Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma

A case showing the typical clinical and pathological features of splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma is presented. Since the series recorded by Dogan et al (Am J Surg Pathol 2003;27:903-911), there have been very few reports on this lymphoma variant. Our case presents minor variations on the recorded features. Possible reasons for the scarcity of reports and for the confirmation of this lymphoma as a variant of T-cell-rich large B-cell lymphoma are discussed.     

Primary T-cell rich B-cell lymphoma of the common bile duct

A 34-year-old woman was hospitalized for the investigation of a one-month history of intestinal disorders, gastric heaviness and transitory icteric episodes. Extensive clinical investigations suggested the diagnosis of gall bladder carcinoma or sclerosing cholangitis. At laparotomy, the proximal part of common bile duct was markedly thickened by a white, firm, fish-flesh like tumour extending in to the cystic duct, gall bladder wall and to the liver. Histological study showed a diffuse lymphoid proliferation of the common bile duct mainly composed of small cells mixed with scattered large atypical cells. Immunohistochemistry revealed that most of the small cells expressed T-cell markers with predominant CD 4 and - T-cell receptors and without phenotypic gap, whereas large atypical cells showed monotypic B phenotype with co-expression of and heavy chains and light chain restriction. No evidence of primary nodal lymphoma was found during extensive clinical, radiological, sonographic or scanographic examinations. Sequential chemotherapy (MACOP-B) was instituted and the patient was still alive 4 years after diagnosis. Morphological and immunohistochemistry findings fulfilled criteria for a primary high grade B-cell lymphoma (centroblastic type, Kiel classification) from common bile duct concealed by numerous small reactive T-cells, so called T-cell rich B-cell lymphoma, not previously described in this location.     

Simultaneous occurrence of peripheral T-cell lymphoma unspecified and B-cell small lymphocytic lymphoma. Report of 2 cases

We report on 2 composite lymphomas occurring in elderly patients, morphologically characterized by the combination of peripheral T-cell lymphoma (PTCL) unspecified and B-cell small lymphocytic lymphoma. Immunohistochemistry provided objective confirmation of the coexistence of the 2 malignancies, as did molecular biology by revealing clonal T-cell receptor gamma and immunoglobulin heavy chain gene rearrangements. One of the patients had no history of indolent lymphoma either at the personal and family level, whereas the other showed a strong familial predisposition, his mother and sister having suffered from B-cell chronic lymphocytic leukemia. Epstein-Barr virus was detected in the PTCL component of 1 case, but was negative in the other. To the best of our knowledge, the simultaneous occurrence of PTCL unspecified and B-cell small lymphocytic lymphoma is an exceptional event; the possible pathogenetic correlations between the 2 neoplasms are discussed.     

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.     

Concurrent T-cell lymphocytic lymphoma and malignant histiocytosis

A case in which both malignant histiocytosis and T-cell lymphocytic lymphoma occurred together is presented. Examples of malignant histiocytosis-like syndromes associated with lymphoreticular malignancies have been previously reported. Many of these represent reactive haemophagocytic syndromes, probably virally induced. The considerable degree of cytological atypia and frequent mitotic figures seen in the histiocytes in this case were indicative of a true malignant histiocytosis.     

The first case of methotrexate-associated lymphoproliferative disorder presenting as follicular T-cell lymphoma

This is the first case of follicular T-cell lymphoma (FTCL) presenting as methotrexate-associated lymphoproliferative disorders (MTX-LPDs). A 69-year-old man treated rheumatoid arthritis with methotrexate presented with cervical swelling, hoarseness and fever. Imaging studies revealed multiple lymphadenopathy and lymphoma was suspected. Lymph node biopsy was performed to confirm the diagnosis. Pathologically, the lymph node was composed of atypical lymphocytes with a follicular growth pattern and area of necrosis. Immunohistochemical examination showed the atypical lymphocytes were positive for CD3, CD4, programmed cell death protein 1, and inducible T-cell co-stimulator. These findings are consistent with FTCL. During hospitalization, the patient's fever subsided and cervical lymphadenopathy improved, probably due to discontinuation of MTX. Here we presented the first case of FTCL presenting as MTX-LPDs. The T-cell phenotype MTX-LPDs are relatively rare and accounts for only 3.4%–6.3% of all MTX-LPD cases. Therefore, detailed clinicopathological features have not been clarified sufficiently. It is hoped that similar cases should be accumulated and studied to better understand the clinical and pathological features of this condition.     

Morphological characteristics of malignant T-cell lymphomas in baboons

Fifteen cases of generalized peripheral T-cell non-Hodgkin's lymphoma in baboons were phenotyped immunologically and morphologically. Using the updated Kiel classification the cases included low-grade and high-grade lymphomas and low-grade lymphomas that had transformed into high-grade lymphomas. In the low-grade group there were seven cases of lymphocytic type, partly corresponding to chronic lymphocytic leukaemia of T type and to T-zone lymphoma in man. In addition there were four cases of prolymphocytic-lymphocytic type, which show large nodules (proliferation centres) and which have no equivalent in the Kiel classification. In four cases there was a progression to an immunoblastic lymphoma and in one case to a large cell anaplastic lymphoma. In addition, three cases of large cell anaplastic lymphoma without a low-grade component were found. Both the immunoblastic lymphomas and the large cell anaplastic lymphomas corresponded well with the same types in the Kiel classification. The cases of large cell anaplastic lymphoma were also CD30 positive. Most of these lymphomas were CD4 positive, but there were rare cases that were either CD8 positive, showed both CD4 and CD8 positivity or had lost both antigens. Antigens associated with cell activation were often revealed. All but one baboon had antibodies in the blood against the retrovirus STLV-1 (simian T-cell leukaemia virus 1), which is very similar to human T-cell leukaemia virus 1 (HTLV-1) in man. Despite this virological resemblance, the morphology of these T-cell lymphomas does not resemble that of the HTLV-1-positive Japanese T-cell lymphomas but is like that of the HTLV-1-negative European cases.     

T-cell lymphoma in Singapore: pathology, clinical findings and association with HTLV-1 antibodies

Of 128 cases of malignant lymphomas studied in Singapore between 1986 and 1988, 28 were identified as peripheral T-cell lymphomas. Sera from two of the 128 cases were positive for HTLV-1 antibodies and both cases had the clinical and pathological features of adult T-cell leukaemia/lymphoma. The pathological and clinical features of the 28 cases of peripheral T-cell lymphoma are presented in detail. Survival data indicated no significant difference between the low grade and high grade histological types. Three of the patients had previous or concomitant malignancies. The percentage of T-cell lymphomas associated with HTLV-1 infection in Singapore is low compared to those areas in which HTLV-1 is endemic.     

Phenotyping of T-cell lymphomas in paraffin sections–which antibodies?

Five antibodies, MT1 (CD43), UCHL1 (CD45RO), OPD4, poly-CD3 and beta F1, were assessed for their reactivity with 50 archival cases of T-cell lymphoma in formalin-fixed paraffin-embedded tissue. All cases had been previously characterized as T-cell lymphomas, and the histological types included 14 cases of small cerebriform lymphoma, six cases of angioimmunoblastic lymphadenopathy-like T-cell lymphoma, four cases of T-zone lymphoma, five cases of pleomorphic small cell lymphoma, 12 cases of pleomorphic medium and large cell lymphoma, four cases of anaplastic large cell lymphoma, two cases of T-lymphoblastic lymphoma and three cases of enteropathy-associated T-cell lymphoma. UCHL1 and MT1 showed reactivity with the highest percentage of cases (94 and 86% respectively) but lack absolute specificity for T-cells, especially in high-grade lymphomas. Poly-CD3 is highly specific for T-cells, and stained neoplastic cells in almost 80% of the cases. beta F1 stained the lowest percentage of cases (40%). UCHL1 and poly-CD3 together identified 98% of cases, and this combination is recommended for the diagnosis of T-cell lymphomas in paraffin sections.     

Primary cutaneous B-cell lymphoma with abundant reactive gamma/delta T-cells within the skin lesion and peripheral blood

T-cell/histiocyte-rich diffuse large B-cell lymphoma is characterized by abundant reactive T-cell and histiocyte infiltration within nodal diffuse large B-cell lymphoma, and only limited cases of primary cutaneous T-cell-rich B-cell lymphoma have been documented. These reactive T-cells usually show a T-helper phenotype. Gamma/delta T-cell is a functionally distinct T-cell lineage, which constitutes on average 5% of all T-cells in the peripheral blood. Herein, we report the first documented case of primary cutaneous malignant B-cell lymphoma with abundant reactive gamma/delta⁺ T-cells within the skin lesion and peripheral blood. An 80-year-old Japanese male presented with a gradually enlarged knee nodule. Histopathological study revealed diffuse infiltration of lymphoid cells in the dermis and subcutis. Proliferation of large-sized atypical lymphoid cells was observed among medium-sized lymphocytes with convoluted nuclei. Immunohistochemically, these large-sized atypical lymphocytes were CD20⁺, and relatively many gamma/delta⁺ cell infiltration was also noted. Flowcytometric analysis revealed deviation of lambda+ cells (lambda/kappa 58) and increase of CD3⁺ gamma/delta⁺ cells (6%). Peripheral blood had CD3⁺ gamma/delta⁺ cells (28.8%). Rearrangement of immunoglobulin heavy chain, but not of T-cell receptor beta and gamma chains, was observed. Accordingly, an ultimate diagnosis of cutaneous B-cell lymphoma with abundant reactive gamma/delta⁺ cells was made. Recent studies have shown reactive gamma/delta⁺ T-cell infiltration and/or elevation in the peripheral blood in patients with various types of carcinoma, and that they play a role in the pathogenesis of some carcinomas. Therefore, additional analysis is needed to clarify the role of reactive gamma/delta⁺ T-cells in malignant lymphoma.     

Sequential demonstration of antigens and AgNORs in frozen and paraffin sections

A technique has been designed which enables the sequential demonstration of nucleolar organizer regions (NORs) and various antigens, in both frozen and paraffin wax-embedded sections. The NORs were demonstrated by the standard argyrophil (AgNOR) method and the antigens were shown by either immunoperoxidase (PAP) or immunoalkaline phosphatase (alkaline phosphatase-anti-alkaline phosphatase or avidin-biotin-alkaline phosphatase) methodology. Clear, reproducible results were obtained and AgNOR sites were enumerated with ease. It is suggested that the sequential method may be of great use in the evaluation of AgNOR numbers in neoplasms, where cell populations are heterogeneous. Cell populations may be demarcated with accuracy prior to the counting the AgNORs.     

Lymphoma phenotyping in formalin-fixed and paraffin wax-embedded tissues. I. Range of antibodies and staining patterns

Recently, monoclonal antibodies capable of phenotyping malignant lymphomas in routinely fixed and processed tissue have become available. Some of these reagents identify lineage-restricted variants of the leucocyte common molecule, whereas others identify unique fixation-resistant epitopes on lymphoid cells, some of which are shared by non-lymphoid tissues. A new generation of antibodies recognizing 'classical' leucocyte antigens such as CD3 are also emerging. Refinements in antigen detection systems, especially for immunoglobulin recognition, combined with these new reagents promise to improve the accuracy of lymphoma diagnosis in routine histopathology. These new antibodies are reviewed, and their limitations, cross reactivities and profiles of staining in lymphoreticular disease are discussed. A strategy for their optimal use is proposed.     

Lymphoma phenotyping in formalin-fixed and paraffin wax-embedded tissues: II. Profiles of reactivity in the various tumour types

Recently, monoclonal antibodies capable of phenotyping malignant lymphomas in routinely fixed and processed tissue have become available. Some of these reagents identify lineage-restricted variants of the leucocyte common molecule, whereas others identify unique fixation-resistant epitopes on lymphoid cells, some of which are shared by non-lymphoid tissues. A new generation of antibodies recognizing 'classical' leucocyte antigens such as CD3 are also emerging. Refinements in antigen detection systems, especially for immunoglobulin recognition, combined with these new reagents promise to improve the accuracy of lymphoma diagnosis in routine histopathology. These new antibodies are reviewed, and their limitations, cross reactivities and profiles of staining in lymphoreticular disease are discussed. A strategy for their optimal use is proposed.     

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.     

Nodular lymphocyte-predominant hodgkin lymphoma or T-cell/histiocyte rich large B-cell lymphoma: the problem in "grey zone" lymphomas

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare indolent B-cell lymphoma. However, its morphology can resemble T-cell/histiocyte rich large B-cell lymphoma (T/HRBCL), a subtype of more aggressive diffuse large B-cell lymphoma. More and more studies suggest that these two entities are closely related. In this report, a 59-year-old man with nodal NLPHL and concomitant T/HRBCL in the bone marrow is presented, the current progress in our understanding of these two closely related B-cell lymphomas reviewed and the problems in the diagnosis and differentiation of NLPHL and T/HRBCL discussed.