T‐cell‐rich B‐cell lymphoma of the spleen presenting with severe hypersplenism

We report a 19‐year‐old woman who was presented with B‐symptoms, massive splenomegaly, hepatomegaly and hypersplenism. She underwent diagnostic/therapeutic splenectomy. Microscopically, the spleen showed a vaguely micronodular and diffuse proliferation of lymphoid cells in the white pulp that also involved the red pulp. On immunohistochemical staining, this proliferation consisted predominantly of CD3⁺, CD7⁺ small T cells with the presence of a minor populat?on of CD15^?,CD30^?, CD20⁺ large atypical B cells. A liver biopsy also showed a similar morphology to that seen in the spleen. After splenectomy, only the pancytopenia improved. A combined immunochemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) was utilized, which resulted in a complete remission.     

Concomitant angioimmunoblastic T‐cell lymphoma and low grade B‐cell lymphoproliferative disorder

The presence of a rearranged immunoglobulin gene, in addition to the expected T‐cell receptor gene rearrangement, is a frequent, albeit poorly understood, finding in the setting of angioimmunoblastic lymphadenopathy. A case of an angioimmunoblastic T‐cell lymphoma is presented, where this apparently paradoxical dual gene rearrangement could be ascribed to the coexistence of an occult B‐cell lymphoproliferative disorder.     

Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma

Although a number of studies suggest that different immune pathways may play a role in the pathogenesis of non‐Hodgkin's lymphomas (NHL), the shape of the T‐cell compartment has been only superficially explored in these patients. In our study, we analyzed the peripheral T‐cell receptor (TCR) repertoire and the distribution of different T‐cell subsets – including regulatory T cells (Treg) – in 30 patients with NHL, by combining flow cytometry and spectratyping. We first demonstrated by flow cytometry an increased frequency of expanded T‐cell subpopulations expressing the same TCR beta variable (BV) subfamilies in CD8+ cells from NHL patients when compared with healthy controls, beside a higher frequency of Treg. Moreover, NHL patients were characterized by a higher percentage of BVs showing a skewed CDR3 profile both in CD4+ and CD8+ cells when analyzed by spectratyping. Our data suggest that the T‐cell branch of the immune system of patients with B‐cell NHL is deeply deranged, as witnessed by the increased degree of activation and skewing of their TCR repertoire along with the higher frequency of Treg.     

B‐cell lymphoma,unclassifiable, with features intermediate between diffuse large B‐cell lymphoma and burkitt lymphoma: study of 39 cases

B‐cell lymphoma, unclassifiable (B‐UCL), with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma, is a poorly characterized entity. Therefore, we investigated cases of B‐UCL treated by the Nebraska Lymphoma Study Group (NLSG). We searched the NLSG registry for years 1985–2010 for cases of B‐UCL. Immunohistochemical stains and fluorescence in situ hybridization studies for MYC, BCL2 and BCL6 gene rearrangements were performed. Among the 39 cases studied, 54% were male and 46% were female, with a median age of 69 years. The majority of patients presented with advanced‐stage disease (62%) and had high (3–5) International Prognostic Index (IPI) scores (54%). The median overall survival (OS) was only 9 months and the 5‐year OS was 30%. Patients with low IPI scores (0–2) had a better survival than those with high scores (3–5). The cases were genetically heterogeneous and included 11 ‘double‐hit’ lymphomas with rearrangements of both MYC and BCL2 or BCL6. None of the immunohistochemical or genetic features was predictive of survival. This B‐cell lymphoma is a morphologically‐recognizable entity with a spectrum of genetic abnormalities. New and better treatments are needed for this aggressive lymphoma.     

Central nervous system involvement in diffuse large B‐cell lymphoma

Background: Malignant lymphoma with central nervous system (CNS) involvement has an extremely poor prognosis. We retrospectively studied the risk factors for CNS involvement in patients with diffuse large B‐cell lymphoma (DLBCL) treated by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab (R) ‐CHOP chemotherapy. Patients and methods: We studied 375 consecutive patients who were newly diagnosed with DLBCL between 1996 and 2006. Patients with primary CNS involvement and patients who received CNS prophylaxis were excluded. All the patients received CHOP (n = 172) or R‐CHOP (n = 203) chemotherapy. The following variables were assessed for their potential to predict CNS involvement: gender, age, serum lactate dehydrogenase (LDH) level, performance status, clinical stage, number of extranodal involvements, International Prognostic Index (IPI), bone marrow involvement, presence of a bulky mass, presence of B symptom, and treatment. Results: CNS involvement was observed in 13 cases (3.5%). In univariate analysis, LDH more than normal range, LDH more than twice as normal range, high IPI, bone marrow involvement, and systemic relapse were the predictors for CNS involvement. In multivariate analysis, no risk factors were detected for CNS involvement. The use of rituximab did not have an impact on CNS involvement. Conclusions: The incidence of CNS involvement dose not decrease in rituximab‐era.     

Diffuse large B‐cell lymphoma resembling a metastatic liver tumour

In November 2014 the International Myeloma Working Group (IMWG) revised the definition of multiple myeloma, such that asymptomatic patients with newly diagnosed multiple myeloma without any of the traditional ‘CRAB’ (hyperc alcaemia, r enal impairment, a naemia, b one disease) end organ damage criteria but with one of three new criteria would be recommended to start treatment. Previously, the standard of care for such patients was expectant management. These three new criteria are: greater than 60% clonal plasma cells on bone marrow biopsy, a serum free light chain (sFLC) ratio of >100 (the involved sFLC must be >100 mg/l) and greater than one unequivocal focal lesion on advanced imaging (low dose whole body computerized tomography, magnetic resonance imaging, ¹⁸F fluorodeoxyglucose positron emission tomography). Although this would appear to affect a small number of patients, the impact of these changes are broad, leading to an increased use of advanced imaging, a debate around the management of patients previously diagnosed with smouldering myeloma, changed terminology and clinical trial design and an extension of the use of biomarkers. For the first time the philosophy of treatment in myeloma will change from treatment initiation only being triggered by overt end organ damage to an era where sub clinical risk factors will also be taken into account.     

Primary bilateral diffuse large B‐cell lymphoma of the adrenals

‘Wrong blood in tube’ (WBIT) errors, where the blood in the tube is not that of the patient identified on the label, may lead to catastrophic outcomes, such as death from ABO‐incompatible red cell transfusion. Transfusion is a multistep, multidisciplinary process in which the human error rate has remained unchanged despite multiple interventions (education, training, competency testing and guidelines). The most effective interventions are probably the introduction of end‐to‐end electronic systems and a group‐check sample for patients about to receive their first transfusion, but neither of these eradicates all errors. Further longer term studies are required with assessment before and after introduction of the intervention. Although most focus has been on WBIT in relation to blood transfusion, all pathology samples should be identified and linked to the correct patient with the same degree of care. Human factors education and training could help to increase awareness of human vulnerability to error, particularly in the medical setting where there are many risk factors.     

Clinicopathological analysis of primary splenic diffuse large B‐cell lymphoma

Splenic infiltration is often seen in diffuse large B‐cell lymphoma (DLBCL). However, primary splenic DLBCL is rare and studies on its clinicopathological features are limited. We assessed 66 cases of primary splenic DLBCL and 309 control DLBCL, not otherwise specified. Hepatitis C virus antibody prevalence, B symptoms, poor performance status and CD5 positivity differed significantly between the primary splenic DLBCL and control DLBCL groups. Primary splenic DLBCL cases were classified histopathologically into two groups [white pulp pattern (n = 46), red pulp pattern (n = 20)]. Survival analysis showed no difference in overall survival between the primary splenic DLBCL and the control group, but the former had a more favourable progression‐free survival. In the examination of primary splenic DLBCL, the white pulp pattern was statistically associated with a lower performance status (2–4), and a lower CD5 positivity than the red pulp pattern. In the survival analysis, the red pulp pattern demonstrated poorer overall survival. Multivariate analysis of overall survival in primary splenic DLBCL cases identified CD5 positivity as an indicator of poor prognosis. Classifying primary splenic DLBCL into white and red pulp patterns was useful in terms of clinicopathological features and overall survival.