Conventional and Atypical Deep Penetrating Nevus, Deep Penetrating Nevus-like Melanoma, and Related Variants

Abstract

Deep penetrating nevus (DPN) is an uncommon acquired melanocytic lesion with a distinct histopathological appearance that typically behaves in an indolent manner. The lesion is characterized by a symmetrical proliferation of epithelioid to spindled melanocytes associated with abundant melanophages and wedge-shaped extension to the deep reticular dermis and subcutis. Pronounced cytologic atypia and mitotic figures are usually absent, which helps distinguish DPN from melanoma with a deep penetrating growth pattern. Recently, the concept of atypical DPN has been proposed for lesions that demonstrate borderline histomorphologic features and may be associated with lymph node deposits but lack the copy number aberrations typical of melanoma by either fluorescence in situ hybridization or comparative genomic hybridization. While most of these lesions have a favorable clinical course, rare lesions may progress to melanoma. In this review, we summarize the current literature on atypical DPNs with uncertain behavior/metastatic potential and outline the characteristics that distinguish these lesions from conventional DPN and melanoma with DPN-like features.

Keywords: deep penetrating nevus; melanocytic lesion; melanoma; metastatic; molecular; nevi.

Figure 1

Deep penetrating nevi present as small, symmetrical, sharply circumscribed, pigmented papules or nodules.

Figure 2

Conventional deep penetrating nevus. (A) There is a wedge-shaped proliferation of melanocytes in the dermis and subcutis with an overlying grenz zone (hematoxylin and eosin, 20×). (B) Lesional cells are arranged in fascicles, cords, and nests (hematoxylin and eosin, 100×). (C) The melanocytes are epithelioid and spindled, with amphophilic cytoplasm and admixed scattered pigmented melanophages (hematoxylin and eosin, 100×).

Figure 3

Deep penetrating nevus associated with a predominantly intradermal melanocytic nevus as part of a combined nevus. (A), Hematoxylin and eosin, 40×. (B) Hematoxylin and eosin, 100×.

Figure 4

Immunohistochemical features of a deep penetrating nevus. (A) Diffuse expression of HMB45 is present (HMB45, 20×). (B) Dual MART1/Ki67 staining reveals a low proliferative index (MART1/Ki67, 200×). (C) Cytoplasmic, membranous, and nuclear expression of beta-catenin is present (beta catenin, 200×). (D) There is nuclear positivity for cyclin D1 (cyclin D1, 200×). (E) P16 is retained (p16, 40×). (F) BAP1 nuclear expression is retained (BAP1, 200×). (G) Lesional cells are negative for preferentially expressed antigen in melanoma (PRAME) (PRAME, 100×).

Figure 5

Atypical deep penetrating nevus. (A) The atypical architectural and cytological features exceed those seen in conventional deep penetrating nevi (hematoxylin and eosin, 40×). (B) The junctional component is predominantly nested and epithelioid with occasional pagetoid upward migration of atypical single cells (hematoxylin and eosin, 200×). (C) The dermal melanocytes are spindled and admixed with melanophages. Scattered cells show severe cytologic atypia (hematoxylin and eosin, 200×). In this case, findings on fluorescence in situ hybridization with probes for RREB1, CCND1, MYC, and CDKN2A were within normal limits.

Figure 6

Sentinel lymph node deposits from a patient with an atypical deep penetrating nevus. (A) Hematoxylin and eosin, 40×. (B) Hematoxylin and eosin, 200×. Multiple clusters of coarsely and densely pigmented epithelioid cells are noted within the lymph node parenchyma and subcapsular space. (C,D) Lesional cells are highlighted on immunohistochemical studies with (C) a melanocytic cocktail (anti-MART1, HMB45, and anti-tyrosinase, 200×) and (D) SOX10 (SOX10, 200×).

Figure 7

Atypical deep penetrating nevus from the eyelid margin. (A) Hematoxylin and eosin, 40×. (B) Hematoxylin and eosin, 200×. There is moderate cytologic atypia and rare mitotic figures. (C–F) Lesional cells demonstrate (C) membranous, cytoplasmic, and nuclear beta-catenin expression (beta-catenin, 200×), (D) nuclear cyclin D1 expression (cyclin D1, 200×), (E) a few proliferating melanocytes on a MART1/Ki67 immunostain (MART1/Ki67, 200×), and (F) no expression of preferentially expressed antigen in melanoma (PRAME) (PRAME, 200×).

Figure 8

Deep penetrating nevus–like melanoma showing a compound, asymmetric melanocytic proliferation. (A) Hematoxylin and eosin, 20×. (B) Hematoxylin and eosin, 40×. (C) Lesional cells share cytomorphologic similarity with conventional deep penetrating nevus (hematoxylin and eosin, 200×). (D) However, there is increased cytologic atypia (hematoxylin and eosin, 400×). Additionally, immunohistochemical studies showed diffuse loss of p16, and the MyPath Myriad score (from qRT-PCR-based molecular analysis) was 2.0 (benign, −16 to −2; intermediate, −2 to 0; malignant, 0 to 10), supporting the interpretation of melanoma.