Two Congenital Cases of Pigmented Epithelioid Melanocytoma Studied by Fluorescent in situ Hybridization for Melanocytic Tumors: Case Reports and Review of These Recent Topics
ABSTRACT The term 'pigmented epithelioid melanocytoma' (PEM) has recently been proposed as a nosological framework grouping lesions formerly known as animal-type melanomas, sporadic epithelioid blue nevi and Carney complex-associated epithelioid blue nevi. Congenital PEMs have been reported extremely rarely and their prognosis is poorly known. Four-color fluorescent in situ hybridization (FISH) for melanocytic lesions is a recent method developed to assess the malignant potential of ambiguous melanocytic lesions. Here we describe 2 cases of congenital epithelioid and strongly pigmented melanocytic lesions consistent with PEM. No BRAF gene mutation was found in the 2 cases. FISH for melanocytic lesions was also performed. The first case proved entirely negative, whereas the second one showed a positive zone with an extra copy of chromosome 6. The prognosis and management of PEM are discussed, with a review of the available data on the history, demographics, molecular alterations and histopathological aspects of this entity. PEM seems to represent a unique low-grade melanocytic tumor with a limited potential of metastasis to lymph nodes, but a favorable long-term clinical course. The published data about FISH for melanocytic tumors, and especially PEM, are reviewed. Four-color FISH may be a useful tool to assess more accurately the prognosis of these tumors.
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ABSTRACT: A slow growing skin tumour was identified on the head of a 6-year-old male Serra da Estrela black sheep. The animal had no previous history of exposure to ultraviolet radiation or illness. The tumour consisted of an irregular mass subdivided into two polypoid regions and there were small alternating pigmented and non-pigmented areas in the surrounding epidermis. Microscopical and immunohistochemical features were consistent with a melanocytic tumour of the melanocytoma type, without signs of vascular or perineural invasion. The tumour cells contained pigment stained by the Masson Fontana reaction, expressed S100 protein and vimentin and displayed a low proliferative rate (Ki67 labelling <1%). No metastases were found at the time of gross necropsy examination. Analyses of the homologous regions of the hot spot mutational exons of BRAF and NRAS (the genes that are most often mutated in human melanocytic tumours) did not reveal alterations, but there were silent polymorphic variations in these genes. No such variation was observed in the GNAQ gene sequence that is mutated in human melanocytomas.Journal of comparative pathology 05/2011; 146(2-3):160-4. DOI:10.1016/j.jcpa.2011.04.001 · 1.14 Impact Factor
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ABSTRACT: Pigmented epithelioid melanocytoma (PEM), or animal-type melanoma, is an unusual variant of melanoma which has been reported to have indolent behavior and a relatively good prognosis. We report a 12-year-old girl with PEM on the third finger web of her right hand. Histopathologically, it was composed of heavily pigmented dermal epithelioid and spindled melanocytic tumor cells. A sentinel lymph node biopsy was negative, and no recurrence was noted 1 year later. We reviewed 173 previously published cases of PEM or so-called animal-type melanoma in the literature. Among the 173 cases and our case, extremities were the most common sites of occurrence (52/129, 40.3%), and most of the depth of invasions were Clark level IV and V [76/114 (66.7%) and 33/114 (28.9%), respectively]. Lymph nodes metastasis was noted in 39/89 (43.8%) of the cases being investigated. Only two cases died of the disease with visceral metastasis. Thus, a more advanced level of invasion and the presence of lymph node metastasis did not imply a definitely malignant clinical course, because spreading beyond lymph nodes was rare (5/174, 2.9%). However, long-term follow-up with more cases and further research are needed to fully delineate the true biological nature of this pigmented melanocytic tumor.Dermatologica Sinica 06/2012; 30(2). DOI:10.1016/j.dsi.2011.09.011 · 0.88 Impact Factor
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ABSTRACT: HRAS is mutated in ∼15% of Spitz nevi, and GNAQ or GNA11 is mutated in blue nevi (46-83% and ∼7% respectively). Epithelioid blue nevi and deep penetrating nevi show features of both blue nevi (intradermal location, pigmentation) and Spitz nevi (epithelioid morphology). Epithelioid blue nevi and deep penetrating nevi can also show overlapping features with melanoma, posing a diagnostic challenge. Although epithelioid blue nevi are considered blue nevic variants, no GNAQ or GNA11 mutations have been reported. Classification of deep penetrating nevi as blue nevic variants has also been proposed, however, no GNAQ or GNA11 mutations have been reported and none have been tested for HRAS mutations. To better characterize these tumors, we performed mutational analysis for GNAQ, GNA11, and HRAS, with blue nevi and Spitz nevi as controls. Within deep penetrating nevi, none demonstrated GNAQ or GNA11 mutations (0/38). However, 6% revealed HRAS mutation (2/32). Twenty percent of epithelioid blue nevi contained a GNAQ mutation (2/10), while none displayed GNA11 or HRAS mutation. Eighty-seven percent of blue nevi contained a GNAQ mutation (26/30), 4% a GNA11 mutation (1/28), and none an HRAS mutation. Within Spitz nevi, none demonstrated GNAQ or GNA11 mutations (0/30). Seventeen percent contained an HRAS mutation (5/30). All GNAQ and GNA11 mutations were p.Q209L (c.626A>T) point mutations, except 2 GNAQ mutations, which contained novel c.625_626CA>TT double mutations. Four HRAS mutations were in exon 2, and three in exon 3. This is the first study to identify HRAS mutations in deep penetrating nevi. The presence of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi suggests classification of these unusual nevi within the Spitz nevus category of melanocytic tumors, rather than the blue nevus category.Modern Pathology (2013) 0, 000-000. advance online publication, 19 April 2013; doi:10.1038/modpathol.2013.77.Modern Pathology 04/2013; 26(10). DOI:10.1038/modpathol.2013.77 · 6.19 Impact Factor