Notably, peripheral blood involvement of lymphoma cells was observed in only one DLBCL case, whereas three of the four follicular lymphoma cases presented peripheral blood involvement (1)

Notably, peripheral blood involvement of lymphoma cells was observed in only one DLBCL case, whereas three of the four follicular lymphoma cases presented peripheral blood involvement (1). of primary bone marrow DLBCL accompanying CAD. Previously, malignant lymphoma exclusively involving the bone marrow, namely primary bone marrow lymphoma (PBML), has been recognized as a rare and aggressive subtype. The analyses of the present study revealed that the incidence of hemolytic anemia in primary bone marrow DLBCL may be high compared with conventional DLBCL. Therefore, additional analyses are required to clarify the clinicopathological features of PBML. Keywords:diffuse large B cell lymphoma, cold agglutinin disease, primary bone marrow lymphoma == Introduction == Bone marrow involvement SJG-136 by malignant lymphoma is generally considered as a systemic dissemination of the disease arising elsewhere, such as the lymph nodes and extranodal organs. However, albeit extremely rare, malignant lymphomas exclusively involving the bone marrow have been previously reported (1). Recently, the diagnostic criteria for primary bone marrow lymphoma (PBML) have been proposed and the clinicopathological features SJG-136 of this extremely rare tumor have also been documented (1). Cold agglutinin disease (CAD) accounts for 1315% of patients with autoimmune hemolytic anemia and is characterized by the presence of cold agglutinins, which are antibodies that agglutinate erythrocytes at an optimum temperature of 04C (2,3). Traditionally, CAD has been classified into a primary type, not associated with malignant lymphoma or other diseases and a secondary type, accompanying infection (such as Epstein-Barr virus andMycoplasma pneumoniae) and malignant disease, most often malignant lymphoma. However, it has been previously recognized that even the primary form is frequently associated with an underlying lymphoproliferative disease in the bone marrow (3). Although 76% of CAD patients Rabbit Polyclonal to NCAPG have been found to exhibit underlying malignant B-cell lymphoma in the bone marrow (2,3), the incidence of CAD in patients with non-Hodgkin lymphoma is low (4). Previously, Varoczyet alreported that of 421 non-Hodgkin lymphoma patients, 7.6% exhibited an autoimmune disease and only one patient exhibited autoimmune hemolytic anemia (5). To the best of our knowledge, only one case of primary bone marrow diffuse large B cell lymphoma (DLBCL) presenting with CAD has been previously reported (6). The present report describes the second case of primary bone marrow DLBCL accompanying CAD. Written informed consent was obtained from the patient. == Case report == == Case presentation == A 76-year-old male with a past history of traumatic epilepsy presented to Shiga University of Medical Science Hospital (Otsu, Japan) with fever and fatigue. Physical examination revealed jaundice in the patients bulbar conjunctiva and no superficial lymph nodes were palpable. The patient did not describe symptoms of acrocyanosis. Laboratory tests demonstrated marked anemia and elevation of total bilirubin and lactate dehydrogenase (hemoglobin, 7.4 g/dl; mean cell volume, 90 fl; white blood cell count, 5.3109/l; lymphocytes, 2.3109/l; lactate dehydrogenase, 558 IU/l; bilirubin, 131.7 mol/l; and soluble interleukin-2 receptor, 1,220 U/ml). Systemic surveillance by imaging studies failed to detect any tumorous lesions, lymphadenopathy or hepatosplenomegaly. The direct antiglobulin test was positive, with anti-C3d specificity. Anti-IgG was negative and indirect antiglobulin test was also positive. Cold agglutinins were present with a titer of 8,192 at 4C and <1 at 37C. Bone marrow aspiration and biopsy were performed. Subsequently, R-THP-COP (rituximab, 375 mg/m2; pirarubicin, 40 mg/m2; vincristine, 0.8 mg/m2; cyclophosphamide, 650 mg/m2; and prednisolone, 40 mg/m2) therapy was performed. Following six cycles of R-THP-COP therapy, the cold agglutinin titer was markedly decreased (by <4), and bilirubin (15.6 mol/l) and lactate dehydrogenase (186 IU/l) levels were also reduced. Bone marrow aspiration revealed no neoplastic lymphocytes. Following 19 months of the initial chemotherapy, malignant lymphoma relapsed. Cold agglutinins were present again with a titer of 4,096 at 4C. The patient ultimately succumbed to the disease. == Immunohistochemistry == The formalin-fixed, paraffin-embedded tissue blocks were sectioned (3-m-thick), deparaffinized and rehydrated. Each SJG-136 section was stained with hematoxylin and eosin and used for immunostaining. Immunohistochemical analyses were performed.