Failure of senescence in the dysplasia-melanoma sequence: demonstration using a tissue microarray and a revised paradigm for melanoma.

In order to correlate changes in morphology to changes in molecular attributes, we constructed a tissue microarray of thin and thick melanomas selected to represent progression from dysplasia to early and advanced melanoma. Hematoxylin and eosin (H&E) staining and immunohistology with antibodies to cyclin D1, p16, Ki67, and Bcl-2 were performed. Observations were interpreted using a revised paradigm for the dysplasia-melanoma sequence in which the early steps of melanomatous growth develop in an accretive fashion similar to the growth of the common acquired nevus. The co-expression of cyclin D1 and p16 persisted from dysplasia to early melanomatous vertical growth. Malignant transformation characterized by absence of p16 and presence of increased cyclin D1 and increased Ki67 and confirmed by clinically documented metastasis occurred during the process of evolving melanomatous vertical growth. The interplay of mutated BRAF, cyclin D1, and p16 with anti-apoptosis and failure of senescence may account for the existence of nevi and dysplastic nevi and for their relationship to melanoma, and may indirectly account for the infrequency of nevi in the lentiginous melanomas that lack mutated BRAF. These observations suggest a need for more detailed study of transformation to malignancy in the various subsets of melanoma.

Cutaneous sarcoidosis presenting as leonine facies.

Cutaneous sarcoidosis often masquerades as many other disease entities. We describe the case of a 56-year-old African American man with a 1-year history of progressively enlarging nodules and plaques of the face resulting in a leonine appearance and madarosis. The diagnosis of cutaneous sarcoidosis was made after skin biopsy results revealed noncaseating granulomas without evidence of foreign body, mycobacteria, or deep fungal infection. A thorough systemic workup was void of other comorbidities. The reports of tumoral sarcoidosis or sarcoidosis presenting with leonine facies are rare, and those cases that have been reported have been linked to other systemic findings.

Ki-67 and p53 expression in minimal deviation melanomas as compared with other nevomelanocytic lesions.

Minimal deviation melanoma is a controversial entity encompassing a heterogeneous group of lesions cytologically in the spectrum between recognized subtypes of nevi and conventional "primary configuration" melanomas and reported to have a better prognosis than the latter. To evaluate the distinctiveness of minimal deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal deviation melanomas were compared with those in compound nevi, Spitz nevi, and vertical growth phase superficial spreading malignant melanoma. Twelve examples of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67 (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and 25%, respectively. The mean Ki-67 proliferation rate was statistically greater in the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P <.05), but the proliferation rates in the two melanoma subtypes were not statistically significant (P =.08). The mean p53 values for these lesions were 0, 9%, 9%, and 26%, respectively; the latter two were statistically different (P <.01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma may represent a distinct entity.