Hideki Tsujimura

Fatal chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis

We report a 22-year-old female who presented with pyrexia, pancytopenia and liver dysfunction. The patient showed mild liver dysfunction with low-grade fever and mild hepatosplenomegaly 6 years previously, and autoimmune hepatitis (AIH) was diagnosed based on the examination of the laboratory data and liver biopsy. On admission, both markers of Epstein-Barr virus (EBV) and in-situ hybridisation from a liver biopsy specimen indicated chronic active EBV infection (CAEBV). The patient was administered an immunosuppressive agent and antiviral drug added to steroid therapy, but ultimately died from liver failure and virus-associated haemophagocytosis 10 months after the definite diagnosis. Retrospective examination of the serum at the diagnosis of AIH revealed extremely high titres of antibody to EBV, and EBV-DNA was also detectable by polymerase chain reaction. These results suggest the possibility that the patient may already have suffered from CAEBV at the initial diagnosis. We presume that hepatic involvement of CAEBV should be considered as differential diagnosis in cases showing liver dysfunction with clinical and biochemical features observed in AIH.

Significance of parathyroid hormone-related protein as a factor stimulating bone resorption and causing hypercalcemia in myeloma

Elevated levels of parathyroid hormone‐related protein (PTHrP) in hypercalcemic myeloma patients were demonstrated in recent reports, suggesting that PTHrP behaves as a humoral mediator of hypercalcemia in myeloma. Herein we describe a hypercalcemic myeloma patient with a high serum PTHrP level. Moreover, the PTHrP level in the supernatant of bone marrow aspirates was about two‐fold of that in serum. Reverve transcriptase‐polymerase chain reaction analysis showed PTHrP m‐RNA in bone marrow containing myeloma cells. After chemotherapy, the concentrations of calcium and PTHrP decreased and PTHrP mRNA in bone marrow became undetectable. We conclude that PTHrP released by myeloma cells acted as the main bone resorption stimulating factor in this case. Am. J. Hematol. 59:168–170, 1998.

Involvement of the Appendix in a Relapsed Case of Primary Nasal NK/T-Cell Lymphoma

We report here a 20-year-old man presenting with primary nasal NWT-cell lymphoma which showed an aggressive clinical course spreading to the spleen and skin despite various treatments. Eight months after high dose chemotherapy followed by autologous peripheral blood stem cell transplantation, acute appendicitis with perforation occurred and the patient underwent appendectomy. The histopathological diagnosis was NKR-cell lymphoma of the appendix. Lymphoma of the appendix is extremely rare and the majority of appendiceal lymphomas are of B-cell origin. This is the first report of involvement of appendix by nasal NKR-cell lymphoma.

Therapy-related leukemia following chemoradiotherapy for esophageal cancer

Chemoradiotherapy has improved the outcome of patients with esophageal cancer. Although a sufficiently long‐time survival has resulted in the increase of several treatment‐related late toxicities, little is still known about the incidence of secondary malignancies. In our hospital, 348 patients with esophageal cancer received chemotherapy consisting of nedaplatin and 5‐fluorouracil and concurrent irradiation. Median and average follow‐up durations were 8 and 21 months (1–92), respectively. Four patients developed leukemia after 19–48 months of follow‐up. Two patients were diagnosed with overt leukemia from myelodysplastic syndrome presenting a complex karyotype, including the deletion of chromosome 5 or 7. Notably, one patient showed an additional chromosomal abnormality with t(9;22)(q34;q11). Other patients developed acute myeloid leukemia with t(9;22)(q34;q11) and Burkitt leukemia with t(8;14)(q24;q32). All patients eventually succumbed to leukemia. Platinum and fluorouracil have shown relatively lower risks for secondary malignancies in comparison with alkylating agents and topoisomerase II inhibitors. Especially, nedaplatin has never been described to introduce secondary neoplasms. Our report supports the idea that the concurrent administration of radiotherapy with these agents affects the risk of leukemia. Interestingly, rare balanced chromosomal abnormalities were observed in the present cases, thus providing new insights into the leukemogenesis of therapy‐related leukemia.

Expression of activation-induced cytidine deaminase is associated with a poor prognosis of diffuse large B cell lymphoma patients treated with CHOP-based chemotherapy

PurposeActivation-induced cytidine deaminase (AID) is involved in somatic hypermutation and class switch recombination processes in the antibody formation. The AID activity induces gene mutations and could be associated with transformation processes of B cells. Nevertheless, the relation between AID expression and the prognosis of B cell lymphoma patients remains uncharacterized.MethodsWe examined expression levels of the AID gene in 89 lymph node specimens from lymphoma and non-lymphoma patients with Northern blot analysis and investigated an association with their survival.ResultsThe AID gene was preferentially expressed in B cell lymphoma in particular in diffuse large B cell lymphoma and follicular lymphoma. We confirmed AID protein expression in the mRNA-positive but not in the negative specimens with Western blot analysis and immunohistochemical staining. Survival of the patients treated with cyclophosphamide-/doxorubicin-/vincristine-/prednisone-based chemotherapy demonstrated that the prognosis of diffuse large B cell patients was unfavorable in the mRNA-positive group compared with the negative group, and that AID expression levels were correlated with the poor prognosis. In contrast, AID expression was not linked with the prognosis of follicular lymphoma patients.ConclusionsAID expression is a predictive marker for an unfavorable outcome in DLBCL patients treated with the chemotherapy.

Translocation (5;9)(q22;q34) in a case of acute lymphoblastic leukemia with multiple bone involvement: effectiveness of donor lymphocyte infusion for relapse after allogeneic stem cell transplantation.

A case of acute lymphoblastic leukemia with a new translocation, t(5;9)(q22;q34) is reported with special reference to the clinical features and the response to treatment. This case exhibited several unique clinical features, including expression of the myeloid antigen on the early pre-B-cell phenotype, multiple bone involvement, and favorable response to donor lymphocyte infusion despite early relapse after allogeneic hematopoietic stem cell transplantation.

Multiple lymphomatous polyposis overexpressing cyclin D1

A case of mantle cell lymphoma (MCL) associated with multiple lymphomatous polyposis (MLP) is reported is a 62-year-old woman, with special reference to the patients clinical features and response to treatment. There were multiple widespread polypoid lesions in the entire gastrointestinal tract, with ileocecal masses. Ileocecal resection was performed on immunohistochemical examination, the neoplastic cells in the polypoid lesions stained positively for cyclin D1. Two conventional anthracycline-containing regimens (adriamycin-cyclophosphamide-vincristine-prednisolone [CHOP] and mitantroxone-etoposide-vindesine-prednisolone [MEVP]) were administered, but had limited success. The patient has since been receiving an irinotecan-adriamycin regimen (irinotecan, 25 mg/m2, days 1 and 2; adriamycin, 40 mg/m2, day 3, once a month) as an outpatient and has achieved good partial remission. She is well with disease 48 months after the initiation of the initial treatment.