Extravascular migratory metastasis in gynaecological carcinosarcoma

Histopathology. 2014 Sep;65(3):363-70. doi: 10.1111/his.12395. Epub 2014 Apr 16.

Abstract

Aims: Extravascular migratory metastasis (EVMM) is a potential mechanism of tumour spread reported most extensively in cutaneous melanoma. It has not been described previously in gynaecological malignancies. We describe EVMM in four gynaecological carcinosarcomas.

Methods and results: Extravascular migratory metastasis was observed in an ovarian carcinosarcoma during routine diagnostic assessment. Twenty-three additional, randomly selected gynaecological carcinosarcomas (11 tubo-ovarian and 12 endometrial) were examined retrospectively and EVMM was identified in three of these. Other than the index case, EVMM was a focal finding, identified in 12-18% of slides. The malignant cells demonstrating EVMM appeared sarcomatoid and were distributed abluminally, partly or completely surrounding the endothelium. Affected vessels often showed mural fibrin deposition. Immunohistochemistry for α-smooth muscle actin (SMA), CD31, CD34, D2-40, laminin and type IV collagen was performed on the EVMM-positive cases. The perivascular malignant cells showed more consistent SMA and laminin immunoreactivity than the non-vascular tumour elements.

Conclusions: Extravascular migratory metastasis is a hitherto unrecognized mechanism of tumour spread in gynaecological carcinosarcomas. The perivascular tumour cells appear to adopt a pericytic phenotype, and this may represent a specific pattern of epithelial-mesenchymal transition. Further studies with pericyte-specific immunohistological markers may better demonstrate the presence and possible prognostic significance of EVMM in gynaecological tumours.

Keywords: angiotropic; carcinosarcoma; extravascular migratory metastasis; gynaecological; invasion.

MeSH terms

  • Actins / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD34 / metabolism
  • Carcinosarcoma / metabolism
  • Carcinosarcoma / pathology*
  • Carcinosarcoma / secondary*
  • Collagen Type IV / metabolism
  • Endometrial Neoplasms / pathology
  • Epithelial-Mesenchymal Transition
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Genital Neoplasms, Female / blood supply
  • Genital Neoplasms, Female / metabolism
  • Genital Neoplasms, Female / pathology*
  • Humans
  • Immunohistochemistry
  • Laminin / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / pathology
  • Ovarian Neoplasms / pathology
  • Pericytes / pathology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Retrospective Studies

Substances

  • ACTA2 protein, human
  • Actins
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD34
  • Collagen Type IV
  • Laminin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • monoclonal antibody D2-40