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.     

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.     

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.     

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.     

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.     

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.     

Primary pulmonary non-Hodgkin's lymphomas

We report a retrospective study of the pathological features in 69 primary pulmonary non-Hodgkin's lymphomas which have previously been clinically reviewed. The tumours consisted of 61 (88%) low-grade and eight (12%) high-grade malignant lymphomas. Fifty-four of the low-grade malignant lymphomas were MALT lymphomas. Lymphoepithelial lesions were observed in bronchial, bronchiolar and alveolar lining. All tumours were composed of nodules, forming a lymphangitic pattern at the periphery and a confluent central mass. Invasion of pleura and vessels was often seen but this without any consequence on survival. Granulomas were found in 20% of cases. Six of the eight high-grade tumours were centroblastic and another two were B-cell lymphomas of undetermined type. In four cases, associated areas of low-grade malignant lymphoma with lympho-epithelial lesions indicated a preexisting MALT lymphoma. Clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasms. However, non-invasive diagnostic methods need to be developed.     

Lymphome composite : Case report d’un ganglion cervical siège d’un lymphome folliculaire et d’un lymphome à cellules du manteau in situ

Composite lymphoma represents 1–4% of lymphomas. Only 8 case reports concerned coexisting follicular lymphoma and mantle cell lymphoma. Here, we report the case of an 81 years old man who has been diagnosed with a composite follicular and in situ mantle cell lymphoma. The use of a large panel of immunohistochemical stains associated with the flow cytometry results have allowed us to make this particular diagnosis. We highlight here a common clonal origin of the composite lymphoma's two entities, as described in previous publications.     

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.     

T-cell lymphomas in children

T-cell lymphomas in children are rare and compromise a rather limited spectrum of entities. Relatively frequently observed are precursor T-cell lymphomas mainly presenting as mediastinal tumors with or without leukemia and ALK-positive anaplastic large cell lymphomas (ALCL) with nodal or extra nodal manifestations. In contrast to adults, where peripheral T-cell lymphoma (PTCL) is the most frequent T-cell neoplasia, PTCL in children is exceptional and remains a challenging diagnosis even for experienced haematopathologists. Other rare T-cell lymphomas occasionally seen in children are panniculitis like T-cell lymphomas, NK/T-cell lymphomas and hepatosplenic gamma delta-lymphomas. Of note angioimmunoblastic T-cell lymphoma is never seen in children. Mimickers of T-cell lymphomas like viral or immunological disorders in children are more frequent than manifest T-cell lymphomas and knowledge of these reactive conditions and their differential diagnosis is essential. The recognition of typical histopathological and clinical features along with knowledgeable use and interpretation of immunohistochemical and molecular markers are mandatory for a reliable diagnosis of childhood T-cell lymphomas.     

Case 8: T-Cell Lymphoma with Large Multilobated Nuclei

The vestibular nerve of patients with Meniere's disease and vascular cross-compression syndrome of the root entry zone due to the antero-inferior cerebellar artery was studied. All patients underwent vestibular neurectomy using the retrosig-moid approach, which permits the removal of a long nerve segment. CA were found in the cytoplasm of astrocytes that had not shown signs of degeneration at the central portion of the vestibular root entry zone. No membrane intervened between CA and the surrounding cytoplasm, which was rich in filaments, in particular near the CA, and poorly equipped with other organelles. CA were round or oval inclusions measuring 10–12 μm in diameter. The matrix of the CA was composed of low-density amorphous material, with irregular masses displaying a medium density. A network of randomly oriented filaments and bilaminar, osmiophilic lipid fragments with the same structure and thickness of myelin layers were embedded in the matrix. The CA rich in bilaminar fragments were recognizable also at low magnification for their high electron density. In the astrocytic cytoplasm, near the CA, round or oval-shaped, electron-dense bodies with a multilamellar structure were often visible. These results confirm the hypothesis that CA may contain degenerating myelin embedded in a microen-vironment rich in glucose polymers and that CA could be an indicator of neurodegeneration.     

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.     

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.     

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.     

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.     

Primary mediastinal clear cell lymphoma

Summary This is a report on 8 mediastinal tumours that occurred in young adults (19–43 years, mean: 29.4); predominantly in females (6/8). Initial symptoms consisted of thoracic pain and venectasia and in only one case in B symptoms. After surgical tumour reduction, radiation and/or chemotherapy, local recurrence was observed in each case under clinical care; abdominal spread is presently suspected in 3 patients; 3 died 11, 13 and 22 months after diagnosis. None developed leukaemia. The tumours are B-cell neoplasms with a characteristic immunophenotype: leucocyte common antigen⁺, common acute lymphoblastic leukaemia antigen^–, B 1-antigen⁺, surface and cytoplasmic immunoglobulin^–. Flow cytometry revealed DNA-diploidy in 7 cases and a moderately (3.2–3.8%) to extremely high (8.0–20.6%) S-phase component. The proliferation associated antigen Ki67 was detectable in 10–60% of the tumour cell nuclei, thus stressing the considerable or rapid growth. Histopathology is characterized by a diffuse growth pattern and a clearness and abundance of cytoplasm of the pleomorphic tumour cells, which vary in size and nuclear morphology from patient to patient. Apoptoses are more numerous than mitoses. Fibrosis and focal necrosis are common, sclerosis is present in 3 cases. We suggest that primary mediastinal lymphoma of B cell type is a novel B-lymphoma variant.This work was supported by the Tumorzentrum Heidelberg/Mannheim and the Land ofThis work was supported by the Tumorzentrum Heidelberg/Mannheim and the Land of     

Composite mantle cell and follicular lymphoma. A case report

We describe the association of 2 types of small B-cell lymphomas with different morphologic and immunophenotype patterns inside the same lymph node. Morphologically distinct zones were detected and studied with immunohistochemistry analyses. Most of the areas examined were characteristic of classic mantle cell lymphoma (CD20+, CD5+, cyclin D1+) with nodular and mantle zone areas. However, other areas had the morphologic and immunohistochemistry pattern of follicular lymphoma (CD20+, CD10+, Bcl2+). The diagnosis of both lymphomas was confirmed by polymerase chain reaction detection of both Bcl-1 MTC and Bcl-2 MBR rearrangements. DNA degradation in fixed tissue prevented a complete polymerase chain reaction analysis of immunoglobulin heavy chain rearrangements, but a single immunoglobulin H rearrangement was detected at the FR3 locus. These findings confirm the presence of a monoclonal cell population but do not demonstrate the same clonal origin for both lymphoma populations.