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Heavily Pigmented Epithelioid Melanoma With Loss of Protein Kinase A Regulatory Subunit-α Expression

Cohen, Jarish N., MD, PhD*,†; Spies, Jessica A., MD; Ross, Fawn, NP-C§; Bohlke, Angela, MD§; McCalmont, Timothy H., MD*,†

The American Journal of Dermatopathology: December 2018 - Volume 40 - Issue 12 - p 912–916
doi: 10.1097/DAD.0000000000001185
Extraordinary Case Report

Abstract: Heavily pigmented melanocytic neoplasms are genotypically and phenotypically diverse. Recently, a subset of this histopathologic spectrum was shown to harbor recurrent genetic alterations in the gene-encoding protein kinase A regulatory subunit-α (PRKAR1A). To date, no histopathologic descriptions of melanomas arising from this pathway have been described. We present a case of a darkly pigmented papule arising on the posterior neck of a 28-year-old man. Microscopically, the heavily pigmented compound melanocytic proliferation was centered in the dermis with permeation into the superficial subcutis. Tumor cells were arranged in large confluent nests and fascicles and lacked maturation with descent. The epithelioid melanocytes were characterized by enlarged vesicular nuclei with prominent nucleoli, nuclear pleomorphism, and plentiful gray-brown granular cytoplasm. Mitotic figures were readily identified. By immunohistochemistry, melanocytes were positive for mutant BRAF V600E and showed loss of Prkar1α and p16 expression. A multiplex MART-1/tyrosinase/phosophohistone-H3 immunostain demonstrated an increased mitotic index in melanocytes. The combination of highly atypical cytomorphology and architecture, increased mitoses, and p16 expression loss compelled the diagnosis of melanoma. Overall, we present the first clinicopathologic description of a PRKAR1A-inactivated melanoma to highlight morphological features and discuss mimics that may enter the differential diagnosis.

Departments of *Pathology, and

Dermatology, the UCSF Dermatopathology Service, University of California, San Francisco, San Francisco, CA;

Curtis Thompson, MD and Associates Lab, Tigard, OR; and

§Silver Falls Dermatology, Salem, OR.

Correspondence: Timothy H. McCalmont, MD (e-mail:

The authors declare no conflicts of interest.

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