PRAME expression in melanocytic proliferations with intermediate histopathologic or spitzoid features

J Cutan Pathol. 2020 Dec;47(12):1123-1131. doi: 10.1111/cup.13818. Epub 2020 Sep 10.

Abstract

Background: PRAME (PReferentially expressed Antigen in MElanoma) has shown utility in distinguishing melanoma from benign melanocytic lesions, but knowledge of its expression pattern in intermediate melanocytic and spitzoid proliferations is limited.

Methods: Immunohistochemical expression of PRAME was examined in 112 melanocytic proliferations with intermediate histopathologic or spitzoid features.

Results: Any intensity of nuclear PRAME staining in at least 60% of lesional melanocytes was determined as the best threshold for diffuse staining in this cohort. Nearly all non-spitzoid melanomas (23/24; 95.8%) demonstrated diffuse PRAME expression. PRAME was completely negative in 95.6% (43/45) of mitotically-active nevi, traumatized nevi, nevi with persistent/recurrent features, and dysplastic nevi. Most Spitz nevi (15/20) and atypical Spitz tumors (10/13) entirely lacked PRAME expression. One Spitz nevus, one atypical Spitz tumor, and one spitzoid melanoma (1/2) demonstrated diffuse PRAME expression.

Conclusions: Although diffuse PRAME expression is generally limited to malignant melanoma, benign Spitz nevi and atypical Spitz tumors can infrequently express diffuse PRAME. PRAME immunohistochemistry can be useful in the evaluation of atypical melanocytic proliferations with intermediate histopathologic features but should be interpreted with caution in the setting of spitzoid neoplasms.

Keywords: PRAME; Spitz nevus; atypical nevus; immunohistochemistry; melanoma.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics*
  • Carrier Proteins / genetics
  • Cell Proliferation / genetics*
  • Cohort Studies
  • Diagnosis, Differential
  • Dysplastic Nevus Syndrome / genetics
  • Dysplastic Nevus Syndrome / pathology
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Melanocytes / pathology*
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Nevus, Epithelioid and Spindle Cell / genetics
  • Nevus, Epithelioid and Spindle Cell / pathology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics

Substances

  • Antigens, Neoplasm
  • BAP1 protein, human
  • Carrier Proteins
  • PRAME protein, human
  • TTLL5 protein, human
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase