Search

Giant cell tumor (GCT) is a bone-destructive benign neoplasm characterized by distinctive multinucleated osteoclast-like giant cells with osteolytic properties distributed among neoplastic stromal cells. GCT is locally aggressive with progressive invasion of adjacent tissues and occasionally displays malignant characteristics including lung metastasis. GCT is characterized genetically by highly recurrent somatic mutations at the G34 position of the H3F3A gene, encoding the histone variant H3.3, in stromal cells. This leads to deregulated gene expression and increased proliferation of mutation-bearing cells. However, when GCT complicates Paget disease of bone (GCT/PDB) it behaves differently, showing a more malignant phenotype with 5-year survival less than 50%. GCT/PDB is caused by a germline mutation in the ZNF687 gene, which encodes a transcription factor involved in the repression of genes surrounding DNA double-strand breaks to promote repair by homologous recombination. Identification of these driver mutations led to novel diagnostic tools for distinguishing between these two tumors and other osteoclast-rich neoplasms. Herein, we review the clinical, histological, and molecular features of GCT in different contexts focusing also on pharmacological treatments.

First described by Smith and Wilson Jones (1985), multinucleate giant cell angiohistiocytoma (MGCA) is a rare benign fibro-histiocytic and vascular proliferation, which occurs predominantly on the ...

A survey of the available ultrastructural data on physiologically and pathologically occurring and virally-induced multinucleate giant cells (MNGCs) is presented. Emphasis is initially placed upon the bone osteoclast, the skeletal muscle myotube and the placental syncytiotrophoblast. The widespread occurence of MNGCs in a range of pathological situations is discussed, with emphasis upon the broad involvement of the macrophage in inflammatory responses. Many viruses produce cell fusion in vivo and in vitro when cell cultures are infected. Several examples are given. A clear distinction is drawn between viral fusion from “without” and viral fusion from “within” the cell. The cytopathic effect (CPE) of the animal and human retroviruses is discussed in considerable detail. The in vivo and in vitro formation of lymphocytic and macrophage MNGCs by HIV-1 is given extensive coverage. The possible significance of the presence of brain MNGCs of macrophage/microglial origin as a cellular feature of AIDS dementia is discussed. A new hypothesis is advanced relating to the possible role of endogenous C-type retrovirus in the physiological fusion of the invasive placental cytotrophoblasts to create the syncytiotrophoblast. The evolutionary and developmental significance of such an event in relation to the evolution of the placental mammals is discussed. The possible importance of MNGC formation in the depletion of the CD4 + population of T-lymphocytes in vivo in the clinical progression of the AIDS-related complex and AIDS is related to the potent fusogenic effect of HIV-1 when cell cultures are infected.

Phagocytes obtained from six echinoderm and four nonechinoderm species are compared in culture with respect to their ability to form syncytium. It is shown that phagocytes of all echinoderm species examined form an extensive syncytium while those of three nonechinoderm species shoe no such activity. Phagocytes of an ascidia, on the other hand, formed a less extensive type of syncytium known as a multinucleate giant cell. Kinetic analyses of the process of fusion were performed. Phagocytes of the asteroid, Asterina pectinifera, fuse more readily when transferred to culture condition in an aggregated state than as single cells. The extraordinarily fusogenic nature of echinoderm phagocyte is discussed in relation to the calcareous body wall structure of the echinoderms. © 1993 Wiley-Liss, Inc.

The sequential pulmonary changes in dermatosis vegetans were studied in pigs aged one, seven, 14, 17, 21 and 28 days, and two and a half, four and 12 months. At one day old the lung tissues appeared normal. At seven days old there was a moderate infiltration of mononuclear inflammatory cells in the alveolar structures, and proliferation of type II pneumocytes was also observed. At 14 and 17 days old the alveolar structures were intensely infiltrated with mononuclear inflammatory cells. At 21 days old, loosely arranged epithelioid and multinucleate giant cell granulomas appeared, and there was a proliferation of alveolar epithelial cells. By four and 12 months old the inflammatory changes diminished, and small granulomas and moderate alveolar fibrosis were present. The initial lesions were characterised by an alveolitis, developing into loosely arranged granulomas by four months old, and persisting to the age of 12 months. These observations suggest that the interpretation of the lung changes and the disease in general should be revised.

This variety, which gets its name from the clear cytoplasm of the chondroblastic cells, is somewhat similar to a chondroblastoma, and behaves as a low-grade malignant tumor.

My intention in this chapter is to summarize some of the salient features of HIV in the nervous system, and in particular to highlight important areas of uncertainty which require further investigation. Although precise figures for nervous system involvement in HIV infection are not available, nevertheless it is abundantly clear that neurologists are seeing an increasing number of HIV-related neurological conditions as the number of individuals infected with HIV steadily increases. The pace of this increase is difficult to predict, but it is a sobering thought that the actual worldwide total of AIDS cases may well be in the region of 500000. At the end of December 1990 there were 4098 cases of AIDS in the UK, with 2256 deaths (Latest AIDS figures, 1990). Statistical predictions suggest that there will be 279000 cases of AIDS with 179 000 deaths in the USA by 1991, but the long-term effects of changes in sexual practices on statistical predictions remain to be seen.

African species of nonhuman primates harboring persistent simian immunodeficiency virus (SIV) infections do not develop clinical illness or gross lesions. These species include: African green monkeys infected with SIVAGM, sooty mangabey monkeys infected with SIVSMM(δ), Sykes’ monkeys infected with SIVSYK; mandrills infected with SIVMND, and chimpanzees infected with SIVCMZ. The gross findings in various Asian species of macaque monkeys dying of naturally acquired or experimental SIVMAC, SIVSMM(δ), SIVMNE, or SIVSTM infection are variable and nonspecific.

Pigmented villonodular synovitis (tenosynovitis, bursitis)(1) is a hyperplastic production of synovial tissue of the joints, the tendinous sheaths, the mucous bursae, or the fibrous tissue adjacent to the tendons.

This pseudotumoral lesion is particularly observed in the maxillae, either under the gengival mucosa (epulid) with little or no penetration in the bone, or in the bone. A similar lesion is only rarely observed in other parts of the skeleton, and these particularly include the small tubular bones of the hand (Fig. 711).

It is a rare but not exceptional occurrence to observe a sarcoma developing on pagetic bone: a 0.2% incidence, that is 1 case out of 600 of Paget’s disease, has been suggested. Nonetheless, it is impossible to figure out the incidence of this complication as most of Paget’s cases are asymptomatic and thus remain unrecognized. We do know that the occurrence of sarcoma is less rare in severe polyostotic forms of Paget’s disease.

With the increasing use of nude mice in cancer research, two problems arise which make it desirable to have a knowledge of their pathology. The first is the difficulty almost every laboratory has encountered at one time or another in keeping the colony healthy. In all but the most perfect set-up there are occasional breakdowns, and a knowledge of some of the major tissue changes in diseases of nude mice may help to minimise the time lost when a colony requires to be re-derived. Second, since these animals are being autopsied more carefully in the search for metastases or for drug effects on xenografted tumours than is sometimes the case in other animal tumour experiments, there is a possibility that unfamiliarity with the normal tissue appearances in health and disease may lead to errors of interpretation. One good illustration of the need for routine naked-eye and histological examination of nude mice is the fact that it took 2 years for it to become known that the nude mouse was athymic (Pantelouris, 1968).

Glass coverslips were implanted in nude athymic mice and normal controls and the development of multinucleated giant cells on the implant investigated. Although the percentage of the surface area of the coverslip covered by cellular exudate was reduced in older implants (12 days or more) in athymic mice, the proportion of nuclei within syncytia was the same as in normal controls. It is concluded that the multinucleated giant cells in this type of inflammatory lesion are not thymus derived nor is the efficiency of fusion between their precursor mononuclear phagocytes thymus dependent. The number of exuded mononuclear phagocytes on the other hand may be influenced directly or indirectly by the thymus.