Ryo Ichinohasama

No evidence of a correlation between BCL10 expression and API2‐MALT1 gene rearrangement in ocular adnexal MALT lymphoma

In the present study, 62 cases of ocular adnexal lymphoproliferative disorders were reviewed clinicopathologically. Of them, 51 were extranodal marginal zone B‐cell lymphoma (MALT lymphoma), five were diffuse large B‐cell lymphoma (DLBCL), one was peripheral T‐cell lymphoma, one was NK/T cell lymphoma, nasal type, and four were reactive lymphoid hyperplasia. These lymphoma cases showed a favorable clinical course and localized disease, except for the case of NK/T cell lymphoma, although 19 cases (32.8%) had a recurrence of disease. To clarify the correlation between BCL10 protein expression and API2–MALT1 gene rearrangement, the 51 cases of MALT lymphoma and 5 cases of DLBCL were analyzed by immunohistochemical and RT‐PCR methods. Nuclear BCL10 expression was identified in 58% of MALT lymphoma cases, but not in any DLBCL cases. There was no evidence of a correlation between aberrant nuclear BCL10 expression and the clinical parameters examined in the present study. API2–MALT1 transcription was not demonstrated in either the MALT lymphoma cases or the DLBCL cases studied using a multiplex one‐tube reverse transcriptase‐PCR method. These findings indicate that the nuclear expression of BCL10 is unlikely to correlate with the API2‐MALT1 fusion gene in ocular adnexal MALT lymphoma.

T-Cell Variant of Classical Hodgkin's Lymphoma with Nodal and Cutaneous Manifestations Demonstrated by Single-Cell Polymerase Chain Reaction

The atypical cells of CD30+ cutaneous lymphoproliferative disorders (CD30CLD) are commonly of T-cell origin and frequently have a similar morphology as Hodgkin or Reed-Sternberg cells of Hodgkins lymphoma (HL). HL is one of the tumors associated with CD30CLD. Although most studies support a B-cell derivation of the tumor cells in HL, recently a few cases of classical HL with T-cell genotype have been reported. We report a patient who presented with CD30CLD whose lymph nodes showed classical HL of mixed cellularity subtype at presentation. By single-cell PCR, the same clonal gene rearrangements of the T cell receptor-β gene locus could be assigned to the CD30+ and CD15+ cells of both skin and lymph node. In a lymph node biopsy specimen taken in relapse after several courses of chemotherapy, the CD30+ tumor cells were abundant. The T cell–derived tumor cells displayed aberrant expression of the Pax-5 gene in all specimens. A common clonal origin of both CD30CLD and HL of the lymph node in the patient presented here suggests that HL with T-cell genotype exists in association with CD30CLD as well as in sporadic cases and may share clonal origin with the skin tumor.

Cytogenetic features of de novo CD5-positive diffuse large B-cell lymphoma: Chromosome aberrations affecting 8p21 and 11q13 constitute major subgroups with different overall survival

De novo CD5‐positive diffuse large B‐cell lymphoma (CD5+DLBCL) is regarded as a different clinicopathological entity from CD5‐negative DLBCL (CD5−DLBCL) and mantle cell lymphoma (MCL). Because only a few published cytogenetic studies of de novo CD5+DLBCL are available, we investigated chromosomal changes in 23 Japanese patients who had de novo CD5+DLBCL. A characteristic of cytogenetic abnormalities in de novo CD5+DLBCL was a high incidence of chromosomal aberrations affecting 8p21 and 11q13. Major chromosomal breakpoints were concentrated at 8p21, 11q13, and 3q27. Patients with 8p21 aberrations showed aggressive clinical features, including advanced stage of disease, elevated serum LDH level, poor performance status, and an inferior survival curve compared with patients who had 11q13 changes (P = .043). Chromosomal abnormalities of both 8p21 and 11q13 were not observed in the same patient, and each abnormality showed different chromosomal gains and losses. These results indicate that de novo CD5+DLBCL may occur in previously unidentified subgroups that differ in their chromosomal abnormalities. The conflicting results of previous studies on prognosis may thus be explained in part by the differences in chromosomal changes.

CD5+ Diffuse Large B-Cell Lymphoma Consists of Germline Cases and Hypermutated Cases in the Immunoglobulin Heavy Chain Gene Variable Region

CD5+ diffuse large B-cell lymphoma (DLBCL) has recently been identified as a subgroup with different clinical characteristics from CD5- DLBCL and as having a poorer outcome than CD5- DLBCL. Data regarding differences in gene alteration between CD5+ and CD5- DLBCL have accumulated. In this article, we report an analysis of the immunoglobulin heavy-chain gene variable region (VH) gene in 35 cases of CD5+ DLBCL and compare these cases with those with the germline of the VH gene (GL-VH) and those with a somatically hypermutated VH gene (HM-VH).When the CD5+ DLBCL cases were subdivided with a cutoff value of 98% homology in the VH gene, there were 7 cases (20%) of GL-VH and 28 cases (80%) of HM-VH. The proportion of GL-VH cases in CD5+ DLBCL was more than that in CD5- DLBCL. Although we found no significant difference in pretreatment clinical parameters between the GL-VH and HM-VH subgroups, there was a tendency for the GL-VH subgroup to show lower incidences of elevation of lactate dehydrogenase and >1 site of extranodal involvement compared to the HM-VH subgroup. The overall survival curve of the HM-VH subgroup showed a rapid decline followed by a plateau, whereas that of the GL-VH subgroup declined constantly after 5 years, suggesting that GL-VH disease may not be curable by standard therapies. These findings suggest that CD5+ DLBCL with GL-VH shares clinical features with mantle cell lymphoma, the cellular origin of which has been considered to be pre-germinal center B-cells. We therefore propose that analysis of the VH gene is important for predicting the clinical course of CD5+ DLBCL.

Natural Killer Cell Lymphoma of the Parotid Gland

The majority of all parotid lymphomas are of the non-Hodgkin type and of B-cell origin. Primary natural killer cell lymphomas of the parotid gland are extremely rare. We present a case of natural killer cell lymphoma in a 34-year-old woman. The disease was refractory to chemotherapy, and the patient eventually succumbed due to lymphoma-associated hemophagocytic syndrome.

Should increasing the dose or adding an AT1 receptor blocker follow a relatively low dose of ACE inhibitor initiated in acute myocardial infarction

OBJECTIVEnBased on currently available clinical evidence, we should use high-dose angiotensin converting enzyme inhibitor (ACE-I) for patients with acute myocardial infarction (MI), initiating it at incremental doses to avoid excessive hypotension. Recent animal studies with acute MI models failed to demonstrate the superiority of the combination therapy of ACE-I and angiotensin receptor blocker (ARB) to high-dose ACE-I treatment with comparable blood pressure reductions, which however might be attributed to the initiation of the targeted doses from the beginning. The aim of this study was to compare the effect of increasing the dose of ACE-I with that of adding ARB following a relatively low dose of ACE-I on the survival and left ventricular (LV) remodeling after MI.nnnMETHODSnRats underwent left coronary artery ligation and were treated with either ACE-I temocapril (5 mg/kg/day) or vehicle for 2 weeks, which was initiated 3 days after the surgery. The rats treated with temocapril were further randomly assigned to receive either high-dose temocapril (10 mg/kg/day) or combination therapy (temocapril 5 mg/kg/day+olmesartan 2.5 mg/kg/day), which was continued for another 6 weeks.nnnRESULTSnBoth treatments similarly reduced the blood pressure, improved survival and ameliorated LV enlargement. In contrast, several parameters of LV function were significantly ameliorated only by the high-dose ACE-I but not by the combination therapy.nnnCONCLUSIONSnAfter the initiation of a relatively low dose of ACE-I in acute MI, increasing the dose of ACE-I or adding ARB may equally improve survival and LV remodeling in the setting of an equal hypotensive effect. Further study with a longer treatment protocol is required to determine whether the several favorable effects on LV function elicited only by the high-dose ACE-I treatment provide further beneficial effects on survival and LV remodeling compared with the combination therapy.