A case of malignant tumor of the ascending part of duodenum with osteoclast-like giant cells

Extraskeletal neoplasms with osteoclast-like giant cells are very rare. These tumors are most frequently reported in the breast and pancreas, and but rarely in other sites. We report a case of duodenal malignant tumor with osteoclast-like giant cells. The patient was a 76-year-old man who presented with vomiting. Computed tomography, magnetic resonance imaging, and gastrointestinal endoscopy revealed a giant tumor in the ascending part of duodenum. Biopsy specimens showed an undifferentiated malignant tumor with benign multinucleated giant cells. Immunohistochemical staining indicated that the tumor cells were reactive with vimentin, but not with epithelial markers or the other mesenchymal markers, and the multinucleated giant cells were reactive with CD68. Thus, we diagnosed a malignant tumor of the ascending part of duodenum with osteoclast-like giant cells. To the best of our knowledge, this is the first case of duodenal malignant tumor with osteoclast-like giant cells in Japan.     

A case of osteoclast-like giant cell tumor of the pancreas]

Osteoclast-like giant cell tumor of the pancreas is a very rare tumor. Despite their striking morphologic resemblance to certain mesenchymal tumors of bone and tendon sheath, it has been suggested that these tumors may arise from epithelial precursors. This unusual tumor presents in the 6th or 7th decade with a nearly equal gender ratio. Pure forms of osteoclast-like giant cell tumor have a better prognosis because they have a predilection to local spread, are slower to metastasize and rarely metastasize to lymph nodes, but these forms are very rare. We present an osteoclast-like giant cell tumor arising in the body of the pancreas in a 71 year-old male patient. The tumor was composed of two major cell types: atypical mononuclear cells and abundant osteoclast-like multinucleated giant cells. Immunohistochemical studies showed that atypical cells were strongly reactive for vimentin and focally reactive for cytokeratin. In contrast, the giant cells were immunoreactive for CD68, but negative for cytokeratin. Three months later, the tumor size increased and liver metastasis was newly developed. He died at 11 months after the diagnosis.     

A case report of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and literature review

Osteoclast-like giant cell tumors rarely arise in the pancreas. Here we report the case of a 78-year-old woman who was diagnosed with a well-defined 3 cm multilocular mass in the pancreatic body by the use of ultrasonography, computed tomography and magnetic resonance imaging. The rim and the septa of the tumor were well enhanced. The distal pancreas was removed with the spleen and the peripancreatic lymph nodes. Macroscopically, the mass was composed predominantly of a multilocular cystic tumor filled with hemorrhagic necrosis, and partly composed of solid components. A histopathological study showed a proliferation of multinucleated osteoclast-like giant cells and spindle cells. Although the predominant tumor cells were strongly positive for vimentin and CD68 and negative for epithelial markers, there were some sparsely scattered cytokeratin-positive neoplastic glands. Seventeen months after surgery, the patient is still alive and has had no recurrence. Below we review 32 cases of osteoclast-like giant cell tumor of the pancreas that have been reported in English literature since 2000.     

Pleomorphic carcinoma of the pancreas with osteoclast-like giant cells

Summary We studied two cases of pleomorphic carcinoma of the pancreas with osteoclast-like giant cells. The cut surface of both tumors was firm and whitish-tan in color, with extensive hemorrhage and necrosis. Microscopically, these tumors were composed mainly of pleomorphic mononuclear cells and numerous bizarre giant cells, with a spindle-cell sarcomatoid appearance and adenocarcinomatous elements exhibiting varying degrees of differentiation. Multinucleated giant cells resembling osteoclasts were frequently located around sites of necrotic hemorrhage. Immunohistochemically, most tumor cells of sarcomatous areas and some anaplastic giant cells were positive for vimentin and cytokeratin. Both carcinoembryonic antigen and CA 19-9 were detected in tumor cells in one case, forming ducts or glands. These findings suggest that the tumors in these two cases originated from pancreatic-duct cells with mesenchymal differentiation. In contrast, osteoclast-like giant cells in both cases showed strong immunoreactivity with vimentin and with KP1 and PG-M1 (CD68), which are monoclonal antibodies that react with a histiocyte-macrophage-associated antigen; however, there was no reaction with any epithelial markers. Thus, osteoclast-like giant cells are not epithelial in nature, suggesting that their origin of histiocyte-macrophage lineage is possibly induced as a paraneoplastic product.     

Mixed pleomorphic-osteoclast-like tumor of the pancreas

Summary The morphological, immunohistochemical, and molecular biological features of a case of giant cell tumor of the pancreas are described. This neoplasm showed mononuclear and multinucleated tumor giant cells as well as numerous osteoclast-like cells with multiple foci of osteoid-osseous metaplasia. The pleomorphic and osteoclastic giant cells displayed extensive homologies in their immunohistochemical profiles. Neither the pleomorphic nor osteoclast-like portion of the tumor showed neither c-Ki-ras nor p53 mutation and did not express the mutated p53 protein. The results suggest that the pleomorphic and osteoclast-like components are histogenetically related and that this rare neoplasm originates from a precursor cell capable of differentiating along divergent cell type.     

Osteoclast-like giant cell tumor (OGCT) of the liver: report of a case

A 57-year-old man presented with jaundice. Abdominal computed tomography showed a 10-cm left hepatic lobe heterogeneous solid mass with low attenuated areas in the mass, multiple liver metastases and lung metastasis. Serology for hepatitis B and C were negative. Serum alpha-fetoprotein, CEA and CA19-9 were normal. The patient died a few weeks later of progressive liver failure and an autopsy was performed. Histologically, the tumor consisted of sarcomatoid mononuclear cells and osteoclast-like giant cells. The liver tissue surrounding the tumor showed no cirrhotic pattern. The osteoclast-like giant cells were uniformly and strongly immunoreactive with CD68. The mononuclear cells demonstrated expression of vimentin but were negative for CAM5.2. The MIB-1 index was 20% for the mononuclear cells. In conclusion, the histopathological diagnosis revealed an osteoclast-like giant cell tumor of the liver.     

Osteoclast-like giant cell tumor of the pancreas associated with mucus-secreting adenocarcinoma. Case report and discussion of the histogenesis.

BACKGROUND/AIMS: The osteoclast-like giant cell tumor of the pancreas is a rare entity that closely resembles giant cell tumor of the bone, which has also been observed in many other organs. Some tumors also contain areas of ductal adenocarcinoma. Conflicting opinions exist regarding the tumor origin, whether it is mesenchymal or epithelial, neoplastic or reactive. METHODS: We report the case of a 69-year-old Brazilian man with a mass in the head of the pancreas, the histological examination of which revealed a predominant component of osteoclast-like giant cells within a background of pleomorphic mononuclear cells with osteoid formation and other areas composed of conventional mucus-secreting adenocarcinoma. RESULTS: Immunohistochemistry showed that carcinoma cells of the usual type expressed epithelial antigens (EMA and cytokeratin) and lysozyme; the giant cells expressed vimentin, CD45, CD68, and lysozyme; and the mononuclear cells expressed macrophage marker (HAM56), vimentin, and lysozyme, and only some of them expressed epithelial markers, CD45, and CD68. CONCLUSION: Our immunohistochemical findings reveal that the giant cells in this case are of mesenchymal origin may be from the bone marrow cells. We believe that it is important to determine the histogenesis in each case to carry out the pertinent adjuvant therapy.     

Human giant cell tumors of the bone (osteoclastomas) are estrogen target cells.

The decrease in estrogen levels that follows the onset of menopause results in rapid bone loss and osteoporosis. The major effect of estrogen deficiency on bone metabolism is an increase in the rate of bone resorption, but the precise mechanism by which this occurs remains unresolved. A recently developed technique for the isolation of avian osteoclasts has been modified to obtain highly purified multinucleated cells from human giant cell tumors. These osteoclast-like cells have been examined for evidence of estrogen receptors (ERs) and responses to 17 beta-estradiol (17 beta-E2). Analysis of giant-cell RNA demonstrated expression of ER mRNA. Furthermore, immunoblot analysis revealed that the giant cells contained a 66-kDa protein that was recognized by a monoclonal antibody specific for the human ER. When isolated multinucleated cells were cultured on slices of bone, there was a dose-dependent decrease in resorption in response to treatment detectable at 10 pM 17 beta-E2. Treatment with 10 nM 17 alpha-estradiol or vehicle (control) did not inhibit resorption. Moreover, the multinucleated cells isolated from these tumors had decreased mRNA levels for cathepsin B, cathepsin D, and tartrate-resistant acid phosphatase (TRAP) as well as secreted cathepsin B and TRAP enzyme activity in response to treatment with 10 nM 17 beta-E2. In contrast to these data, no change in gene expression was detected in mononuclear cells from these tumors in response to 17 beta-E2 treatment. These data support the proposition that human osteoclasts are target cells for estrogen and that estrogen can inhibit bone resorption by human osteoclasts.     

Gastric stromal tumor with osteoclast-like multinucleated giant cells during Lynch II syndrome

We report an unusual case of gastric tumor: a stromal tumor with osteoclast-like giant cells. This type of cells has been described in epithelial tumors, especially in adenocarcinoma of the pancreas, lung, thyroid and breast. It has also been reported in smooth cell tumors such as uterine leiomyosarcoma and malignant fibrous histiocytoma. In our patient, this gastric stromal tumor with osteoclast-like giant cells was diagnosed in a man with adenocarcinoma of the colon in the context of a familial cancer syndrome. This is the first report of stromal tumor with osteoclast-like giant cells associated with Lynch syndrome.     

The nature of giant cell tumor of bone

Giant cell tumor of bone (GCT) is a locally osteolytic tumor with variable aggressiveness. In rare cases, pulmonary metastasis can be observed. The lesion most frequently occurs in the epiphysis of long tubular bones of the knee region, predominantly affecting young adults after closure of the growth plate. The characteristic histological appearance of GCT displays a high number of osteoclast-like multinucleated giant cells, which resulted in the classification "osteoclastoma" or "giant cell tumor". Apart from the multinucleated giant cells, there are two mononuclear cell types in GCT. The first one has a round morphology and resembles monocytes. The second cell type is the spindle-shaped, fibroblast-like stromal cell. Cell culture experiments with GCT cells revealed the stromal cell to be the proliferating component of the GCT. The other two cell types, the monocyte and the multinucleated giant cell, were lost after a few cell culture passages. Furthermore, latest results from GCT reveal that the stromal cells secrete a variety of cytokines and differentiation factors, including MCP1, ODF, and M-CSF. These molecules are monocyte chemoattractants and are essential for osteoclast differentiation, suggesting that the stromal cell stimulates blood monocyte immigration into tumor tissue and enhances their fusion into osteoclast-like, multinucleated giant cells. The multinucleated giant cell itself resembles a normal osteoclast that is able to resorb bone leading to extended osteolysis. This new model of GCT genesis supports the hypothesis that the stromal cell is the neoplastic component whilst the monocytes and the multinucleated giant cells are just reactive components of this tumor. Taking this into consideration, the nomenclature of the "giant cell tumor" needs to be reconsidered.     

Gastric carcinoma with osteoclast-like giant cells

Extraskeletal neoplasms with osteoclast-like giant cells are uncommon. These tumors are most frequently reported in the breast and pancreas, and are relatively rare in other sites. We report a case of primary gastric adenocarcinoma with an infiltrate of osteoclast-like giant cells. The patient is a 64-yr-old black woman who presented with epigastric pain and was found to have a mass in the gastric antrum. Histological examination showed a poorly differentiated adenocarcinoma with an infiltrate of osteoclast-like giant cells. The giant cells were present both in the primary gastric adenocarcinoma and in the lymph node metastases. Immunohistochemical stains demonstrated that the giant cells were of monocytic/histiocytic origin and probably represent a distinctive host response to the tumor. The patient is alive and well 12 months after resection. This is the second published report of gastric carcinoma with osteoclast-like giant cells. Based on this limited experience, gastric carcinoma with osteoclast-like giant cells may represent a distinct clinicopathological entity with a more favorable prognosis.     

Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma

Summary We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The finding of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor.     

Successful treatment of multicentric reticulohistiocytosis with alendronate: evidence for a direct effect of bisphosphonate on histiocytes

We describe the case of a 44-year-old Japanese woman with severe nodular erythematous skin lesions and arthritis mutilans who was admitted for further treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies showed heavy infiltration with tartrate-resistant acid phosphatase-positive histiocytes and multinucleated giant cells. Immunohistochemical analysis showed that some of the mononuclear cells in the skin were positive for RANKL. After 1 month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a week intravenously for the first 6 weeks and then once a month thereafter, the arthritis and skin nodules improved, and the remission has continued for more than 2 years. The findings in this patient suggest that osteoclast-like multinucleated giant cells differentiate locally in the skin from infiltrating histiocytes with the help of RANKL-positive stromal cells and that alendronate acts directly on cells of monocyte/macrophage lineage in humans. Thus, alendronate should be added to the list of drugs for the treatment of multicentric reticulohistiocytosis.     

A case of choledochal cyst associated with adenocarcinoma exhibiting sarcomatous features

One complication of choledochal cyst in adulthood is the development of secondary carcinoma, usually well-differentiated adenocarcinoma. We report a case of extrahepatic bile duct carcinoma associated with choledochal cyst and presenting predominantly sarcomatous features. The patient was a 52-year-old female who presented with abdominal fullness and pain. Ultrasound (US), computed tomography (CT), and cholangiography revealed a choledochal cyst with a tumor. The resected choledochal cyst was 10×7.5 cm and contained a protruding, ulcerated tumor, measuring about 4.0×2.5 cm. Histologically, the tumor was composed of spindle-shaped or fusiform cells with occasional pleomorphic or bizarre giant cells and abundant fibrous stroma, similar to malignant mesenchymal tumors. However, further histologic and immunohistochemical examination revealed that the tumor was adenocarcinoma with prominent sarcomatous features. To our knowledge, sarcomatous change in extrahepatic bile duct carcinoma associated with choledochal cyst has not been previously described.     

Carcinoid Tumor of the Common Bile Duct: Evidence for Its Origin in Metaplastic Endocrine Cells

Carcinoid tumors of the extrahepatic bile ducts are extremely rare neoplasms. The authors report the case of a 36-yr-old male patient with a carcinoid tumor that arose in the common hepatic bile duct. The non-neoplastic mucosa showed areas of gastric and intestinal metaplasia that included scattered argyrophil endocrine cells. Since the normal mucosa of the bile ducts lacks the latter type of cells, this case provides evidence for the first time that carcinoid tumors of this anatomic site probably originate from metaplastic endocrine cells.     

A case of primary small cell carcinoma arising from the common bile duct]

Small cell carcinoma is usually seen in the lung, but rarely involves the gastrointestinal tract including biliary tract. A 65 year-old man was admitted because of obstructive jaundice. A smooth-surfaced round intraluminal mass with proximal bile duct dilatation was seen in the proximal common bile duct on endoscopic retrograde cholangiogram. Under the diagnosis of bile duct cancer, pylorus-preserving pancreatoduodenectomy was done. Pathology revealed a 2 cm sized small cell carcinoma in the proximal common bile duct and distal common hepatic duct. On immunohistochemical stain, the tumor cells were positive for neuroendocrine markers CD56 and synaptophysin. After surgery, the patient received 5 cycles of adjuvant chemotherapy with VIP (etoposide, ifosfamide, and cisplatin) regimen. However, the patient died of liver metastasis 12 months after the diagnosis. We report a case of extrapulmonary small cell carcinoma arising from the common bile duct.     

"Duodenal intussusception" due to adenoma of the papilla of Vater

The case of a 55-year-old woman with a pedunculate adenoma of the papilla of Vater is presented. Diagnostic imaging modalities including ultrasonography, CT scan, magnetic resonance of cholangiopancreatography, simultaneous duodenography and cholangiography, and angiography showed a giant tumor protruding intraluminally and moving forward in the duodenum by peristalsis. It had a duodenal intussusception-like appearance, with remarkable left-lower deviation of the common bile duct and major pancreatic duct in the papilla of Vater as far as the left side of the aorta. Episodes of jaundice or ileus were absent, probably because the tumor was mobile in the duodenum. As biopsy specimens showed no malignancy and intraductal ultrasonography in the common bile duct revealed no intraductal invasion of the tumor in the papilla of Vater, the patient underwent transduodenal papillectomy with papilloplasty with pancreatic ductoplasty. Pathological diagnosis of consecutive specimens was a papillary adenoma with moderate atypia and occasional tubular structure. There seems to be an exceptional subtype of the tumor in the papilla of Vater, like this case, demonstrating the duodenal intussusception-like appearance without prominent clinical symptoms.     

Primary malignant peripheral nerve-sheath tumor of the common bile duct

Primary malignant peripheral nerve-sheath tumors of the common bile duct are extremely rare. To our knowledge, the published literature contains no previous case report of this disease. Here we report on a 58-year-old Japanese woman with a primary malignant peripheral nerve-sheath tumor of the common bile duct, which was completely resected. A hypoechoic mass was identified in the hepatic hilus, using ultrasonography and computed tomography. Endoscopic retrograde cholangiography revealed a smooth stricture and deviation of the common bile duct. Laparotomy exposed a firm mass around the common bile duct that had not invaded the surrounding tissues. Partial resection of the common bile duct and cholecystectomy were performed as the treatment of choice. The final histopathological diagnosis was malignant peripheral nerve-sheath tumor arising from the wall of the common bile duct.     

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas]

Undifferentiated carcinoma with osteoclast-like giant cells is a rare neoplasm of exocrine pancreas. Till recently, some cases have been reported, however histogenesis of the tumors are controversial and their characteristic findings have not been described yet. Thirty five-year-old men and 75-year-old men were presented with upper abdominal pain and a palpable mass. On computed tomography, one case showed a well enhancing solid tumor with low density and the other was showed a mainly cystic tumor with peripheral enhancement in the body and tail of the pancreas. One case accompanied multiple metastatic liver masses with subhepatic lymph node enlargement. Tumor staining was seen on angiography. Biopsy and pancreatectomy were performed. Pathological findings revealed tumors composed of neoplastic spindle shaped or pleomorphic large cells with scattered non-neoplastic osteoclast-like giant cells. In one case, there were small foci of adenocarcinoma components in the periphery of the tumor. On immunohistochemical stain, neoplastic cells showed focal positivity for epithelial membrane antigen and vimentin. Tumors were diagnosed as undifferentiated carcinoma with osteoclast-like giant cells. We report these rare cases with a review of literature.     

Gallbladder carcinoma with osteoclast-like giant cells

Extraskeletal tumors containing multinucleated, osteoclast-like giant cells (OGCs) are uncommon. These neoplasms are most frequently reported in the breast and pancreas. Recently, some authors have suggested that carcinomas containing OGCs may represent a distinct clinicopathological entity with a more favorable prognosis. Occurrence in the gallbladder is extremely rare, with only one previous case. We report here on an additional case of gallbladder carcinoma with an infiltrate of OGCs. A 72-year-old woman presented with postprandial abdominal pain and was found to have a mass in the body of the gallbladder with direct liver invasion. Histological examination showed an adenosquamous carcinoma with an infiltrate of benign OGCs. Immunohistochemical analysis demonstrated that the giant cells were of histiocytic origin. The patient survived for 6 years without evidence of recurrence. This case adds to a small body of literature on gallbladder carcinoma with OGCs. Further studies are required to clearly define the prognostic significance of these giant cells in gallbladder cancer and the differences between adenosquamous carcinoma with OGCs and other gallbladder carcinomas (such as adenocarcinoma and squamous cell carcinoma) with those cells.