Section 10 -

Acral Lentiginous Melanoma Neil Crowson, MD Cynthia M. Magro, MD Martin C. Mihm, Jr., MD

Case # 9: Acral Lentiginous Melanoma Acral lentiginous melanoma occurs mainly on the palms, soles, subungual regions, and digits of Africans and Asians and is similar microscopically to a form of melanoma in mucosal areas termed mucosal lentiginous melanoma (Reed et al, 1975; Reed, 1976; Jimbow et al, 1984; Kato et al, 1996; Levit et al, 2000; Massi et al,1999). Although usually pigmented, rare examples are amelanotic (Yusuoka et al, 1999). Not all acral melanomas are of acral lentiginous type; of 62 plantar melanomas in one series, 14.5% were classified as nodular melanoma and 3.2% as superficial spreading melanoma histologically (Kato et al, 1999). Superficial spreading melanomas in acral sites in Caucasions are most frequent on the dorsal aspect of the hands and feet. Although the tumor usually arises from the proximal nail fold from which the biopsy must be procured, biopsies of subungual pigmented lesions necessitate splitting of the nail plate. Clinical features Acral melanoma in the radial growth phase presents as a very dark brown slightly raised plaque. In contrast to benign nevi, the flare of pigmentation uniformly affects the ridges and the valleys of the palmar and plantar surfaces reflecting the involvement of the entire epidermis including the acrosyringium. Benign nevi on the other hand exhibit pigmentation in the valleys and spare the ridges, as junctional nests favor the valley and not the acrosyringium. The presence of areas of regression are expressed as grey areas in the brown-black lesion. Once the vertical growth phase supervenes a black nodule appears and may be hyperkeratotic. Ulceration of the nodules is frequent (Saida, 2000). Subungual melanoma presents as streaks of irregular pigmentation that discolor the nail plate usually in shades of brown, dark brown and black. A characteristic feature of the pigmentation is involvment of the cuticle, so-called Hutchinson's sign. Histology of Radial Growth Phase-Confined Acral Lentiginous Malignant Melanoma Acral melanomas may assume one of four patterns: acral lentiginous, superficial spreading, nodular and type unclassified. The characeristic features of the acral lentiginous melanoma will be stressed. At the outset, lesions of acral lentiginous melanoma manifest atypical melanocytes disposed as single units in a confluent array along the epidermal basal layer. Areas of epidermal hyperplasia alternate with zones of epidermal effacement. Transepithelial pigment elimination with haphazard melanization of the dense acral keratin layer is distinctly different from the organized pigment columns seen with benign acral nevi. A dermal mononuclear cell inflammatory infiltrate is present, in contrast to its uniform absence in acquired acral nevi; the infiltrate can have a lichenoid pattern with associated subepidermal cleft formation. Progression of the radial growth phase is associated with pagetoid epidermal infiltration, often of epithelioid melanocytes, that may come to comprise the dominant pattern of intraepidermal growth.Pagetoid spread also occurs in acral nevi but is confined to the area over the foci of nesting. Pagetoid spread between nests can be seen. On the other hand, in acral melanoma the cells extend well beyond the nested areas and show no patterning with regard to the nests. The lentiginous component comprises cells with hyperchromatic angulated nuclei and scant cytoplasms. Prominent melanocytic dendritic processes may extend into the upper stratum spinosum. Adnexotropism is often present. A single-cell growth pattern typically predominates over a nested one and is the converse of benign nevi. The nests are variable in size and shape and comprise dyshesive epithelioid or spindled cells. Large or variably-sized nests of haphazard disposition may be seen in the prototypic benign acral nevus, but the cells of acral melanoma show severe nuclear atypia and the single-cell pattern of growth is dominant. The latter findings are not seen in prototypic acral nevi (Kato et al, 1996). Invasive radial growth phase acral lentiginous melanoma manifests intradermal cells in a single-cell or nested disposition with a cytology similar to those cells in the epidermis but often with more abundant cytoplasms and fine pigment granules. Mitoses are often seen in the intraepidermal component. As at any anatomic site, dominant thèques with dermal mitoses signify progression to vertical growth phase melanoma (see below). Mucosal Melanoma The mucosal melanomas include, in descending order of frequency, those of vulva and vagina, oral cavity, anorectum, nasal cavity, penis and esophagus (Pandey et al, 1998). The National Cancer Data Base of the American Cancer Society lists the distribution as being in the head and neck area, female genital tract, anorectal region and urinary tract in 55%, 18%, 24%, and 3% of cases respectively (Chang et al, 1998). A consideration of conjunctival and occular melanoma is beyond the scope of this chapter. Of the above we will first consider vulvar melanoma. Melanoma of the Vulva Clinical Features Roughly 3–8% of all primary vulvar malignancies are melanomas; these account for 3–7% of all melanomas in women (Chung et al, 1975; Raber et al, 1996; Ragnarsson-Olding et al, 1999) and may present as a polypoid mass that in some cases is amelanotic. Ragnarrson-Olding et al determined the mucosal-lentiginous type to be the most common form, although in our experience only 15% of vulvar melanomas are of this type. The mean age of patients with vulvar melanoma is 61.4 years (DeMatos et al, 1998) although it is reported in children (Egan et al, 1997) including in the setting of lichen sclerosis. We have reported atypical but non-cancerous melanocytic proliferations in patients with lichen sclerosis (Carlson et al., 2001), and suspect that the melanoma association may be spurious (Carlson and Mihm, 1997). Only long-term follow-up will resolve this question. The majority of vulvar melanomas have a radial growth phase. Although the Swedish study referenced above found that 22% of tumors were of nodular subtype, in our experience the incidence is lower (Crowson et al, 2001). Vulvar melanoma most commonly presents as a patch of darkly pigmented skin that exhibits irregular borders and irregular coloration. The commonest color is dark brown, but this is admixed with black, grey or blue-grey in sites of regression. The lesions may vary in size from a few millimeters to several centimeters. Vertical growth supervening on this macule or plaque usually presents as one or several nodules of black, reddish brown, blue grey coloration or as amelanotic protuberances. The labium majus and labium minus are commonly affected. In our experience about 15% affect the clitoris. A desmoplastic variant presents as a firm discolored area. As regards prognostic microstaging, the vulvar skin lacks a clear distinction between the papillary and reticular dermis; attempting to link survival to anatomic level of invasion, Chung and co-workers correlated depth of invasion, as measured from the top of the keratin layer in vulvar epithelium to the Clark level as follows: level 2 up to 1 mm depth, level 3 up to 2 mm depth, level 4 up to 4 mm depth, and level 5 greater than 4 mm in depth. Differential Diagnosis Of Vulvar Melanoma Vulvar melanosis is the main differential diagnostic consideration. Lesions of vulvar melanosis manifest irregular pigmentation with skip areas up to several centimeters in size, but with well-defined borders and uniform pigmentation. Histologically, vulvar melanosis manifests prominent basal layer keratinocytic proliferation with either a normal or slightly increased density of cytologically banal melanocytes having prominent elongated dendrites. If cytologic atypia is identified in the melanocytic populace, such lesions are designated as atypical genital melanosis or atypical genital melanocytic hyperplasia. Pigmented Bowen's disease and pigmented extramammary Paget's disease can also mimic vulvar melanoma and can only be confirmed by histologic examination (Crowson et al, 2001). Malignant Melanoma of the Penis Although melanoma of the glans penis is usually pigmented, urethral melanomas are not uncommonly amelanotic (Oliva et al, 2000). Penile melanomas usually present with an irregular patch surmounted by a nodule. Sometimes the only clue to urethral melanoma is a flare of pigmentation around the meatus; change in urine color and dark flecks of pigment in the urine are late signs. Prognostic microstaging is difficult and due to the rarity of these neoplasms, lends uncertain weight to the clinical assessment. Malignant Melanoma of the Oral, Esophageal and Nasal Mucosae Oral mucosal melanoma usually presents as an irregular brown patch or mass on the oral mucosa extending to the gingival margins (Gorsky and Epstein, 1998) but can be amelanotic. Esophageal and nasal mucosal melanomas are usually occult and present with obstruction or bleeding (Crawford et al, 1995). Sometimes advanced cases of nasal melanoma present with rhinorrhea with dark pigment flecks in a serosanguinous discharge. Endoscopy reveals a variegate mucosa with shades of brown-tan, red, and white. Histology of Radial Growth Phase-Confined Mucosal Melanoma Radial growth phase vulvar melanoma assumes a pattern similar to superficial spreading melanoma or nodular melanoma in one-half of cases (Piura et al, 1999), a lentiginous pattern in 15% and a mixed pattern in the remainder. When a pagetoid intraepidermal growth predominates there is often coexisting single-cell permeation of the papillary dermis while a dominant lentiginous pattern of radial growth is associated with dendritic melanocytes that are heavily laden with melanin pigment. Transepidermal melanin pigment elimination typically manifests irregular pigment columns in the stratum corneum. The esophageal, urethral, oral, and nasal mucosal radial growth phases are most commonly lentiginous in their architectural and cytologic patterns. The invasive component typically assumes a spindled morphology from its inception and may have an associated desmoplastic stromal response. Osteoid formation is frequent in nasal melanomas (Hoorweg et al, 1987).