title: Extravascular migratory metastasis in gynaecological carcinosarcoma.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Anatomical Pathology, PathWest, QEII Medical Centre, Perth, WA, Australia.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Dyke
authors.forename: Maxine L
authors.initials: ML
authors.lastname: Crook
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.forename: Colin J R
authors.initials: CJ
authors.lastname: Stewart
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34 / Q000378:metabolism; D002296:Carcinosarcoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D024141:Collagen Type IV / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005185:Fallopian Tube Neoplasms / Q000473:pathology; D005260:Female; D005833:Genital Neoplasms, Female / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D010051:Ovarian Neoplasms / Q000473:pathology; D020286:Pericytes / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D024141:Collagen Type IV; D007797:Laminin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C500987:monoclonal antibody D2-40
keywords: angiotropic; carcinosarcoma; extravascular migratory metastasis; gynaecological; invasion