Expression of Grb2 distinguishes classical Hodgkin lymphomas from primary mediastinal B-cell lymphomas and other diffuse large B-cell lymphomas

Growth factor receptor-bound protein 2 is an adaptor molecule that mediates B-cell receptor (BCR) signaling pathways, but the expression of growth factor receptor-bound protein 2 in lymphoma tissues has not been reported. We sought to characterize growth factor receptor-bound protein 2 protein expression in reactive tonsillar tissues and lymphoma tissues obtained from diagnostic biopsies of classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and 20 low-grade B-cell lymphomas. Growth factor receptor-bound protein 2 expression was assessed in tissues by immunohistochemistry and in lymphoma cell lines by immunoblotting. In reactive lymphoid tissues, growth factor receptor-bound protein 2 was expressed in the cytoplasm of B-cells and histiocytes but not T-cells. Strong, cytoplasmic growth factor receptor-bound protein 2 expression was seen in the neoplastic cells of follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, splenic marginal zone lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, and nodular lymphocyte predominant Hodgkin lymphoma. In contrast, only 10% of the classical Hodgkin lymphomas showed growth factor receptor-bound protein 2 expression in the neoplastic cells. Growth factor receptor-bound protein 2 protein expression was detected by Western blotting in all lymphoma cell lines tested with higher levels in primary mediastinal large B-cell lymphoma compared with classical Hodgkin lymphoma cell lines. These findings support a role for growth factor receptor-bound protein 2 in the diagnostically challenging workup of classical Hodgkin lymphoma versus primary mediastinal large B-cell lymphoma and warrant further studies to evaluate the biologic significance of growth factor receptor-bound protein 2 in the pathogenesis of classical Hodgkin lymphoma.     

Molecular profiling provides evidence of primary mediastinal large B-cell lymphoma as a distinct entity related to classic Hodgkin lymphoma: implications for mediastinal gray zone lymphomas as an intermediate form of B-cell lymphoma

Expanding on prior studies that have used molecular profiling to elucidate the heterogeneity of diffuse large B-cell lymphomas (DLBCLs), two recent studies (Rosenwald et al and Savage et al) have characterized a third molecularly distinct subtype of DLBCL, primary mediastinal (thymic) large B-cell lymphoma (PMLBCL). Both groups found distinct gene expression patterns that were able to reliably diagnose PMLBCL and distinguish it from other DLBCLs. Notably, the signature gene expression profile of PMLBCL was more closely related to classic Hodgkin lymphoma (CHL) than other DLBCL subtypes. These studies provide further evidence that PMLBCL and nodular sclerosis CHL may represent related tumors on either ends of a continuum, whose interface includes an intermediate form of disease, mediastinal gray zone (MGZL) lymphoma. MGZLs are tumors that have a transitional morphology and phenotype, combining features of both PMLBCL and nodular sclerosis CHL, and provide a diagnostic challenge to pathologists. These studies provide insights into the biology of PMLBCL and CHL and demonstrate the utility of genomic technologies in defining and diagnosing hematopoietic tumors. The ability to map specific pathologic signal transduction pathways regulating hematopoietic differentiation, proliferation, and apoptosis through genomic or proteomic technologies promises to provide the basis for the development of individualized molecularly targeted therapies for specific tumors.     

Clinicopathological analysis of a composite lymphoma containing both T‐ and B‐cell lymphomas

Composite lymphomas (CLs) have been reported in 1–4.7% of all lymphomas, however, CLs containing both T‐ and B‐cell lymphomas (CTBLs) are very rare. Here, we examined the clinical and pathological features of 29 CTBLs. These CTBLs included 21 patients with angioimmunoblastic T‐cell lymphoma (AITL) and diffuse large B‐cell lymphoma (DLBCL), two with adult T‐cell leukemia/lymphoma and DLBCL, one with AITL and Follicular lymphoma, one with Lennert lymphoma and DLBCL, one with subcutaneous panniculitis‐like T‐cell lymphoma and DLBCL, one with peripheral T‐cell lymphoma (PTCL) and DLBCL, one with cutaneous T‐cell lymphoma and DLBCL, and one with PTCL and chronic lymphocytic leukemia. Eighteen of 27 patients (67%) were shown to be Epstein‐Barr virus (EBV)‐encoded RNA‐positive in their B‐cell lymphoma component. T‐cell and B‐cell clonality were confirmed by flow cytometry, Southern blot analysis, and/or polymerase chain reaction (PCR). Using Southern blot analysis, clonal immunoglobulin heavy chain (IgH) and T‐cell receptor (TCR) rearrangements were detected in 11 of 21 and 15 of 24 cases, respectively. Using PCR analysis, clonal IgH and TCR rearrangements were detected in 7 of 8 and 7 of 7 Southern blot‐negative cases, respectively. Our results suggested that PCR analysis was useful in diagnosing CTBL.     

B-cell lymphomas with coexpression of CD5 and CD10

Coexpression of CD5 and CD10 is highly unusual in B-cell lymphomas and may pose a diagnostic challenge. We report 42 cases of B-cell lymphoma with simultaneous expression of CD5 and CD10. They made up approximately 0.4% of all B-cell lymphomas seen during the study period and included the following cases: large B-cell lymphoma (LBCL), 14 (33%); follicular lymphoma (FL), 10 (24%); mantle cell lymphoma (MCL), 9 (21%); chronic lymphocytic leukemia, 4 (10%); acute precursor B-cell lymphoblastic leukemia/lymphoma, 2 (5%); and other low-grade B-cell lymphomas, 3 (7%). All MCLs had overexpression of bcl-1 or the t(11;14) and were CD43+. All FLs had typical histomorphologic features and were bcl-2+ and bcl-6+ but CD43-. Of 14 LBCLs, 5 were histologically high-grade. Six (43%) of 14 patients with LBCL died within 10 months of diagnosis of CD5+CD10+ lymphoma (median survival, 4 months), including all 3 patients with stage IV disease and 2 of 5 with histologically high-grade lymphoma. Our findings indicate that coexpression of CD5 and CD10 is rare but occurs in diverse subtypes of B-cell lymphoma. Investigation of bcl-1, bcl-6, and CD43 and morphologic evaluation may resolve the potential confusion in diagnosis and lead to the recognition of the correct lymphoma subtype.     

ZAP-70 expression in B-cell hematologic malignancy is not limited to CLL/SLL

ZAP-70 is a tyrosine kinase expressed in normal T cells and NK cells. Expression of ZAP-70 has been associated with poor prognosis in B-cell chronic lymphocytic leukemia and might be a surrogate marker for immunoglobin heavy chain (IGH) mutational status in that disease. Little is known about ZAP-70 expression in other hematologic malignant neoplasms. We examined 446 specimens representing a range of hematopoietic malignant neoplasms for ZAP-70 expression by immunohistochemical analysis. As expected, most T cell-lineage disorders and a subset of small lymphocytic lymphomas were positive. IGH mutational status corresponded to ZAP-70 expression in a small subset of small lymphocytic lymphoma cases subjected to sequence analysis. Of note, however, ZAP-70 was expressed in a minority of other types of B-cell lymphomas, including precursor B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, mantle cell lymphoma, and very rare cases of classic Hodgkin lymphoma. Immunohistochemical analysis represents an alternative method for assessing ZAP-70 expression and reveals that other B-cell malignant neoplasms express ZAP-70.     

Aggressive B cell lymphomas in the 2017 revised WHO classification of tumors of hematopoietic and lymphoid tissues

The recent 2017 update of the World Health Organization classification of lymphomas has significant changes from the previous edition. Subtypes of large B cell lymphoma and related aggressive B cell lymphomas are addressed. Clinicopathological features of entities as related to morphology, immunophenotype, cell of origin, and molecular/genetic findings are reviewed with emphasis on changes or updates in findings. Specific subtypes addressed include: T cell/histiocyte-rich large B cell lymphoma, primary diffuse large B cell lymphoma (DLBCL) of the CNS, primary cutaneous DLBCL leg-type, EBV-positive DLBCL, NOS, DLBCL associated with chronic inflammation, primary mediastinal large B cell lymphoma, intravascular large B cell lymphoma, ALK-positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma, HHV8-positive diffuse large B-cell lymphoma, NOS, Burkitt lymphoma, Burkitt-like lymphoma with 11q aberration, high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high grade B cell lymphoma, NOS, B cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma and large B cell lymphoma with IRF4 translocation. In addition, EBV positive mucocutaneous ulcer is addressed.     

Pitfalls in diagnostic hematopathology �C Part II

The overlapping features of malignant lymphomas create a diagnostic “grey zone” , and lead to the invention of “grey zone lymphomas”. There are several major grey zone lymphomas: 1) Lymphomas with overlapping features of Hodgkin lymphoma and large B-cell lymphoma; 2) Lymphomas with overlapping features of Burkitt lymphoma and diffuse large B-cell lymphoma; 3) Lymphomas with overlapping features of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte rich large B-cell lymphoma; 4) Lymphomas with overlapping features of Hodgkin lymphoma, anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL); 5) T-cell classical Hodgkin lymphoma and ALCL-HL. The second review of this series will be dedicated to discussion of the “grey zone” features of the lymphomas and how to narrow down the “grey zone” between those lymphomas.     

A case of composite classical and nodular lymphocyte predominant Hodgkin lymphoma with progression to diffuse large B‐cell non‐Hodgkin lymphoma: Diagnostic difficulty in fine‐needle aspiration cytology

A small percentage of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) progresses to diffuse large B‐cell lymphoma (DLBCL). There have also been rare reports of gray zone lymphoma with features intermediate between classical Hodgkin lymphoma (CHL) and DLBCL. We report a very rare case of composite lymphoma (CHL and NLPHL) progressing to DLBCL, and highlight the diagnostic difficulty faced during its fine‐needle aspiration (FNA) cytology diagnosis. A 65‐year‐old woman presented with a right axillary swelling which was subjected to FNA cytology. The routine FNA cytology diagnosis was anaplastic large cell lymphoma (ALCL) but immunocytochemistry did not support this diagnosis completely. The histopathological diagnosis of the excised lymph node was NLPHL with progression to DLBCL in our hospital but in a hospital abroad where the patient was treated, the reviewed diagnosis was CHL. The patient had a rapid downhill course with development of terminal pleural effusion and died approximately one year from initial diagnosis.The review of the cyto‐histologic material along with additional immunocyto/histochemical studies and the clinical course of the disease support the diagnosis of a composite lymphoma (CHL and NLPHL) with progression to DLBCL. It is suggested that all the three lesions were clonally related. Diagn. Cytopathol. 2017;45:262–266. © 2016 Wiley Periodicals, Inc.     

De novo CD5 positive diffuse large B-cell lymphomas with bone marrow involvement in Korean

In CD5 positive (CD5+) mature B-cell lymphomas, newly recognized CD5+ diffuse large B-cell lymphoma (DLBCL) has been characterized by aggressive features. We studied twenty-five cases with CD5+ lymphomas involving bone marrow. Eleven cases were diagnosed as chronic lymphocytic leukemia, six cases were diagnosed as mantle cell lymphoma (MCL), and three cases with morphologic characteristics of MCL and without both the cyclin D1 expression and IGH/CCND1 rearrangement were unclassifiable. The remaining five cases, showing large to medium-sized lymphoid cells with prominent nucleoli and a moderate amount of cytoplasm, were diagnosed as DLBCL. Five DLBCL cases were positive for CD5, CD20, surface immunoglobulin, but negative for CD23. Patients with CD5+ DLBCL showed a high age of onset (median, 68 yr) and two patients expired one month after the diagnosis. Since CD5+ DLBCL forms a distinct subgroup of DLBCL, a study of CD5 expression in DLBCL would be helpful to predict prognosis and to determine future therapeutic strategy. To the best of our knowledge, this is the first report on de novo CD5+ DLBCL in Koreans.     

B细胞特异性激活蛋白Pax-5在淋巴瘤组织中的表达

目的探讨B细胞特异性激活蛋白(BSAP)／Pax-5在淋巴瘤的表达情况及应用价值。方法按2001年WHO关于淋巴造血组织肿瘤分类标准收集102例弥漫性大B细胞淋巴瘤(DLBCL)、3例滤泡型淋巴瘤(FL)、3例黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT淋巴瘤)、1例结节性淋巴细胞为主型的霍奇金淋巴瘤(NLPHL)、10例间变性大细胞淋巴瘤(ALCL)和10例浆细胞瘤,用免疫组织化学LSAB法同步检测比较BSAP与CD20的表达情况。结果102例DLBCL全部表达CD20,100例表达BSAP,3例FL、3例MALT淋巴瘤和1例NLPHL BSAP和CD20全部阳性表达,10例ALCL、10例浆细胞瘤BSAP和CD20全部阴性表达。BSAP与CD20的表达差异无统计学意义。结论。BSAP/Pax-5是一种新的B细胞标记,阳性信号定位于细胞核,抗BSAP抗体在常规外科病理诊断工作中的应用价值有限。     

Clusterin expression in malignant lymphomas: a survey of 266 cases.

Clusterin expression has been reported to be characteristic of systemic anaplastic large cell lymphoma and usually negative in cutaneous anaplastic large cell lymphoma as well as other lymphoma types. We surveyed clusterin expression using immunohistochemical methods in 266 cases of non-Hodgkin's lymphoma and Hodgkin's disease to further assess the diagnostic utility of this marker. Clusterin immunostaining was observed in 40 of 49 (82%) systemic anaplastic large cell lymphomas and 12 of 29 (41%) cutaneous anaplastic large cell lymphomas. Clusterin also was expressed in 5 of 43 (12%) diffuse large B-cell lymphomas (4 of 5 CD30+), 1 of 14 (7%) peripheral T-cell lymphomas, 1 of 32 (3%) cases of nodular sclerosis Hodgkin's disease, and 1 case of mycosis fungoides in large cell transformation. Clusterin was negative in all other neoplasms assessed including follicular lymphoma of all grades (n = 24), mantle cell lymphoma (n = 13), marginal zone B-cell lymphoma (n = 12), precursor T-cell or B-cell lymphoblastic leukemia/lymphoma (n = 10), mixed cellularity Hodgkin's disease (n = 8), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7), Burkitt lymphoma (n = 7), mycosis fungoides (n = 4), nodular lymphocyte predominant Hodgkin's disease (n = 3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (n = 2), and plasmacytoma (n = 2). We conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin's disease is useful. However, clusterin is also positive in a substantial subset of cutaneous anaplastic large cell lymphomas, a smaller subset of diffuse large B-cell lymphomas, and rarely in cases of peripheral T-cell lymphoma and nodular sclerosis Hodgkin's disease.     

De novo CD5+ diffuse large B-cell lymphomas. A heterogeneous group containing an unusual form of splenic lymphoma

We reviewed our institutional experience with de novo CD5+, large B-cell lymphomas to determine whether they represent a distinct entity and are related to CD5+ small B-cell disorders. We identified 13 cases with multiparameter flow cytometry over a period of 58 months (5% of large B-cell lymphomas) in 7 females and 6 males. Three groups were identified. Group 1 (2 cases) had diffuse splenic red pulp involvement with a distinctive cordal pattern of infiltration, no other clinical evidence of mass disease, microscopic disseminated disease on further workup, and an identical immunoglobulin-negative immunophenotype. Group 2 cases (7 cases) were clinically and morphologically heterogeneous and had an immunophenotype resembling mantle cell lymphoma (FMC7-positive, CD23-). Group 3 (4 cases) had miscellaneous immunophenotypes, including one closely resembling chronic lymphocytic leukemia. Cyclin D1 was positive in only 1 of 10 evaluable cases (group 2). We conclude that CD5+ diffuse large B-cell lymphomas are heterogeneous; most cases do not seem to be related to chronic lymphocytic leukemia or mantle cell lymphoma. However, we identified a subgroup of primary splenic CD5+ large B-cell lymphoma with diffuse red pulp involvement and believe this may represent a distinct clinicopathologic entity.     

Expression of the Leu-8 antigen by B-cell lymphomas

The Leu-8 antigen is found on the surface of many hematologic cells, including many T- and B-lymphocytes. With the use of a frozen-section immunoperoxidase technic, 152 B-cell non-Hodgkin's lymphomas were examined for Leu-8 expression. Of these lymphomas, 53% expressed Leu-8. Subclassification of the lymphomas with the use of the International Working Formulation showed that most small lymphocytic, intermediate lymphocytic, and diffuse large cell lymphomas and about half of diffuse small cleaved, diffuse mixed, and follicular lymphomas expressed Leu-8. In contrast, all 17 cases of small noncleaved cell (Burkitt's) lymphoma and 9 of 10 cases of multiple myeloma/plasmacytoma were Leu-8 negative. These results indicate that Leu-8 is expressed on a wide variety of B-cell lymphomas and that differences in Leu-8 expression may be useful in the diagnostic separation of small lymphocytic lymphoma with plasmacytoid features from multiple myeloma/plasmacytoma, and diffuse large cell lymphoma from Burkitt's lymphoma.     

Programmed death 1 expression in variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma: comparison with CD57 and lymphomas in the differential diagnosis

Recent studies have exploited an antibody directed against programmed death 1 expressed by follicular helper T-cells in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. We had previously described clinically relevant, variant immunoarchitectural patterns of nodular lymphocyte predominant Hodgkin lymphoma and, in this study, sought to address the diagnostic utility of programmed death 1 in comparison with CD57 in variant nodular lymphocyte predominant Hodgkin lymphoma. Immunohistologic staining for programmed death 1 was carried out on biopsies of 67 patients with variant nodular lymphocyte predominant Hodgkin lymphoma. Thirty-four additional cases of nodular lymphocyte predominant Hodgkin lymphoma with associated diffuse areas, de novo T-cell and histiocyte-rich large B-cell lymphoma, and lymphocyte-rich classic Hodgkin lymphoma were also studied. Our results show that programmed death 1 positivity was found in the majority of nodular lymphocyte predominant Hodgkin lymphoma cases with a classic nodular architecture (87%) as compared with 50% for CD57 and was particularly helpful in identifying extranodular large atypical cells. Nodular lymphocyte predominant Hodgkin lymphoma with diffuse areas showed a gradual decrease in programmed death 1 reactivity from nodular to diffuse areas, although a significant proportion (40%-50%) of cases retained programmed death 1 positivity also in diffuse areas. In addition, T-cell and histiocyte-rich large B-cell lymphoma and lymphocyte-rich classic Hodgkin lymphoma displayed programmed death 1 positivity in a significant subset of cases (33%-40%). In conclusion, our study supports the utility of programmed death 1 in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma and shows greater sensitivity of staining of programmed death 1 as compared with CD57 across all variants of nodular lymphocyte predominant Hodgkin lymphoma. Loss of programmed death 1 reactivity did not correlate with diffuse areas, progression, or the ability to differentiate nodular lymphocyte predominant Hodgkin lymphoma from T-cell and histiocyte-rich large B-cell lymphoma. These findings suggest the need for continued vigilance in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma and its immunoarchitectural variants as well as related lymphomas in their differential diagnosis.     

Expression of the diffuse B-cell lymphoma family molecule SWAP-70 in human B-cell neoplasms: immunohistochemical study of 86 cases.

SWAP-70 is a recently discovered member of the Dbl (diffuse B-cell lymphoma) family of signal transduction molecules that is abundantly expressed in B cells. SWAP-70 mediates lipid second-messenger signals to the cytoskeletal-organizing GTPase Rac, functioning as a guanine-nucleotide exchange factor. SWAP-70 is strongly expressed in germinal center B cells, with low-level expression in resting B-cells. Expression of SWAP-70 in neoplastic B cells has not been described. We report the immunohistochemical expression of SWAP-70 in 86 B-cell neoplasms. SWAP-70 was strongly expressed in 59 of the 86 cases: 2 of 10 (20%) precursor B-cell lymphoblastic leukemias, 2 of 2 (100%) precursor B-cell lymphoblastic lymphomas, 2 of 4 (50%) mantle cell lymphomas, 7 of 9 (78%) Burkitt lymphomas, 9 of 9 (100%) diffuse large B-cell lymphomas, 8 of 8 (100%) follicular lymphomas, 6 of 6 (100%) nodular lymphocyte predominant Hodgkin lymphomas, 0 of 8 (0%) classic Hodgkin lymphomas, 12 of 13 (92%) chronic lymphocytic leukemias, 3 of 3 (100%) nodal marginal zone lymphomas, 5 of 5 (100%) extranodal marginal zone lymphomas, 1 of 2 (50%) splenic marginal zone lymphomas, 2 of 3 (66%) hairy cell leukemias, and 0 of 4 (0%) plasma cell neoplasms. All 4 T-cell lymphomas were nonreactive for SWAP-70: 0 of 3 peripheral T-cell lymphomas and 0 of 1 anaplastic large cell lymphoma. These results suggest that a spectrum of neoplastic B cells maintains activation of this signal transduction pathway. This is the first report of the expression of a Dbl family molecule in human lymphoma and leukemia tissues.     

Flow cytometric analysis of surface light chain expression patterns in B-cell lymphomas using monoclonal and polyclonal antibodies

Light chain (LC) expression by flow cytometry (FC) in B cell non-Hodgkin lymphomas (B-NHLs) can occasionally be detected with one anti-LC antibody but not with another. We retrospectively analyzed 564 four-color FC files from B-NHLs, assessing LC staining with monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs). Discrepancies in LC expression between mAbs and pAbs were present in 9.2% of cases, mainly in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 11.1%), diffuse large B-cell lymphoma (DLBCL; 10.2%), follicular lymphoma (9.5%), and mantle cell lymphoma (11.1%) and most frequently in body fluids. Equal proportions of cases were LC+ only with pAbs (4.8%) or mAbs (4.4%). Negative LC expression with both antibodies was present in 7.5% of cases, most frequently in DLBCL (21.6%) and body fluids (27.6%). Evaluation with both mAbs and pAbs increases the sensitivity for LC detection, with no single reagent outperforming the other, although CLL/SLL preferentially showed LC expression with pAbs.     

Epstein–Barr virus‐positive diffuse large B cell lymphoma arising from a chronic lymphocytic leukemia: Overlapping features with classical Hodgkin lymphoma

A small proportion of patients with chronic lymphocytic leukemia (CLL) may progress to large cell lymphoma, or Richter syndrome (RS). The large cells of RS may arise through transformation of the original CLL clone (clonally related) or represent a new neoplasm (clonally unrelated), which might be Epstein–Barr virus (EBV)‐associated. We present a 61‐year‐old male with 5‐year history of CLL who developed RS on bilateral adrenal glands. The tumor showed a vague nodular growth pattern separated by thick fibrous bands and the tumor cells were large and pleomorphic, with focal sheet‐like growth pattern, in a background of small B and T‐lymphocytes. The large tumor cells were positive for CD15, CD19, CD20 (intensely and diffusely), CD30, fascin, PAX5, MUM1, OCT2, and LMP‐1 by immunohistochemical stains, and EBV by in situ hybridization. The tumor was diagnosed as EBV‐positive diffuse large B cell lymphoma (DLBCL), with overlapping features of classic Hodgkin lymphoma (CHL). The patient received salvage chemotherapy and was free of disease 2 years after adrenalectomy. We speculated that our case was a clonally unrelated tumor with his underlying CLL and discussed the differential diagnoses between EBV‐positive DLBCL and CHL in the setting of RS.     

Concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine: a dimorphic presentation of iatrogenic immunodeficiency-associated lymphoproliferative disorder with evidence suggestive of multiclonal transformability of B cells by Epstein-Barr virus

A small fraction of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma develop Epstein-Barr virus–positive B-cell lymphoproliferative disorders. These Epstein-Barr virus–B-cell lymphoproliferative disorders are thought to be related to immune suppression induced by fludarabine/other chemotherapeutic regimens. As in other immunodeficiency-associated lymphoproliferative disorders, these disorders demonstrate a heterogeneous histological spectrum that ranges from polymorphic to monomorphic to classical Hodgkin lymphoma–like lesions. We report a case of concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine. Both classical Hodgkin lymphoma and plasmablastic lymphoma were positive for Epstein-Barr virus-encoded RNA, whereas classical Hodgkin lymphoma was also positive for Epstein-Barr virus- latent membrane protein 1, suggesting a different viral latency. Immunoglobulin gene rearrangement studies demonstrated distinct clones in the plasmablastic lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. These findings suggest biclonal secondary lymphomas associated with iatrogenic immunodeficiency. Epstein-Barr virus–B-cell lymphoproliferative disorders in the setting of chronic lymphocytic leukemia/small lymphocytic lymphoma, in particular those arising after chemotherapy, should be separated from true Richter's transformation, and be categorized as (iatrogenic) immunodeficiency-associated lymphoproliferative disorder.     

Nodal T-cell lymphomas with a T-follicular helper cell phenotype

The discovery and characterisation of T-follicular helper (TFH) cells, a distinct functional subset of T-helper cells has led to the recognition that some peripheral T-cell lymphomas (PTCLs) have a TFH cell immunophenotype. Due to the overlap in clinical, morphological, immunophenotypic and genetic characteristics, the revised 4^th edition to the WHO classification recognises one umbrella category of ‘angioimmunoblastic T-cell lymphoma and other nodal TCLs of TFH cell origin’. This review provides a brief overview of TFH cells with special emphasis on function and phenotype and a more detailed discussion of clinical, morphologic, immunophenotypic and genotypic characteristics of AITL, follicular T-cell lymphoma and nodal PTCL with TFH phenotype which constitute nodal TCLs of TFH origin. Secondary B-cell proliferations (often EBV positive) and features that help differentiate reactive lymphoid hyperplasia and other types of lymphoma, including PTCL, NOS and secondary B-cell lymphomas and classic Hodgkin lymphoma, from nodal TCLs with a TFH phenotype are discussed.