Chikara Sakai

Histiocytic sarcoma of the spleen associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia as a possibly unique clinical entity--report of three cases.

We report three patients with histiocytic sarcoma of the spleen associated with severe hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia. After the clinical diagnosis of splenic tumor of unknown origin was made, all three patients underwent splenectomy. The histiocytic origin of the tumor was confirmed histopathologically and immunohistochemically using a panel of antibodies. In contrast to malignant histiocytosis (MH), which typically reveals severe generalized clinical manifestations and a rapidly fatal course caused by the disseminated proliferation of neoplastic histiocytes, these patients were asymptomatic or showed only mild clinical symptoms for a long period of time until the recurrence was detected by which time the tumor cells had already spread to other organs. All three cases were characteristically associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia, which returned to normal after splenectomy. Splenic histiocytic sarcoma with the features described here may represent a unique clinical entity, distinct from MH.

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.

Scleroderma-like lesions and Epstein-Barr virus-associated B-cell lymphoma presenting with a huge splenomegaly

To the Editor: The association between scleroderma and lymphoma has been an area of debate (1-4). Recently, some investigators have shown that some lymphomas complicating rheumatoid arthritis or dermatomyositis are related to Epstein-Barr virus (EBV) (5-7). We experienced an EBV-associated B-cell lymphoma developing in a patient with eosinophilic fasciitis (EF), one of the scleroderma syndromes (8, 9). Although EF is occasionally accompanied by haematological diseases including malignant lymphomas (2, 9), an EBV-associated lymphoma complicating EF has not been reported previously. A 74-yr-old woman was referred to our hospital for evaluation of right axillary lymphadenopathy in January 1994. She had a past history of left-breast cancer which had been radically resected in April 1986, and she had received tamoxifen for 2 yr after mastectomy. In November 1988 she had become aware of stiffened skin. A skin biousv. performed at receptor beta chain gene or the BCL-2 gene was seen. A southern blot hybridization analysis using a DNA probe specific for the fused termini of the EBV genome revealed two bands with the same intensity, indicating two clonal populations (Fig. 3). The patient received CHOP therapy and gained a partial remission lasting 5 months. However, the lymphoma recurred and the patient died of cytomegalovirus pneumonia in July 1995. At autopsy residual lymphoma cells were detected in the spleen (240 g) and para-aortic lymph nodes. No carcinoma cells were seen anywhere. Usually EBV-associated lymphomas develop in immunosuppressed patients such as recipients of organ transplantation or patients with acquired immunodeficiency syndrome, and these lymphoma cells are often positive for LMP-1 (10, 11). On the other hand, Ki-1 (CD30) positive ALCL is frequently EBV-related, irrespective of whether

T CELL-RICH B CELL LYMPHOMA BEARING EPSTEIN-BARR VIRUS IN TUMOR CELLS : A CASE OF IBL-T-LIKE LESION FOLLOWING LENNERT'S LESION

A case of T cell‐rich B cell lymphoma (TCRBCL) with Epstein‐Barr virus (EBV) infection in tumor cells is reported. A 50 year old male developed right cervical lymph node swelling in July 1988. Initial biopsy in April 1989 demonstrated many scattered Hodgkinoid atypical cells with Lennerts lesion. After partial remission following chemotherapy, the lymph nodes enlarged again, and a second biopsy in February 1991 showed an IBL‐T‐like lesion. Only a small number of Hodgkinoid atypical cells were still observed. After apparently, complete remission, the lesion soon recurred and the patient died in November 1992. Immunohistochemically the Hodgkinoid cells were positive for L26, but negative for LN2, LN3, UCHL‐1, MT1, lysozyme, Ber‐H2 and Leu‐M1. Reactivity for immunoglobulins showed falsepositive because of poly‐clonal staining. IgH monoclonality was detected by the poly‐merase chain reaction method in the first biopsied specimen, and by Southern blotting in the second biopsied snap‐frozen specimen. Monoclonal TCRβ rearrangement was not detected. The Hodgkinoid atypical cells were positive for EBVencoding RNA by in situ hybridization, and LMP‐1 by immunostaining. Occasionally, EBV‐bearing immunoblastic, medium sized, or small lymphocytic cells were also observed. This case indicates the possibility that EBV is related to the pathogenesis of TCRBCL.

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.

Meningeal myelomatosis developed after treatment with novel agents

A 66-year-old woman was diagnosed in March 2007 with Bence-Jones protein-lambda positive (BJP k) multiple myeloma. After four cycles of bortezomib and dexamethasone, complete response was achieved in 2009. Radiotherapy was performed for skull and spine lesions in 2010 and 2011. She remained in stable disease with disappearance of M protein and bone marrow plasma cells on maintenance therapy with bortezomib, thalidomide, and dexamethasone. However, in May 2012, serum LDH began to elevate and multiple subcutaneous plasmacytoma appeared. Subcutaneous tumors increased following administration of lenalidomide and dexamethasone. Bone marrow examination in September 2012 demonstrated 50.8 % plasma cells. Cytogenetic analysis revealed a complex karyotype including chromosome 13 deletion and t(8;14)(q24;q32) in 19 of 20 metaphase cells. Although VCAP (vincristine, cyclophosphamide, doxorubicin, and prednisolone) slightly decreased subcutaneous tumors, she complained of headache, pain in the neck, dizziness, nausea, and vomiting in February 2013. Laboratory studies showed serum protein 6.2 g/dL, LDH 711 IU/L (normal range 80–200 IU/L), b2 microglobulin 2.5 mg/L, free light chain (FLC) j\ 0.6 mg/L (3.3–19.4 mg/L), k 269.0 mg/L (5.7–26.3 mg/L), and urine M protein 118 mg/24 h. Brain magnetic resonance imaging demonstrated meningeal contrast enhancement, particularly in the posterior fossa (Fig. 1). A lumbar puncture revealed a cerebrospinal fluid (CSF) protein of 48 mg/dL (10–53 mg/dL) and a marked pleocytosis of 300 cells/lL. The CSF cytology showed numerous plasma cells with prominent nucleoli (Fig. 2). FLC assay of the CSF demonstrated k chain restriction: j\ 0.6 mg/L, and k 435.0 mg/L. A diagnosis of meningeal myelomatosis was made. No plasma cells were identified in the peripheral blood. The patient received intrathecal chemotherapy of methotrexate and dexamethasone with no response, and died 1 month after the diagnosis. Meningeal myelomatosis, defined by the presence of monoclonal plasma cells in the CSF, is extremely rare and accounts for approximately 1 % of myeloma patients. Previous reports suggest an association of meningeal myelomatosis with extramedullary disease, plasmablastic morphology, cytogenetic abnormalities, high LDH levels, and circulating plasma cells. These are characteristics of aggressive myeloma, some of which we confirmed in our patient. Meningeal myelomatosis occurs as a terminal event in the majority of patients. The prognosis remains poor despite aggressive local and systemic treatment, including stem cell transplantation, with a median overall survival of only a few months. Recently, investigators have showed that the novel agents, thalidomide and lenalidomide, cross the blood–brain barrier and are effective for the management of meningeal myelomatosis [1–3]. However, our patient developed meningeal myelomatosis after receiving these same agents. Cerebral symptoms are commonly seen in terminal-stage myeloma patients from hypercalcemia, uremia, hyperviscosity syndrome, or toxicity of treatment. Physicians should be alert to the possibility of meningeal myelomatosis. The FLC assay of CSF will be helpful for diagnosis even when the CSF cell count and protein level are not elevated. To our knowledge, this is the first report of the use of FLC assay of CSF for diagnosis of meningeal myelomatosis. M. Ise (&) C. Sakai K. Kumagai Department of Hematology-Oncology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba, Chiba 260-8717, Japan e-mail: mise@chiba-cc.jp

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.

Peripheral T-cell lymphoma developed in a patient with 4-year-latency following transient systemic lymphadenopathy.

A 36-year-old male developed systemic lymphadenopathy with Coombs-positive hemolytic anemia and polyclonal hypergammaglobulinemia.Histological diagnosis of the biopsied lymph node was undetermined, and suspected of reactive lymphadenopathy probably due to viral infection. The symptoms spontaneously disappeared within a half year.Systemic lymphadenopathy recurred 4 years later without hemolytic anemia and polyclonal hypergammaglobulinemia. Biopsied lymph node was diagnosed as peripheral T-cell lymphoma. The lack of manifestation of immunological abnormalities at the neoplastic stage of the disease suggests the probable different clonal origins of cells proliferating in the lymph node biopsied initially. The patient achieved complete remission by CHOP therapy, and remains free of disease a year to date.