Chemically induced transplantable malignant fibrous histiocytoma of the rat. Analyses with immunohistochemistry, immunoelectron microscopy and [3H]thymidine autoradiography

Malignant fibrous histiocytoma was produced in rats by injection of 9,10-dimethyl-1,2-benzanthracene into their knee joints. The original tumors consisted mainly of fibroblast-like cells and histiocyte-like cells, often intermixed with bizarre giant cells, and they frequently showed the storiform-pleomorphic pattern. By immunohistochemistry, anti-rat macrophage monoclonal antibodies, TRPM-3, RM-1, and Ki-M2R, and anti-rat leukocyte common antigen reacted to the histiocyte-like cells but not to the fibroblast-like cells. By the single cell cloning method, we established six tumor cell lines, none of which reacted with the anti-rat macrophage monoclonal antibodies, possessed any Fc receptors, or conducted immune phagocytosis and Latex particle phagocytosis. The ultrastructure of the cloned tumor cells resembled that of long-term cultured dermal fibroblasts. Collagen production by the tumor cells was demonstrated immunohistochemically with a monoclonal antibody for type I collagen. Inoculation of the cloned tumor cells into rats produced tumors with the histology of malignant fibrous histiocytoma and induced prominent macrophage infiltration. In the rat tumors produced by the inoculation of [3H]thymidine labeled cells, no reactivity of tumor cells with the anti-rat macrophage monoclonal antibodies was observed. Transplantation of the cultured rat tumor cells into nude mice produced tumors similar in histology to the original rat malignant fibrous histiocytoma. Tumor cells in nude mice induced marked macrophage infiltration as detected by immunohistochemistry with the anti-mouse macrophage monoclonal antibody F4/80. No differentiation of tumor cells into macrophages was detected, since no cells were stained with biotinylated anti-rat macrophage monoclonal antibody TRPM-3. By the flash labeling method with [3H]thymidine, infiltrating macrophages in the nude mouse tumors were proved to derive from the bone marrow of the host animals. These results indicate a possible experimental reproduction of malignant fibrous histiocytoma by proliferation of malignant fibroblasts or their related cells in combination with macrophage infiltration.     

Expression of Ia and monocyte-macrophage lineage antigens in giant cell tumor of bone and related lesions

An immunohistochemical study of six giant cell tumors of bone and eight related lesions (aneurysmal bone cyst, fibrous histiocytoma, and giant cell tumor of tendon sheath) was performed using a panel of monoclonal antibodies directed to the Ia and monocyte-macrophage lineage antigens. In all types of lesion, osteoclastlike multinucleate giant cells were negative for both types of antigen, but a proportion of mononuclear cells gave positive reactions. While the possibility that these cells are reactive cannot be excluded, in giant cell tumor and malignant fibrous histiocytoma, their frequency and their morphologic similarity to the rest of the tissue suggest that they may be an intrinsic part of the neoplasm. This finding is consistent with the presumed fibrohistiocytic nature of these tumors.     

Immunophenotypic heterogeneity in osteosarcomas.

Eighteen osteosarcomas were studied immunohistochemically. The tumors were classified into the following six histologic subtypes: five osteoblastic, four chondroblastic, four malignant fibrous histiocytoma-like, two telangiectatic, two low-grade central, and one giant cell-rich. Variable amounts of osteocalcin immunoreactivity were found in all tumors. Factor XIIIa-positive cells, which may be of fibrohistiocytic lineage, were present in three tumors of the malignant fibrous histiocytoma-like type, one of the telangiectatic type, one of the low-grade central type, and the tumor of the giant cell-rich type. One tumor of the osteoblastic type showed cytokeratin and epithelial membrane antigen immunoreactivities. The positive reactions for desmin in four tumors, for alpha-smooth muscle actin in 11 tumors, and for type IV collagen in one tumor seemed to indicate myofibroblastic differentiation of some tumor cells. S-100 protein-positive tumor cells were detected not only in all four tumors of the chondroblastic type, but also in three of the osteoblastic type, one of the low-grade central type, and in the tumor of the giant cell-rich type. These immunohistochemical results suggest that osteosarcomas are composed of heterogeneous cell populations, such as those of the osteoblastic, chondroblastic, myofibroblastic, and fibrohistiocytic types, and occasionally also of cells with epithelial features.     

Enzyme histochemical study on bone tumors

A total of 19 cases with bone tumors, including six osteosarcomas. three giant cell tumors of bone, one malignant fibrous histiocytoma, four nonossifying fibromas, four chondromas and one chondrosarcoma, were examined as to enzyme histochemistry; the enzymes consisted of alkaline phosphatase (ALPase), acid phosphatase (ACPase), nonspecific esterase (NSE), adenosine triphosphatase (ATPase), 5'-nucleotidase (5'-Nucl) and beta-glucuronidase (beta-Gl). Osteosarcoma was strongly positive for ALPase followed by 5'-Nucl. Giant cell tumor, malignant fibrous histiocytoma and nonossifying fibroma showed enzyme histochemistry similar to each other: multinucleated giant cells and round cells in these tumors were strongly positive for ACPase, NSE, ATPase and 5'-Nucl simulating osteoclasts and histiocytes, whereas spindle cells were positive for ATPase and 5'-Nucl in their cytoplasm and weakly positive for ACPase. Chondroma and chondrosarcoma were focally positive for ACPase and NSE; the ACPase was sensitive to tartaric acid treatment. These observations showed that ALPase activity is very characteristic to osteosarcoma, and is useful for its diagnosis. From enzyme histochemistry, giant cell tumor, malignant fibrous histiocytoma and nonossifying fibroma can be regarded as a histiocyte-derived tumor of bone in contrast to osteosarcoma and cartilaginous tumors.     

Immunopathology of diffuse malignant mesothelioma

A so-called diffuse biphasic pleural and a monophasic malignant "fibrous" peritoneal mesothelioma were examined using monoclonal anticytoskeleton-antibodies and polyclonal antibodies against macrophage markers. Cytokeratin, vimentin and desmin were each expressed in both of the tumors. GFAP could not be detected. In addition the tumor cells differed in the quantity of macrophage markers. The immunologic findings corresponded to the histologic features of particular areas of the carcinosarcoma. This supports the view that malignant mesotheliomas derive from pluripotential mesothelial cells capable of both epithelial and mesenchymal differentiation. Contrary to some opinions expressed in the literature this histogenesis applies equally to the so-called monophasic diffuse "fibrous" mesotheliomas.     

h-Caldesmon as a specific marker for smooth muscle tumors. Comparison with other smooth muscle markers in bone tumors

Caldesmon is a protein widely distributed in smooth and non-smooth muscle cells and is thought to regulate cellular contraction. Its isoform, high-molecular-weight caldesmon (h-CD), was demonstrated to be specific for smooth muscle cells and smooth muscle tumors of the soft tissue and to never be expressed in myofibroblasts. We performed an immunohistochemical study to examine h-CD expression in the following bone tumors: conventional and non-conventional osteosarcoma, 13; malignant fibrous histiocytoma of bone, 5; giant cell tumors of bone, 5; chondroblastoma, 3; metastatic leiomyosarcoma, 2; and rhabdomyosarcoma, 1. Frequent immunoreactivity for muscle actin (alpha-smooth muscle actin or muscle-specific actin) was seen in 11 of 13 osteosarcomas and all other tumors, whereas h-CD was expressed intensely only in 2 leiomyosarcomas. h-CD is considered a specific and useful marker to distinguish smooth muscle tumor from bone tumors with myoid differentiation.     

Expression of E-cadherin in bone and soft tissue sarcomas: a possible role in epithelial differentiation

The cadherin-mediated cell-cell adhesion system is now known to play a critical role in both the morphogenesis of cancer cells and suppression of their invasion. However, the pattern of expression of E-cadherin, the major cadherin of epithelial cells in bone and soft tissue sarcomas, remains unclear. This prompted us to study E-cadherin expression in a variety of bone and soft tissue sarcomas. Using the monoclonal antibody HECD-1, raised against the extracellular domain of E-cadherin, we observed immunoreactivity in 1 pleomorphic rhabdomyosarcoma, 2 of 5 diffuse mesotheliomas, 4 of 5 clear cell sarcomas, 1 of 5 epithelioid sarcomas, and 10 synovial sarcomas. Other types of bone and soft tissue sarcoma (4 osteosarcomas, 4 chondrosarcomas, 3 primitive neuroectodermal tumors, 1 fibrosarcoma, 4 malignant fibrous histiocytomas, 5 liposarcomas, 4 leiomyosarcomas, 6 alveolar and 5 embryonal rhabdomyosarcomas, 4 angiosarcomas, 4 malignant peripheral nerve sheath tumors, 2 extraskeletal myxoid chondrosarcomas, 2 extraskeletal osteosarcomas, and 3 alveolar soft part sarcomas) were completely negative for E-cadherin. Our findings indicate that E-cadherin is expressed in certain kinds of soft tissue sarcomas, especially those with epithelioid features, suggesting that E-cadherin plays a role in the constitution of their architecture.     

Immunohistochemical study of mononuclear phagocyte antigens in giant cell tumor of bone.

The cytogenesis of giant cell tumor of bone (GCT) was assessed by immunohistochemical methods. Three GCT were analyzed by a sensitive immunoalkaline phosphatase technique with a panel of monoclonal antibodies, including eight reacting with separate antigens previously found to be present on mononuclear phagocytes (MPs) and one specific for the endothelial marker, coagulation Factor 8. Among the MP-associated antigens evaluated were leukocyte common antigen (LCA), HLA-DR, C3b receptor, and C3bi receptor. Also incorporated in the panel were antibodies to MP-associated antigens with well-characterized tissue distribution but of currently unknown function. Constituent cells of the tumors varied in their reactions with the antibodies of the panel. Although mononuclear cells in tumor stroma were labeled with all of the antibodies against the MP markers, giant cells reacted strongly only with antibodies to LCA and the MP-associated antigen recognized by the antibody EBM11. Giant cells were weakly and focally labeled with antibodies (KB90 and UCHM1) against two additional MP-associated determinants and were unreactive with the remaining antibodies in the panel. Spindled stromal cells, which appeared to produce collagen, were not labeled with any of the antibodies in the panel. Only endothelial cells reacted with antibody to Factor 8. The results of this study suggest that giant cells of GCT are derived from stromal cells of mononuclear phagocyte lineage, and that the stromal precurser cells lose some, but not all, MP-associated antigens as they mature into giant cells.     

Matrix vesicles in bone tumors. Ultrastructural analysis and their significance in neoplastic bone formation.

Bone tumors were categorized into alkaline phosphatase (ALPase)-positive (2 ossifying fibromas, 1 benign osteoblastoma and 16 osteosarcomas) and negative (2 chondromas, 2 chondrosarcomas, 3 non-ossifying fibromas, 2 malignant fibrous histiocytomas and 6 giant cell tumors of bone) groups. Production and distribution of matrix vesicles (MVs) in the tumor tissues were examined to clarify their role in neoplastic bone formation. Four distinct types of MV were isolated primarily in ALPase positive bone tumors: empty, amorphous, crystalline and ruptured MVs. They were formed by budding off from the cytoplasmic projections of the osteoblastic tumor cells. The significance of differences in the production rate of MVs between ALPase-positive and negative bone tumors was investigated in view of the predominantly high production of MVs in ALPase-positive bone tumors. Many more mature MVs (crystalline and ruptured) were observed in the osteoblastic lesions of osteosarcoma than in the fibroblastic and MFH-like lesions, suggesting an intimate relationship with maturation and differentiation of the osteoblastic tumor cells. The above findings indicate that production of MVs is one of the diagnostic parameters for osteoblast-derived bone tumors, as well as ALPase activity, and that vesicle-induced mineralization is a major mineralization mechanism in neoplastic bone formation.     

Lysozyme and alpha 1-antitrypsin in giant-cell tumor of bone and in other lesions that contain giant cells

We performed an immunohistochemical study of 24 giant-cell tumors of bone and 30 other lesions (fibrous histiocytoma, nonossifying fibroma, and giant-cell tumor of the tendon sheath) using lysozyme and alpha 1-antitrypsin as markers for histiocytic cells. The presence of histiocytic cells in giant-cell tumors of bone is confirmed by the finding of a positive reaction for alpha 1-antitrypsin in both multinucleate giant cells and mononuclear stromal cells in some cases. It is not clear whether the positive cells are to be regarded as neoplastic or reactive and alpha 1-antitrypsin is not considered as a diagnostically useful marker for giant-cell tumor of bone. In malignant fibrous histiocytoma, too, histiocytic cells could be identified by their positive reaction for alpha 1-antitrypsin; some of these cells had the morphologic features of tumor cells. Cells with a positive reaction for lysozyme were rarely found, except in giant-cell tumors of the tendon sheath.     

Matrix Vesicles in Bone Tumors

Bone tumors were categorized into alkaline phosphatase (ALPase)-positive (2 ossifying fibromas, 1 benign osteoblastoma and 16 osteosarcomas) and negative (2 chondromas, 2 chondrosarcomas, 3 non ossifying fibromas, 2 malignant fibrous histiocytomas and 6 giant cell tumors of bone) groups. Production and distribution of matrix vesicles (MVs) in the tumor tissues were examined to clarify their role in neoplastic bone formation. Four distinct types of MV were isolated primarily in ALPase-positive bone tumors: empty, amorphous, crystalline and ruptured MVs. They were formed by budding off from the cytoplasmic projections of the osteoblastic tumor cells. The significance of differences in the production rate of MVs between ALPase positive and negative bone tumors was investigated in view of the predominantly high production of MVs in ALPase-positive bone tumors. Many more mature MVs (crystalline and ruptured) were observed in the osteoblastic lesions of osteosarcoma than in the fibroblastic and MFH-like lesions, suggesting an intimate relationship with maturation and differentiation of the osteoblastic tumor cells. The above findings indicate that production of MVs is one of the diagnostic parameters for osteoblast- derived bone tumors, as well as ALPase activity, and that vesicle-induced mineralization is a major mineralization mechanism in neoplastic bone formation. Acta Pathol Jpn 41: 610-617, 1991.     

Malignant fibrous histiocytoma of bone and osteosarcoma. A comparative light and electron microscopic study.

Malignant fibrous histiocytomas are well-described tumors of the soft tissues. Recent investigations have shown that malignant histiocytoma may also occur as a primary bone tumor. However, difficulties may arise to distinguish malignant histiocytoma of bone from other malignant bone tumors, such as osteosarcoma. In the present study, the ultrastructure of five cases of malignant fibrous histiocytoma of bone is compared with that of osteosarcoma. The results show that malignant fibrous histiocytoma is composed mainly of histiocytic cells and fibroblastic cells. In addition, xanthomatous cells, undifferentiated cells, and giant cells may be observed. By contrast, the predominant cell type in osteosarcoma is the neoplastic osteoblast, characterized by abundant rough endoplasmic reticulum. Signs of matrix calcification in the intercellular matrix between the collagen fibrils are regularly observed in osteosarcoma, but not in malignant histiocytoma. From these results it is concluded that the ultrastructure of malignant fibrous histiocytoma arising in bone is morphologically identical with the soft tissue counterpart of this tumor. The components of the tumor are derived from neoplastic histiocytes. This cytogenesis differs from that of osteosarcoma, which is derived from neoplastic osteoblasts. Therefore, from the ultrastructural point of view, malignant fibrous histiocytoma of bone should be accepted as a distinct histologic entity among bone tumors.     

Characterization of tumor cells in malignant fibrous histiocytomas and other soft-tissue tumors, in comparison with malignant histiocytes. II. Immunoperoxidase study on cryostat sections.

The authors have investigated a possible relationship between tumor cells of malignant fibrous histiocytomas (MFHs) and histiocytes. This relationship was studied by means of immunophenotyping using monoclonal antibodies specific for the monocyte cell lineage (FMC-17, Mac-1, OKM-1, Leu-M1, and lysozyme) and mono- and polyclonal antibodies specific for fibroblasts (respectively, FIB-86 and FSG). The immunophenotypes of the MFH tumor cells were compared with those of tumor cells of "true" histiocytic tumors. Monocyte lineage-specific determinants could be demonstrated in varying amounts on cells of the "true" histiocytic tumors but not on cells of MFH or other soft-tissue tumors. The reverse was true for determinants on fibroblasts. The absence of these determinants on malignant histiocytes, and their presence on MFH (and also on benign fibrous histiocytomas, fibrosarcomas, schwannomas, osteosarcomas, hemangiosarcomas, leio- and rhabdomyosarcomas) supported the conclusion that MFH tumor cells originate from mesenchymal cells which do not belong to the mononuclear phagocytic system. Subdivision of the MFH tumors revealed that the storiform-pleomorphic subtypes could express HLA-Dr/Ia antigens, like histiocytic tumors. The inflammatory cell subtype, however, lacked these antigens.     

Osteocalcin expression in primary bone tumors--in situ hybridization and immunohistochemical study.

Osteocalcin is one of the most abundant noncollagenous proteins found in adult bone. It is a highly conserved gamma-carboxyglutamic acid-containing protein that is believed to be produced exclusively by osteoblasts. In this study, intracellular and extracellular localization of osteocalcin in osteosarcoma was examined with anti-osteocalcin antibody and in situ hybridization using a synthetic oligonucleotide. Immunohistochemically, osteoblastic osteosarcomas were all positive for osteocalcin. The chondroblastic osteosarcomas were positive on the neoplastic chondrocytes. The five fibroblastic osteosarcomas out of seven were positive for osteocalcin immunostaining over the neoplastic spindle cells. Five cases of osteoblastic osteosarcomas out of seven were positive for osteocalcin in situ hybridization. Two cases of chondroblastic osteosarcomas and three cases of fibroblastic osteosarcomas were positive for in situ demonstration of osteocalcin. The malignant tumor giant cells were positive for osteocalcin immunostaining 83%. They were also positive for in situ hybridization. The benign giant cells in five giant cell tumors and five aneurysmal bone cysts were negative for osteocalcin immunostaining. The benign giant cells in three chondroblastoma and three Paget''s disease were positive for osteocalcin. In this study, the osteocalcin in situ hybridization and immunostaining has very important meaning for making differential diagnoses of, especially giant cell rich bone forming tumors.     

Fibrohistiocytic tumors of soft tissues. An immunohistochemical study of 183 cases

183 cases of soft tissue tumors were studied utilizing the immunoperoxidase technique to demonstrate alpha-1-antitrypsin, ferritin and lysozyme. The series comprises 50 malignant lesions, 34 intermediate malignancy lesions, 99 benign lesions of fibrohistiocytic origin, and 23 malignant tumors of non fibrohistiocytic origin. The actual results of the study are as follows: alpha-1-antitrypsin, ferritin and lysozyme were always absent in 10 fibrosarcomas, 2 liposarcomas, 2 Ewing sarcomas, 3 synovial sarcomas, 4 neurofibrosarcomas, and 2 rhabdomyosarcomas, but in 24 malignant fibrous histiocytomas, 34 cases of dermatofibrosarcoma protuberans and 102 benign fibrohistiocytic lesions, these activities were present in a percentage that ranged between 12% and 38% (average 25%). Differences in the frequency of positive reactions did not occur between benign and malignant fibrohistiocytic lesions. The immunohistological examinations carried out have, therefore, only a very limited value for the practical diagnostic evaluation, but, when positive, are important to clarify the histogenesis of the tumor.     

Biologic characterization of human bone tumors. III. Giant cell tumor of bone. A combined electron microscopical, histochemical, and autoradiographical study

The cytogenesis of giant cell tumors of bone was studied in 6 cases by combined electron microscopical, histochemical and autoradiographical investigations. Electron microscopy identified two different types of mononuclear stromal cells: fibroblast-like cells with spindly shape and numerous membranes of the granular ER occur together with macrophages bearing many large lysosomes and a prominent Golgi apparatus. Enzyme histochemical results reflect the same diversity: One portion of mononuclear cells exhibits strong alpha-naphthyl acetate esterase (ANAE) activity, known as a marker for cells of the mononuclear phagocyte system, while the other, fibroblast-like cell type is ANAE negative. Tumor giant cells contain numerous membranes of granular ER, mitochondria, and a few isolated lysosomes. They lack the typical brush border of osteoclasts. Moderate to strong ANAE activity of these giant cells reflects their belonging to the mononuclear phagocyte system. Consequently, the giant cell tumor of bone consists of two different cell types, i.e. fibroblast-like cells and cells of the mononuclear phagocyte system, and so is appraised as a fibrohistiocytic tumor. A new inference from our autoradiographic findings is that tritiated thymidine is incorporated only by mononuclear cells, but not by giant cells. Electron microscopical autoradiography demonstrated that among the mononuclear cells, only fibroblasts are found to proliferate, but not macrophages. Thus, the giant cell tumor of bone is seen as a neoplasm of fibroblastic cells with a strong reactive infiltration of cells from the mononuclear phagocyte system.     

A histiocyte-specific marker in the diagnosis of malignant fibrous histiocytoma. Use of monoclonal antibody KP-1 (CD68)

KP-1 (CD68) is a recently described monoclonal antibody to a cytoplasmic epitope present on tissue histiocytes and macrophages. To determine the specificity and sensitivity of this marker in the evaluation of cases of malignant fibrous histiocytoma (MFH), this reagent and a panel of commercially antibodies were used to stain formalin-fixed paraffin sections from 25 cases of MFH and 25 other tumors, including a variety of soft-tissue sarcomas. Eighteen of 25 cases of MFH stained for KP-1 (72%), whereas all other tumors were negative, including 12 cases of pleomorphic soft-tissue sarcoma other than MFH. The percentage of tumor cells staining for KP-1 varied. In 11 cases KP-1 was only focally present, but staining was of a high intensity and associated with minimal nonspecific or background staining. Pleomorphic histiocytic cells and spindle cells from storiform tumors were strongly decorated with antibodies to KP-1 in most cases, and antigen also was present on tumor giant cells. Although alpha-1-antitrypsin and alpha-1-chymotrypsin stained a higher percentage of cases of MFH (92%), immunoreactivity for these markers also was noted in other tumors. Because of its specificity as a histiocyte marker, KP-1 is a useful component in a panel of antibodies for the characterization of soft-tissue sarcomas and the diagnosis of MFH.     

Osteosarcomas and Ewing's sarcomas

Summary Primary malignant bone tumors, osteosarcomas (9 cases), and Ewing's sarcomas (10 cases) were examined for their reactivities with monoclonal and polyclonal antibodies against filamentous proteins and cell membrane determinants of the lymphoid and macrophage marker series. The reactivity of antibodies was studied on snap-frozen tissue probes by using a triple layer immunoperoxidase method. Osteosarcomas were positive for vimentin and, in part, for HLA-DR. Other types of intermediate-sized filaments were not detected in tumour cells. In a small number of cases (2/9) tumour cells were reactive with antibodies of the macrophage series (Leu M2).In Ewing's sarcomas, vimentin and HLA-DR was also demonstrated. It was particularly interesting that Leu M2 staining was found in the majority of cases (8/10). The staining pattern supports the assumption that this peculiar tumour is of mesenchymal (monocyte/macrophage) histogenesis.It was evident from the present study that, in primary osteogenic tumors, none of the examined tumour markers were as distinctive as they are for bone metastases. Nevertheless, the reactivity of Ewing's sarcoma cells with monoclonal antibodies of the Leu M2 type throws some highlights on the, as yet, obscure histogenesis of the neoplasm and may be of diagnostic value in conjunction with the known light and electron microscope features of the tumour.The study was supported by a grant of the Deutsche Forschungsgemeinschaft (Lo 285/2-2)     

Soft tissue giant cell tumor of low malignant potential: a proposal for the reclassification of malignant giant cell tumor of soft parts.

Although "giant cell tumor of soft parts" has traditionally been considered a single entity as reflected in the original term "malignant giant cell tumor of soft parts (MGCT)" and later by the term "malignant fibrous histiocytoma, giant cell type" the degree of atypia and mitotic activity varies in this group, suggesting biologic heterogeneity. The clinicopathologic features of 31 tumors meeting the traditional criteria of MGCT but having only mild to moderate nuclear atypia are presented. Patients with these tumors (19 females; 12 males) ranged in age from 14 to 84 years (mean, 40 years) and presented with masses of involving either superficial (n = 16) or deep (n = 13) soft tissue. Most occurred on the arm or hand (n = 16) and ranged in size from 0.7 to 6.5 cm (mean, 2.1 cm). The tumors consisted of sheets and nodules of rounded mononuclear cells that blended with spindled cells and benign osteoclastic giant cells. Pleomorphic giant cells were absent. Osteoid was noted in 10 cases, but features typically associated with tenosynovial giant cell tumors (such as dense stromal hyaline, siderophages, and xanthoma cells) were nearly always absent. Mitotic figures ranged from 1-10/10 HPF (mean, 2-3/10 high-powered field), and angiolymphatic invasion was present in 10 cases. Necrosis was absent, however. The mononuclear cells expressed CD68, tartrate-resistant acid phosphatase, and smooth muscle actin, but lacked CD45, S100 protein, desmin, and lysozyme, an immunophenotypic profile identical to that of giant cell tumor of bone. Follow-up information in 19 patients (mean, 3 yrs; median, 1-7 yrs) indicated recurrences in four patients, but none developed metastasis. This behavior contrasts significantly with the high-grade behavior traditionally associated with MGCT of soft parts. These giant cell tumors can be consistently recognized by the lack of cytologic atypia even in the face of mitotic activity and vascular invasion. Although their long term metastatic risk is not fully defined, we propose they be termed "giant cell tumors of low malignant potential" and regarded as the soft tissue analogue of giant cell tumor of bone. The term "malignant giant cell tumor of soft parts" or giant cell malignant fibrous histiocytoma should be restricted to histologically high-grade lesions.     

Immunostaining in atypical fibroxanthoma of the skin

We have studied 12 cases of cutaneous atypical fibroxanthoma using immunohistochemistry to demonstrate lysozyme, alpha-1-antitrypsin, S-100-protein, receptors for peanut agglutinin, and intermediate filaments. Results were compared with immunostaining in 24 cases of other so-called fibrohistiocytic tumours. In addition 2 cases of atypical fibroxanthoma and 6 cases of fibrohistiocytic tumours were stained by monoclonal antibodies specific for the monocyte cell lineage (Ki-M1, Ki-M2, Ki-M6, Ki-M7, Ki-M8, OKM-1 and Leu-M1) and double-stained by monocyte-markers and Ki-67. The immunophenotype of atypical fibroxanthoma was rather similar to the marker profile found in malignant fibrous histiocytoma. All atypical fibroxanthomas were positive for vimentin and negative for epithelial markers. Monocyte lineage-specific determinants could be demonstrated in varying amounts in cells suggestive of being reactive. In contrast proliferating--Ki-67 positive--cells did not express monocyte/macrophage related antigens in atypical fibroxanthoma and malignant fibrous histiocytoma both. As to the histogenesis of these tumours our findings speak in favour of a derivation from primitive mesenchymal cells rather than from histiocytes.