Intratumoural lymphatics in benign and malignant soft tissue tumours.

Soft tissue sarcomas do not generally metastasise via lymphatics, and the presence or absence of lymphatic vessels within sarcomas and benign soft tissue tumours is not known. In this study, we determined whether lymphatic vessels were present in a wide range of benign and malignant soft tissue lesions by examining intratumoural expression of the lymphatic endothelial cell markers, Lyve-1 and podoplanin. Intratumoural Lyve-1+/podoplanin+ lymphatics were not identified in sarcomas apart from all cases of epithelioid sarcoma (a tumour which is known to metastasise to lymph nodes) and a few cases of leiomyosarcoma, rhabdomyosarcoma and synovial sarcoma. Intratumoural lymphatics were also absent in most benign soft tissue tumours. Reparative and inflammatory soft tissue lesions contained lymphatics, as did all (pseudosarcomatous) proliferative myofibroblastic lesions including nodular, proliferative and ischaemic fasciitis, elastofibroma, nuchal fibroma and deep fibromatosis. Our results show that most soft tissue sarcomas do not contain intratumoural lymphatics, a finding which is consistent with the infrequent finding of sarcoma metastasis to lymph nodes. In contrast to fibrosarcoma and a number of other malignant spindle cell tumours, proliferative fibroblastic/myofibroblastic lesions of soft tissue contain intralesional lymphatic vessels.

Immunophenotypic distinction between pigmented villonodular synovitis and haemosiderotic synovitis.

AIM: Haemosiderotic synovitis (HS) is caused by excessive bleeding into a joint. It occurs secondary to a variety of conditions and needs to be distinguished from pigmented villonodular synovitis (PVNS) for the purposes of treatment. The histopathological distinction between these conditions, particularly in biopsy specimens, can be problematic. METHODS: Immunophenotypic findings in 20 cases of PVNS and 20 cases of HS were analysed using monoclonal antibodies against proliferation (Ki-67), apoptosis (bcl2), macrophage (CD14, CD68, HLA-DR) and osteoclast (CD51) antigens. RESULTS: Macrophages in PVNS and HS expressed CD14 and HLA-DR. The giant cells in PVNS, but not those in HS, expressed CD51 and were negative for CD14 and HLA-DR, indicating that these cells had an osteoclast phenotype. Considerably more CD51-expressing mononuclear cells were noted in PVNS compared with HS. The Ki-67 proliferation index was higher in PVNS than in HS. CONCLUSIONS: The findings indicate that there are immunophenotypic differences in giant cells between PVNS and HS, and that expression of CD51 and a high Ki-67 index effectively distinguishes between these two conditions.

Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone.

Giant cell tumour of bone (GCTB) is a primary tumour of bone that may rarely, in the absence of malignant cytological features, produce metastatic lesions, most commonly in the lungs. Whether these lung nodules represent true neoplastic secondaries or implants derived from the primary tumour is not certain. In this study, we have analysed the morphological and immunophenotypic features of 19 conventional GCTBs and corresponding lung nodules for expression of macrophage, osteoclast, proliferation and tumour-associated markers. A striking morphological feature of all GCTBs that produced lung secondaries was the presence of large areas of haemorrhage and thrombus formation; mononuclear and multinucleated cells of GCTB were frequently found within these areas of haemorrhage and thrombus. A similar pattern of CD14, CD33, HLA-DR and CD51 expression was seen in macrophages and giant cells in primary and secondary tumours. Smooth muscle actin expression was frequently noted in primary GCTBs that recurred and metastasised. No difference was seen in the expression of p53, p63, Ki-67, cyclin D1 or Bcl-2 in primary and secondary tumours. Our findings suggest that most lung nodules associated with primary conventional GCTBs are implants derived from tumour emboli formed in areas of haemorrhage and thrombus formation within the primary tumour.

Osteoclast-like cells in soft tissue leiomyosarcomas.

Giant cell-rich leiomyosarcoma of soft tissues is an unusual variant of malignant smooth muscle tumor characterized by the presence of numerous multinucleated giant cells (MNGCs). The nature of MNGCs and the cellular mechanisms underlying their accumulation in this tumor are poorly understood. Analysis of the expression of osteoclast, macrophage, and smooth muscle markers in two cases of giant cell-rich leiomyosarcoma revealed that the MNGCs in giant cell-rich leiomyosarcoma were negative for smooth muscle markers and that these cells expressed an osteoclast-like phenotype, being positive for CD45, CD68, tartrate-resistant acid phosphatase, and CD51 but negative for CD14 and HLA-DR. Scattered tumor-associated macrophages (TAMs) also expressed this phenotype. Leiomyosarcoma tumor cells strongly reacted for CD51 but were negative for CD14, CD45, and CD68. An analysis of 25 conventional (nongiant cell-containing) leiomyosarcomas found isolated CD68(+) MNGCs in three cases (12%), all of which were grade II/III leiomyosarcomas containing a prominent TAM infiltrate. Leiomyosarcoma-derived TAMs in the presence of receptor activator for nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor were capable of differentiating into osteoclast-like cells capable of resorbing bone. Reverse transcription polymerase chain reaction studies showed that RANKL, osteoprotegerin, and TNF-related apoptosis-inducing ligand were expressed by leiomyosarcoma cells. Our findings indicate that the giant cells found in leiomyosarcomas are osteoclast-like and that they are formed from TAMs by a RANKL-dependent mechanism.