Osteoclast-like giant cell tumor of the liver

A 66-year-old male with osteoclast-like giant cell tumor of the liver that arose in the non-cirrhotic liver is presented. The liver tests were almost normal, and plasma levels of alpha-fetoprotein and carcinoembryonic antigen were within normal limits. The findings of liver scan by 99mTc phytate, celiac angiography, and CT scans are described for the first time for this rare neoplasm, showing a large, unresectable liver tumor. Histologically, the tumor mainly consisted of osteoclast-like giant cells and mononuclear cells, which were focally arranged in a vaguely trabecular pattern and sarcomatous pattern. By an electromicroscopic study, however, no definitive evidence was obtained whether it arose from epithelial cells or nonepithelial cells. Various clinicopathological features were described and compared with previously reported cases including two cases arising in the liver.     

Atypical fibrous histiocytoma of the humerus: a light and electron microscopic study.

A unique osseous tumor, which arose in the humerus of a 44-year-old white man, is reported. The lesion was designated atypical fibrous histiocytoma because of the absence of atypical mitoses despite prominent nuclear pleomorphism of tumor cells. The tumor was composed mainly of spindle cells, tightly packed in a storiform pattern. Clear histiocytes and tumor giant cells were occasionally seen. Toward the proximal and distal ends, the tumor showed increasing fibrogenesis, and the ends were composed of areas of packed clear histiocytes and acellular myxoid matrix with focal calcification. Ultrastructurally, five cell types comprised the tumor, but fibroblast-like cells predominated. Histiocyte-like, xanthomatous, giant and undifferentiated cells were observed only occasionally. The patient has been followed for five years after disarticulation without developing evidence of distant metastasis.     

Diffuse type of giant-cell tumor of tendon sheath: an ultrastructural study of two cases with cytogenetic support

Two cases of the diffuse type of giant-cell tumor of the tendon sheath (GCTTS) are described. Both tumors arose in the vicinity of large joints of the lower extremity, showing similar clinical and radiological features. Histologically, a proliferation of polygonal mononuclear cells was seen, together with osteoclastlike giant cells, foam cells, and siderophages. The tumors were poorly delineated, displaying an infiltrative pattern into the neighboring soft tissues. Immunohistochemically, strong expression of vimentin, neuron-specific enolase, A 1 -antitrypsin, and CD68 was found in both mono- and multinucleated tumor cells. At the ultrastructural level, mononuclear cells revealed a diverse morphology, displaying features of histiocytelike and fibroblastlike cells, with the former being more numerous. Scarce neurosecretorylike granules, made up of electrondense membrane-bound material, were found in the cytoplasm of the mononuclear cells. Cytogenetic analysis of one case shows the presence of a clonal population with 47 chromosomes and two different translocations, t(2;3) and der(8) t(8;12). Present findings provide further support regarding the neoplasic nature of this tumoral entity.     

Histological and clinical characteristics of malignant giant cell tumor of bone

Malignant giant cell tumors of bone (MGCTB) are rare, and the diagnosis can be difficult due to the occurrence of a variety of malignant tumors containing giant cells. To better understand its clinicopathological features, we have reviewed our experience with 17 cases of MGCTB. Five cases were primary malignant giant cell tumor of bone (PMGCTB), and 12 cases were giant cell tumors of bone initially diagnosed as benign but malignant in a recurrent lesion (secondary MGCTB, SMGCTB). The patients included six women and 11 men (age ranged from 17 to 52 years; mean, 30.5 years). The tumor arose in the femur (six cases), the tibia (seven cases), the humerus (three cases), and the fibula (one case). Microscopically, PMGCTB showed both conventional giant cell tumor and malignant sarcoma features. SMGCTB were initially diagnosed as conventional giant cell tumor of bone, the recurrent lesion showing malignant features. Histologically, the malignant components included osteosarcoma (11 cases), undifferentiated high-grade pleomorphic sarcoma (two cases), and fibrosarcoma (four cases). SMGCTB cases showed strong expression of p53. Follow-up information revealed that four patients died of lung metastasis, two patients are alive with lung metastases, and 11 patients are alive without tumor. MGCTB should be considered as a high-grade sarcoma. It must be distinguished from GCTB and other malignant tumors containing giant cells. p53 might play a role in the malignant transformation of GCTB.     

Giant-cell tumor of bone arising from the falx cerebri. A case report

The histological and ultrastructural features of a giant-cell tumor of bone arising in the falx cerebri of a 27 year-old man are described. The tumor was embedded in the medial aspect of the left frontal lobe and was not attached to any of the bones of the skull. At surgery, the tumor was lightly adherent to the falx and was easily extracted. Histologically, the tumor was composed of mononuclear spindle-shaped and ovoid stromal cells, multinuclear giant cells containing 20-30 nuclei, and foci of osteoid and bone production. Hemorrhagic and cystic areas were also present within the tumor. Ultrastructurally, the spindle-shaped cells resembled fibroblasts and were surrounded by small bundles of collagen fibrils. The ovoid cells contained numerous mitochondria, abundant rough endoplasmic reticulum, vesicles, lysosomes, phagosomes and osseous material in the cytoplasm suggesting their monocyte-macrophage lineage. These cells were closely apposed and displayed evidence of fusion in the form of focal and linear subplasmalemmal densities to form multinucleated giant cells with similar organelles and multiple nuclei. It is suggested that the primary giant cell tumor of the one arose from the metaplastic ossification of the falx. To our knowledge, a giant-cell tumor of bone arising from the falx cerebri has not been previously described.     

Stromal osteoclast-like giant cells in an adenosquamous carcinoma of the gallbladder.

We report a case an adenosquamous carcinoma of the gallbladder that extended to the proximal transverse colon. Metastatic tumor was present in regional lymph nodes and the liver. Microscopically, the tumor was composed of malignant epithelial cells that were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-positive. The adjacent desmoplastic stroma of the primary tumor, as well as the metastasis, contained giant cells that morphologically resembled osteoclasts. Immunohistochemical studies showed that the giant cells were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-negative but weakly alpha 1-antichymotrypsin-positive. While tumors containing osteoclast-like giant cells have been described in the breast, lung, liver, and thyroid, this is the first report of a tumor with this morphology originating in the gallbladder. The presence of the giant cells adjacent to both the primary and metastatic tumor and not at any other location suggests that the tumor cells are producing a substance that induces the formation of the nontumoral giant cells.     

Endoscopic ultrasound-guided fine-needle aspiration of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a report of 2 cases with literature review

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas is rare. Histologically it mimics the giant cell tumor of the bone and may be associated with a ductal adenocarcinoma. We recently encountered two such cases, both of which were biopsied by EUS-guided FNA. Abundant multinucleated osteoclast-like giant cells and many uniform mononuclear cells were present in case 1 so that the diagnosis was made. In case 2, many mononuclear tumor cells with vacuolated and basophilic cytoplasm were present, and rare osteoclast-like giant cells were seen. A diagnosis of adenocarcinoma was made. In both cases, no conspicuous nuclear pleomorphism was noted in the mononuclear cells or the multinucleated giant cells. The histology of case 2 revealed a pure undifferentiated carcinoma with osteoclast-like giant cells. In addition, a liver biopsy revealed globular amyloidosis. To our knowledge, this is the first report of pancreatic undifferentiated carcinoma with osteoclast-like giant cells sampled by EUS-guided FNA and the first case of hepatic globular amyloidosis associated with this tumor.     

Undifferentiated (embryonal) sarcoma of the liver in middle-aged adults: smooth muscle differentiation determined by immunohistochemistry and electron microscopy

Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare pediatric liver malignancy that is extremely uncommon in middle-aged individuals. We studied 2 cases of UESL in middle-aged adults (1 case in a 49-year-old woman and the other in a 62-year-old man) by histology, immunohistochemistry, and electron microscopy to clarify the cellular characteristics of this peculiar tumor. One tumor showed a mixture of spindle cells, polygonal cells, and multinucleated giant cells within a myxoid matrix and also revealed focal areas of a storiform pattern in a metastatic lesion. The other tumor was composed mainly of anaplastic large cells admixed with few fibrous or spindle-shaped components and many multinucleated giant cells. In both cases, some tumor cells contained eosinophilic hyaline globules that were diastase resistant and periodic acid-Schiff positive. Immunohistochemically, the tumor cells showed positive staining for smooth muscle markers, such as desmin, alpha-smooth muscle actin, and muscle-specific actin, and also for histiocytic markers, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, and CD68. Electron microscope examination revealed thin myofilaments with focal densities and intermediate filaments in the cytoplasm of tumor cells. Our studies suggest that UESL exhibits at least a partial smooth muscle phenotype in middle-aged adults, and this specific differentiation may be more common in this age group than in children. Tumor cells of UESL with smooth muscle differentiation in middle-aged adults show phenotypic diversity comparable to those of malignant fibrous histiocytoma with myofibroblastic differentiation.     

Combined hepatocellular carcinoma and osteoclast-like giant cell tumor of the liver: Possible clue to histogenesis

Hepatic giant cell tumor is extremely rare, and only five cases have been reported of overt hepatocellular carcinoma, thus its histogenesis is controversial. Herein is reported a case of simultaneous hepatocellular carcinoma and osteoclast-like giant cell tumor in a single tumor. A liver tumor was found in a 74-year-old woman. Histologically the tumor consisted of two distinct components: mononuclear and multinuclear giant cells with osteoclastic giant cells, and a conventional hepatocellular carcinoma. The boundary between the two components showed transitional features. Immunohistochemistry showed that the osteoclast-like giant cells were CD68 and vimentin positive, but cytokeratin and AFP negative, while spindle-shaped cells were positive only for vimentin. In a portion of the hepatocellular carcinoma the cells were cytokeratin-8 and AFP positive. Ki-67 positivity was 10% for the hepatocellular carcinoma, 60% for the spindle-shaped cells, and 0% for the giant cells. It is possible that the tumor might have had a hepatocellular carcinoma origin, given the more highly proliferative sarcomatous changes and reactive osteoclast-like cells. This case provides a clue to the histogenesis of hepatic giant cell tumors.     

Histologic growth pattern of hepatocellular carcinoma: relationship to orcein (hepatitis B surface antigen)-positive cells in cancer tissue

The histologic pattern of tumor growth at tumor-nontumor boundaries was studied in 60 livers bearing hepatocellular carcinoma. Three growth patterns, arbitrarily described as "sinusoidal," "replacing," and "encapsulated," were distinguished. Cancer cells growing in the sinusoids between liver cell cords (sinusoidal pattern) were anaplastic; those growing in an expansile fashion and acquiring a fibrous capsule (encapsulated pattern) were most differentiated; and those growing into the cord of liver cells and replacing them (replacing pattern) were differentiated to an intermediate degree. There was certain relation between the histologic growth patterns and gross morphologic features of the tumors. Test results for 20 of the 60 cases were positive for serum hepatitis B surface antigen (HBsAg), and the livers also contained orcein-positive cells. Orcein-positive cells were frequently seen at the border between tumor and parenchyma. Cells containing HBsAg as an orcein-positive inclusion were present in cancer tissue in three cases. When serial sections were made from such areas and stained alternately with hematoxylin and eosin and orcein, it was found that these cells were hepatocytes blended with cancer cells. This phenomenon was related to the growth pattern of tumor cells. Orcein-positive cells were never found in metastatic lesions.     

Comparison of cytologic features of giant-cell tumor and giant-cell tumor of tendon sheath

The cytologic features in twelve cases of giant-cell tumor (GCT) and five cases of giant-cell tumor of tendon sheath (GCTTS) diagnosed by fine-needle aspiration cytology (FNAC) are described. All of these cases were histopathologically confirmed. The aspirates of GCT are composed of a dual population of mononucleated spindle cell and multinucleated giant cells. The peripheral adherence of giant cells to the spindle cell is the feature of diagnostic significance in GCT. In GCTTS, the aspirate consists of a polymorphic population composed of mononuclear histiocyte-like cells, hemosiderin laden macrophages, foamy macrophages, and a few multinucleated giant cells. FNAC can be used as a diagnostic tool for an early and accurate detection of these two giant cell-rich lesions, since the cytologic features when evaluated in conjunction with the clinical and radiologic features are sufficiently diagnostic.     

Tenosynovialer Riesenzelltumor

Morphological, ultrastructural, and immunohistochemical findings of 12 diffuse type-tenosynovial giant cell tumors/pigmented villonodular synovitis are presented compared to 30 localized tenosynovial giant cell tumors (giant cell tumor of tendon sheath). Diffuse-type-tenosynovial giant cell tumor is characterized by a striking vascularisation pattern composed of densely arranged thin-walled, partly slit-like and partly hyalinized small blood vessels within the papillary synovial fronds. These vessels may show abnormal structures with incompletely arranged endothelial cells/pericytes. The fibrohistiocytic tumor cells probably cause considerable compression/distortion or destruction of the small vessels which might be responsible for an increased blood deposition and massive hemosiderosis. Accompanying multinucleated osteoclast-like giant cells seemingly are recruited from circulating blood monocytes. Microhemorrhagic foci with multinucleated giant cells could be detected in 83% of diffuse-type and 67% of localized-type tumors. Apart from the described vessels, typical morphological findings in diffuse-type tenosynovial giant cell tumors included "giant" hemosiderotic granules, (at least 2-3 times the diameter of an erythrocyte) "giant" siderophages, pseudoalveolar clefts and irregularly anastomosing synovial fronds. Neither mitotic rate nor the amount of giant cells/amount of nuclei of giant cells revealed statistically significant differences between localized-type and diffuse-type of tenosynovial giant cell tumor. Immunohistochemically, the diffuse-type exhibited focal expression of CD31 (in 75% of tumors) and calretinin (in 63%) besides CD68-staining.     

Histiocytic sarcoma in Wistar rats. A light microscopic, immunohistochemical, and ultrastructural study

Histiocytic sarcoma, a recently described tumor entity in rats, was studied by light microscopy in 20 male and female Wistar rats. The tumors originated from subcutaneous tissues; metastasis involved primarily the liver with sinusoidal spread and the lungs with peribronchiolar distribution. The characteristic features of this tumor were the uniform population of tumor cells, palisading necrosis, and abundant multinucleated giant cells. Immunocytochemical and ultrastructural findings confirmed the histiocytic nature of the tumor cells.     

Hepatoid adenocarcinoma of the stomach with multi-nucleated giant cell proliferation in a 100-year-old man

Few cases of gastric carcinoma with infiltrating multi-nucleated giant cells (MGCs) have been reported, and giant cells infiltrating the gastric carcinoma were previously described as osteoclast-like giant cells (OGCs). However, hepatoid adenocarcinomas have never been reported previously, and the present case is extremely rare. A 100-year-old Japanese man with gastralgia was found to have a mass in his gastric body. Histological examination showed a poorly differentiated adenocarcinoma with infiltration of MGCs. Vascular and lymphatic invasion were noted but there were no metastases. Almost all the tumor comprised cells with hepatoid-like features. The MGCs proliferated, with infiltration of lymphoid cells. A few MGCs contained mucous material in their cytoplasm, indicating these were foreign-body giant cells. Immunohistochemically, the hepatoid-like components were positive for AFP, and staining with polyclonal antibodies against carcinoembryonic antigen (CEA) showed the canalicular pattern. We concluded that this component was hepatoid adenocarcinoma. The MGCs were positive for CD68, and surrounding infiltrating lymphoid cells were diffusely positive for CD3. Infiltration of MGCs in gastric cancer may represent a cellular immune response against gastric cancer invasion. Further studies are required to elucidate the etiology of MGCs in gastric cancer.     

Synovial sarcoma: an immunohistochemical study

The immunohistochemical staining pattern of 18 cases of synovial sarcoma with two epithelial-specific monoclonal antibodies is described. This is compared with normal synovium, cases of giant cell tumour of tendon sheath (benign synovioma) and a variety of spindle celled sarcomas. Sixteen cases of synovial sarcoma showed staining of the epithelial component with at least one antibody. No staining was seen in normal synovium or in giant cell tumours of tendon sheath. A small number of malignant schwannomas contained groups of cells which stained positively whilst other spindle cell sarcomas either did not stain or showed 'cross-reaction' type staining only. These results add weight to the proposition that synovial sarcomas do not arise from normal synovium, despite their morphological similarities, but from mesenchymal connective tissue. It is also shown that immunohistochemical staining with anti-epithelial antibodies will emphasize the biphasic pattern of synovial sarcomas allowing their distinction from other sarcomas.     

Osteoclast-like giant cell tumor of the pancreas: immunophenotypic similarity to giant cell tumor of bone

An immunophenotype was performed on an osteoclast-like giant cell tumor of the pancreas using a panel of antibodies to epithelial and leukocyte antigens. Several antibodies to cytokeratin and carcinoembryonic antigen were negative in the tumor. Osteoclast-like cells were positive for CD4, CD13, CD45, CD68, CD71, and vimentin, but negative for lysozyme and HLA-DR. Mononuclear tumor cells were positive for CD4, CD11c, CD13, CD14, CD45, CD68, CD71, HLA-DR, and vimentin, but negative for lysozyme. The phenotype is similar to that previously described for giant cell tumor of bone. The osteoclast-like cell phenotype is also similar to that reported for normal osteoclasts. The findings support a nonepithelial origin for osteoclast-like giant cell tumor of the pancreas, and suggest a derivation similar to giant cell tumor of bone.     

Pleomorphic giant cell carcinoma of the prostate

We report the clinical and pathologic features of 2 cases of pleomorphic giant cell carcinoma of the prostate. One case was found at autopsy in a 77-year-old man and was composed of high-grade prostatic adenocarcinoma with prominent anaplastic giant cells. The patient presented with metastases to multiple retroperitoneal lymph nodes, liver, and lumbar vertebrae. The second case occurred in a 45-year-old man who underwent transurethral resection of the prostate and was found to have high-grade prostatic adenocarcinoma with an extensive anaplastic giant cell component. The patient presented with distant metastases and died within 9 months. Both regular adenocarcinoma and anaplastic giant tumor cells displayed cytoplasmic immunoreactivity for prostate-specific antigen, prostatic acid phosphatase, and keratin AE1/AE3; in one case, scattered cells were also positive for chromogranin and epithelial membrane antigen. Pleomorphic giant cell carcinoma is a rare variant of prostatic adenocarcinoma with a poor prognosis that should be considered in the differential diagnosis of prostatic pleomorphic tumors.     

Histological and immunohistochemical observations of dedifferentiated leiomyosarcoma of the uterus.

A case of dedifferentiated leiomyosarcoma of the uterus was examined using immunohistochemistry. The tumor arose in the myometrium, and was a whitish large nodule with hemorrhage and necrosis. Histologically it was a well differentiated leiomyosarcoma with foci showing epithelioid pattern, and in part resembling malignant fibrous histiocytoma (MFH) and giant cell tumor (GCT). Additionally, small round neoplastic cells arranged in an alveolar manner, simulating alveolar rhabdomyosarcoma, were seen in some areas. Neoplastic cells in well differentiated areas expressed desmin, muscle-specific actin and LeuM1, whereas those in epithelioid and poorly differentiated areas lacked these antigens. Instead, tumor cells in epithelioid and small round cell areas were positive for keratin. Interestingly, most tumor cells in well differentiated, epithelioid and small round cell areas were also positive for MB1. However, tumor cells in GCT- and MFH-like areas reacted with none of the antibodies used. Ultrastructurally, some tumor cells possessed various amounts of microfilaments with or without dense patches, whereas others lacked them. These findings suggest that the divergent antigen expression was attributable to different levels of differentiation, and that poorly differentiated components had lost their native features.     

The ultrastructure of nuclear inclusions in the giant-cell tumor of bone

The ultrastructural study of three cases of giant-cell tumor of bone showed two types of nuclear inclusions. The first type, common to giant cells and stromal cells was granular, and sometimes associated with a fibrillar pattern observed only in giant cells. The second type was represented by nuclear bodies, encountered mostly in the stromal cells. The nuclear bodies were made up of a granular core enveloped in a multilayered coat. The nature of these nuclear inclusions might be viral and thus a viral pathogenesis of the giant-cell tumor of bone is discussed.