[Aplastic anemia complicated with ulcerative colitis].

A 37-year-old female who presented with pancytopenia in April 2008 was diagnosed with aplastic anemia stage 2 with a normal karyotype. She had a PNH phenotype in her red blood cells (RBC) and granulocytes, and HLA DR15. Her aplastic anemia was deteriorated from stage 2 to stage 3, and she required periodic RBC transfusions. Four months after cyclosporine therapy, the pancytopenia improved and she did not need RBC transfusion. However, three months thereafter, she again required RBC transfusions after developing severe ulcerative colitis. Although mesalazine and steroid pulse therapy improved her ulcerative colitis, her transfusion dependency persisted. Eleven months after the diagnosis of aplastic anemia, equine anti-thymocyte globulin (ATG) and cyclosporine were administered, but no hematological improvement was obtained. Six months after the administration of ATG and cyclosporine, transformation to refractory cytopenia with multilineage dysplasia (RCMD) with 7-monosomy was observed. An allogeneic bone marrow transplant (BMT) from a HLA-identical sibling was performed 23 months after the diagnosis of aplastic anemia. Complete remission of both the aplastic anemia and ulcerative colitis was obtained without medication. Although the relationship between aplastic anemia and ulcerative colitis remains unclear, immunological abnormalities might be involved in the pathogenesis of both disorders because she had PNH phenotype in RBC and HLA DR15 and because allogeneic BMT improved both disorders.

[Case with hairy cell leukemia-Japanese variant following radiotherapy for orbital adnexal MALT lymphoma].

We report a patient with hairy cell leukemia Japanese variant (HCL-Jv) that developed after radiotherapy for orbital adnexal MALT lymphoma. A 78-year-old man was diagnosed as having MALT lymphoma in the left conjunctiva in December 2003. The patient was treated by local radiotherapy and the tumor disappeared. Thereafter, he gradually developed leukocytosis and mild splenomegaly. In May 2009, the leukocyte count was 34,300 with 80% lymphoid cells. A diagnosis of HCL-Jv was made since the lymphoid cells showed a hairy morphology with round nuclei and indistinct nucleoli. These cells expressed CD11c, CD19, CD20, CD103 and showed weak reaction for tartrate-resistant acid phosphatase (TRAP). Bone marrow was infiltrated by atypical cells with an intrasinusoidal pattern. No treatment was needed as the patient was asymptomatic without anemia, thrombocytopenia or lymphadenopathy. Results of the immunoglobulin light chain expression and the heavy chain rearrangement in the tumor cells indicated that the two mature B-lymphoid neoplasms, MALT lymphoma and HCL-Jv, in this patient were derived from independent clones. This appears to be the first reported case of HCL-Jv associated with other lymphoid tumor. Further analysis is needed to clarify the risk of secondary malignancy in HCL-Jv.

[Diffuse large B-cell lymphoma with strongly positive MIB-1 stain and clinical features resembling Burkitt lymphoma].

A 62-year-old woman was admitted to our hospital because of gastric mucosal bleeding. Gastroendoscopy revealed a gastric tumor which was diagnosed from the biopsied specimen as diffuse large B-cell lymphoma (DLBCL). Lymphoma cells had infiltrated the bone marrow showed morphological features resembling Burkitt lymphoma (BL). Nearly 100% of the cells in the bone marrow were positive for MIB-1 immunostaining. The chromosomal study was normal. Surface marker analysis disclosed that the cells were positive for CD10, CD19, CD20 and CD25. As lymphoma cells had infiltrated the central nervous system, combined chemotherapy was performed accompanied with intrathecal administration of anticancer drugs. Although transient improvement was observed, the patient died of the advanced disease three months after admission. As we have shown here, there are some cases of DLBCL with immunohistochemical features resembling BL. Further consideration about the appropriate chemotherapy program for this type of disease might be necessary.

[Successful treatment with CHOP therapy for progressive of primary macroglobulinemia without further increase of serum IgM].

A 61-year-old man with primary macroglobulinemia (PMG) had been followed without any treatment as he had no apparent manifestations. After 1 year and 3 months, he was admitted to our hospital with a fever. No signs or symptoms of infection and no progressive increase of serum IgM levels was observed. Non-Hodgkin's lymphoma was not additionally found. Fever without infection, elevated serum LDH level and further enlargement of the spleen compelled us to diagnose his condition as deterioration of the PMG. An immediate fall in his temperature and serum IgM levels was observed after CHOP therapy. Effective therapy must be discussed in the deterioration of this type of disease.

[Disappearance of CD 20 after treatment with rituximab of mantle cell lymphoma].

A 60-year-old female visited our hospital in May 2001 because of systemic lymphadenopathy. Her white blood cell count was 25,510/microliters with 93% of lymphocytes. Bone marrow aspiration revealed that 86% of nucleated cells were lymphocytes. Lymphocytes in the peripheral blood and bone marrow were positive for CD 5, 19, 20, and sIgx and negative for CD 23. FISH analysis detected the chimeric bcl 1/IgH fusion gene. Immunohistochemistry of a biopsied lymph node revealed that lymphoma cells were positive for cyclin D 1. Mantle cell lymphoma (MCL) was diagnosed at clinical stage IV A. Although a partial remission was obtained after CHOP plus rituximab therapy, the patient's disease recurred in March 2002 and she died in spite of salvage therapy including rituximab. Immunohistochemistry of the bone marrow cells after salvage rituximab therapy revealed that lymphoma cells were still positive for CD 5 and cyclin D 1, but negative for CD 20 and sIgx. We could not exactly determine how frequently CD 20 expression becomes negative in B-cell lymphomas after treatment with rituximab. We found only two reported cases that suggested rituximab down-regulated CD 20 expression in MCL. We herein describe a case of MCL with very notable clinical features.

[Systemic capillary leak syndrome presenting remarkable erythrocytosis].

Systemic capillary leak syndrome (SCLS) is a disorder characterized by hypotension, edema, and an increased hematocrit (Ht) due to sudden leakage of plasma into the extravascular space through some unknown mechanism, in which monoclonal gammopathy is observed. A 30-year-old man visited our emergency department because of abdominal pain, and was admitted to our hematology department because of a markedly increased hemoglobin concentration reaching 26.2 g/dl. The polycythemia was thought to be pseudo-polycythemia due to hemoconcentration, and we diagnosed the patient as having SCLS based on the triad of increased hematocrit, whole-body edema which was especially marked in the lower extremities, and monoclonal gammopathy. The patient recovered after administration of extracellular fluids and albumin, but the attacks recurred. Prophylaxis with terbutaline sulfate, theophylline and corticosteroid reduced the frequency of severe attacks. Because there is possibility that patients with SCLS may be admitted to hematology departments due to severe erythrocytosis, we report this case to increase the awareness of hematologists that SCLS is one of the important differential diagnoses of erythrocytosis.

A Case of Monoclonal Lymphoplasmacytosis of the Bone Marrow with IgM-Positive Russell Bodies.

A 71-year-old Japanese male patient infected with HCV was diagnosed with thrombocytopenia. Histological examination of the bone marrow aspirate showed numerous lymphoid aggregates with Russell bodies. Immunohistochemistry and flow cytometric analysis demonstrated clonal expansion of CD5+ CD23+ B cells. Russell bodies were positive for IgM and lambda immunoglobulin light chain. The patient also underwent gastric biopsy, which revealed Helicobacter pylori (HP) infection. Subsequent eradication of the bacteria resulted in improvement of his thrombocytopenia. The clinical course remained uneventful at 15-month follow-up, consistent with monoclonal B-cell lymphocytosis. The observed clonal expansion with plasmacytic differentiation may have occurred under the influence of HCV with HP infection.

Plasma cell granuloma of the sigmoid colon associated with diverticular disease and accompanying IgM-type monoclonal gammopathy.

Plasma cell granuloma is a pseudoneoplastic lesion composed of reactive plasma cells of a polyclonal nature and must be distinguished from plasmacytoma. We report a case of plasma cell granuloma in the sigmoid colon associated with diverticulosis. In this case, the lesion consisted of multiple submucosal tumors with prominent infiltration of polyclonal plasma cells. Although the patient exhibited IgM-type monoclonal gammopathy, the expression of a monoclonal immunoglobulin was not detected in the sigmoid colonic lesion, but in the bone marrow cells. Plasma cell granuloma in the lower alimentary tract has been rarely reported. Recurrent inflammatory process with diverticular disease was considered as a pathogenesis of the pseudoneoplasm and a possible cause of monoclonal proliferation of IgM-producing lymphoid cells in this case.

Soluble transferrin receptor and its ratio to erythroblasts in bone marrow may be a new diagnostic tool to distinguish between aplastic and refractory anemia.

Myelodysplastic syndromes (MDS), especially refractory anemia (RA) are very heterogeneous diseases regarding their morphological, biological and clinical features. One important clinical problem is the difficulty of diagnosis. Soluble transferrin receptors (sTfRs) reflect the erythropoietic activity in the bone marrow (BM). To establish whether determination of serum sTfR could be useful for the differential diagnosis between RA and aplastic anemia (AA), we measured the serum sTfR concentrations, BM cellularity and BM erythroblast percentages in 14 untreated AA and 7 untreated RA patients. The serum sTfR levels of the RA patients (820.1 +/- 402.8 ng/ml) were significantly higher than those of the AA patients (491.1 +/- 195.2 ng/ml; p = 0.0207). However, the serum sTfR values of RA and AA patients also overlapped. A new index, the 'sTfR-E index' [the ratio of serum sTfR level (ng/ml) to BM cellularity (%) x BM erythroblasts (%)] is proposed, which is expected to reflect the number of transferrin receptors (TfR) on the cell membrane per BM erythroblast. The sTfR-E index values of the 7 RA patients (0.395 +/- 0.234) were significantly lower than those of the 14 AA patients (2.669 +/- 1.633; p = 0.0003). The sTfR-E index values of AA and RA patients overlapped only marginally. In conclusion, the sTfR-E index may be a useful new diagnostic tool to distinguish between AA and RA patients.