Journal of Clinical and Experimental Hematopathology
Online ISSN : 1880-9952
Print ISSN : 1346-4280
ISSN-L : 1346-4280
Volume 54 , Issue 3
Showing 1-10 articles out of 10 articles from the selected issue
Review Article
  • Nozomi Niitsu
    2014 Volume 54 Issue 3 Pages 171-177
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    nm23-H1 was originally identified as a protein that is expressed at a lower than usual level in metastatic cancer cells. The nm23 genes play critical roles in cellular proliferation, differentiation, oncogenesis, and tumor metastasis. Peripheral T-cell lymphoma (PTCL) is relatively rare, accounting for only 10% to 15% of non-Hodgkin's lymphomas. We examined whether nm23-H1 is a prognostic factor of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). PTCL is more aggressive and has a poorer prognosis than diffuse large B-cell lymphoma. nm23-H1 was positive in 44.1% of PTCL-NOS patients. nm23-H1 expression was not correlated with age, performance status (PS), lactate dehydrogenase (LDH) level, or stage. The nm23-H1-positive group had significantly shorter overall survival (OS). OS was significantly shorter in patients with the following clinicopathologic features: age > 60 years, PS of 2-4, LDH > normal, bone marrow involvement, or nm23-H1-positive lymphoma. The nm23-H1 protein may be an important prognostic factor in PTCL-NOS. Because our results suggest that nm23-HI is produced by lymphoma cells, we expect to see the development of new treatments targeting nm23 overexpression.
    Download PDF (740K)
Original Article
  • Kazunari Maekawa, Sayaka Moriguchi-Goto, Ayako Kamiunten, Yoko Kubuki ...
    2014 Volume 54 Issue 3 Pages 179-185
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    Primary central nervous system lymphoma (PCNSL) is a rare and aggressive brain tumor. The aim of this study was to clarify the prevalence of T-cell-type PCNSL (T-PCNSL) in a human T-lymphotropic virus type-1 (HTLV-1)-endemic area of Southwestern Japan. We retrospectively investigated 31 PCNSL cases diagnosed between 1996 and 2013 at the University of Miyazaki Hospital. These cases accounted for 4.4% of all nodal or extranodal malignant lymphomas. Histologically, most of these cases were diagnosed as diffuse large B-cell lymphoma, while only two cases were considered to be low-grade and high-grade B-cell lymphoma (not otherwise specified). No T-PCNSL was found in this series. In addition, Epstein-Barr virus-encoded RNAs were not detected by in situ hybridization in any of the cases. Overall, no T-PCNSL cases were found in 18 years in a region with a high frequency of HTLV-1 seropositivity, namely, Southwestern Japan. This suggests that PCNSL and lymphomas of other anatomical sites are biologically distinct.
    Download PDF (666K)
  • Noriaki Kawano, Nobuyuki Ono, Sayaka Kawano, Takuro Kuriyama, Shuro Yo ...
    2014 Volume 54 Issue 3 Pages 187-196
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    Immunodeficiency-associated lymphoproliferative disorders (LPD) represent a rare life-threatening clinical entity characterized by heterogeneous histological findings that range from polymorphic to monomorphic proliferated abnormal lymphocytes. Currently, there is no standard treatment for LPD. To elucidate the clinical features and treatment outcomes of immunodeficiency-associated LPD patients with rheumatoid arthritis (RA), we retrospectively evaluated 9 cases observed over a 5-year period. The diagnoses of these patients included 5 diffuse large B-cell lymphomas, 3 LPD, and 1 mucosa-associated lymphoid tissue lymphoma. At initial diagnosis, 6 patients had advanced-stage RA, and half of these underwent total knee arthroplasty. All patients with RA received methotrexate (MTX) and low-dose prednisolone. Biologics were administered to 4 of 9 patients. After the development of immunodeficiency-associated LPD, MTX discontinuation resulted in 5 complete remissions (CR), 1 partial remission, and 3 cases of stable disease. Relapse was observed in 3 of 5 CR patients in the MTX-withdrawal remission group. Subsequently, conventional chemotherapy, rituximab, and radiation were administered to 4, 3, and 1 patient, respectively. These treatments induced a second CR. In the chemotherapy group, 1 patient developed acute myocardial infarction and another experienced ileus and pulmonary abscess. In the rituximab group, no severe complications were observed. Consequently, all patients remained disease-free during the median 23-month follow-up period. Our results indicate that, depending on the RA disease stage, performance status, and extent of treatment response, less intensive treatments than those commonly indicated for non-Hodgkin lymphoma, involving MTX discontinuation and subsequent therapy containing rituximab, might be an efficient therapeutic strategy for immunodeficiency-associated LPD.
    Download PDF (704K)
  • Koiti Inokuchi, Takashi Kumagai, Eri Matsuki, Kazuteru Ohashi, Atsush ...
    2014 Volume 54 Issue 3 Pages 197-204
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    Dasatinib is a BCR-ABL kinase inhibitor with improved potency compared with imatinib, for which efficacy and safety in imatinib-resistant and imatinib-intolerant patients with chronic myelogenous leukemia (CML) have been established. Here, an open-label phase II study evaluated the efficacy and safety of dasatinib in 50 Japanese patients with imatinib-resistant or imatinib-intolerant CML during the chronic phase (CML-CP). Dasatinib was effective in imatinib-resistant and imatinib-intolerant patients. After 12 months of dasatinib therapy, 35 patients (70%) had achieved a major molecular response (MMR) and 16 patients (32%) had achieved a complete molecular response (CMR). Among the imatinib-resistant CML-CP cohort, 21 and 8 patients had achieved an MMR and a CMR after 12 months of dasatinib therapy, respectively. Among the imatinib-intolerant CML-CP cohort, 14 and 8 patients had achieved an MMR and a CMR after 12 months of dasatinib therapy, respectively. After 18 months of dasatinib therapy, 38 out of 50 patients (76.0%) had achieved an MMR and 19 patients (38.0%) had achieved a CMR. A lower level of BCR-ABL transcript at 1 or 3 months after the initiation of dasatinib treatment was more strongly correlated with the BCR-ABL transcript level at 12 and 18 months (p < 0.001) than a higher level of BCR-ABL. The T315I mutation was identified in two patients receiving dasatinib therapy. Dasatinib was generally well tolerated, with only 3 patients (5%) having treatment discontinuation as a result of adverse hematologic events (thrombocytopenia, anemia, neutropenia) and/or non-hematologic events at a 12-month follow-up evaluation. Dasatinib was a safe and effective treatment for Japanese patients with imatinib-resistant or imatinib-intolerant CML. In addition, the molecular response at 1 or 3 months predicted a response to dasatinib at 12 or 18 months.
    Download PDF (518K)
Case Study
  • Akiko Yashima-Abo, Takashi Satoh, Kenji Shimosegawa, Yoji Ishida, Tomo ...
    2014 Volume 54 Issue 3 Pages 205-209
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    Progressive transformation of germinal center (PTGC) represents an asymptomatic persistent form of lymphadenopathy. We present a case of classical Hodgkin lymphoma occurring in association with PTGC. The patient was a 60-year-old woman who had noted swelling of the submandibular lymph nodes. Histopathologically, the enlarged lymph nodes appeared as multiple nodules with ill-defined and irregularly expanded germinal centers. Immunohistochemical studies indicated that the germinal center cells comprised B cells that were positive for CD10 and CD20, and negative for bcl-2. Enlarged vascular endothelial cells were present in the interfollicular areas. CD30-positive Hodgkin & Reed-Sternberg cells were seen between the interfollicular area and the mantle zone, and were surrounded by CD3-positive T-cells. In situ hybridization studies demonstrated no expression of Epstein-Barr virus-encoded small RNA in the Hodgkin & Reed-Sternberg cells. A diagnosis of classical Hodgkin lymphoma complicated by PTGC was made from the lymph node specimen.
    Download PDF (591K)
  • Toru Kawakami, Kaoko Sakai, Yuto Mimura, Yasushi Senoo, Yukio Hirabaya ...
    2014 Volume 54 Issue 3 Pages 211-217
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    We report here a case of a 37-year-old man with human immunodeficiency virus (HIV) infection followed by JC virus (JCV) infection and primary central nervous system lymphoma (PCNSL). The patient had been infected with HIV type 1 due to blood products for hemophilia A during infancy. He had progression of nervous symptoms and was diagnosed with progressive multifocal leukoencephalopathy (PML) clinically at the age of 36, when his CD4-positive lymphocyte counts ranged between 350 and 450/μl. Oral mefloquine, intravenous methylprednisolone pulse therapy, and intravenous immunoglobulin were not effective for the PML, and the patient entered a vegetative state. Brain biopsy revealed JCV infection without pathological findings of PML. Eight months after the clinical diagnosis of PML, he developed respiratory failure and brain magnetic resonance imaging revealed a mass lesion in the brain stem. The patient died 19 months after the diagnosis of PML. Autopsy findings were compatible with PCNSL. EBV-encoded small RNA-1-positive cells were not detected. We present a case of JCV-positive PCNSL with HIV infection complicated with clinical PML.
    Download PDF (1628K)
  • Futoshi Iioka, Takashi Akasaka, Masahiko Hayashida, Atsuko Okumura, Hi ...
    2014 Volume 54 Issue 3 Pages 219-224
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    An 80-year-old man was referred to our department because of lymphocytosis. His white cell count was 17.1 × 103/μL, with 64% prolymphocytes. He did not exhibit splenomegaly or lymphadenopathy. Prolymphocytes were CD5+, CD10-, CD19+, CD20+, CD21+weak, CD22+, CD23-, and HLA-DR+, and expressed μδ/λ cell-surface immunoglobulins. G-banding and fluorescence in situ hybridization using c-MYC and immunoglobulin heavy-chain (IgH) gene probe revealed that leukemia cells carried the t(8;14)(q24;q32)/c-MYC-IgH fusion gene, and breakage and reunion occurred within the non-coding region of c-MYC exon 1 as well as the α switch region of IgH. Nine months after the initial presentation, the patient's hemoglobin level fell to 5.7 g/dL. Coombs' test was positive and marked hypoplasia of erythroid precursors was detected in his bone marrow. The patient was treated with prednisolone followed by 4 weekly doses of rituximab, which led to resolution of the anemia and complete response of the underlying leukemia. The role of t(8;14)(q24;q32)/c-MYC-IgH in the pathogenesis of B-cell prolymphocytic leukemia (B-PLL) may not be identical to that in aggressive lymphoid neoplasms, and, in the present case, autoantibodies targeting both mature red cells and erythroid precursors may have been concurrently produced in the setting of B-PLL.
    Download PDF (566K)
  • Kayo Takeoka, Atsuko Okumura, Gen Honjo, Hitoshi Ohno
    2014 Volume 54 Issue 3 Pages 225-235
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    In anaplastic large cell lymphoma (ALCL), the anaplastic lymphoma kinase (ALK) gene is rearranged with diverse partners due to variant translocations/inversions. Case 1 was a 39-year-old man who developed multiple tumors in the mediastinum, psoas muscle, lung, and lymph nodes. A biopsy specimen of the inguinal node was effaced by large tumor cells expressing CD30, epithelial membrane antigen, and cytoplasmic ALK, which led to a diagnosis of ALK+ ALCL. Case 2 was a 51-year-old man who was initially diagnosed with undifferentiated carcinoma. He developed multiple skin tumors eight years after his initial presentation, and was finally diagnosed with ALK+ ALCL. He died of therapy-related acute myeloid leukemia. G-banding and fluorescence in situ hybridization using an ALK break-apart probe revealed the rearrangement of ALK and suggested variant translocation in both cases. We applied an inverse cDNA polymerase chain reaction (PCR) strategy to identify the partner of ALK. Nucleotide sequencing of the PCR products and a database search revealed that the sequences of ATIC in case 1 and TRAF1 in case 2 appeared to follow those of ALK. We subsequently confirmed ATIC-ALK and TRAF1-ALK fusions by reverse transcriptase PCR and nucleotide sequencing. We successfully determined the partner gene of ALK in two cases of ALK+ ALCL. ATIC is the second most common partner of variant ALK rearrangements, while the TRAF1-ALK fusion gene was first reported in 2013, and this is the second reported case of ALK+ ALCL carrying TRAF1-ALK.
    Download PDF (1298K)
  • Satoshi Ichikawa, Mihyun Kim, Shin Hasegawa, Keiichi Ohashi, Aiko Kond ...
    2014 Volume 54 Issue 3 Pages 237-241
    Published: 2014
    Released: December 15, 2014
    JOURNALS FREE ACCESS
    A middle-aged woman who had undergone autologous hematopoietic stem cell transplantation (HSCT) 1 month previously suffered severe epigastralgia and relapse of lymphoma. The epigastralgia was not relieved by chemotherapy. Thereafter, her pancreatic and hepatic enzyme levels were markedly elevated and disseminated varicella emerged. Despite acyclovir administration, her general condition deteriorated rapidly and she died. Serum varicella zoster virus (VZV) DNA level was shown to be elevated and a diagnosis of disseminated VZV infection was established postmortem. In patients with severe abdominal pain following HSCT, early suspicion and therapeutic intervention for VZV are important, even in the absence of skin lesions.
    Download PDF (246K)
Letter to the Editor
feedback
Top