PRAME and LEF1 in Combined Deep Penetrating Nevus and Combined Blue Nevus: Utility and Pitfall

Authors

Kaitlin Vanderbeck
Aimi T Rothrock
Woo Cheal Cho
Priyadharsini Nagarajan
Phyu P Aung
Courtney Hudgens
Roland L Bassett
Doina Ivan
Victor G Prieto
Jonathan L Curry
Carlos A Torres-Cabala

Publication Date

8-1-2023

Journal

The American Journal of Dermatopathology

Abstract

Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME was negative in most DPN (n = 10/10, n = 9/10, one case with discrepancy between readers) and all BN (n = 16/16), while the 2 melanomas included were positive (n = 2/2). All DPN were positive for LEF1 (n = 9/9) while only a subset of BN were positive (n = 6/16, P = 0.0028; n = 5/16, P = 0.001, per both readers). LEF1 seemed to be easier to interpret than β-catenin because of its nuclear pattern of expression. The expression of LEF1 in the regular nevus component of combined BN presents a potential pitfall in practice because it may lead to misinterpretation of LEF1 as positive in the BN component of the lesion. However, a subset (approximately one-third) of combined BN seemed to show true LEF1 expression. Taking into account pitfalls in interpretation, the combinatorial panel of PRAME and LEF1, in addition to conventional histopathological features, may be useful to distinguish CDPN from combined BN and other benign and malignant mimics.

Keywords

Humans, Nevus, Blue, beta Catenin, Skin Neoplasms, Lymphoid Enhancer-Binding Factor 1, Melanoma, Nevus, Epithelioid and Spindle Cell, Nevus, Transcription Factors, Diagnosis, Differential, Antigens, Neoplasm, Deep penetrating nevus, blue nevus, melanoma, PRAME, LEF1

Comments

PMID: 37462205