Precursors To Melanoma And The Problematic Nevomelanocytic Proliferation
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.
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).
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
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
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).