Multilobated B-cell lymphoma, a variant of centroblastic lymphoma. Report of four cases

Four cases of multilobated B-cell lymphoma, one follicular and three diffuse, are described. Many of the lymphoma cells show marked lobulation of the nuclei, and possess multiple prominent nucleoli. There are admixed classical centrocytes, classical centroblasts, and cells with morphology intermediate between classical centroblasts and multilobated cells. Multilobated cells are also observed in small numbers in germinal centres of lymph nodes showing reactive follicular hyperplasia. We believe that the multilobated B-cell may represent one form of centroblast during transition between the centroblastic and centrocytic stages. Multilobated B-cell lymphoma may be its neoplastic counterpart in which the nuclear lobulation is further exaggerated.     

High-grade non-Hodgkin''s lymphoma of B-cell type. I. Histopathology

One hundred and twenty-eight cases of high-grade malignant B-cell lymphoma were studied with a plastic re-embedding technique and classified according to the Kiel classification. The cytological details could be better recognized than in the original paraffin sections, thus permitting a more precise definition of the various lymphoma types. The entities centroblastic and immunoblastic lymphoma are more precisely defined and supplemented by the addition of several new variants. In contrast to the present Kiel classification we separate Burkitt's from lymphoblastic lymphoma. In all cases investigated, the B-cell nature of the tumour cells was proven by immunohistochemistry using monoclonal antibodies. The four entities of high-grade malignant B-cell lymphoma described in this paper are: (1) centroblastic lymphoma with four morphological variants (monomorphic, polymorphic, multilobated and centrocytoid); (2) immunoblastic lymphoma with three morphological variants (with or without plasmacytic differentiation, with many lymphocytes); (3) Burkitt's lymphoma and the closely related Burkitt's lymphoma-like lymphoma with plasmablastic differentiation; and (4) lymphoblastic lymphoma. Only the centroblastic lymphomas (in 17%) showed occasional follicular growth pattern, which further confirms the view that they are derived from germinal centre cells.     

Biclonality of Composite B- and T-cell Lymphomas A Case Report

Most composite lymphomas which are composed morphologically of two different tumor cell types are considered to represent different morphological expressions of a single clone. However, in recent years, composite B- and T cell lymphomas and biclonality of B cell lymphoma have been reported. We experienced a case of composite lymphoma which initially developed as cutaneous lymphoma composed of lymphoplasmacytes associated with large clear cells. It was confirmed that the tumor cells of these two systems were biclonal on the basis of surface markers and DNA rearrangements, i.e. B cells of the IgG kappa type, showing IgH and kappa chain DNA rearrangement, and Tcells with CD4 surface marker, showing rearrangement of the T cell receptor beta chain gene. This case showed a predominant B cell pattern at the initial stage, and terminated in T cell lymphoma, as revealed at autopsy. Therefore we considered this case to be a unique composite lymphoma showing biclonality of both B- and T-cell systems, providing a number of suggestions for future study of malignant lymphoma.     

Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non-cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept

Aigner F, Korol D, Schmitt A M & Kurrer M O
(2012) Histopathology  60, 774–784 Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non‐cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept Aims: Follicle centre cell lymphoma of small cell type showing either a follicular or diffuse growth pattern similar to cutaneous follicle centre lymphoma (cFCL) has been recognized in extranodal non‐cutaneous sites. Our aim was (i) to investigate whether diffuse large B cell lymphoma (DLBCL) of cFCL type could be identified in extranodal non‐cutaneous sites and (ii) whether clinical characteristics similar to primary cFCL could be recognized. Methods and results: Of 24 extranodal non‐cutaneous DLBCLs, nine (38%) had large centrocytoid morphology and 15 (62%) were either ‘centrocytoid and centroblastic’ or ‘centroblastic and immunoblastic’. Six centrocytoid cases were Irf‐4 negative, Bcl‐6 positive and at most weakly CD10‐ or Bcl‐2‐positive by immunohistochemistry, consistent with DLBCL of cFCL type. All patients with cFCL type were stage IE and were significantly younger than other patients. Recurrences occurred in two patients and were exclusively extranodal. Conclusion: Our results suggest that DLBCL of cFCL type can be identified in extranodal non‐cutaneous sites and shows clinical characteristics similar to genuine cFCL. We propose to expand the concept of cFCL to encompass large cell lymphomas in extranodal sites.     

Diagnostic features of gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

Gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue may be difficult to distinguish from florid gastritis and other small B-cell lymphomas. The following review details a practical summary of the morphologic features, immunohistochemical markers, and molecular tests that currently provide for an accurate diagnosis in daily practice.     

Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases

AIMS: Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology. METHODS AND RESULTS: Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL. CONCLUSIONS: MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.     

Mediastinal large-cell lymphoma of B-type, with sclerosis: Histopathological and immunohistochemical study of eight cases

Eight cases of mediastinal non-lymphoblastic large-cell lymphoma have been studied by histopathological and immunohistochemical methods. A common clinical, morphological and immunophenotypic pattern was identified. Six of eight cases proved to be of B-cell origin by the expression of B-associated antigens detected by specific monoclonal antibodies. Cells of large size with nuclei of varying morphology and a peculiar type of fine compartmentalizing fibrosis were observed in all specimens. Clinically the disease was characterized by the young age of the patients, primary mediastinal involvement, aggressive behaviour and spread to unusual sites (kidneys in four cases). This seems to be a hitherto unrecognized entity in the field of non-Hodgkin's lymphomas, often misdiagnosed because of location and a morphology uncommon for B-cell malignancies. Immunohistochemical analysis on frozen tissue sections appears to be mandatory for a correct diagnosis. Nevertheless, this type of lymphoma could be suspected also on the basis of its peculiar clinicopathological characteristics.     

Malignant lymphoma with myxoid stroma: a new pattern in need of recognition

We report a case of malignant lymphoma in the soft tissues exhibiting prominent myxoid stromal changes and cord-like cellular arrangement, mimicking the architectural as well as cytological features of myxoid chondrosarcoma, except for the absence of tumour lobulation. The only clue to the possible lymphomatous nature of the lesion was the past history of lymphoma. Immunohistochemical studies showed that this represented a B-cell lymphoma, staining positively for leucocyte common antigen and five B-lineage markers L26, MB2, B1 (CD20), B4 (CD19) and To15 (CD22). We conclude that malignant lymphoma should not be excluded from consideration when one encounters a myxoid tumour.     

Development of angioimmunoblastic T-cell lymphoma after treatment of diffuse large B-cell lymphoma: a case report and review of literature

Cases of diffuse large B-cell lymphoma (DLBCL) arising after the initial diagnosis of angioimmunoblastic T-cell lymphoma (AITL) and DLBCL synchronous with AITL have been reported. To date, there is no report on the subsequent development of AITL in patients with DLBCL. Here we presented a rare case of AITL developing six months after the initial diagnosis of DLBCL. In order to investigate the clinical and molecular features of patients with AITL and DLBCL, we also reviewed the literature on AITL patients developing DLBCL, and patients with composite AITL and DLBCL.     

Peripheral T-cell lymphoma: a clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification

A total of 41 non-cutaneous peripheral T-cell lymphomas were classified following the updated Kiel classification. Of these, 20 cases belonged to the low-grade group (T-cell chronic lymphocytic leukaemia, 3; lymphoepithelioid, 5; angioimmunoblastic, 4; pleomorphic small cell, 8) and 21 to the high grade group (pleomorphic medium and large cell, 11; immunoblastic, 3; large-cell anaplastic Ki-1 positive, 7). Seventy per cent showed a CD4+/CD8-phenotype, 39% a defective phenotype and 88% an activation phenotype. Eighty per cent had B-symptoms, 63% hepatomegaly, 48% splenomegaly and 26% had involvement of more than three lymphoid areas. Bone marrow was infiltrated in 34% central nervous system in 4%, lung in 12% and skin in 14.6%. Seventeen per cent presented with extranodal disease and 82.8% had stage III/IV disease. Hypergammaglobulinaemia was found in 29%, hypercalcaemia in 7%, raised LDH serum levels in 58% and HTLV-I antibodies in only one case. Of the 37 treated patients 18 (48%) achieved a complete remission, but 33% relapsed. Mortality was 59% and actuarial overall survival at 38 months was 0.32. In the comparison of the clinical, analytical and immunophenotypic variables and outcome between low and high grade groups, only the average of bone marrow infiltration in the low grade and stage I–II, presence of defective phenotypes and higher Ki-67 positivity in the high grade group were significantly different. In the statistical studies, extranodal prentation and the failure to achieve a complete remission were the only variables that influenced mortality; there weere no significant differences in the general features of the low and high grade groups and only minor differences were found in the immunoblastic and angioimmunoblastic subgroups. There were no differences in the actuarial survival between the low and high grade groups, among the subgroups of the Kiel classification, among stages I to IV, between patients with or without B-symptoms, with or without defective phenotypes, Ki-67 positivity over or under 60%, or among different CD4/CD8 phenotypes. The updated Kiel classification did not separate groups with a prognostic significance.     

The use of the polymerase chain reaction in the diagnosis of B-cell lymphomas from formalin-fixed paraffin-embedded tissue

In this study the use of the polymerase chain reaction (PCR) to detect monoclonality in B-cell lymphoid proliferations in archival formalin-fixed paraffin-embedded tissue was assessed. Using consensus primers against the framework 3 (FR 3) region of the immunoglobulin heavy chain gene (IgH), PCR analysis was performed on 29 low grade B-cell non-Hodgkin's lymphomas. Cases of benign lymphoid hyperplasia served as polyclonal controls. Sequenced cases of acute lymphoblastic leukaemia served as positive controls. In the lymphomas, monoclonality could be demonstrated in 18 of 29 (62%) cases. Only five of 11 (45%) follicle centre cell lymphomas were positive by this method whilst the success rate for the remainder was 13 of 18 (72%). None of the polyclonal controls gave false positive results although occasional non-specific dominant bands were present which disappeared on repeating the experiments. These results show that this method will identify monoclonality in 62% of low grade B-cell non-Hodgkin's lymphomas in archival material. The success rate is increased to 72% if follicle centre cell lymphomas are excluded. Thus, this method is a useful adjunctive test to aid diagnosis in lymphoid infiltrates when standard morphology and immunohistochemistry are equivocal.     

Immunohistochemical diagnosis of alimentary lymphomas and severe intestinal inflammation in cats

Intestinal tissue samples were examined from 32 cats in which a histopathological diagnosis of alimentary lymphoma or multicentric lymphoma affecting the gastrointestinal tract had been made. These samples were re-evaluated histopathologically and serial sections were examined immunohistochemically with antisera specific for the lymphoid markers CD3, CD79a and BLA-36 and for class II molecules of the major histocompatability complex. The cats ranged in age from 4-16 years (median 10.5 years). The main presenting clinical signs were vomiting, diarrhoea and weight loss. The majority of alimentary lymphomas were of the B-cell type (n=15), whereas cases of T-cell lymphoma were fewer in number (n=8). Four cats had lymphoma of a mixed T-and B-cell phenotype. In five of the cats, immunohistochemistry suggested an inflammatory process, in contradiction to the original histopathological diagnosis of lymphoma. Immunolabelling would appear to be a useful adjunct to histopathology in classifying cases of feline alimentary lymphoma, and may help in distinguishing lymphoma from severe intestinal inflammation.     

Mantle cell lymphoma as a component of composite lymphoma: clinicopathologic parameters and biologic implications

Composite lymphoma is a rare circumstance in which 2 or more distinct types of lymphoma occur in a single anatomical location. Although composite lymphoma has been increasingly identified with the advent of molecular genetic techniques, this topic has only rarely been a specific focus of the medical scientific literature. In this review, we focus on mantle cell lymphoma occurring as a major pathologic component of composite lymphoma and emphasize the clinicopathologic features of these tumors and associated biologic implications. To date, 26 cases of composite lymphoma including a component of mantle cell lymphoma have been previously published. Issues of clonal relatedness between the individual lymphoma components and emerging biologic implications as well as potential diagnostic pitfalls are evaluated.     

Study of Vimentin Expression in Non-Hodgkin's Lymphoma Using Paraffin Sections

Human non-Hodgkin's lymphomas were studied by means of an avidin biotin complex immunoperoxidase method using several monoclonal antibodies against the intermediate filament protein, vimentin. The study cases were 61 B cell lymphomas (including 2 plasmacytomas) and 30 T cell lymphomas (including 8 cases of mycosis fungoides). Twelve of the 61 B cell lymphomas were positive for vimentin, and were composed of extrafollicular center cells such as immunoblastic and plasmacytoid cells. On the other hand, lymphomas of follicular center cell origin were negative for vimentin. All cases of T cell lymphoma except for 14 (all of 9 AlLD- type lymphomas, all of 4 lymphoblastic lymphomas and one diffuse mixed small/ large lymphoma) were positive for vimentin. Although vimentin expression appeared to be influenced by various conditions such as the proportion of T- and B cell subsets, or B cell proliferation rate, follicular center cells were constantly negative for vimentin.     

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study

IntroductionWe aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey.Material and methodsIn this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity.ResultsNinety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2–8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%).ConclusionsObjective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.     

Update on extranodal lymphomas. Conclusions of the Workshop held by the EAHP and the SH in Thessaloniki, Greece

Classification and proper treatment of extranodal lymphoma is hindered by the diversity of lymphoma types and the relative rarity of many of these tumour types. In order to review controversial issues in extranodal lymphoma diagnosis, a joint Workshop of the European Haematopathology Association (EAHP) and the Society for Hematopathology (SH) was held, where 99 selected cases were reviewed and discussed. This Workshop summary is focused on the most controversial aspect of cutaneous B-cell lymphoma, other extranodal B-cell lymphomas, plasmablastic lymphoma and anaplastic large-cell lymphoma in extranodal sites, and makes practical recommendations about diagnosis and therapeutic approaches.     

Primary lymphomas of the small intestine in Iraq: a pathological study of 145 cases

The histopathology of 145 malignant lymphomas of the small intestine in Iraq have been studied and results compared with the clinical and immunological findings. The most common pathology was an intense mucosal lymphoplasmacytic proliferation effacing the villi and crypts partially or completely. This was either 'pure', usually of mature plasma cells limited to the lamina propria or associated with a fullblown lymphoplasmacytic lymphoma, almost always of the upper small intestine. The syndrome presented as abdominal pain, chronic diarrhoea, clubbing and, sometimes, the serological demonstration of alpha heavy chains. Other types of lymphomas were associated with 'non-specific' mucosal inflammation or follicular lymphoid hyperplasia. They were either lymphocytic, plasmacytic or lymphoblastic with 'starry sky' histiocytic reaction, representing distinct clinicopathological entities unrelated to 'alpha heavy chain disease'. Hodgkin's disease was extremely rare in this series.