Primary penile mesenchymal tumors: A clinicopathologic analysis of 48 cases

Hum Pathol. 2025 May:159:105814. doi: 10.1016/j.humpath.2025.105814. Epub 2025 May 22.

Abstract

Introduction: While the vast majority of penile malignancies are of epithelial origin, most commonly squamous cell carcinoma, mesenchymal tumors of the penis, though rare, represent an important and diagnostically diverse group of neoplasms with variable clinical behavior.

Materials and methods: We retrieved cases of primary penile mesenchymal tumors diagnosed or treated at our institution over a 24-year period. Histologic diagnoses were confirmed through systematic review of archived hematoxylin and eosin and immunohistochemical slides. Clinical data were extracted from electronic medical records and pathology reports.

Results: A total of 48 tumors were identified in 48 individual patients. Of these, 22 (46 %) were benign, 23 (48 %) malignant, and 3 (6 %) were classified as intermediate tumors. Vascular tumors, including epithelioid hemangioma, Kaposi sarcoma, and epithelioid hemangioendothelioma, accounted for 48 % of cases, making them the most common category. Smooth muscle tumors were the next most frequent (17 %), comprising seven cases of leiomyosarcoma, further classified into deep (n = 4) and superficial (n = 3) types. The most common individual diagnoses were epithelioid hemangioma (27 %), Kaposi sarcoma (19 %), and leiomyosarcoma (15 %). One high-grade leiomyosarcoma demonstrated diffuse p16 expression and was positive for high-risk human papillomavirus (HPV) by RNA in situ hybridization.

Conclusions: This series provides a contemporary overview of primary penile mesenchymal tumors, with vascular neoplasms emerging as the most common subtype. To our knowledge, we report the first case of HPV-associated leiomyosarcoma in the male genital tract, broadening the anatomic spectrum of HPV-driven smooth muscle tumors beyond previously described cases in the female lower genital tract.

Keywords: HHV8; HPV; Kaposi sarcoma; Leiomyosarcoma; Mesenchymal neoplasms; Penile cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Hemangioendothelioma, Epithelioid / chemistry
  • Hemangioendothelioma, Epithelioid / pathology
  • Humans
  • Immunohistochemistry
  • Leiomyosarcoma / chemistry
  • Leiomyosarcoma / pathology
  • Leiomyosarcoma / virology
  • Male
  • Mesenchymoma* / pathology
  • Middle Aged
  • Penile Neoplasms* / chemistry
  • Penile Neoplasms* / pathology
  • Penile Neoplasms* / virology
  • Retrospective Studies
  • Sarcoma, Kaposi / chemistry
  • Sarcoma, Kaposi / pathology
  • Sarcoma, Kaposi / virology

Substances

  • Biomarkers, Tumor