title: Two cases of breast carcinoma with osteoclastic giant cells: are the osteoclastic giant cells pro-tumoural differentiation of macrophages?
abstract: Breast carcinoma with osteoclastic giant cells (OGCs) is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1) had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2) with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K) and a histiocyte marker (CD68), but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.
authors: Department of Pathology, Kyorin University School of Medicine 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors: Yukiko
authors: Y
authors: Shishido-Hara
authors: Atsushi
authors: A
authors: Kurata
authors: Masachika
authors: M
authors: Fujiwara
authors: Hiroki
authors: H
authors: Itoh
authors: Shigeru
authors: S
authors: Imoto
authors: Hiroshi
authors: H
authors: Kamma
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000737:chemistry / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D018286:Carcinoma, Giant Cell / Q000098:blood supply / Q000737:chemistry / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D002296:Carcinosarcoma / Q000098:blood supply / Q000737:chemistry / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D054338:Cell Transdifferentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D008408:Mastectomy; D055806:Microvessels / Q000473:pathology; D009367:Neoplasm Staging; D010010:Osteoclasts / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor