Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features

Ann Diagn Pathol. 2021 Jun:52:151719. doi: 10.1016/j.anndiagpath.2021.151719. Epub 2021 Feb 17.

Abstract

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

Keywords: Dedifferentiation; Immunohistochemistry; Molecular; NKX3.1; Pleomorphic giant cell carcinoma; Prostate; Variant.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Carcinoma, Acinar Cell / pathology
  • Carcinoma, Giant Cell / diagnosis*
  • Carcinoma, Giant Cell / metabolism*
  • Cell Dedifferentiation
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Diagnosis, Differential
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading / methods
  • Prognosis
  • Prostatic Neoplasms / pathology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Urothelium / pathology

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • NKX3-1 protein, human
  • Transcription Factors
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human