Giant-cell tumor of bone with pathological evidence of blood vessel invasion.

Giant cell tumor of bone is a rare but aggressive benign tumor that arises at the end of long tubular bones. The tumor rarely metastasizes; however, we report a case in which a giant cell tumor of bone presented with progressive pulmonary metastases. There has been no clear pathologic evidence of the definitive cause or route of metastasis. In our case, the primary tumor site was located in the left femur with pathological evidence of blood vessel invasion. The histological and pathological features of this entity are discussed in this letter to the editor.

Two cases of breast carcinoma with osteoclastic giant cells: are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

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.

[Regulatory effect of antisense VEGF121 cDNA transfection on angiogenesis and metastasis of human lung giant cell carcinoma].

OBJECTIVE: To study the regulatory effect of antisense VEGF121 cDNA transfection on endogenous VEGF secretion and angiogenesis of human metastatic lung carcinoma cell line PG and explore the significance of microvessel density (MVD) in tumor growth and metastasis. METHODS: The eukaryotic expression vectors bearing antisense VEGF121 cDNA was transfected into PG cells. Human umbilical vein endothelial cells (HUVEC) were cultured in conditioned mediums from transfected cells, and proliferation was determined by methyl thiazolyl tetrazolium (MTT) and 3H thymidine incorporation (3H TdR) assays in vitro. Microvessel density (MVD) in xenografted tumors in nude mice was analyzed by immunohistochemistry. RESULTS: The transfectant of antisense VEGF121 cDNA exhibited a reduction in VEGF secretion. HUVEC grown in conditioned medium from the antisense VEGF transfected cells exhibited a decrease in capacities of DNA syntheses and cell proliferation. MVD of tumor with transfected antisense VEGF gene was significantly lower than that in control vector. CONCLUSION: Antisense VEGF gene transfection can inhibit vascular endothelial cell proliferation in vitro and tumor angiogenesis in vivo, which may explain its inhibitory effects on tumor growth and metastasis.