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Mucosal Melanoma: a Clinically and Biologically Unique Disease Entity

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Mucosal Melanoma: a Clinically and Biologically Unique Disease Entity Focused 345 Review Mucosal Melanoma: A Clinically and Biologically Unique Disease Entity Richard D. Carvajal, MDa; Sharon A. Spencer, MDb; and William Lydiatt, MD,c New York, New York; Birmingham, Alabama; and Omaha, Nebraska Key Words of these arise from mucosal surfaces.1–3 Despite a com- Mucosal melanoma, melanoma of the head and neck, anorectal mon cell of origin, MM is a clinical and pathologic entity melanoma, vulvovaginal melanoma, KIT distinct from its more common cutaneous counterpart. MM can arise from any mucosal surface of the body, with Abstract 55% arising from the head and neck, 24% from the ano- Mucosal melanoma (MM) is an aggressive and clinically complex 2 malignancy made more challenging by its relative rarity. Because rectal mucosa, and 18% from the vulvovaginal mucosa. of the rarity of MM as a whole, and because of the unique biology Disease arising from the mucosa of the pharynx, larynx, and clinical challenges of MM arising from each anatomic location, urinary tract, cervix, esophagus, gallbladder, or other mu- understanding of this disease and its optimal management remains cosal sites is less common. limited. The impact of various treatment strategies on disease con- This article summarizes the clinical, pathologic, and trol and survival has been difficult to assess because of the small size of most reported series of MM arising from any one particular site, molecular features, and the diagnostic and therapeutic the retrospective nature of most series, and the lack of a uniform considerations for the management of MM, underscoring comprehensive staging system for this disease. This article summa- the similarities and differences from cutaneous melanoma rizes the clinical, pathologic, and molecular features, and the diag- (CM). Furthermore, the distinct clinical features and man- nostic and therapeutic considerations for the management of MM, agement implications unique to melanoma arising from underscoring the similarities and differences from cutaneous mela- the mucosal surfaces of the head and neck, the anorectal noma. Furthermore, the distinct clinical features and management implications unique to melanoma arising from the mucosal surfaces region, and the female genital tract are highlighted. of the head and neck, the anorectal region, and the female genital tract are highlighted. (JNCCN 2012;10:345–356) Epidemiology and Clinical Features of Mucosal Melanoma The epidemiology and clinical features of MM differ ucosal melanoma (MM) is an aggressive and clini- M significantly from those of CM (Table 1). MM devel- cally complex malignancy made more challenging by its ops at a later age than does CM, with a median age at relative rarity. Of the 68,130 cases of melanoma diag- diagnosis of 70 years compared with 55 years for CM.2 nosed in 2010 in the United States, only 0.8% to 1.8% Although CM is slightly more common in men, with a male-to-female ratio of 1.2:1.0, MM is more commonly From the aDepartment of Medicine, Melanoma/Sarcoma Service, diagnosed in women, primarily because of the occur- Memorial Sloan-Kettering Cancer Center, New York, New York; rence of melanoma arising within the female genital bDepartment of Radiation Oncology, University of Alabama, Birmingham, Alabama; and cDepartment of Otolaryngology-Head tract, with a male-to-female ratio of 1.0:1.8.2 The in- and Neck Surgery, University of Nebraska and Nebraska Methodist Hospital, Omaha, Nebraska. cidence of CM has been increasing at rate greater than Submitted October 17, 2011; accepted for publication December that of any other cancer in the United States, whereas 12, 2011. the incidence of MM has remained stable over time.4 The authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any Although CM is associated with exposure to ultraviolet products discussed in this article or their competitors. Correspondence: Richard D. Carvajal, MD, Memorial Sloan- light, the anatomic location of MM precludes this expo- Kettering Cancer Center, 300 East 66th Street, BAIC1071, New York, sure as a predisposing risk factor, and no clear predispos- NY 10065. E-mail: [email protected] ing risk factors have been identified in MM. © JNCCN–Journal of the National Comprehensive Cancer Network | Volume 10 Number 3 | March 2012 346 Focused Review Carvajal et al. Table 1 Clinical and Pathologic Features of Cutaneous and Mucosal Melanomas Cutaneous Melanoma Mucosal Melanoma Proportion of all melanomas 90% < 2% Demographics Median age at diagnosis 55 y 67 y Male:female ratio 60:40 35:65 Race White 94% 85% Black < 1% 7% Epidemiology Incidence over time Rising Stable Risk factors Ultraviolet radiation Unknown Pathology Multifocality < 5% 20% Amelanotic < 10% Up to 40% Clinical outcomes Advanced stage at diagnosis < 30% > 50% 5-Year overall survival rate 81% 25% CM is uncommon in blacks, Asians, and Hispan- due to later diagnosis because of lack of clinical sus- ics, with an annual age-adjusted incidence of only 1% picion in the setting of relative rarity, more advanced of that observed in whites. Although the absolute in- disease at initial diagnosis, and the rich lymphovascu- cidence of MM is greatest in whites, the proportion of lar supply of the mucosal surfaces. MM in blacks, Asians, and Hispanics is greater than Mucosal Melanoma of the Head and Neck that observed in whites. Overall, MM does not seem MMHN accounts for 6.3% to 8% of all melanomas to have a racial predilection, except possibly melano- arising in this region, occurring, in decreasing order ma arising from the oral cavity, which may be more of frequency, within the nasal cavity, oral cavity, 2 common in black and Japanese populations. nasal sinuses, pharynx, larynx and upper esopha- When diagnosed early, most CMs are cured with gus.2,3,6 Of MMHNs, 70% to 80% arise in the pa- surgical excision; however, patients with locoregion- ranasal sinuses and nasal cavity, representing 4% ally advanced or metastatic disease fare poorly, with a of all sinonasal tumors.2 Although the exact site median overall survival of 6 to 8 months. Outcomes of origin of these tumors is often difficult to deter- for MM are inferior irrespective of stage at diagno- mine because of the presence of locally advanced sis. Although the 5-year overall survival rate for CM disease, 80% of sinonasal melanomas and approxi- is 80%,5 the rate for MM is only 25% (Figure 1A).2 mately 55% of all MMHNs arise from the nasal cav- Prognosis depends on the primary site of disease (Fig- ity, with the remainder arising from the paranasal ure 1B).2 Patients with disease arising from the head sinuses.6 Within the nasal cavity, the turbinates and neck, anorectal mucosa, and vulvovaginal muco- and nasal wall are most commonly involved, fol- sa have 5-year overall survival rates of 31.7%, 19.8%, lowed by the nasal septum. Among the paranasal and 11.4%, respectively, with survival rates for MM of sinuses, the maxillary sinuses are most commonly the head and neck (MMHN) significantly better than involved, followed by the ethmoid, frontal, and those for MM from the other subsites.2 Locoregional sphenoid sinuses. Oral cavity MM constitutes 0.5% nodal metastasis at presentation is more frequent in of all oral malignancies and approximately 40% of MM than in CM. Although 9% of CMs will present all MMHNs, and most commonly affects the hard with locoregional nodal disease, 21% of MMHNs, palate and upper alveolus.2,6 61% of anorectal mucosal melanomas (ARMMs), and Median age at diagnosis ranges from 60 to 69 23% of vulvovaginal mucosal melanomas (VVMMs) years7; however, oral cavity MM presents at a younger present with involved nodes.2 Patients with nodal dis- age compared with sinonasal melanomas, with many ease have poorer outcomes, with a 5-year survival rate affected individuals younger than 40 years.8 The fre- of 16.4% versus 38.7% for those with negative nodes.2 quency of disease in men and women is equivalent in The inferior outcomes observed in MM may be partly most7,9 but not all reports.8,10 As with other sinona- © JNCCN–Journal of the National Comprehensive Cancer Network | Volume 10 Number 3 | March 2012 Focused Review 347 Mucosal Melanoma Cutaneous melanoma: Cutaneous melanoma: Mucosal melanoma: Head and neck Anorectal Vulvovaginal all stages (n = 23,696) stages III and IV (n = 2074) (n = 306) (n = 163) (n = 74) (n = 59) 100 90 A B 90 80 80 70 % 70 60 60 50 50 40 40 Disease-Specic Survival 30 Disease-Specic Survival % 30 20 20 10 10 0 0 1 2345 1 2 34 5 Time Since Diagnosis (y) Time Since Diagnosis (y) Figure 1 (A) Disease-specific survivals for patients diagnosed with all stages of cutaneous melanoma, stage III or IV cutaneous melanoma, and mucosal melanoma. (B) Disease-specific survivals for patients diagnosed with mucosal melanoma arising from the head and neck, anorectal region, and vulvovaginal region. Data from 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;83:1664–1678. sal malignancies, inhaled and ingested carcinogens, Anorectal Mucosal Melanoma such as tobacco and formaldehyde, are implicated as ARMM represents 0.4% to 1.6% of all melanomas potential risk factors for the development of sinona- and 1% of all malignancies arising in the anorectal sal MM, although strong evidence is lacking.3 Oral region. One-third of ARMMs are located within the melanosis has been implicated as a possible precursor anal canal, with 42% arising from the rectum and lesion for up to one-third of oral melanoma cases.8 25% with an indeterminate site of origin.13 Unlike The clinical course differs significantly for MM MM arising from other sites, the incidence of ARMM of the oral cavity and sinonasal MM.
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