Immunohistochemical expression of PAX8, PAX2, and cytokeratin in melanomas

J Cutan Pathol. 2021 Oct;48(10):1246-1251. doi: 10.1111/cup.14041. Epub 2021 May 13.

Abstract

Background: Deviations from the classic melanocytic immunophenotype in melanoma can present a diagnostic challenge. PAX8 and PAX2 are common markers for renal or Müllerian differentiation. While most PAX8+ or PAX2+ carcinomas are seldom confused with melanoma, some cases may show a more ambiguous immunophenotype, especially when MiTF family altered renal cell carcinoma (MiTF-RCC) is in the differential diagnosis. Neither PAX8 nor PAX2 expression has been reported in melanoma to date. We aimed to better characterize PAX8, PAX2, and cytokeratin immunoreactivity in a large series of melanomas.

Methods: Tissue microarrays consisting of 263 melanomas were immunostained for PAX8, PAX2, and cytokeratin and graded by an h-score.

Results: PAX8 expression was seen in 7.9% of melanomas and was significantly associated with spindle cytomorphology. PAX2 was positive in one (0.4%) melanoma. Cytokeratin positivity was seen in three (1.2%) cases and was associated with metastases.

Conclusions: PAX8 is expressed in a subset of melanomas and may be strong/extensive. As PAX8 positivity does not exclude a diagnosis of melanoma, it should be used in conjunction with other immunohistochemical markers, such as cytokeratin and PAX2, when melanoma, MiTF-RCC, and other PAX8+ tumors are in the differential diagnosis.

Keywords: MiTF; PAX2; PAX8; cytokeratin; melanoma; renal cell carcinoma.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma / diagnosis
  • Diagnosis, Differential
  • Humans
  • Immunohistochemistry
  • Keratins / analysis*
  • Keratins / biosynthesis
  • Melanoma / diagnosis*
  • Melanoma, Cutaneous Malignant
  • PAX2 Transcription Factor / analysis*
  • PAX2 Transcription Factor / biosynthesis
  • PAX8 Transcription Factor / analysis*
  • PAX8 Transcription Factor / biosynthesis
  • Skin Neoplasms / diagnosis*

Substances

  • Biomarkers, Tumor
  • PAX2 Transcription Factor
  • PAX2 protein, human
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Keratins