (come back). No two people are alike, and responses to treatment can vary greatly. Your child’s cancer care team is in the best position to talk with you about your child’s prognosis.

Cancer treatments can cause side effects. Which side effects your child might have depends on the type of treatment they receive, the dose, and how their body reacts. Talk with your child’s treatment team about which side effects to look for and ways to manage them.

To learn more about side effects that begin during treatment for cancer, visit Side Effects.

Problems from cancer treatment that begin 6 months or later after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include:

Some late effects may be treated or controlled. It is important to talk with your child’s doctors about the possible late effects caused by some treatments. Learn more about Late Effects of Treatment for Childhood Cancer.

As your child goes through treatment, they will have follow-up tests or check-ups. Some tests that were done to diagnose or stage the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child’s condition has changed or if the cancer has recurred (come back).

When your child has cancer, every member of the family needs support. Taking care of yourself during this difficult time is important. Reach out to your child’s treatment team and to people in your family and community for support. To learn more, visit Support for Families: Childhood Cancer and the booklet Children with Cancer: A Guide for Parents. 

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

Childhood laryngeal tumors form in the voice box, also called the larynx. These tumors may be benign (which means they are not cancer) or cancer. Most laryngeal tumors in children are not cancer and do not spread to other tissues. Both types of tumors need treatment.

The most common type of benign laryngeal tumor is papillomatosis of the larynx. In this condition, papillomas (benign tumors that look like warts) form in the lining of the larynx. These tumors may block the airway and cause trouble breathing. They often come back after treatment and, in rare cases, may turn into cancer in the larynx or the lung.

The larynx is a part of the throat, between the base of the tongue and the trachea (windpipe). The larynx contains the vocal cords, which vibrate and make sound when air is directed against them. The sound echoes through the pharynx, mouth, and nose to make a person’s voice.

There are three main parts of the larynx:

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Laryngeal cancer in children is caused by certain changes to the way cells in the larynx function, especially how they grow and divide into new cells. Often, the exact cause of these cell changes is unknown. Learn more about how cancer develops at What Is Cancer?

Laryngeal papillomatosis is caused by infection with low-risk HPV (human papillomavirus), most often types 6 and 11. Children can get the HPV infection that causes laryngeal papillomatosis from an infected mother during birth. Most children with an HPV infection do not develop laryngeal papillomatosis. Talk with your child’s doctor if you think your child may be at risk.

Getting the HPV vaccine can help protect against HPV infection and reduce the risk of transmitting it during childbirth. Learn more about HPV Vaccines.

Children may not have symptoms of a laryngeal tumor until the tumor has grown bigger. It’s important to check with your child’s doctor if your child has:

Infants and young children with these tumors may grow slowly and not eat well or meet developmental milestones such as sitting, walking, and talking in sentences.

These symptoms may be caused by problems other than a laryngeal tumor. The only way to know is to see your child’s doctor.

If your child has symptoms that suggest a laryngeal tumor, the doctor will need to find out if these are due to cancer or some other problem. The doctor will ask when the symptoms started and how often your child has been having them. They will also ask about your child’s personal and family medical history and do a physical exam. Depending on these results, they may recommend other tests. If your child is diagnosed with a laryngeal tumor, the results of these tests will help you and your child’s doctor plan treatment.

The tests used to diagnose laryngeal tumors may include:

CT scan

CT scan (CAT scan) uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-D views of tissues and organs. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. Learn more about Computed Tomography (CT) Scans and Cancer.

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PET scan

PET scan (positron emission tomography scan) uses a small amount of radioactive sugar (also called radioactive glucose) that is injected into a vein. The PET scanner rotates around the body and makes pictures of where sugar is being used by the body. Cancer cells show up brighter in the pictures because they are more active and take up more sugar than normal cells do.

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You may want to get a second opinion to confirm your child’s cancer diagnosis and treatment plan. If you seek a second opinion, you will need to get medical test results and reports from the first doctor to share with the second doctor. The second doctor will review the pathology report, slides, and scans. This doctor may agree with the first doctor, suggest changes to the treatment plan, or provide more information about your child’s cancer.

To learn more about choosing a doctor and getting a second opinion, visit Finding Cancer Care. You can contact NCI’s Cancer Information Service via chat, email, or phone (both in English and Spanish) for help finding a doctor or hospital that can provide a second opinion. For questions you might want to ask at your child’s appointments, visit Questions to Ask Your Doctor About Cancer.

There are different types of treatment for children with laryngeal tumors. You and your child’s care team will work together to decide on treatment. Many factors will be considered, such as your child’s overall health and whether the tumor is newly diagnosed or has come back.

Your child’s treatment plan will include information about the tumor, the goals of treatment, treatment options, and the possible side effects. It will be helpful to talk with your child’s care team before treatment begins about what to expect. For help every step of the way, see our booklet, Children with Cancer: A Guide for Parents.

For some children, joining a clinical trial may be an option. There are different types of clinical trials for childhood cancer. For example, a treatment trial tests new treatments or new ways of using current treatments. Supportive care and palliative care trials look at ways to improve quality of life, especially for those who have side effects from cancer and its treatment.

You can use the clinical trial search to find NCI-supported cancer clinical trials accepting participants. The search allows you to filter trials based on the type of cancer, your child’s age, and where the trials are being done. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Learn more about clinical trials, including how to find and join one, at Clinical Trials Information for Patients and Caregivers.

As your child goes through treatment, they will have follow-up tests or check-ups. Some of the tests that were done to diagnose the cancer may be repeated to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child’s condition has changed or if the cancer has recurred (come back).

When your child has cancer, every member of the family needs support. Taking care of yourself during this difficult time is important. Reach out to your child’s treatment team and to people in your family and community for support. To learn more, visit Support for Families: Childhood Cancer and the booklet Children with Cancer: A Guide for Parents.

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

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage I paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage II paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage III paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity.

If cancer is in the maxillary sinus, treatment may include:

If cancer is in the ethmoid sinus, treatment may include:

If cancer is in the sphenoid sinus, treatment is the same as for nasopharyngeal cancer, usually radiation therapy with or without chemotherapy. For more information, see Nasopharyngeal Cancer Treatment.

If cancer is in the nasal cavity, treatment may include:

For inverting papillomas, treatment is usually surgery with or without radiation therapy.

For melanomas and sarcomas, treatment may include:

For midline granulomas, treatment is usually radiation therapy.

If cancer is in the nasal vestibule, treatment may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage IV paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity.

If cancer is in the maxillary sinus, treatment may include:

If cancer is in the ethmoid sinus, treatment may include:

If cancer is in the sphenoid sinus, treatment is the same as for nasopharyngeal cancer, usually radiation therapy with or without chemotherapy. For more information, see Nasopharyngeal Cancer Treatment.

If cancer is in the nasal cavity, treatment may include:

For inverting papillomas, treatment is usually surgery with or without radiation therapy.

For melanomas and sarcomas, treatment may include:

For midline granulomas, treatment is usually radiation therapy.

If cancer is in the nasal vestibule, treatment may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of recurrent paranasal sinus and nasal cavity cancer depends on where cancer is found in the paranasal sinuses and nasal cavity.

If cancer is in the maxillary sinus, treatment may include:

If cancer is in the ethmoid sinus, treatment may include:

If cancer is in the sphenoid sinus, treatment is the same as for nasopharyngeal cancer and may include radiation therapy with or without chemotherapy. For more information, see Nasopharyngeal Cancer Treatment.

If cancer is in the nasal cavity, treatment may include:

For inverting papillomas, treatment is usually surgery with or without radiation therapy.

For melanomas and sarcomas, treatment may include:

For midline granulomas, treatment is usually radiation therapy.

If cancer is in the nasal vestibule, treatment may include:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For more information from the National Cancer Institute about paranasal sinus and nasal cavity cancer, see:

For general cancer information and other resources from the National Cancer Institute, visit:

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment for stage I salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

If the cancer is high-grade, treatment may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment for stage II salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

If the cancer is high-grade, treatment may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment for stage III salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

If the cancer is high-grade, treatment may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of stage IVA, stage IVB, and stage IVC salivary gland cancer may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For information about the treatments listed below, see the Treatment Option Overview section.

Treatment of recurrent salivary gland cancer may include the following:

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

For more information from the National Cancer Institute about salivary gland cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, visit:

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Springer-Verlag, 1989.
3. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. WB Saunders, 1999.
4. Johns ME, Kaplan MJ: Advances in the management of paranasal sinus tumors. In: Wolf GT, ed.: Head and Neck Oncology. Martinus Nijhoff Publishers, 1984, pp 27-52.
5. Alos L, Moyano S, Nadal A, et al.: Human papillomaviruses are identified in a subgroup of sinonasal squamous cell carcinomas with favorable outcome. Cancer 115 (12): 2701-9, 2009. [PUBMED Abstract]

The most common cell type for paranasal sinus and nasal cavity cancers is squamous cell carcinoma. Minor salivary gland tumors comprise 10% to 15% of these neoplasms. Malignant melanoma presents in less than 1% of neoplasms in this region. Some 5% of cases are malignant lymphomas.[1,2]

Esthesioneuroepithelioma, sometimes confused with undifferentiated carcinoma or undifferentiated lymphoma, arises from the olfactory nerves.[3]

Chondrosarcoma, osteosarcoma, Ewing sarcoma, and most soft tissue sarcomas have been reported for this region.

Inverting papilloma is considered a low-grade benign tumor with a tendency to recur and, in a small percentage of cases, to transform into a malignant tumor.

Midline granuloma, a progressively destructive condition, also involves this region.

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Goldenberg D, Golz A, Fradis M, et al.: Malignant tumors of the nose and paranasal sinuses: a retrospective review of 291 cases. Ear Nose Throat J 80 (4): 272-7, 2001. [PUBMED Abstract]
3. Jethanamest D, Morris LG, Sikora AG, et al.: Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 133 (3): 276-80, 2007. [PUBMED Abstract]

The staging systems are clinical estimates of the extent of disease. The assessment of the tumor is based on inspection, palpation, and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathological data obtained on biopsy may be included. The appropriate nodal drainage areas are examined by careful palpation. Computed tomographic and/or magnetic resonance imaging studies are generally required to adequately evaluate tumor extent before surgical resection or definitive radiation therapy. If a patient’s disease relapses, complete restaging must be done to select the appropriate additional therapy.[1,2]

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Springer-Verlag, 1989.
3. Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 137-47.

Except for patients with T1 mucosal carcinomas, the accepted method of treatment is a combination of radiation therapy and surgery. The incidence of lymph node metastases is generally low (approximately 20% of cases). Thus, routine radical neck dissection or elective neck radiation therapy is recommended only for patients presenting with positive nodes.

For patients with operable tumors, radical surgery is generally performed first to remove the bulk of the tumor and to establish drainage of the affected sinus(es). This is followed by postoperative radiation therapy. Some institutions continue to give a full dose of radiation therapy preoperatively for all patients with stage II and stage III tumors and operate 4 to 6 weeks later.[1–3] A review of published clinical results of radical radiation therapy for head and neck cancer suggested a significant loss of local control with prolonged radiation therapy; therefore, lengthening of standard treatment schedules should be avoided whenever possible.[4]

References

1. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
2. Laramore GE, ed.: Radiation Therapy of Head and Neck Cancer. Springer-Verlag, 1989.
3. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. WB Saunders, 1999.
4. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992. [PUBMED Abstract]
5. Ganly I, Patel SG, Singh B, et al.: Craniofacial resection for malignant paranasal sinus tumors: Report of an International Collaborative Study. Head Neck 27 (7): 575-84, 2005. [PUBMED Abstract]
6. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995. [PUBMED Abstract]
7. Constine LS: What else don’t we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995. [PUBMED Abstract]
8. Jacobs C, Lyman G, Velez-García E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10 (2): 257-63, 1992. [PUBMED Abstract]
9. Schornagel JH, Verweij J, de Mulder PH, et al.: Randomized phase III trial of edatrexate versus methotrexate in patients with metastatic and/or recurrent squamous cell carcinoma of the head and neck: a European Organization for Research and Treatment of Cancer Head and Neck Cancer Cooperative Group study. J Clin Oncol 13 (7): 1649-55, 1995. [PUBMED Abstract]
10. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [PUBMED Abstract]
11. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
12. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
13. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
14. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
15. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
16. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
17. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [PUBMED Abstract]

Stage I disease includes small lesions.

References

1. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
2. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
3. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
4. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
5. Ang KK, Jiang GL, Frankenthaler RA, et al.: Carcinomas of the nasal cavity. Radiother Oncol 24 (3): 163-8, 1992. [PUBMED Abstract]
6. Levendag PC, Pomp J: Radiation therapy of squamous cell carcinoma of the nasal vestibule. Int J Radiat Oncol Biol Phys 19 (6): 1363-7, 1990. [PUBMED Abstract]
7. Wong CS, Cummings BJ: The place of radiation therapy in the treatment of squamous cell carcinoma of the nasal vestibule. A review. Acta Oncol 27 (3): 203-8, 1988. [PUBMED Abstract]

Stage II disease includes small and moderately advanced lesions.

References

1. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
2. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
3. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
4. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
5. Ang KK, Jiang GL, Frankenthaler RA, et al.: Carcinomas of the nasal cavity. Radiother Oncol 24 (3): 163-8, 1992. [PUBMED Abstract]
6. Levendag PC, Pomp J: Radiation therapy of squamous cell carcinoma of the nasal vestibule. Int J Radiat Oncol Biol Phys 19 (6): 1363-7, 1990. [PUBMED Abstract]
7. Wong CS, Cummings BJ: The place of radiation therapy in the treatment of squamous cell carcinoma of the nasal vestibule. A review. Acta Oncol 27 (3): 203-8, 1988. [PUBMED Abstract]

Stage III disease includes small and moderately advanced lesions.

References

1. Johnson CR, Schmidt-Ullrich RK, Wazer DE: Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck. Cancer 69 (11): 2749-54, 1992. [PUBMED Abstract]
2. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
3. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
4. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
5. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
6. Ang KK, Jiang GL, Frankenthaler RA, et al.: Carcinomas of the nasal cavity. Radiother Oncol 24 (3): 163-8, 1992. [PUBMED Abstract]
7. Wong CS, Cummings BJ: The place of radiation therapy in the treatment of squamous cell carcinoma of the nasal vestibule. A review. Acta Oncol 27 (3): 203-8, 1988. [PUBMED Abstract]

Stage IV disease includes advanced lesions.

Neoadjuvant chemotherapy as used in clinical trials has been used to shrink tumors and to render them more definitively treatable with either surgery or radiation therapy. This chemotherapy is given before the other modalities; therefore, the designation of neoadjuvant is used to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy.[6–8]

References

1. Johnson CR, Schmidt-Ullrich RK, Wazer DE: Concomitant boost technique using accelerated superfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck. Cancer 69 (11): 2749-54, 1992. [PUBMED Abstract]
2. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
3. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
4. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]
5. Hawkins RB, Wynstra JH, Pilepich MV, et al.: Carcinoma of the nasal cavity–results of primary and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 15 (5): 1129-33, 1988. [PUBMED Abstract]
6. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Semin Oncol 21 (3): 349-58, 1994. [PUBMED Abstract]
7. Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Semin Oncol 15 (1): 70-85, 1988. [PUBMED Abstract]
8. Dimery IW, Hong WK: Overview of combined modality therapies for head and neck cancer. J Natl Cancer Inst 85 (2): 95-111, 1993. [PUBMED Abstract]

Chemotherapy for recurrent head and neck squamous cell cancer has shown promise. Chemotherapy may be indicated when there is recurrence in either distant or local disease after primary surgery or radiation therapy, and when there is residual disease after primary treatment.[1,2] Survival may be improved in those achieving a complete response to chemotherapy.[3] Combined-modality therapy with platinum and radiation therapy has been used in clinical trials such as UMCC-8810.[4]

References

1. Kies MS, Levitan N, Hong WK: Chemotherapy of head and neck cancer. Otolaryngol Clin North Am 18 (3): 533-41, 1985. [PUBMED Abstract]
2. LoRusso P, Tapazoglou E, Kish JA, et al.: Chemotherapy for paranasal sinus carcinoma. A 10-year experience at Wayne State University. Cancer 62 (1): 1-5, 1988. [PUBMED Abstract]
3. Al-Kourainy K, Kish J, Ensley J, et al.: Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer. Cancer 59 (2): 233-8, 1987. [PUBMED Abstract]
4. Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987. [PUBMED Abstract]
5. Brasnu D, Laccourreye O, Bassot V, et al.: Cisplatin-based neoadjuvant chemotherapy and combined resection for ethmoid sinus adenocarcinoma reaching and/or invading the skull base. Arch Otolaryngol Head Neck Surg 122 (7): 765-8, 1996. [PUBMED Abstract]
6. Licitra L, Locati LD, Cavina R, et al.: Primary chemotherapy followed by anterior craniofacial resection and radiotherapy for paranasal cancer. Ann Oncol 14 (3): 367-72, 2003. [PUBMED Abstract]
7. Kraus DH, Sterman BM, Levine HL, et al.: Factors influencing survival in ethmoid sinus cancer. Arch Otolaryngol Head Neck Surg 118 (4): 367-72, 1992. [PUBMED Abstract]
8. Cantù G, Solero CL, Mariani L, et al.: Anterior craniofacial resection for malignant ethmoid tumors–a series of 91 patients. Head Neck 21 (3): 185-91, 1999. [PUBMED Abstract]
9. Shah JP: Surgery of the anterior skull base for malignant tumors. Acta Otorhinolaryngol Belg 53 (3): 191-4, 1999. [PUBMED Abstract]

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

Treatment Option Overview for Paranasal Sinus and Nasal Cavity Cancer

Added Fluorouracil dosing as a new subsection.

This summary is written and maintained by the PDQ Adult 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. 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.
2. Speight PM, Barrett AW: Salivary gland tumours. Oral Dis 8 (5): 229-40, 2002. [PUBMED Abstract]
3. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
4. Ellis GL, Auclair PL: Tumors of the Salivary Glands. Armed Forces Institute of Pathology, 1996. Atlas of Tumor Pathology, 3.
5. Wahlberg P, Anderson H, Biörklund A, et al.: Carcinoma of the parotid and submandibular glands–a study of survival in 2465 patients. Oral Oncol 38 (7): 706-13, 2002. [PUBMED Abstract]
6. Scanlon EF, Sener SF: Head and neck neoplasia following irradiation for benign conditions. Head Neck Surg 4 (2): 139-45, 1981 Nov-Dec. [PUBMED Abstract]
7. van der Laan BF, Baris G, Gregor RT, et al.: Radiation-induced tumours of the head and neck. J Laryngol Otol 109 (4): 346-9, 1995. [PUBMED Abstract]
8. Spiro RH, Thaler HT, Hicks WF, et al.: The importance of clinical staging of minor salivary gland carcinoma. Am J Surg 162 (4): 330-6, 1991. [PUBMED Abstract]
9. Gooden E, Witterick IJ, Hacker D, et al.: Parotid gland tumours in 255 consecutive patients: Mount Sinai Hospital’s quality assurance review. J Otolaryngol 31 (6): 351-4, 2002. [PUBMED Abstract]
10. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
11. Brandwein MS, Ferlito A, Bradley PJ, et al.: Diagnosis and classification of salivary neoplasms: pathologic challenges and relevance to clinical outcomes. Acta Otolaryngol 122 (7): 758-64, 2002. [PUBMED Abstract]
12. Seifert G, Sobin LH: Histological Typing of Salivary Gland Tumours. 2nd ed. Springer-Verlag, 1991.
13. Guzzo M, Andreola S, Sirizzotti G, et al.: Mucoepidermoid carcinoma of the salivary glands: clinicopathologic review of 108 patients treated at the National Cancer Institute of Milan. Ann Surg Oncol 9 (7): 688-95, 2002. [PUBMED Abstract]
14. Goode RK, Auclair PL, Ellis GL: Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 82 (7): 1217-24, 1998. [PUBMED Abstract]
15. Spiro RH, Huvos AG, Strong EW: Cancer of the parotid gland. A clinicopathologic study of 288 primary cases. Am J Surg 130 (4): 452-9, 1975. [PUBMED Abstract]
16. Parsons JT, Mendenhall WM, Stringer SP, et al.: Management of minor salivary gland carcinomas. Int J Radiat Oncol Biol Phys 35 (3): 443-54, 1996. [PUBMED Abstract]
17. Vander Poorten VL, Balm AJ, Hilgers FJ, et al.: The development of a prognostic score for patients with parotid carcinoma. Cancer 85 (9): 2057-67, 1999. [PUBMED Abstract]
18. Terhaard CH, Lubsen H, Van der Tweel I, et al.: Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group. Head Neck 26 (8): 681-92; discussion 692-3, 2004. [PUBMED Abstract]
19. Spiro RH: Factors affecting survival in salivary gland cancers. In: McGurk M, Renehan AG, eds.: Controversies in the Management of Salivary Gland Disease. Oxford University Press, 2001, pp 143-50.
20. Gormley WB, Sekhar LN, Wright DC, et al.: Management and long-term outcome of adenoid cystic carcinoma with intracranial extension: a neurosurgical perspective. Neurosurgery 38 (6): 1105-12; discussion 1112-3, 1996. [PUBMED Abstract]
21. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
22. Borthne A, Kjellevold K, Kaalhus O, et al.: Salivary gland malignant neoplasms: treatment and prognosis. Int J Radiat Oncol Biol Phys 12 (5): 747-54, 1986. [PUBMED Abstract]
23. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
24. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996. [PUBMED Abstract]
25. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
26. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992. [PUBMED Abstract]
27. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
28. Naumann M, Zellner M, Toyka KV, et al.: Treatment of gustatory sweating with botulinum toxin. Ann Neurol 42 (6): 973-5, 1997. [PUBMED Abstract]
29. Arad-Cohen A, Blitzer A: Botulinum toxin treatment for symptomatic Frey’s syndrome. Otolaryngol Head Neck Surg 122 (2): 237-40, 2000. [PUBMED Abstract]
30. von Lindern JJ, Niederhagen B, Bergé S, et al.: Frey syndrome: treatment with type A botulinum toxin. Cancer 89 (8): 1659-63, 2000. [PUBMED Abstract]

Salivary gland neoplasms are remarkable for their histological diversity. These neoplasms include benign and malignant tumors of epithelial, mesenchymal, and lymphoid origin. Salivary gland tumors pose a particular challenge to the surgical pathologist. Differentiating benign from malignant tumors may be difficult, primarily because of the complexity of the classification and the rarity of several entities, which may exhibit a broad spectrum of morphological diversity in individual lesions.[1] In some cases, hybrid lesions may be seen.[2] The key guiding principle to establish the malignant nature of a salivary gland tumor is the demonstration of an infiltrative margin.[1]

The following cellular classification scheme draws heavily from a scheme published by the Armed Forces Institute of Pathology (AFIP).[3] Malignant nonepithelial neoplasms are included in the scheme because these neoplasms comprise a significant proportion of salivary gland neoplasms seen in the clinical setting. For completeness, malignant secondary tumors are also included in the scheme.

Where AFIP statistics regarding the incidence, or relative frequency, of particular histopathologies are cited, some bias may exist because of the AFIP methods of case accrual as a pathology reference service. When possible, other sources are cited for incidence data. Notwithstanding the AFIP data, the incidence of a particular histopathology has been found to vary considerably depending upon the study cited. This variability in reporting may be partially caused by the rare incidence of many salivary gland neoplasms.

References

1. Speight PM, Barrett AW: Salivary gland tumours. Oral Dis 8 (5): 229-40, 2002. [PUBMED Abstract]
2. Seifert G, Donath K: Hybrid tumours of salivary glands. Definition and classification of five rare cases. Eur J Cancer B Oral Oncol 32B (4): 251-9, 1996. [PUBMED Abstract]
3. Ellis GL, Auclair PL: Tumors of the Salivary Glands. Armed Forces Institute of Pathology, 1996. Atlas of Tumor Pathology, 3.
4. Cheuk W, Chan JKC: Salivary gland tumors. In: Fletcher CDM, ed.: Diagnostic Histopathology of Tumors. 3rd ed. Churchill Livingstone, 2007, pp 239-326.
5. Spiro RH, Huvos AG, Berk R, et al.: Mucoepidermoid carcinoma of salivary gland origin. A clinicopathologic study of 367 cases. Am J Surg 136 (4): 461-8, 1978. [PUBMED Abstract]
6. Goode RK, Corio RL: Oncocytic adenocarcinoma of salivary glands. Oral Surg Oral Med Oral Pathol 65 (1): 61-6, 1988. [PUBMED Abstract]
7. Guzzo M, Di Palma S, Grandi C, et al.: Salivary duct carcinoma: clinical characteristics and treatment strategies. Head Neck 19 (2): 126-33, 1997. [PUBMED Abstract]
8. Stephen J, Batsakis JG, Luna MA, et al.: True malignant mixed tumors (carcinosarcoma) of salivary glands. Oral Surg Oral Med Oral Pathol 61 (6): 597-602, 1986. [PUBMED Abstract]
9. Auclair PL, Ellis GL, Gnepp DR, et al.: Salivary gland neoplasms: general considerations. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 135-64.
10. Eveson JW, Cawson RA: Salivary gland tumours. A review of 2410 cases with particular reference to histological types, site, age and sex distribution. J Pathol 146 (1): 51-8, 1985. [PUBMED Abstract]
11. Spitz MR, Batsakis JG: Major salivary gland carcinoma. Descriptive epidemiology and survival of 498 patients. Arch Otolaryngol 110 (1): 45-9, 1984. [PUBMED Abstract]
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32. Waldron CA, el-Mofty SK, Gnepp DR: Tumors of the intraoral minor salivary glands: a demographic and histologic study of 426 cases. Oral Surg Oral Med Oral Pathol 66 (3): 323-33, 1988. [PUBMED Abstract]
33. Vincent SD, Hammond HL, Finkelstein MW: Clinical and therapeutic features of polymorphous low-grade adenocarcinoma. Oral Surg Oral Med Oral Pathol 77 (1): 41-7, 1994. [PUBMED Abstract]
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38. Ellis GL, Wiscovitch JG: Basal cell adenocarcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol 69 (4): 461-9, 1990. [PUBMED Abstract]
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40. Ogawa I, Nikai H, Takata T, et al.: Clear cell tumors of minor salivary gland origin. An immunohistochemical and ultrastructural analysis. Oral Surg Oral Med Oral Pathol 72 (2): 200-7, 1991. [PUBMED Abstract]
41. Milchgrub S, Gnepp DR, Vuitch F, et al.: Hyalinizing clear cell carcinoma of salivary gland. Am J Surg Pathol 18 (1): 74-82, 1994. [PUBMED Abstract]
42. Ellis GL, Auclair PL, Gnepp DR, et al.: Other malignant epithelial neoplasms. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 455-88.
43. Gnepp DR: Sebaceous neoplasms of salivary gland origin: a review. Pathol Annu 18 Pt 1: 71-102, 1983. [PUBMED Abstract]
44. Gnepp DR, Brannon R: Sebaceous neoplasms of salivary gland origin. Report of 21 cases. Cancer 53 (10): 2155-70, 1984. [PUBMED Abstract]
45. Linhartová A: Sebaceous glands in salivary gland tissue. Arch Pathol 98 (5): 320-4, 1974. [PUBMED Abstract]
46. Sugimoto T, Wakizono S, Uemura T, et al.: Malignant oncocytoma of the parotid gland: a case report with an immunohistochemical and ultrastructural study. J Laryngol Otol 107 (1): 69-74, 1993. [PUBMED Abstract]
47. Delgado R, Klimstra D, Albores-Saavedra J: Low grade salivary duct carcinoma. A distinctive variant with a low grade histology and a predominant intraductal growth pattern. Cancer 78 (5): 958-67, 1996. [PUBMED Abstract]
48. Barnes L, Rao U, Krause J, et al.: Salivary duct carcinoma. Part I. A clinicopathologic evaluation and DNA image analysis of 13 cases with review of the literature. Oral Surg Oral Med Oral Pathol 78 (1): 64-73, 1994. [PUBMED Abstract]
49. Osaki T, Hirota J, Ohno A, et al.: Mucinous adenocarcinoma of the submandibular gland. Cancer 66 (8): 1796-801, 1990. [PUBMED Abstract]
50. Röijer E, Nordkvist A, Ström AK, et al.: Translocation, deletion/amplification, and expression of HMGIC and MDM2 in a carcinoma ex pleomorphic adenoma. Am J Pathol 160 (2): 433-40, 2002. [PUBMED Abstract]
51. LiVolsi VA, Perzin KH: Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors: a clinicopathologic study. Cancer 39 (5): 2209-30, 1977. [PUBMED Abstract]
52. Gnepp DR: Malignant mixed tumors of the salivary glands: a review. Pathol Annu 28 Pt 1: 279-328, 1993. [PUBMED Abstract]
53. Seifert G: [Diseases of the Salivary Glands: Pathology, Diagnosis, Treatment, Facial Nerve Surgery]; translated by Philip M. Stell. Thieme, 1986.
54. Brandwein MS, Ferlito A, Bradley PJ, et al.: Diagnosis and classification of salivary neoplasms: pathologic challenges and relevance to clinical outcomes. Acta Otolaryngol 122 (7): 758-64, 2002. [PUBMED Abstract]
55. Wenig BM, Hitchcock CL, Ellis GL, et al.: Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow cytometric analysis. Am J Surg Pathol 16 (9): 845-58, 1992. [PUBMED Abstract]
56. Schneider AB, Favus MJ, Stachura ME, et al.: Salivary gland neoplasms as a late consequence of head and neck irradiation. Ann Intern Med 87 (2): 160-4, 1977. [PUBMED Abstract]
57. Shemen LJ, Huvos AG, Spiro RH: Squamous cell carcinoma of salivary gland origin. Head Neck Surg 9 (4): 235-40, 1987 Mar-Apr. [PUBMED Abstract]
58. Sterman BM, Kraus DH, Sebek BA, et al.: Primary squamous cell carcinoma of the parotid gland. Laryngoscope 100 (2 Pt 1): 146-8, 1990. [PUBMED Abstract]
59. Gaughan RK, Olsen KD, Lewis JE: Primary squamous cell carcinoma of the parotid gland. Arch Otolaryngol Head Neck Surg 118 (8): 798-801, 1992. [PUBMED Abstract]
60. Batsakis JG, el-Naggar AK, Luna MA: Epithelial-myoepithelial carcinoma of salivary glands. Ann Otol Rhinol Laryngol 101 (6): 540-2, 1992. [PUBMED Abstract]
61. Daley TD, Wysocki GP, Smout MS, et al.: Epithelial-myoepithelial carcinoma of salivary glands. Oral Surg Oral Med Oral Pathol 57 (5): 512-9, 1984. [PUBMED Abstract]
62. Collina G, Gale N, Visonà A, et al.: Epithelial-myoepithelial carcinoma of the parotid gland: a clinico-pathologic and immunohistochemical study of seven cases. Tumori 77 (3): 257-63, 1991. [PUBMED Abstract]
63. Simpson RH, Clarke TJ, Sarsfield PT, et al.: Epithelial-myoepithelial carcinoma of salivary glands. J Clin Pathol 44 (5): 419-23, 1991. [PUBMED Abstract]
64. Noel S, Brozna JP: Epithelial-myoepithelial carcinoma of salivary gland with metastasis to lung: report of a case and review of the literature. Head Neck 14 (5): 401-6, 1992 Sep-Oct. [PUBMED Abstract]
65. Koss LG, Spiro RH, Hajdu S: Small cell (oat cell) carcinoma of minor salivary gland origin. Cancer 30 (3): 737-41, 1972. [PUBMED Abstract]
66. Gnepp DR, Wick MR: Small cell carcinoma of the major salivary glands. An immunohistochemical study. Cancer 66 (1): 185-92, 1990. [PUBMED Abstract]
67. Perez-Ordonez B, Caruana SM, Huvos AG, et al.: Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. Hum Pathol 29 (8): 826-32, 1998. [PUBMED Abstract]
68. Gnepp DR, Corio RL, Brannon RB: Small cell carcinoma of the major salivary glands. Cancer 58 (3): 705-14, 1986. [PUBMED Abstract]
69. Scher RL, Feldman PS, Levine PA: Small-cell carcinoma of the parotid gland with neuroendocrine features. Arch Otolaryngol Head Neck Surg 114 (3): 319-21, 1988. [PUBMED Abstract]
70. Hui KK, Luna MA, Batsakis JG, et al.: Undifferentiated carcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol 69 (1): 76-83, 1990. [PUBMED Abstract]
71. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
72. Batsakis JG, Luna MA: Undifferentiated carcinomas of salivary glands. Ann Otol Rhinol Laryngol 100 (1): 82-4, 1991. [PUBMED Abstract]
73. Bosch JD, Kudryk WH, Johnson GH: The malignant lymphoepithelial lesion of the salivary glands. J Otolaryngol 17 (4): 187-90, 1988. [PUBMED Abstract]
74. Hamilton-Dutoit SJ, Therkildsen MH, Neilsen NH, et al.: Undifferentiated carcinoma of the salivary gland in Greenlandic Eskimos: demonstration of Epstein-Barr virus DNA by in situ nucleic acid hybridization. Hum Pathol 22 (8): 811-5, 1991. [PUBMED Abstract]
75. Leung SY, Chung LP, Yuen ST, et al.: Lymphoepithelial carcinoma of the salivary gland: in situ detection of Epstein-Barr virus. J Clin Pathol 48 (11): 1022-7, 1995. [PUBMED Abstract]
76. Borg MF, Benjamin CS, Morton RP, et al.: Malignant lympho-epithelial lesion of the salivary gland: a case report and review of the literature. Australas Radiol 37 (3): 288-91, 1993. [PUBMED Abstract]
77. Saw D, Lau WH, Ho JH, et al.: Malignant lymphoepithelial lesion of the salivary gland. Hum Pathol 17 (9): 914-23, 1986. [PUBMED Abstract]
78. Cleary KR, Batsakis JG: Undifferentiated carcinoma with lymphoid stroma of the major salivary glands. Ann Otol Rhinol Laryngol 99 (3 Pt 1): 236-8, 1990. [PUBMED Abstract]
79. Savera AT, Sloman A, Huvos AG, et al.: Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. Am J Surg Pathol 24 (6): 761-74, 2000. [PUBMED Abstract]
80. Kassan SS, Thomas TL, Moutsopoulos HM, et al.: Increased risk of lymphoma in sicca syndrome. Ann Intern Med 89 (6): 888-92, 1978. [PUBMED Abstract]
81. Abbondanzo SL: Extranodal marginal-zone B-cell lymphoma of the salivary gland. Ann Diagn Pathol 5 (4): 246-54, 2001. [PUBMED Abstract]
82. Ihrler S, Baretton GB, Menauer F, et al.: Sjögren’s syndrome and MALT lymphomas of salivary glands: a DNA-cytometric and interphase-cytogenetic study. Mod Pathol 13 (1): 4-12, 2000. [PUBMED Abstract]
83. Harris NL: Lymphoid proliferations of the salivary glands. Am J Clin Pathol 111 (1 Suppl 1): S94-103, 1999. [PUBMED Abstract]
84. DiGiuseppe JA, Corio RL, Westra WH: Lymphoid infiltrates of the salivary glands: pathology, biology and clinical significance. Curr Opin Oncol 8 (3): 232-7, 1996. [PUBMED Abstract]
85. Harris NL: Extranodal lymphoid infiltrates and mucosa-associated lymphoid tissue (MALT). A unifying concept. Am J Surg Pathol 15 (9): 879-84, 1991. [PUBMED Abstract]
86. Burke JS: Waldeyer’s ring, sinonasal region, salivary gland, thyroid gland, central nervous system, and other extranodal lymphomas and lymphoid hyperplasias. In: Knowles DM, ed.: Neoplastic Hematopathology. Williams & Wilkins, 1992, pp 1047-79.
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88. Schmid U, Helbron D, Lennert K: Primary malignant lymphomas localized in salivary glands. Histopathology 6 (6): 673-87, 1982. [PUBMED Abstract]
89. Gleeson MJ, Bennett MH, Cawson RA: Lymphomas of salivary glands. Cancer 58 (3): 699-704, 1986. [PUBMED Abstract]
90. Seifert G, Oehne H: [Mesenchymal (non-epithelial) salivary gland tumors. Analysis of 167 tumor cases of the salivary gland register] Laryngol Rhinol Otol (Stuttg) 65 (9): 485-91, 1986. [PUBMED Abstract]
91. Auclair PL, Ellis GL, Gnepp DR, et al.: Salivary gland neoplasms: general considerations. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 135-64.
92. Auclair PL, Ellis GL: Nonlymphoid sarcomas of the major salivary glands. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 514-27.
93. Luna MA, Tortoledo ME, Ordóñez NG, et al.: Primary sarcomas of the major salivary glands. Arch Otolaryngol Head Neck Surg 117 (3): 302-6, 1991. [PUBMED Abstract]
94. Auclair PL, Langloss JM, Weiss SW, et al.: Sarcomas and sarcomatoid neoplasms of the major salivary gland regions. A clinicopathologic and immunohistochemical study of 67 cases and review of the literature. Cancer 58 (6): 1305-15, 1986. [PUBMED Abstract]
95. Weiss SW, Goldblum JR: Enzinger and Weiss’s Soft Tissue Tumors. 4th ed. Mosby, 2001.
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97. Gnepp DR: Metastatic disease to the major salivary glands. In: Ellis GL, Auclair PL, Gnepp DR, eds.: Surgical Pathology of the Salivary Glands. Saunders, 1991, pp 560-9.
98. Seifert G, Hennings K, Caselitz J: Metastatic tumors to the parotid and submandibular glands–analysis and differential diagnosis of 108 cases. Pathol Res Pract 181 (6): 684-92, 1986. [PUBMED Abstract]
99. Batsakis JG, Bautina E: Metastases to major salivary glands. Ann Otol Rhinol Laryngol 99 (6 Pt 1): 501-3, 1990. [PUBMED Abstract]

In general, tumors of the major salivary glands are staged according to size, extraparenchymal extension, lymph node involvement (in parotid tumors, whether or not the facial nerve is involved), and presence of metastases.[1–4] Tumors arising in the minor salivary glands are staged according to the anatomical site of origin (e.g., oral cavity and sinuses).

Clinical stage, particularly tumor size, may be the critical factor in determining the outcome of salivary gland cancer and may be more important than histological grade.[5,6] Diagnostic imaging studies may be used in staging. With excellent spatial resolution and superior soft tissue contrast, magnetic resonance imaging (MRI) offers advantages over computed tomographic scanning in the detection and localization of head and neck tumors. Overall, MRI is the preferred modality for evaluation of suspected neoplasms of the salivary glands.[7]

References

1. Spiro RH, Huvos AG, Strong EW: Cancer of the parotid gland. A clinicopathologic study of 288 primary cases. Am J Surg 130 (4): 452-9, 1975. [PUBMED Abstract]
2. Fu KK, Leibel SA, Levine ML, et al.: Carcinoma of the major and minor salivary glands: analysis of treatment results and sites and causes of failures. Cancer 40 (6): 2882-90, 1977. [PUBMED Abstract]
3. Levitt SH, McHugh RB, Gómez-Marin O, et al.: Clinical staging system for cancer of the salivary gland: a retrospective study. Cancer 47 (11): 2712-24, 1981. [PUBMED Abstract]
4. Kuhel W, Goepfert H, Luna M, et al.: Adenoid cystic carcinoma of the palate. Arch Otolaryngol Head Neck Surg 118 (3): 243-7, 1992. [PUBMED Abstract]
5. Major salivary glands. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp. 95–101.
6. Spiro RH: Factors affecting survival in salivary gland cancers. In: McGurk M, Renehan AG, eds.: Controversies in the Management of Salivary Gland Disease. Oxford University Press, 2001, pp 143-50.
7. Shah GV: MR imaging of salivary glands. Magn Reson Imaging Clin N Am 10 (4): 631-62, 2002. [PUBMED Abstract]

The minimum therapy for patients with low-grade malignancies of the superficial portion of the parotid gland is a superficial parotidectomy. For all other lesions, a total parotidectomy is often indicated. The facial nerve or its branches should be resected if involved by tumor; repair can be done simultaneously. Evidence suggests that postoperative radiation therapy augments surgical resection, particularly for the high-grade neoplasms, when margins are close or involved, when tumors are large, or when histological evidence of lymph node metastases is present.[1–8] Clinical trials in the United States and England indicated that fast neutron-beam radiation therapy improves disease-free survival and overall survival in patients with unresectable tumors or for patients with recurrent neoplasms.[9–12] The availability of facilities with fast neutron-beam radiation therapy is limited in the United States. Accelerated hyperfractionated photon-beam radiation therapy has also resulted in high rates of long-term local regional controls.[13,14] The use of chemotherapy for malignant salivary gland tumors remains under evaluation.[15–19]

References

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8. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
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10. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
11. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
12. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
13. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
14. Douglas JG, Koh WJ, Austin-Seymour M, et al.: Treatment of salivary gland neoplasms with fast neutron radiotherapy. Arch Otolaryngol Head Neck Surg 129 (9): 944-8, 2003. [PUBMED Abstract]
15. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986. [PUBMED Abstract]
16. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]
17. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
18. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
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References

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2. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
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5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
6. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
7. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
8. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
9. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997. [PUBMED Abstract]
10. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005. [PUBMED Abstract]
11. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
12. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986. [PUBMED Abstract]
13. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]

References

1. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
2. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
3. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973. [PUBMED Abstract]
4. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
5. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975. [PUBMED Abstract]
6. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975. [PUBMED Abstract]
7. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
8. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997. [PUBMED Abstract]
9. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005. [PUBMED Abstract]
10. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
11. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
12. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
13. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
14. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
15. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982. [PUBMED Abstract]
16. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982. [PUBMED Abstract]

References

1. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
2. Catterall M, Errington RD: The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int J Radiat Oncol Biol Phys 13 (9): 1313-8, 1987. [PUBMED Abstract]
3. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986. [PUBMED Abstract]
4. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]
5. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973. [PUBMED Abstract]
6. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 729-80.
7. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975. [PUBMED Abstract]
8. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975. [PUBMED Abstract]
9. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb. [PUBMED Abstract]
10. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986. [PUBMED Abstract]
11. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999. [PUBMED Abstract]
12. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997. [PUBMED Abstract]
13. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005. [PUBMED Abstract]
14. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007. [PUBMED Abstract]
15. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
16. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
17. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
18. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982. [PUBMED Abstract]
19. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982. [PUBMED Abstract]

References

1. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991. [PUBMED Abstract]
2. Laramore GE, Krall JM, Griffin TW, et al.: Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council. Int J Radiat Oncol Biol Phys 27 (2): 235-40, 1993. [PUBMED Abstract]
3. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [PUBMED Abstract]
4. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999. [PUBMED Abstract]
5. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000. [PUBMED Abstract]
6. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985. [PUBMED Abstract]
7. Venook AP, Tseng A, Meyers FJ, et al.: Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group. J Clin Oncol 5 (6): 951-5, 1987. [PUBMED Abstract]
8. Rentschler R, Burgess MA, Byers R: Chemotherapy of malignant major salivary gland neoplasms: a 25-year review of M. D. Anderson Hospital experience. Cancer 40 (2): 619-24, 1977. [PUBMED Abstract]
9. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982. [PUBMED Abstract]
10. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982. [PUBMED Abstract]
11. Catterall M, Errington RD: The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int J Radiat Oncol Biol Phys 13 (9): 1313-8, 1987. [PUBMED Abstract]
12. Ono M, Watanabe A, Matsumoto Y, et al.: Methamphetamine modifies the photic entraining responses in the rodent suprachiasmatic nucleus via serotonin release. Neuroscience 72 (1): 213-24, 1996. [PUBMED Abstract]
13. Saroja KR, Mansell J, Hendrickson FR, et al.: An update on malignant salivary gland tumors treated with neutrons at Fermilab. Int J Radiat Oncol Biol Phys 13 (9): 1319-25, 1987. [PUBMED Abstract]
14. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996. [PUBMED Abstract]
15. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021. [PUBMED Abstract]
16. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016. [PUBMED Abstract]
17. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021. [PUBMED Abstract]
18. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018. [PUBMED Abstract]
19. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018. [PUBMED Abstract]
20. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022. [PUBMED Abstract]
21. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022. [PUBMED Abstract]
22. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023. [PUBMED Abstract]

The prognosis for any patient with progressing or relapsing salivary gland cancer is poor, regardless of cell type or stage. Selecting further treatment depends on many factors, including the specific cancer, prior treatment, site of recurrence, and individual patient considerations. Fast neutron-beam radiation therapy is superior to conventional radiation therapy using x-rays and may be curative in selected patients with recurrent disease.[1]

Patients with inoperable, unresectable, or recurrent malignant salivary gland tumors treated with fast neutron-beam radiation therapy have better disease-free survival and overall survival than patients treated with conventional x-ray radiation therapy.[2–5] Clinical trials are appropriate and should be considered when possible.

References

1. Laramore GE, Krall JM, Griffin TW, et al.: Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council. Int J Radiat Oncol Biol Phys 27 (2): 235-40, 1993. [PUBMED Abstract]
2. Laramore GE: Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice? Int J Radiat Oncol Biol Phys 13 (9): 1421-3, 1987. [PUBMED Abstract]
3. Saroja KR, Mansell J, Hendrickson FR, et al.: An update on malignant salivary gland tumors treated with neutrons at Fermilab. Int J Radiat Oncol Biol Phys 13 (9): 1319-25, 1987. [PUBMED Abstract]
4. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992. [PUBMED Abstract]
5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996. [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.

General Information About Salivary Gland Cancer

Revised text about the incidence and mortality rates of salivary gland cancer in the United States (cited National Cancer Institute as reference 1).

This summary is written and maintained by the PDQ Adult 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.