Precursors To Melanoma And The Problematic Nevomelanocytic Proliferation
Neil Crowson, MD
Cynthia M. Magro, MD
Martin C. Mihm, Jr., MD
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Freckles and lentigines are not classified with precancerous melanocytic proliferations. However, their importance to the surgical pathologist is twofold: first, they can be mistaken for precancrous melanoses. Second, in the context of lentiginosis syndromes, they may be a clue to a systemic disease capable of generating non-melanocytic cancers. In consequence, we will address them briefly.
The dermal melanocytoses are a group of pigmented lesions characterized by dendritic melanocytes within the dermis, a group which includes the mongolian spot, the blue nevus and its variants, the nevus of Ota, the nevus of Ito, Sun's nevus and the dermal melanocytic hamartoma. These lesions are thought to evolve from a dermal arrest in the migration of melanocytes from the neural crest to the epidermis.
Nevi are circumscribed anomalies of embryonic development that may be present at birth or may appear later during life. The term "nevus" originates from the Latin word for maternal impression; many authors consider it to be a synonym for "hamartoma". Melanocytic nevi are collections of pigment-producing cells of melanocytic origin present in the epidermis, the dermis or both.
Darier and Civatte first noted that certain pigmented lesions of childhood with a morphology similar to that of melanoma behaved in an indolent fashion. It was thought that melanoma behaved better in children due to endocrine factors. Despite the absence of metastases in the vast majority of these prepubertal or juvenile "melanomas", the prevalent approach was to widely excise them before puberty to avoid risk.
The term combined nevus is applied to lesions with mixed patterns of nevomelanocytic proliferation that combine, in variable proportions, type A, B, and C nevomelanocytes with cells identical to those of Spitz and/or blue nevi. Combined nevi represent 1% of nevi and in our view reflect divergent terminal differentiation, reflecting genotypic or epigenetic phenomena.
Previously precursors to melanoma were generally considered to be nevi, either acquired or congenital. In recent decades the systematic study of patients with malignant melanoma has revealed the presence in a significant number of patients of precursor lesions which could be more specifically subclassified; a certain group of lesions was found that in themselves were precursors but the presence of which were a clinical sign that the patients harbored a genetic anomaly that placed them at an increased risk for the development of malignant melanoma and were carriers of susceptibility trait for the disease, now known as dysplastic nevi.
Recurrence of a nevus manifests as repigmentation in the scar at the site of a previous incomplete elliptical, punch or shave excision, electrodessication, or dermabrasion of a melanocytic lesion. The pigmentation within or adjacent to the scar is irregular, stippled or scalloped with a variegated color ranging from tan to dark brown or black. Similar changes appear in nevi partly ablated through trauma of which the patient may be unaware.
Melanoma was for many years considered a single neoplasm with a uniformly bad prognosis. In 1969 Clark and McGovern described new classifications based on clinicopathologic features that led to a new understanding of the pathogenesis and developmental biology of the tumor and to increased awareness of early diagnostic features. This in turn led to a more complete understanding of histologic factors important in diagnosis. Another impetus is the increasing incidence that has been described as 'a melanoma epidemic'.
The presence of the vertical growth phase signifies the acquisition by a melanoma of the capacity for metastasis. The vertical growth phase usually manifests as a pigmented or amelanotic nodule supervening on a preexisting macule or plaque, the sole exception being nodular melanoma in which occurs the rapid appearance of a nodule in previously unremarkable skin. Nodular melanoma lacks a concomitant or pre-existing radial growth phase component by definition.
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. Although usually pigmented, rare examples are amelanotic.
First decribed in 1975 by Reed, minimal deviation melanoma is a tumorigenic lesion with a low metastatic potential. While not widely accepted, we hold that there is a distinct entity that fits this description. These tumors form nodules that resemble vertical growth phase melanoma, but comprise cells that are nevoid in character with atypia that lacks the cytologic character of malignant cells.
The prognosis of patients with invasive malignant melanoma in vertical growth phase can be predicted by specific light microscopic parameters including the measured depth, mitotic count, host response, sex, anatomic site, and presence or absence of regression, angioinvasion, or ulceration. All of this information should appear in the pathology report.