Abstract
Mucosal melanoma represents a rare subtype of melanoma with distinct biological, clinical, and management considerations. Knowledge regarding optimal treatment strategies for mucosal melanoma is limited and based primarily upon small case series and single-institution, retrospective analyses. Surgery remains the standard of care for loco-regional management, but the common presence of multifocal disease and the high rate of distant recurrence should be considered before pursuing aggressive surgical interventions associated with inherent significant morbidity. The role of sentinel lymph node biopsy and lymph node dissection remains unclear. Radiotherapy has not been shown to improve overall survival but may reduce the rate of local recurrence. Significant advances in the treatment of metastatic disease have been made with novel immunotherapeutic agents, the discovery of KIT and BRAF mutations and the development of targeted agents that inhibit these oncogenic pathways.
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McLaughlin CC, Wu XC, Jemal A, et al. Incidence of noncutaneous melanomas in the U.S. Cancer. 2005;103:1000–7.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. Cancer J Clin. 2012;62:10–29.
Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83:1664–78.
Patrick RJ, Fenske NA, Messina JL. Primary mucosal melanoma. J Am Acad Dermatol. 2007;56:828–34.
Garland CF, Garland FC, Gorham ED. Epidemiologic evidence for different roles of ultraviolet A and B radiation in melanoma mortality rates. Ann Epidemiol. 2003;13:395–404.
Takagi M, Ishikawa G, Mori W. Primary malignant melanoma of the oral cavity in Japan. With special reference to mucosal melanosis. Cancer. 1974;34:358–70.
Axell T, Hedin CA. Epidemiologic study of excessive oral melanin pigmentation with special reference to the influence of tobacco habits. Scand J Dental Res. 1982;90:434–42.
Lotem M, Anteby S, Peretz T, et al. Mucosal melanoma of the female genital tract is a multifocal disorder. Gynecol Oncol. 2003;88:45–50.
Verschraegen CF, Benjapibal M, Supakarapongkul W, et al. Vulvar melanoma at the M. D. Anderson Cancer Center: 25 years later. Int J Gynecol Cancer. 2001;11:359–64.
Watanabe J, Yamamoto S, Souma T, et al. Primary malignant melanoma of the male urethra. Int J Urol. 2000;7:3513.
Patel SG, Prasad ML, Escrig M, et al. Primary mucosal malignant melanoma of the head and neck. Head Neck. 2002;24:247–57.
Bachar G, Loh KS, O'Sullivan B, et al. Mucosal melanomas of the head and neck: experience of the Princess Margaret Hospital. Head Neck. 2008;30:1325–31.
Prasad ML, Patel SG, Huvos AG, et al. Primary mucosal melanoma of the head and neck: a proposal for microstaging localized, Stage I (lymph node-negative) tumors. Cancer. 2004;100:1657–64.
Thompson LD, Wieneke JA, Miettinen M. Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system. Am J Surg Pathol. 2003;27:594–611.
Pfister DG, Ang KK, Brizel DM, et al. Mucosal melanoma of the head and neck. JNCCN. 2012;10:320–38.
Ganly I, Patel SG, Singh B, et al. Craniofacial resection for malignant melanoma of the skull base: report of an international collaborative study. Arch Otolaryngol. 2006;132:73–8.
Hanna E, DeMonte F, Ibrahim S, et al. Endoscopic resection of sinonasal cancers with and without craniotomy: oncologic results. Arch Otolaryngol. 2009;135:1219–24.
Stern SJ, Guillamondegui OM. Mucosal melanoma of the head and neck. Head Neck. 1991;13:22–7.
Starek I, Koranda P, Benes P. Sentinel lymph node biopsy: a new perspective in head and neck mucosal melanoma? Melanoma Res. 2006;16:423–7.
Shah GD, Chapman PB. Adjuvant therapy of melanoma. Cancer J. 2007;13:217–22.
Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–17.
Manolidis S, Donald PJ. Malignant mucosal melanoma of the head and neck: review of the literature and report of 14 patients. Cancer. 1997;80:1373–86.
Temam S, Mamelle G, Marandas P, et al. Postoperative radiotherapy for primary mucosal melanoma of the head and neck. Cancer. 2005;103:313–9.
Meleti M, Leemans CR, de Bree R, et al. Head and neck mucosal melanoma: experience with 42 patients, with emphasis on the role of postoperative radiotherapy. Head Neck. 2008;30:1543–51.
Wu AJ, Gomez J, Zhung JE, et al. Radiotherapy after surgical resection for head and neck mucosal melanoma. Am J Clin Oncol. 2010;33:281–5.
Cote TR, Sobin LH. Primary melanomas of the esophagus and anorectum: epidemiologic comparison with melanoma of the skin. Melanoma Res. 2009;19:58–60.
Iddings DM, Fleisig AJ, Chen SL, et al. Practice patterns and outcomes for anorectal melanoma in the USA, reviewing 3 decades of treatment: is more extensive surgical resection beneficial in all patients? Ann Surg Oncol. 2010;17:40–4.
Brady MS, Kavolius JP, Quan SH. Anorectal melanoma. A 64-year experience at Memorial Sloan-Kettering Cancer Center. Dis Colon Rectum. 1995;38:146–51.
Yeh JJ, Shia J, Hwu WJ, et al. The role of abdominoperineal resection as surgical therapy for anorectal melanoma. Ann Surg. 2006;244:1012–7.
Pessaux P, Pocard M, Elias D, et al. Surgical management of primary anorectal melanoma. Br J Surg. 2004;91:1183–7.
Ballo MT, Gershenwald JE, Zagars GK, et al. Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma. J Clin Oncol. 2002;20:4555–8.
Kelly P, Zagars GK, Cormier JN, et al. Sphincter-sparing local excision and hypofractionated radiation therapy for anorectal melanoma: a 20-year experience. Cancer. 2011;117:4747–55.
Ragnarsson-Olding BK, Kanter-Lewensohn LR, Lagerlof B, et al. Malignant melanoma of the vulva in a nationwide, 25-year study of 219 Swedish females: clinical observations and histopathologic features. Cancer. 1999;86:1273–84.
Weinstock MA. Malignant melanoma of the vulva and vagina in the United States: patterns of incidence and population-based estimates of survival. Am J Obstet Gynecol. 1994;171:1225–30.
Sugiyama VE, Chan JK, Shin JY, et al. Vulvar melanoma: a multivariable analysis of 644 patients. Obstet Gynecol. 2007;110(2 Pt 1):296–301.
Piura B, Rabinovich A, Yanai-Inbar I. Primary malignant melanoma of the vagina: case report and review of literature. Eur J Gynaecol Oncol. 2002;23:195–8.
Ballantyne AJ. Malignant melanoma of the skin of the head and neck. An analysis of 405 cases. Am J Surg. 1970;120:425–31.
Frumovitz M, Etchepareborda M, Sun CC, et al. Primary malignant melanoma of the vagina. Obstet Gynecol. 2010;116:1358–65.
Suwandinata FS, Bohle RM, Omwandho CA, et al. Management of vulvar melanoma and review of the literature. Eur J Gynaecol Oncol. 2007;28:220–4.
de Hullu JA, Hollema H, Hoekstra HJ, et al. Vulvar melanoma: is there a role for sentinel lymph node biopsy? Cancer. 2002;94:48691.
Dhar KK, Das N, Brinkman DA, et al. Utility of sentinel node biopsy in vulvar and vaginal melanoma: report of 2 cases and review of the literature. Int J Gynecol Cancer. 2007;17:720–3.
van Geel AN, den Bakker MA, Kirkels W, et al. Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature. Urology. 2007;70:143–7.
Heath DI, Womack C. Primary malignant melanoma of the gall bladder. J Clin Pathol. 1988;41:1073–7.
Habeck JO. Primary malignant melanoma of the gallbladder. Case report and literature review. Zentralbl Pathol. 1993;139:367–71.
Lam KY, Law S, Wong J. Malignant melanoma of the oesophagus: clinicopathological features, lack of p53 expression and steroid receptors and a review of the literature. Eur J Surg Oncol. 1999;25:168–72.
Lens M, Bataille V, Krivokapic Z. Melanoma of the small intestine. Lancet. 2009;10:516–21.
Blecker D, Abraham S, Furth EE, et al. Melanoma in the gastrointestinal tract. Am J Gastroenterol. 1999;94:3427–33.
Yi JH, Yi SY, Lee HR, et al. Dacarbazine-based chemotherapy as first-line treatment in noncutaneous metastatic melanoma: multicenter, retrospective analysis in Asia. Melanoma Res. 2011;21:223–7.
Bartell HL, Bedikian AY, Papadopoulos NE, et al. Biochemotherapy in patients with advanced head and neck mucosal melanoma. Head Neck. 2008;30:1592–8.
Kim KB, Sanguino AM, Hodges C, et al. Biochemotherapy in patients with metastatic anorectal mucosal melanoma. Cancer. 2004;100:1478–83.
Harting MS, Kim KB. Biochemotherapy in patients with advanced vulvovaginal mucosal melanoma. Melanoma Res. 2004;14:517–20.
Ives NJ, Stowe RL, Lorigan P, et al. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2621 patients. J Clin Oncol. 2007;25:5426–34.
Atkins MB, Hsu J, Lee S, et al. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2008;26:5748–54.
•• Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23. First phase III study to show an improvement in overall survival for patients with metastatic melanoma. Results of this study contributed to the US FDA approval of ipilimumab..
• Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–26. Second phase III study to demonstrate an improvement in overall survival for patients who received ipilimumab compared to those who did not..
•• Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16. First demonstration of the overall survival benefit of vemurafenib, the targeted inhibitor of oncogenic BRAF..
Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.
Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353:2135–47.
Maldonado JL, Fridlyand J, Patel H, et al. Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst. 2003;95:1878–90.
Curtin JA, Busam K, Pinkel D, et al. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24:4340–6.
Rivera RS, Nagatsuka H, Gunduz M, et al. C-KIT protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma. Virchows Arch. 2008;452:27–32.
Hodi FS, Friedlander P, Corless CL, et al. Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol. 2008;26:2046–51.
•• Carvajal RD, Antonescu CR, Wolchok JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011;305:2327–34. Phase II study showing the efficacy of imatinib for patients with KIT genetic aberrations, including patients with mucosal melanoma who achieved durable partial and complete responses..
•• Guo J, Si L, Kong Y, et al. Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-KIT mutation or amplification. J Clin Oncol. 2011;29:2904–9. Phase II study showing the efficacy of imatinib for patients with KIT genetic aberrations..
Minor DR, Kashani-Sabet M, Garrido M, et al. Sunitinib therapy for melanoma patients with KIT mutations. Clin Cancer Res. 2012;18:1457–63.
Si L, Xu X, Kong Y, et al. Major response to everolimus in melanoma with acquired imatinib resistance. J Clin Oncol. 2012;30:e37–40.
Tsao H, Zhang X, Fowlkes K, et al. Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines. Cancer Res. 2000;60:1800–4.
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M. A. Postow: none; O. Hamid: none; R. D. Carvajal: consultant to Novartis.
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Postow, M.A., Hamid, O. & Carvajal, R.D. Mucosal Melanoma: Pathogenesis, Clinical Behavior, and Management. Curr Oncol Rep 14, 441–448 (2012). https://doi.org/10.1007/s11912-012-0244-x
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DOI: https://doi.org/10.1007/s11912-012-0244-x