Plasma cell myeloma (PCM) is a devastating disease with a highly heterogeneous outcome, with survival ranging from a few months to longer than 10 years. Treatment of multiple myeloma has changed markedly in the past decade due to the development of new drugs such as bortezomib, lenalidomide and thalidomide, which have greatly improved the outcome of PCM. The clinical and prognostic value of immunophenotyping in PCM remains questionable. The aim of this study was to determine the diagnostic and prognostic significance of CD200 expression in newly diagnosed PCM. We retrospectively reviewed the records of 107 patients newly diagnosed with PCM at Showa University Hospital between January 2004 and September 2013. Expression of CD200 was studied by immunohistochemistry. Clinical and pathological parameters were compared between CD200-positive and CD200-negative cases. CD200-positive PCM cases had lower serum albumin (p = 0.0001) compared to those without CD200 expression. Our results showed no significant difference in median overall survival between patients with CD200-positive and CD200-negative PCM. However, there was a strong correlation between CD200 expression and serum albumin level. In the CD200-negative group, median overall survival was significantly longer in patients who received new drug treatment. These findings suggest that CD200 expression is a useful marker for evaluation of the severity of PCM and that lack of CD200 expression may improve the sensitivity of PCM to therapy with new drugs. [J Clin Exp Hematop 55(3) : 121-126, 2015]
We confirmed the characteristic clinical features of necrotizing lymphadenitis (NEL) in 66 cases (23 male, 43 female) in Japan, which included high fever (38-40°), painful cervical lymphadenopathy (62/66, 93.9%), and leukopenia (under 4,000/mm3) (25/53, 47.2%), without seasonal occurrence, in a clinicopathological, immunohistochemical, electron microscopic serological study. Patient age varied from 3-55 years, and 72.7% (44/66) of patients were younger than 30 years. Histopathology of NEL was characterized by the presence of CD8+ immunoblasts, CD123+ cells (plasmacytoid dendritic cells; PDCs), histiocytes and macrophages phagocytizing CD4+ apoptotic lymphocytes, but no granulocytes or bacteria. The number of PDCs and CD8+ cells in lesions tended to increase with time, and PDCs tended to be larger and irregular in the lesions compared with the non-lesion tissue of the lymph nodes. In addition, PDCs showed no temporal morphological change in the lymph nodes. The number of CD4+ cells in the lymph node lesions sharply decreased from the 2nd to the 4th week, and then tended to increase; however, CD4+ cells gradually decreased with time in non-lesion tissue. PDCs may produce interferon-α (IFN-α), which induces Mx1 expression. Strong Mx1 immunoreactivity is indicative of IFN-α production. IFN-α induces transformation of CD8+ cells into immunoblasts, as well as phagocytosis of apoptotic cells derived from CD4+ cells by macrophages. Thus, PDCs may play an important role with immune cells, including CD8+ and CD4+ cells, in necrotizing lymphadenitis. [J Clin Exp Hematop 55(3) : 127-135, 2015]
The t(11;14)(q13;q32) translocation is the most common chromosomal translocation in plasma cell myeloma (PCM), but the cytogenetic and immunophenotypic features of PCM with t(11;14)(q13;q32) remain to be fully elucidated. To address the issue, we retrospectively analyzed 21 newly diagnosed PCM patients with the t(11;14)(q13;q32) translocation in our institute. CD20 is a B-cell-specific transmembrane protein that is the topic of much focus as a potential target in immunotherapy. We observed a low incidence of CD20 expression (2 of 21 patients, 11%), although the expression of CD20 was previously reported to be associated with t(11;14)(q13;q32). PAX5 is an essential transcriptional factor involved in B-cell development and commitment, and is down-regulated upon plasma cell differentiation. We observed one patient (6%) with expression of PAX5. The expression of CD19, CD56, and CD138 was detected in one (0.7%), nine (60%), and 13 patients (87%), respectively. Cyclin D1, CD38, and BCL2 were detected in all patients; on the other hand, neither BCL6 nor SOX11 was detected in any of the evaluated patients. Abnormalities of chromosome 13 were detected in six patients (38%), but deletion of TP53 was not observed in any of the evaluated patients. Our results suggest the absence of BCL6 and SOX11 expression, and infrequent expression of CD20, PAX5, and CD56 in PCM with t(11;14)(q13;q32), in contrast to the findings of earlier reports. [J Clin Exp Hematop 55(3) : 137-143, 2015]
Loss-of-function of ten-eleven translocation-2 (TET2) is a common event in myeloid malignancies, and plays pleiotropic roles, including augmenting stem cell self-renewal and skewing hematopoietic cells to the myeloid lineage. TET2 mutation has also been reported in lymphoid malignancies; 5.7～12% of diffuse large B-cell lymphomas and 18～83% of angioimmunoblastic T-cell lymphomas had TET2 mutations. We investigated TET2 mutations in 22 adult T-cell leukemia/lymphoma (ATLL) patients and identified a missense mutation in 3 cases (14%). TET2 mutation occurred in a number of ATLL patients and was likely involved in their leukemogenesis. [J Clin Exp Hematop 55(3) : 145-149, 2015]
A 61-year-old Japanese woman presented with hemophagocytic syndrome (HPS) and suffered from intravascular large B-cell lymphoma (IVLBCL). After a few days of supportive care, her condition improved without any anti-cancer drugs or steroids. She experienced recurrences of HPS at 15 mon and 21 mon after first presentation, but lymphoma cells were not observed. Relapse of IVLBCL with pulmonary involvement occurred 27 mon after first presentation. She underwent R-CHOP therapy followed by autologous stem cell transplantation. She is currently alive and without lymphoma. Immunostaining by anti-ssDNA suggested that spontaneous regression may have been due to apoptosis of the lymphoma cells. [J Clin Exp Hematop 55(3) : 151-156, 2015]
We report a case of intraocular relapse of extranodal NK/T-cell lymphoma with anterior chamber hypopyon and retinal infiltrates. A 55-year-old man developed fever, malaise, anorexia, and hepatosplenomegaly, and was diagnosed with NK/T-cell lymphoma by liver biopsy. He underwent 2 courses of SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy, followed by myeloablative peripheral blood stem cell transplantation, donated by his brother. Two months later, he developed high-grade fever, hepatosplenomegaly, and peritoneal lymphadenopathy, and the relapse with hemophagocytic syndrome was diagnosed by bone marrow biopsy. He underwent 2 courses of SMILE salvage chemotherapy, followed by non-myeloablative peripheral blood stem cell transplantation, donated by his son. Two months later, he noticed blurred vision in both eyes. The right eye had aqueous cells and keratic precipitates, but no retinal lesions. The left eye had hypopyon in the anterior chamber with numerous aqueous cells, and retinal white infiltrates with retinal hemorrhages. The aqueous cells, obtained by anterior chamber paracentesis, were positive for CD3, CD56, and Epstein-Barr virus-encoded RNA, but negative for CD20 by immunocytochemical staining. Head magnetic resonance imaging demonstrated white matter lesions in the anterior to parietal lobes on the right side. The patient underwent intrathecal methotrexate injection and external beam radiation at 40 Gy, covering the entire brain and both eyes. The retinal lesions and hypopyon disappeared. Two months later, the patient died of renal failure, and autopsy demonstrated multi-organ involvement of lymphoma cells. In conclusion, we report a case of NK/T-cell lymphoma relapse with intraocular lesions, after combined chemotherapy and hematopoietic stem cell transplantation. [J Clin Exp Hematop 55(3) : 157-161, 2015]
Severe acute lung injury is a rare but life-threatening complication associated with bortezomib. We report a patient with multiple myeloma who developed a severe diffuse alveolar hemorrhage (DAH) immediately after the first bortezomib administration. The patient was suspected to have pulmonary involvement of myeloma, which caused DAH after rapidly eradicating myeloma cells in the lungs with bortezomib. Rechallenge with bortezomib was performed without recurrent DAH. In patients with multiple myeloma who manifest abnormal pulmonary shadow, we should be aware of early-onset severe DAH after bortezomib administration, which might be due to pulmonary involvement of myeloma cells. [J Clin Exp Hematop 55(3) : 163-168, 2015]
Concurrent seminoma and malignant lymphoma of the testis is rare. We present a case of concurrent seminoma and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in a 54-year-old man who complained of painless left testicular enlargement. Radical left orchiectomy was performed. Macroscopically, the tumor (4.0 × 3.0 cm) was creamy, soft, and homogeneous, and microscopic evaluation revealed an alveolar structure of large cells that formed sheets, as well as colonization by other abnormal cells in a 1.0 × 1.0 cm area. The portion of the tumor comprising large abnormal cells was diagnosed as a seminoma, which was positive for c-kit by immunohistochemistry; the other portion was diagnosed as CD3/CD8, TIA, and granzyme B-positive PTCL-NOS. These two portions were clearly differentiated from one another. The patient received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and achieved complete response for 50 months. To our knowledge, this is the first reported case of synchronous advanced seminoma and PTCL. [J Clin Exp Hematop 55(3) : 169-174, 2015]
We report the first case of a nodal marginal zone large B-cell lymphoma and the first with MYC rearrangement. This high proliferation rate lymphoma (40% of cells) occurred in the bilateral cervical, axillary, and para-aortic lymph nodes of an 82 year old woman. It involved extensively her bone marrow, and was lethal. Malignant B-cells were CD10 negative, harbored Burkitt translocation, and multiple chromosomal changes including trisomies of chromosomes 3 and 18, and three copies of 8q with an intact q24 cytoband (in addition to MYC rearrangement), associated with overexpression of BCL6, BCL2, and MYC respectively. We suggest that in aggressive nodular marginal zone lymphomas (clinical picture or high proliferation rate of lymphoma cells), fluorescence in situ hybridization analysis for MYC rearrangement, with break-apart probe, and for MYC/IGH translocation, in addition to chromosome analysis, should be performed. MYC rearrangement associated with a more rapid progression of the neoplasia, might warrant a more aggressive treatment. [J Clin Exp Hematop 55(3) : 175-180, 2015]
The t(8;21)(q22;q22) translocation is specifically observed in acute myeloid leukemia (AML) M2 subtype, whereas del(5q) is one of the most common cytogenetic aberrations in myelodysplastic syndromes (MDS). Thus, t(8;21)(q22;q22) and del(5q) appear to be mutually exclusive, and the association between them has not been characterized yet. Here, we report an 81-year-old woman with coexistent t(8;21)(q22;q22) and del(5q) at initial diagnosis. The bone marrow was infiltrated with 18.4% myeloblasts, and showed marked myeloid and erythroid dysplasia. Myeloblasts were positive for CD19 and CD56 as well as CD13, CD33, CD34 and HLA-DR. G-banding and spectral karyotyping showed 46,XX,del(5)(q?),t(8;21)(q22;q22)/46,XX. Both del(5)(q?) and t(8;21)(q22;q22) were present in a single clone. Fluorescence in situ hybridization (FISH) on metaphase spreads detected a RUNX1/RUNX1T1 fusion signal on the der(8)t(8;21)(q22;q22), and confirmed deletion of CSF1R signaling at 5q33-q34 on the del(5)(q?). Furthermore, FISH on interphase nuclei revealed that the RUNX1/RUNX1T1 fusion signal and deletion of CSF1R signaling were found in 66.0% and 58.0% of interphase cells, respectively, suggesting that del(5)(q?) occurred in cells with RUNX1/RUNX1T1. These results indicated a diagnosis of AML with t(8;21)(q22;q22)/RUNX1/RUNX1T1 rather than MDS, even though the percentage of bone marrow myeloblasts was less than 20%. Based on these findings, together with those of other reported cases, del(5q) seems to be an extremely rare but recurrent secondary aberration in AML with t(8;21)(q22;q22). [J Clin Exp Hematop 55(2) : 181-185, 2015]
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