Deep penetrating nevus: A review

Institute of Pathology, Medical Faculty University of Ljubljana, Slovenia.
Archives of pathology & laboratory medicine (Impact Factor: 2.84). 03/2011; 135(3):321-6. DOI: 10.1043/2009-0493-RA.1
Source: PubMed


Deep penetrating nevus is a distinctive melanocytic lesion that may simulate melanoma both clinically and histologically.
To review clinical and histologic features of deep penetrating nevi and discuss their differential diagnosis, especially regarding melanoma.
The literature on deep penetrating nevi is reviewed and supplemented by our experiences with deep penetrating nevi.
One or more disturbing histologic features may frequently be found in deep penetrating nevi, including asymmetry, plump but fairly regular nests of melanocytes in the dermis, cytologic atypia with some nuclear pleomorphism, a small to medium-sized eosinophilic nucleolus, absence of maturation, occasional presence of normal dermal mitoses, and a patchy mononuclear inflammatory cell infiltrate. Although unusual, such histologic features should not be regarded as a sign of malignancy in deep penetrating nevi.

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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.
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    ABSTRACT: The deep penetrating nevus (DPN), also known as the plexiform spindle cell nevus, is a pigmented lesion that commonly arises on the head and neck in the first few decades of life. Histopathologically, the DPN is wedge-shaped and contains melanocytes that exhibit deep infiltration into the dermis. Given these features, DPN may clinically and histopathologically mimic malignant melanoma, sparking confusion about the appropriate evaluation and management of these lesions. The goal of this review is to summarize the clinical and histopathological features of DPN and to discuss diagnostic and treatment strategies for dermatologists.
    Journal of the American Academy of Dermatology 08/2014; 71(6). DOI:10.1016/j.jaad.2014.07.026 · 4.45 Impact Factor