Takahiro Tamura

Diffuse Large B-cell Lymphoma Presenting with Hypercalcemia and Multiple Osteolysis

Osteolysis and hypercalcemia are observed in 5 – 15%, and 10%, respectively, of malignant lymphoma patients during their clinical course. However, both osteolysis and hypercalcemia are uncommon at onset of the disease. We encountered a 24-year-old male non-Hodgkins lymphoma patient who had multiple osteolytic lesion from the onset of the disease and repeated episodes of hypercalcemia during the clinical course. The patient died with refractory disease. We studied the expression of chemokines which might affect bone resorption using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Increased expressions of MIP-1α, MIP-1β and RANKL, which are osteoclast-activating factors, were observed in the RNA derived from the patients lymphoma cells. The secretion of osteoclast-activating factors such as MIP-1α by the tumor cells (and/or bone marrow stromal cells) might be involved in the etiology of osteolysis and hypercalcemia in some malignant lymphoma cases.

Secondary acute monocytic leukemia with a translocation t(8;16)(p11;p13): Case report and review of the literature

Acute myeloblastic leukemia cases carrying the translocation t(8;16) (p11;p13) are characterized by the M4 and M5 subtypes, erythrophagocytosis by the blast cells and a poor prognosis, suggesting a new clinical entity. The t(8;16) fuses the MOZ gene which encodes a histone acetyltransferase, located on 8p11 with the CBP gene which also encodes a histone acetyltransferase, located on 16p13, and recent reports suggested that the chimeric transcription MOZ-CBP is essential for leukemogenesis. A 68-year-old woman who had been treated mainly with paclitaxel and carboplatin for preceding ovarian cancer was admitted to our hospital, complaining of right breast mass. She was diagnosed as having breast cancer and acute monocytic leukemia (M5b). Cytogenetic study with spectral karyotyping analysis revealed the development of 47 XX, + 8, t(8;16)(p11;p13). Eleven cases of therapy-related t(8;16) leukemia including the present case have been reported, but prior treatment with paclitaxel and carboplatin-based chemotherapy has never been reported. The relation of histone acetylase and therapy-related leukemia is discussed.

Peripheral T-cell lymphoma presenting with rapidly progressing myelofibrosis.

Myelofibrosis following peripheral T-cell lymphoma has rarely been reported. Described here is a case of peripheral T-cell lymphoma with myelofibrosis and elevated transforming growth factor beta (TGF- β ). A 69 years old male was admitted due to anemia and thrombocytopenia. His bone marrow showed fibrosis and was infiltrated with small lymphoid cells and a few residual normal hematopoietic cells. He had presented with hepatosplenomegaly and left inguinal lymph node swelling. Biopsy of the left inguinal lymph node revealed diffuse mature small lymphoid cells with atypical nuclei. Immunophenotyping of the small lymphoid cells were positive for CD3, CD8, TCR α β and HLA-DR and were negative for CD4, CD19, CD20 and CD56. T-cell receptor β -chain gene was rearranged in bone marrow cells. He was diagnosed as having peripheral T-cell lymphoma complicated with myelofibrosis. Chemotherapy was administrated which improved his pancytopenia and symptoms. Two years later, anemia and thrombocytopenia developed rather quickly, he died because of progression of myelofibrosis with severe pancytopenia.

EBV associated hemophagocytic syndrome accompanied by central pontine myelinolysis

The development of central pontine myelinolysis (CPM) has rarely been reported in association with hemophagocytic syndromes (HPS). Here we report a unique case of Epstein-Barr Virus (EBV)-related HPS which was accompanied with CPM. A 72-year-old man who had no significant medical history was admitted to our hospital due to high fever and progressing dysphasia and dysarthria. Physical examination revealed anisocoria of the right pupil, fixed reaction to light, and paralysis of the left vagus nerves. Magnetic resonance imaging revealed low signal intensity on T1-weighted images and high signal intensity T2-weighted images in the patients central midpontine lesion. Initial work-up showed anemia and thrombocytopenia with elevated levels of serum ferritin, lactate dehydrogenase, and soluble IL-2 receptor. Bone marrow aspiration revealed hemophagocytosis. The EBV genome was detected in the peripheral blood using the polymerase chain reaction method. He was diagnosed as having EBV-related HPS and CPM. Despite intensive treatment with methyl-predonisolone, immunoglobulin, and etoposide, he died due to progressive disease and fungal septicemia. The etiology and relation between CPM and HPS are discussed.

Increased expression of c-maf in pure red cell aplasia secondary to plasma cell dyscrasia.

Th2 dominancy in the peripheral T helper (Th) cell subsets were reported to be involved in the pathogenesis of pure red cell aplasia (PRCA). We encountered a PRCA case secondary to plasma cell dyscrasia that showed Th2 dominancy at the relapse of PRCA. Increased expression of c-maf, a transcriptional factor which induces Th2 differentiation of naive T-cells, and elevated expression of interleukin (IL)-4 were observed in the RNA derived from patients bone marrow at relapse of PRCA. Following the administration of methylprednisolone which improved PRCA, normalization of Th1/Th2 ratio and decreased expression of c-maf and IL-4 were observed, which suggests that the upregulation of c-maf might have played a role in the pathogenesis of PRCA secondary to plasma cell dyscrasia.

Marked thrombocytosis following relapse of acute myeloblastic leukemia associated with development of translocation (2;14) (p13;q32).

Thrombocytosis is a rare finding in acute myeloblastic leukemia (AML). Here, we describe a patient with AML who relapsed with marked thrombocytosis. The patient was initially diagnosed as having AML (M4) with a low platelet count. The patient was started on combination chemotherapy including high-dose etoposide and achieved complete remission. However, the patient relapsed six months later with an extremely high platelet count (72.5 2 10 4 / w l). Cytogenetic analysis at relapse revealed the development of t(2;14)(p13;q32). Despite the repeated combination chemotherapy, the patient died with progressive disease. This case suggests that the additional chromosomal aberration t(2;14)(p13;q32) may be related to abnormal thrombocytosis in AML.