Masahide Watanabe

Overexpression of the PRAD1 Oncogene in a Patient with Multiple Myeloma and t(11;14)(q13;q32)

The t(11;14)(q13;q32) chromosomal translocation is associated with several B-cell lymphoproliferative disorders and is thought to result in upregulation of expression of PRAD1/cyclin D1 proto-oncogene. A patient with multiple myeloma of IgG kappa-type with t(11;14)(q13;q32) is now shown to overexpress PRAD1. The clinical stage of the disease was advanced (IIIA), with a myeloma cell count of 94.6% in the bone marrow. Chromosomal analysis of bone marrow cells showed t(11;14)(q13;q32) in five of 20 metaphases as well as other karyotypic features. Northern blot analysis of RNA prepared from myeloma cells revealed overexpression of PRAD1. Multiple myeloma with t(11;14)(q13;q32) has been associated with an aggressive clinical course. Although neither myeloma cells in the peripheral blood nor extramedullary lesions were apparent in the present patient, the myeloma was refractory to several chemotherapeutic regimens from the beginning. Detection of PRAD1 expression may offer an easier alternative to cytogenetic analysis in myeloma and is a potentially useful indicator of a poor prognosis.

Gastrointestinal post-transplant lymphoproliferative disorder with rapidly forming characteristic lesions after cord blood transplantation: a report of two cases.

Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder (PTLD) frequently involves the gastrointestinal tract, but the endoscopic characteristics of this condition have not been discussed in detail. We report two cases of EBV-related PTLD involving rapidly forming characteristic lesions. Case 1 was a 60-year-old man with acute myeloid leukemia who underwent cord blood transplantation (CBT) after which he initially achieved complete remission (CR). He developed nausea and vomiting on day 99. Gastrointestinal endoscopy showed no tumor-like lesions in his stomach. However, a second endoscopic evaluation, which was performed 7 days after the first, revealed multiple raised lesions in his stomach, and a histopathological examination of the biopsy specimen resulted in a diagnosis of EBV-related PTLD. Case 2 was a 36-year-old man with acute myeloid leukemia who underwent CBT after achieving his second CR. He suffered nausea and pharyngalgia on day 309. Although the initial gastrointestinal endoscopic examination showed only multiple erosive or small ulcerative lesions, a second endoscopic evaluation, which was performed 10 days after the first, revealed a raised lesion with a central ulcer in the duodenum. Histopathological examination of the biopsy specimen yielded a diagnosis of EBV-related PTLD. Both patients were successfully treated by reducing the dose of immunosuppressive agents and administering rituximab.

[Discordant lymphoma of duodenal EBV-positive peripheral T-cell lymphoma not otherwise specified and ileal diffuse large B-cell lymphoma].

A 79-year-old woman was admitted with a 5-kg weight loss and anorexia. Computed tomography showed diffuse lymphadenopathy, and thickening of the duodenal and ileal walls. The patient then underwent biopsy of these sites. Pathological examination revealed duodenal Epstein-Barr virus (EBV)-positive peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) and EBV-negative ileal diffuse large B-cell lymphoma (DLBCL) to be present simultaneously. Combination chemotherapy including rituximab produced a reduction of the duodenal EBV-positive PTCL-NOS lesion, but had no effect on the EBV-negative ileal DLBCL lesion. Thereafter, new lymphadenopathy, high fever, and lactate dehydrogenase (LD) elevation developed, complicated by pneumonia. The patient died due to rapid deterioration of the lymphoma and pneumonia on day 108 after initiation of treatment. EBV-positive PTCL-NOS is reportedly rare and the prognosis is poor. Moreover, EBV-negative ileal DLBCL was diagnosed simultaneously. This case is considered to have had an extremely rare discordant lymphoma, although the exact etiology of its development remains unknown. We speculate that age-related disorders of the immune system and HCV infection may have been associated with the pathogenic mechanism of lymphomagenesis in this case.

[Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life.

Bone Marrow Metastasis of Rhabdomyosarcoma Mimicking Acute Leukemia: A Case Report and Review of the Literature

Bone marrow metastasis of rhabdomyosarcoma has been reported to be difficult to distinguish from acute leukemia. We herein describe a case of rhabdomyosarcoma with bone marrow metastasis mimicking acute lymphoblastic leukemia. A 29-year-old woman was admitted with thrombocytopenia, blast-like cells in the peripheral blood and a coagulation disorder. Bone marrow aspirates showed 94.8% blast-like cell infiltration (CD45(-), myeloperoxidase(-), and CD56(+)), and CT scan revealed the presence of an infiltrating mass in the nasal cavity. Based on a biopsy of the nasal cavity, the patient was diagnosed with rhabdomyosarcoma exhibiting bone marrow metastasis. She received chemotherapy, followed by radiation therapy, and has since remained alive for 26 months, as of the last follow-up.