Pigmented Epithelioid Melanocytoma: Favorable Outcome After 5-year Follow-up

Abstract

Pigmented epithelioid melanocytoma (PEM) is a recently described entity encompassing epithelioid blue nevus (of Carney complex) and most tumors earlier considered as so-called "animal-type melanoma". Loss of expression of a Carney complex gene, cyclic adenosine 3',5' monophosphate-dependent protein kinase regulatory subunit 1alpha, is observed in the majority of PEMs. Initial reports with short-term follow-up have suggested that although PEMs frequently metastasize to lymph nodes, they have a more favorable outcome than conventional melanomas. In this report, we present the results of long-term follow-up in 26 patients with PEMs from North America and Australia. There were 9 males and 17 females, with a median age of 20 years. The tumors involved the trunk (6 cases), extremities (12 cases), genitalia (1 case), and the head and neck region (7 cases) had a median Breslow thickness of 2.2 mm (range 0.80 to 10.0 mm) and a median Clark level of 4. Eight of the patients developed lymph node metastases. After a median follow-up period of 67 months (range 39 to 216 mo), all patients are alive and free of disease. These findings provide further evidence that PEM is a unique low-grade melanocytic tumor with limited metastatic potential (to lymph nodes), but a favorable long-term clinical course.

In Reply

“…We pointed out that this subgroup of tumors has a much more favorable prognosis than ''conventional'' melanomas and that the well-known, important prognosticators for conventional melanomas, such as tumor thickness and sentinel lymph node tumor-harboring status, do not appear to have the same significance for them. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] These facts support our proposal that such melanocytic tumors are biologically distinct and should be classified in a nosologic category separate from both melanomas and nevi.…”

“…[19][20][21] Although some of these previously reported, metastasizing Spitz nevi and blue nevi have since been reinterpreted as melanomas, 22,23 numerous large series with significant follow-up have highlighted the apparently favorable outcome of some ''borderline'' melanocytic tumors associated with regional lymph node metastases, such as atypical Spitzoid tumors and pigmented epithelioid melanocytomas. 2,5,[8][9][10][11][12][13][14][15][16][17][18]24 Despite this compelling evidence, Drs Sepehr and Tahan contend that even larger studies with longer follow-up are required before they will consider it appropriate to recognize additional, biologically distinct subgroups of melanocytic tumors. This begs the philosophic and rhetoric question, ''How much evidence is required to challenge accepted dogma and present new hypotheses that better explain the data?''…”

Animal‐type melanoma – tumor cell invasion of dermal lymphatics and molecular identification of lymph node metastasis

“…Therapy of melanocytic borderline tumors consists of excision with clear margins and removal of suspicious lymph nodes (clinical inspection and/or radiological examination) [13,18,24,25]. Aggressive surgical and systemic therapies are not advised as there is no benefit for the patient [18,24,25]. Long-term observations and additional molecular studies are needed in order to establish a generally accepted nomenclature as well as guidelines for treatment of melanocytic borderline tumors.…”

“…We believe that the simultaneous detection of identical molecular changes in tumor cells of the skin and those in the lymph node are a sign of (locoregional) metastasis and should be considered suggestive of a malignant process [23] (Figure 5). Therapy of melanocytic borderline tumors consists of excision with clear margins and removal of suspicious lymph nodes (clinical inspection and/or radiological examination) [13,18,24,25]. Aggressive surgical and systemic therapies are not advised as there is no benefit for the patient [18,24,25].…”

Identification of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi

“…The concept of epithelioid blue nevus/pigmented epithelioid melanocytoma as a low-grade melanoma/borderline tumor of unpredictable malignant potential is based on several case series demonstrating that while a subset of these lesions have metastasized (predominantly locoregionally), none has resulted in death, with a median clinical follow-up period of 5 years. 14 No histological features distinguish non-metastasizing lesions from those with metastatic potential.…”