© 2005 Foundation for Promotion of Cancer Research
Case Report |
CD56-positive Small Round Cell Tumor: Osseous Plasmacytoma Manifested in Osteolytic Tumors of the Iliac Bone and Femora
1 Hematology, 2 Orthopedics and 3 Pathology Divisions, National Cancer Center Hospital, Tokyo, Japan
For reprints and all correspondence: Takashi Watanabe, Hematology Division, National Cancer Center Hospital 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. E-mail: tkouno{at}ncc.go.jp
Received April 29, 2004; accepted September 6, 2004
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Abstract |
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Monoclonal gammopathy of undetermined significance does not overexpress cluster of differentiation (CD) 56, but plasma cell myeloma frequently overexpressed it. However, plasma cell leukemia and extramedullary plasmacytoma usually down-regulate CD56 expression. Plasmacytoma, especially ‘solitary plasmacytoma of bone’, is difficult to diagnose as plasma cell neoplasm, because it occasionally appears similar to other bone tumors, both clinically and pathologically, and is rarely accompanied by monoclonal protein in the serum or urine. The present case was a patient with an osteolytic ‘small round cell tumor’ of the iliac bone, which also invaded the femora. An immunohistopathological finding of CD56 expression played a key role in making a diagnosis. The definitive diagnosis of plasmacytoma was made based on the electron microscopic findings. The plasma cells which infiltrated her sternum showed the same restriction to kappa light chain expression in their cytoplasms as that of the iliac bone tumor cells, but did not express CD56. Locally infiltrating osteolytic bone tumors should be examined for surface immunoglobulin light chains as well as CD56 expression when plasmacytoma is suspected.
Key Words: CD56 • osseous plasmacytoma • osteolytic bone tumor • plasmacytoma • SBP
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INTRODUCTION |
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‘Plasmacytoma’ is one of the plasma cell neoplasms locally infiltrating bones or spreading to extramedullary sites from the bones (1). The new World Health Organization (WHO) criteria defines solitary plasmacytoma of bone (SBP) as ‘a localized bone tumor consisting of plasma cells identical to those seen in plasma cell myeloma, which appears as a solitary lytic lesion on radiological examination’ (1). Electrophoreses of serum and urine samples in patients with SBP tend to reveal monoclonal proteins less frequently than plasma cell myeloma, and clinical diagnosis of SBP is generally difficult in such cases without monoclonal proteins (2). Previous reports showed that 65–78% of cases with plasma cell myeloma strongly expressed cluster of differentiation (CD) 56, but patients with monoclonal gammopathy of undetermined significance (MGUS) seldom showed CD56 expression (3,4). On the other hand, plasma cells obtained from patients with plasma cell leukemia (PCL) were reported to lack or barely express CD56 in either the peripheral blood (PB) or the bone marrow (BM) (5). Myeloma cells obtained from extramedullary sites revealed absence of CD56, although those of BM expressed CD56 in the same patients (6). Furthermore, CD56-negative multiple myeloma had a higher incidence of extramedullary disease, a plasmablastic morphology, and poor prognosis (7). The present case was one in which the CD56 expression played a key role in reaching a definitive diagnosis of plasma cell neoplasm.
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CASE REPORT |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONCONCLUSIONReferences |
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In February 2000, a 57-year-old female suffered from severe pain in her buttocks. She had been to a chiropractor but her pain had not been improved. In December 2000, she was referred to a hospital, where an iliac bone biopsy was performed. The histopathological diagnosis was a ‘small round cell tumor’. In January, 2001, she was referred to and admitted to our hospital. Computerized tomography (CT) revealed an extensive osteolytic tumor in her right iliac bone (Fig. 1). Magnetic resonance imaging (MRI) also showed a bone tumor in her right iliac bone and osteolytic lesions at the necks of her bilateral femora (Fig. 2). She had been lying in bed with such severe pain on her right hip joint that she required a lumbar subdural morphine infusion. Re-biopsy of her iliac bone tumor was performed and hematoxylin–eosin staining of the specimen showed the diffuse proliferation of condensed small round cells (Fig. 3). Although the tumor cells had scant cytoplasms, their nuclei appeared rather eccentric. Her blood tests were almost normal except for a low hemoglobin level of 10.2 g/dl and a slightly high calcium concentration of 10.9 mg/dl. As for the levels of immunoglobulins, only IgA was abnormal and slightly declined to 92 mg/dl [normal range (NR), 107–390 mg/dl]. A bone marrow aspiration of her sternum revealed 4% of plasma cells. Her findings did not meet any major diagnostic criteria of the Southwest Oncology Group for multiple myeloma (8). Immunohistochemical analysis of her iliac bone tumor specimen showed neither epithelial markers such as cytokeratin or epithelial membrane antigen nor the markers for neural differentiation such as neuron-specific enolase, CD57 (Leu7), synaptophysin or neurofilament. Hematopoietic cell markers such as leukocyte common antigen (CD45), CD34, terminal deoxynuceotidyl transferase, myeloperoxidase, CD3 and CD79a were not expressed, but CD56 was expressed (Fig. 4A). In February 2001, the pain worsened, because the head of her right femur was dislocated into the acetabular fossa necessitating the towing of her right femur. She had become progressively worse and it was suggested that there was a strong possibility of either malignant lymphoma or plasma cell neoplasm. Therefore, we started chemotherapy with 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, and 1.4 mg/m2 vincristine i.v., and 100 mg prednisolone orally for five consecutive days.
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The study by Van Camp et al. (3), which concluded that strong CD56 expression was common in multiple myeloma, suggested that there was a great likelihood of plasma cell neoplasms. We therefore performed additional immunohistochemical stainings of the specimens, and plasmacytoma was confirmed by the positive immunostaining in the cytoplasms of tumor cells with an anti-kappa light chain antibody (Fig. 4B), but negative with an anti-lambda antibody (data not shown). We re-performed bone marrow aspiration and plasma cells from her sternum were clearly distinguished from other BM cells or lymphoid cells of her sternum on two-color cytogram (performed with EPICS XL-MCL flow cytometer, Beckman Coulter Inc., Miami, FL) with a fluorescein isothiocyanate (FITC)-anti-CD38 antibody staining (Immunotech, a Beckman Coulter Company, Marseille, France). The result revealed an increased ratio of the cytoplasmic kappa/lambda chains [32.2 (61.1%/1.9%)]. Furthermore, the electron microscopic examination of her iliac bone tumor cells showed abundant rough endoplasmic reticula with regular parallel arrays, which were consistent with plasma cells (Fig. 5). The immunohistochemical analysis of the plasma cells in the clot section of her sternal BM showed the same pattern of the restricted kappa chain expression as that of the tumor specimen obtained from her iliac bone (Fig. 4C). However, the plasma cells in her sternum lacked CD56 expression (Fig. 4D). Additional serum examination showed 2.58 mg/l of ß2-microglobulin (NR 0.92–1.40 mg/l). Although ordinary urine examination showed no protein, immunoelectrophoresis of her concentrated urine disclosed kappa type of Bence–Jones protein (BJP).
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After six courses of the described chemotherapy, partial remission was obtained. She underwent surgery for residual tumor resection in the iliac bone and artificial hip–femur joint replacement. The resected specimen revealed fibrotic and bleeding tissue without any residual tumor. The postoperative recovery was uneventful and she recovered mobility with the use of a wheelchair through rehabilitation.
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DISCUSSION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONCONCLUSIONReferences |
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When a bone tumor is encountered which is histopathologically diagnosed as ‘small round cell tumor’, the differential diagnosis includes Ewing sarcoma, osteosarcoma of small cell type, malignant lymphoma, plasmacytoma, metastatic small cell lung cancer and so on. To make a definitive diagnosis, immunohistochemistry is usually necessary in addition to hematoxylin–eosin staining. As for non-Hodgkin's lymphoma (NHL), some anaplastic large cell lymphomas (9) as well as NK/T-cell lymphomas have been reported to express CD56 (10). However, CD30 was negative and the sites frequently involved in NK/T-cell lymphoma were not affected in the present case. Although some tumor cells of osteosarcoma also show positive immunoreactivity for CD56 (11), the present case had CD56-positive cells in her iliac bone tumor and this was a clue to carrying the investigation forward to reach a definitive diagnosis. In plasma cell neoplasms, it has been reported that CD56 expression is common in plasma cell myeloma, but normal plasma cells of healthy volunteers and benign plasma cells of MGUS were negative for CD56 (3,4). On the other hand, expression of CD56 was down-regulated in PCL (5) and extramedullary plasmacytoma (6). CD56-negative myeloma is characterized by higher levels of ß2-microglobulin, BJP, renal insufficiency, thrombocytopenia, plasmablastic morphology and high incidence of extramedullary disease (7). The level of serum ß2-microglobulin in this case was not so high, and the tumor cells showed very small round shapes without blastic appearance. Renal function was intact and platelet counts were within normal limits. CD56 is a neural cell adhesion molecule (NCAM), one of the recognition molecules which operate via both homophilic (NCAM to NCAM) and heterophilic (NCAM to heparan sulfate proteoglycan and various other collagens) binding mechanisms. During embryogenesis, this molecule is down-regulated during migrating events but re-expression usually occurs when target organs are reached (12).
Furthermore, comparing the presence of lytic bone lesions on radiography, Pellat-Deceunynck et al. (5) reported that 80% of patients with plasma cell myeloma which expressed CD56 had one or more lytic bone lesions but that they were found only in 44% of patients who lacked or weakly expressed CD56. Ely and Knowles (13) also reported that strong expression of CD56 by plasma cells correlated with the presence of lytic bone regions and strong CD56 expression by osteoblasts in BM. Although the levels of CD56 expression on plasma cells of SBP have not been reported, they were supposed to be high according to the above-mentioned reports. Although the present case with femoral invasion does not fit with the strict definition of SBP as described in the new WHO classification (1), it is suggested that such an ‘osseous plasmacytoma’ as an osteolytic, relatively localized plasmacyotma with CD56 expression is the opposite manifestation of plasma cell neoplasms to PCL or extramedullary myeloma. Plasma cells in the osseous plasmacytoma that overexpress CD56 might adhere to and proliferate in BM. Homophilic interactions among myeloma cells through CD56 might facilitate a mass formation of plasma cells. Moreover, the destruction of bone trabeculae can be attributable to heterophilic interactions between plasma cells and osteoblasts through CD56 (13). CD56 seemed to be up-regulated and down-regulated during development of plasma cell dyscrasia and changed its character according to the relationship of myeloma cells to BM.
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CONCLUSION |
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TOPAbstractINTRODUCTIONCASE REPORTDISCUSSIONCONCLUSIONReferences |
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"Osseous plasmacytoma" might present itself histopathologically as "small round cell tumor" and often remains undiagnosed if only hematoxylin–eosin staining is performed. In addition, low levels of the serum or urine monoclonal protein make its clinical diagnosis difficult. From previous observations and the present finding, the level of CD56 expression is suggested to be high in "osseous plasmacytoma". Therefore, locally infiltrating osteolytic bone tumors should be examined for surface immunoglobulin kappa and lamda light chains as well as CD56 expression when "osseous plasmacytoma" is suspected.
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Acknowledgments |
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This study was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (11-8). We thank Atsuya Nakano for technical assistance with the two-color cytograms with FITC-anti-CD38 antibody staining.
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References |
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