Co-expression of CD79a (JCB117) and CD3 by lymphoblastic lymphoma

Acute lymphoblastic leukaemia/lymphoma is a malignant disorder derived from the clonal proliferation of lymphoid precursor cells. Whether the tumour cells are of B- or T-cell type is an important criterion for prognosis which has not been available previously to pathologists, due to the lack of a reliable early B-cell marker functioning on routinely processed material. This has changed with the production of monoclonal antibodies against the B-cell signalling molecule CD79a. CD79a is expressed on normal and neoplastic B cells from the early stages of B-cell maturation and has been considered to be B-cell-specific. Currently available antibodies against CD79a, in particular JCB117, allow the identification of B cells, and hence B lymphoblastic disease, in paraffin-embedded material. In this study, the expression of CD79a (JCB117) and CD3 has been investigated in 149 cases of T and 68 cases of B lymphoblastic leukaemia/ lymphoma. For the first time, co-expression of CD79a (JCB117) and CD3 is reported in 10 per cent of cases of T lymphoblastic leukaemia/lymphoma. This finding raises questions about the co-expression of T- and B-cell markers in the development of lymphocytes, benign as well as malignant, and alerts pathologists to a potential problem in diagnosis. Copyright © 1998 John Wiley & Sons, Ltd.     

Primary hepatic marginal zone B-cell lymphoma with mantle cell lymphoma phenotype

We report a rare case of primary hepatic lymphoma, Stage II disease, in a 48-year-old male who had a solitary hepatic tumour measuring 4×4.5×3 cm. The tumour showed a nodular growth pattern and lymphoepithelial lesions with bile ducts. Some neoplastic nodules had a non-neoplastic atrophic germinal centre and/or a thin mantle cell layer. Morphologically, the neoplastic cells were centrocyte-like cells or intermediate lymphocytes. They expressed L26(CD20)⁺/LN-1(CDw75)^±/LN-2(CD74)⁺/cyclin D1^– and had a monotypic immunoglobulin of cytoplasmic IgM () on paraffin sections. The neoplastic cells or neoplastic nodules expressed surface IgM⁺/surface IgD^±/Leu-1(CD5)⁺/DRC-1⁺/alkaline phosphatase⁺/B1(CD20)⁺/B4(CD19)^– on fresh frozen sections. We therefore diagnosed this case as primary hepatic marginal zone B-cell lymphoma with mantle cell lymphoma phenotype. We confirm that it is difficult to differentiate extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of mucosa-associated lymphoid tissue type; MALT lymphoma) and mantle cell lymphoma.     

Malignant lymphoma in pleural effusions: an immunocytochemical cell surface analysis

Nine malignant pleural effusions due to lymphoma were immunocytochemically analyzed with the peroxidase-antiperoxidase adhesive slide assay for detection of cell surface antigens using a broad panel of monoclonal antibodies. The study population included one case of hairy-cell leukemia; four cases of B cell non-Hodgkin's lymphoma (B-NHL), low malignant grade; two cases of B-NHL, high malignant grade; one case of Hodgkin's disease; and one case of plasmacytoma. In the cases of B cell lymphoma, high percentages of B cells with monoclonal staining for kappa were found. In hairy-cell leukemia, the hairy cells reacted with the monoclonal antibodies CD20, CD25, HLA-DR, CD45, and HLA-1. In Hodgkin's disease, the Hodgkin cells reacted with CD15, CD20, CD25, CD30, Tü9, and OKT9. The plasmacytoma case showed tumor cells negative for CD20, HLA-DR, and CD45; partially positive for CD38; positive for HLA-1; monoclonally positive for lambda; and negative for heavy-chain immunoglobulins. The analysis of nonmalignant lymphocyte subpopulations revealed CD4/CD8 ratios similar to those in effusions of other etiologies. The percentages of natural killer cells (Leu-7-positive and CD16-positive) were small and also similar to percentages in effusions of other etiologies. We conclude that immunocytochemical analysis of pleural effusions allows a clear recognition of B lymphoma cells and also of Hodgkin and hairy cells and that the distribution of nonmalignant lymphocyte subsets is indistinguishable from those found in other malignant and nonmalignant effusions.     

Spontaneous regression of malignant lymphoma of the breast

A complete spontaneous regression of diffuse large B cell lymphoma involving the right breast, confirmed by aspiration cytology, is reported. The patient visited a hospital due to the rapid growth of a tumor in the right breast. Five years previously she underwent a craniotomy for a brain tumor, diagnosed as B-cell malignant lymphoma, and received several courses of irradiation to the brain. Analysis of the breast tumor cells obtained by aspiration revealed lymphoma cells morphologically, which were similar to the tumor cells in the brain expressing CD20. While waiting for further examination, the tumor regressed rapidly and was not palpable after 20 days. An excisional biopsy of the breast exhibited no definite malignant lymphoma cells among a diffuse population of CD45RO and CD8-positive small lymphocytes. Nucleotide sequencing of HCDR3s of the brain tumor and breast tumor cells showed a completely matched sequence, revealing the breast mass to be a metastatic lesion from the tumor of the brain. Although there was no tumorous lesion, the patient received additional chemotherapy and has shown no sign of recurrence in the breast for 7 years. We were able to confirm that the breast lymphoma shown in the aspiration cytology was a metastatic one, which was not proven histologically prior to chemotherapy, and regard the present case as a malignant lymphoma of the breast showing spontaneous regression. The present case shows a rare occurrence of spontaneous regression of diffuse large B cell malignant lymphoma after aspiration and suggests that CD8-positive T cells might be related to the regression.     

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.     

Primary mediastinal anaplastic alk-1-positive large-cell lymphoma of T/NK-cell type expressing CD20

We describe an unusual case of ALK-1-positive primary mediastinal lymphoma with the morphology of an anaplastic large-cell lymphoma (ALCL) of T/NK cell type but expressing CD20. This tumour had T/NK morphology and immunophenotype, as demonstrated by its expression of CD30, EMA, ALK-1, CD7 and TiA-1 and the lack of expression of B-cell markers other than CD20. The significance of such a co-expression of a B cell-associated antigen in a case of ALCL of T/NK cell type is discussed.     

Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma

Regulatory T cells (T(regs)) may inhibit immunity against cancer. Induction and expansion of T(regs) in the immunosuppressive microenvironment created by a growing tumour appear to be one of the mechanisms by which it can evade host defence. We studied the impact of CD25+ T(regs) in a B cell lymphoma model in which Rag2-/- mice received adoptive transfer of wild-type spleen cells with or without CD25+ cells, and concurrently subcutaneous inoculation of the B cell lymphoma cell line A20. We also examined the effect of engaging the glucocorticoid-induced tumour necrosis factor receptor (GITR) - an approach reported previously to abrogate the suppressive effects of T(regs). Mice that received spleen cells depleted of CD25+ T(regs) showed significantly slower tumour growth and increased survival compared with mice that received unsorted spleen cells. The T(reg)-depleted group also had significantly more CD8+ T cells infiltrating the tumours and higher levels of serum immunoglobulin G subclasses. The anti-GITR treatment had no significant effect on tumour growth, survival or immunoglobulin production. In the CD25-depleted group four of 10 mice developed clinical signs of autoimmunity, in contrast to none in the non-depleted group. Forkhead box P3+ T cells were found in tumour-draining lymph nodes in mice in the CD25-depleted group, suggesting an in vivo induction or expansion of rare transferred donor T(regs). Thus, our study showed that removal of CD25+ T(regs) enhanced anti-tumour immunity against local growth of a B cell lymphoma and that induction or expansion of T(regs) could be one mechanism by which the growing tumour evades immune surveillance.     

Lack of adhesion molecules in testicular diffuse centroblastic and immunoblastic B cell lymphomas as a contributory factor in malignant behaviour

Diffuse large B-cell lymphoma of the testis is a rare tumour, often with disseminated disease. According to the Kiel Classification, these lymphomas are of centroblastic or immunoblastic type, corresponding in the Working Formulation to malignant lymphoma, large cell non-cleaved and large cell immunoblastic, respectively. Adhesive cell-cell and cell-matrix interactions are generally assumed to play an important part in the metastatic process, and to find clues to the highly malignant biological behaviour of this tumour we examined expression of integrins and other adhesion molecules on the tumour cells and the presence of matrix proteins. Few adhesion molecules appeared to be expressed. CD44 was expressed in 10/12 lymphomas, CD49f/VLA-6 was positive in 5/12 cases, and CD49d/VLA-4, CD54 and CD62L were detectable in a small number (2–3) of lymphomas. All other adhesion molecules were lacking. This expression pattern is suggestive of a high metastatic potential: the tumour cells seem to be poorly attached to the extracellular matrix, to each other and to other cells (CD54-, CD11a-, CD58-). The adhesion molecules expressed, CD44, CD49f/VLA-6 and CD49d/VLA-4, have been reported to play a part in dissemination, mediating intravasation (CD49f/VLA-6) and extravasation (CD44, CD49d/VLA-4). This profile of adhesion molecules may explain, at least in part, the specific biological behaviour of these lymphomas with early and rapid dissemination.     

Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Some of the HML-1 positive ATLL cases co-expressed CD30. Furthermore, three of six cases of Ki-1 lymphoma (large anaplastic cell lymphoma) were positive for HML-1. We conclude that expression of HML-1 in ATLL reflects an activated state of the lymphoma cells, but not the intestinal origin of ATLL cells.     

Lymphoplasmacytoid lymphoma: an immunohistological study

Eighteen cases of lymphoplasmacytoid lymphoma (LPL) have been immunophenotypically characterized with a panel of 26 monoclonal antibodies. All cases expressed leucocyte common antigen, class II MHC and stained with B cell markers (CD19, CD20, CD22) although a variable proportion of tumour cells were noticed to have lost some B cell marker expression. There was some phenotypic heterogeneity with variable immunostaining with KB61, CD21, and CD5. A variable proportion of cells in all cases contained cytoplasmic immunoglobulin. Surface immunoglobulin light chain restriction was demonstrated in 11 cases and heavy chain predominance in 16 cases. Few tumour cells were proliferating as indicated by Ki67 immunostaining. A wide variation in number of macrophages and T lymphocytes were present in association with the tumours. A significant association between the expression of CD5 and the presence of peripheral blood lymphocytosis was noticed (p less than 0.003) but there was no association between CD5 and co-expression of IgM and IgD. This data supports an origin from non-germinal centre cells for LPL and suggests that CD5 expression by B cells may be related to lymphocyte migration. LPL shows some immunological heterogeneity and can present diagnostic difficulties, but its poor prognosis makes it an important category of lymphoma to recognise.     

CK阳性T细胞淋巴瘤1例报道并文献复习

目的 研究CK呈阳性表达的非霍奇金小T细胞性淋巴瘤的病理学特征及鉴别诊断。方法 运用光镜、电镜及免疫组化技术，观察1例CK呈阳性表达非霍奇金小T细胞性淋巴瘤的组织学、超微结构形态及免疫组化特征并复习相关文献。结果 肿瘤组织主由弥漫分布的小圆形细胞构成。核仁不明显。CD45、CD45RO、和CK(广谱、低分子量、高分子量和19、)均为( )。CD20和CD79均为(-)。电镜观察瘤细胞胞核圆形，居中。胞质少．可见线粒体．未见上皮细胞分化特征、神经内分泌颗粒。结论 非霍奇金小T细胞性淋巴瘤偶可呈CK阳性表达，在应用免疫组化技术对低分化肿瘤进行鉴别诊断时应注意肿瘤组织的异常表达。     

Granzyme B-positive primary gastric T-cell lymphoma: gastric T-cell lymphoma with the possibility of extrathymic T cell origin

A case of primary gastric T-cell lymphoma, which was positive for granzyme B, is reported. The patient was a 47-year-old Japanese female who complained of a dull upper abdominal pain. Radiographic and endoscopic examinations revealed an ulcerative infiltrative lesion in her stomach. Following the confirmation of a high-grade malignant lymphoma, a distal gastrectomy with regional lymph nodal dissection was performed. The histology of the gastric lesion revealed a malignant lymphoma of the diffuse pleomorphic type without lymph nodal involvement. Immunohistochemistry revealed that the tumor cells were positive for LCA, CD3, TIA-1 and granzyme B, but were negative for CD4, CD8, CD56, CD30, L-26, EMA, TCR alpha/beta and TCR gamma/delta. Because the tumor cells showed T cell nature with cytotoxic activity proved by TIA-1 and granzyme B, and without evidence of further maturation of T cell, a malignant lymphoma originating from extrathymic-derived T cells was suggested.     

The anaplastic variant of centrocytic lymphoma is marked by frequent rearrangements of the bcl-1 gene and high proliferation indices

Ten cases of classic centrocytic lymphoma as defined in the Kiel classification system were investigated for their immunophenotype, their proliferation activity and by means of molecular diagnostics. The findings were compared to those obtained from a group of nine cases of anaplastic centrocytic lymphoma. Both groups showed virtually identical immunohistochemical characteristics with positivity for CD5 and negativity for CD10 and CD23. In the group of anaplastic centrocytic lymphoma, there were considerably higher proliferation indices as documented by staining for the Ki-67 antigen, up to 80% of the tumour cells being positive. Moreover, the cases of anaplastic centrocytic lymphoma had bcl-1 gene rearrangements in eight out of nine cases compared with three out of 10 cases of classic centrocytic lymphoma. DNA analysis was not able to detect bcl-2 gene rearrangement in any case, pointing to a difference compared with lymphomas of germinal centre origin. The coincidence of anaplastic and sometimes blast-like morphology of the tumour cells, high proliferation index and a rearranged bcl-1 gene in nearly all cases of anaplastic centrocytic lymphoma support their classification as high-grade malignant variants of centrocytic lymphoma and suggest a possible role for the bcl-1 locus not only in the origin but also in the progression of centrocytic lymphomas.     

Prominent intrasinusoidal infiltration of the bone marrow by mantle cell lymphoma

Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.     

The classical Hodgkin's lymphoma microenvironment and its role in promoting tumour growth and immune escape

It has become clear that cancer is not merely a growth of autonomously proliferating cells, but that other non‐malignant cell types are a functional part of the disease. Immune cells, fibroblasts, specialized mesenchymal cells and microvasculature together make up the tumour microenvironment and have functional interactions with tumour cells. Classical Hodgkin's lymphoma (cHL) is characterized by only a few malignant cells and an abundance of inflammatory cells. Hodgkin and Reed–Sternberg (HRS) cells are surrounded by T and B cells admixed with plasma cells, macrophages, eosinophils and mast cells. A constitutive activity of NF‐κB and an altered JAK–STAT signalling pathway are part of the biological background associated with the increased expression of cytokines and cytokine receptors seen in HRS cells. Over‐expression of the members of the TNF receptor family, especially CD30 and CD40, is a hallmark of HRS cells. cHL is a tumour where aberrant cytokine production contributes not only to the proliferation of HRS cells but also to the maintenance of an appropriate environment for the tumour cells. In addition, several chemokines contribute to the composition of the inflammatory background in cHL. This review summarizes updated information on the complex interactions between the HRS cells and their tissue microenvironment and highlights the development of newer therapeutic strategies aimed at targeting the non‐malignant inflammatory/immune cellular components of HL that are involved in cancer cell growth and/or immune escape. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Nodal T/NK-cell lymphoma of nasal type: a clinicopathological study of six cases

Aims:  To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein–Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement ( n  = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type ( n  = 21).
Methods and results:  All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3ε+, CD4−, CD5−, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor γ-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences.
Conclusions:  Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.     

Morphological variability of lymphohistiocytic variant of anaplastic large cell lymphoma (former lymphohistiocytic lymphoma according to the Kiel classification)

According to the WHO classification, anaplastic large cell lymphoma (ALCL) is a distinct T-cell lymphoma entity with a number of morphological variants. The characteristic feature of lymphohistiocytic variant of ALCL according to the WHO classification is the abundance of histiocytes that exceed and mask the tumour cell population. In the current, study we reanalysed a historical series of 17 lymphomas, diagnosed as lymphohistiocytic lymphoma according to the criteria of the Kiel classification, with the presence of large purple macrophages (LPM) as the decisive finding for diagnosing this lymphoma subtype. We assessed the cellular composition of the tumour and correlated the results with the definition of lymphohistiocytic variant of ALCL given in the WHO classification. Although all cases in our cohort matched the criteria of ALCL according to the WHO, in 30% of the cases, the total amount of macrophages did not exceed the number of CD30-positive tumour cells. Our results indicate that the presence of LPM might be helpful to identify this subgroup of ALCL. Because the distinction of morphological subtypes of ALCL is of clinical relevance, improved criteria for subtyping ALCL are urgently needed that might include the presence LPM as one criteria.     

Gastric T-cell lymphoma with cytotoxic phenotype

Primary gastric lymphoma usually originates from B cells of mucosa-associated lymphoid tissue (MALT) infected with Helicobacter pylori. When T-cell lymphomas develop in the stomach, they usually occur in association with infection by human T-lymphotropic virus type 1 and gastric involvement of adult T-cell leukemia. Reported herein is a unique and informative case of gastric peripheral T-cell lymphoma with a cytotoxic phenotype that histologically mimicked, and had to be carefully distinguished from, MALT-type B-cell lymphoma. The patient, a 73-year-old woman, underwent a gastric endoscopy examination, and the histological findings suggested MALT-type gastric lymphoma. Analysis of the immunoglobulin heavy chain (IgH) gene and T cell receptor gamma (TCRgamma) gene revealed monoclonal rearrangement of the TCRgamma gene. The tumor cells exhibited mild atypia and immunoreactivity with anti-CD3, anti-CD8, anti-T-cell intracellular antigen-1, antigranzyme B and antiperforin antibodies, but not with anti-CD20, anti-CD10, and anti-CD79a antibodies. The case was finally diagnosed as gastric T-cell lymphoma with cytotoxic phenotype, and this was confirmed after surgical resection. In cases such as this, small biopsy specimens from the stomach should be examined carefully for low grade B-cell-type malignant lymphoma (MALT lymphoma), because sometimes the proliferating B cells can hide the truly malignant T cells, and rearrangement analysis is useful for diagnosing T-cell malignancy.     

A study of PD‐L1 expression in intravascular large B cell lymphoma: correlation with clinical and pathological features

Intravascular large B cell lymphoma (IVLBCL) is a rare, aggressive, extranodal large B cell lymphoma characterised by growth of tumour cells within the lumen of vessels, particularly capillaries. Programmed cell death ligand 1 (PD‐L1) is a cell surface glycoprotein that interacts with programmed death 1 (PD‐1) on the T cell surface, leading to modulation of the immune response. PD‐L1 is a targetable immune check‐point molecule that is expressed on neoplastic cells in various cancers, including a subset of lymphomas. We correlated the expression of PD‐L1 with clinical and pathological findings in this rare disease. Eleven cases of IVLBCL were identified in the archives of Laboratory of Pathology at the National Cancer Institute, NIH. A panel of immunostains (CD20, CD3, CD5, PD‐L1) was performed. The cases were classified as the classic form or the variant associated with haemophagocytic syndrome (HPS) based on published 2017 WHO criteria. Three cases (27.3%) were HPS variant and eight cases (72.7%) were the classic form. Five (45.5%) of 11 cases were CD5‐positive; two of three (66%) were HPS variants and three of eight (37.5%) were classic form. Overall, four of nine evaluable cases (44.4%) were positive for PD‐L1, three of which were classic. Only one CD5‐positive case was PD‐L1‐positive, a classic variant. In summary, a subset of IVLBCL express PD‐L1. Although limited, these data suggest that PD‐L1 is expressed in both the so‐called classic form as well as the HPS variant. PD‐L1 is expressed irrespective of CD5 expression. Finally, detection of PD‐L1 expression in a subset of IVLBCL lymphoma cases may identify patients who might benefit from targeted immunotherapy.