Primary central nervous system lymphoma: Comprehension of cell-of-origin subtypes

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is an uncommon extranodal lymphoma that accounts for more than 95% of all the CNS lymphomas. Unlike its systemic/nodal counterpart, which is currently subtyped into cell-of origin (COO) subtypes, its feasibility and utility are largely debatable in PCNS-DLBCL. Objectives: To classify PCNS-DLBCL into COO-subtypes based on immunohistochemical algorithms by Hans and Choi and evaluate concordance between the two. A further aim is to investigate the clinicoradiological and histomorphological parameters of the subtypes thus obtained. Materials and Methods: As many as 143 cases of primary CNS lymphoma were evaluated by immunohistochemistry for CD10, BCL6, MUM1, GCET, and FOXP1 and based on which the said 143 cases were further classified into COO subtypes using Hans and Choi algorithms. Results: Mean age was 53.8 years with marginal male preponderance and predominantly centroblastic morphology (75.5%). CD 10 was positive in 8.9% of the cases, BCL6 in 58.6%, MUM1 in 89.9%, GCET in 32.9%, and FOXP1 in 79.5%. As much as 84.9% cases were of non-germinal center B-cell (GCB) subtype and 15.1% cases were of GCB subtype as determined based on Hans algorithm. Furthermore, 90.7% cases were of activated B-cell (ABC) subtype and 9.3% cases were of GCB subtype according to Choi algorithm. A 91.8% concordance was observed between Hans and Choi algorithms. Among the 6 discordant cases, 5 cases were subtyped as GCB by Hans and ABC by Choi and 1 case as ABC by Hans and GCB by Choi. Conclusion: Most of PCNS-DLBCLs are of non-GCB/ABC COO subtype, but inconsistences abound in the utility of IHC algorithms in PCNS-DLBCL COO subtypes.

Paediatric type diffuse high grade gliomas in the WHO CNS5 classification: What the pathologist needs to know?

Pediatric-type of diffuse high-grade gliomas (HGG) are classified as a distinct group in the current fifth edition of WHO classification. This group of high-grade tumors is no more called as glioblastoma (GBM), which has been reserved for adult isocitrate dehydrogenase (IDH)-wild type HGG. These tumors are uncommon as compared to embryonal tumors and low-grade gliomas (LGG). Pediatric-type of diffuse HGG biologically differs from their adult counterparts in that they are therapeutically less sensitive to alkylating chemotherapies. They comprise a heterogeneous group of molecularly defined tumors – predominantly histone gene altered, less common receptor tyrosine kinase (RTK)-mediated, and syndrome-associated. This review provides an overview of these uncommon tumors and discusses the diagnostic approach of this heterogeneous group of tumors.

An unusual presentation of large B-cell lymphoma with interferon regulatory factor 4 gene rearrangement

Rearrangements involving interferon regulatory factor 4 (IRF4) gene has been recently described in a subtype of diffuse large B-cell lymphoma (DLBCL). They occur in a typical clinical setting of a pediatric age group, predominantly with tonsillar mass, usually as a low-stage disease and with good response to chemotherapy. Histomorphologically, they show nodular/follicular architecture with diffuse strong immunopositivity for multiple myeloma oncogene 1. Here, the authors describe one such unusual case of large B-cell lymphoma with IRF4 gene rearrangement in a young child with the unusual location of inguinal region and detailed pathological (histological, immunohistochemical, and molecular) findings.

Applicability of 2008 World Health Organization classification system of hematolymphoid neoplasms: Learning experiences

Background: 2008 World Health Organization (WHO) classification of hematolymphoid neoplasms (HLN) has classified them based on morphology, results of various ancillary techniques, and clinical features.[1] There are no studies looking at the applicability of WHO classification. Aims: The aim of the study was to calculate proportions of all HLN subtypes seen during 1-year period based on 2008 WHO classification of HLN and study applicability and also shortcomings of practices in a tertiary care center in India. Materials and Methods: This was a 1-year retrospective study (January 1st, to December 31st, 2010) where cases were identified using hospital/laboratory electronic records. Old follow-up and referral cases were excluded from the study. Only newly diagnosed cases classified into categories laid down by 2008 WHO classification of HLN included. Results: Out of 2118 newly diagnosed classifiable cases, 1602 (75.6%) cases were of lymphoid neoplasms, 489 (23.1%) cases of myeloid neoplasms, 16 (0.8%) cases of histiocytic and dendritic cell neoplasms, and 11 (0.5%) cases of acute leukemias of ambiguous lineage. Overall, most common HLN subtype was diffuse large B-cell lymphoma (n = 361, 17.0%). Precursor B-lymphoblastic leukaemia/lymphoma (n = 177, 48.2%) was the most common subtype within pediatric age group. Conclusions: All major subtypes of HLN were seen at our center and showed trends almost similar to those seen in other Indian studies. Molecular/cytogenetic studies could not be performed on a significant number of cases owing to logistic reasons (unavailability of complete panels and also cost-related issues) and such cases could not be classified as per the WHO classification system.

Histopathological audit of splenectomies received at a cancer hospital.

Background: There are few studies in the literature studying the yield of the diagnostic splenectomy in a suspicious lymphoma case. Moreover, their relevance is limited owing to low number of cases, the use of selection criteria, and the lack of modern ancillary studies. We present a histopathological review of splenectomy specimens referred as a case of lymphoma to our center. Materials and Methods: The medical charts and laboratory data on all patients of all splenectomy specimens between the years 2003 and 2008 were reviewed. Morphological and immunohistochemical features were analyzed and the lymphomas were sub-typed in accordance to 2008 WHO Classification of Hematolymphoid Neoplasms. Flow cytometry immunophenotyping available in few cases was correlated. Results: A total of 46 cases studied included splenic marginal zone lymphoma (SMZL) (19 cases), splenic diffuse large B-cell lymphoma (DLBCL) (14 cases), splenic diffuse red pulp B-cell lymphoma (DRP) (five cases), follicular lymphoma (three cases), hairy cell leukemia (HCL) (two cases), HCL variant (HCLv) (1 case), 1 case of hepatosplenic gamma delta T-cell lymphoma (TCL), and 1 cases of TCL (not otherwise specified). Conclusions: Predominantly splenic lymphoma is a biologically heterogeneous entity, ranging from low-grade SMZL to high-grade DLBCLs. TCLs constituted only 4% of all our cases. DRP, HCL, and HCLv have similar diffuse red pulp patterns of splenic involvement and are differentiated based on flow cytometric immunophenotyping. We had a large number of splenic DLBCL and none of these involved bone marrow (BM), while all other lymphoma subtypes had BM involvement (stage IV disease). Morphological and immunophenotypic (immunohistochemistry and flow cytometry) features of BM and splenectomy specimen need to be correlated to differentiate these rare though similar-looking entities with overlapping features.

Study of the morphological patterns and association of Epstein-Barr virus and human herpes virus 8 in acquired immunodeficiency deficiency syndrome-related reactive lymphadenopathy.

Aims: Study of the morphological patterns of acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy. Settings and Design: We retrospectively selected cases of AIDS-related benign lymphadenopathy. Cases with lymphomas, frank granulomas and necrosis were excluded. We analyzed different morphological patterns and correlated these with immunophenotypic markers along with viral markers human herpesvirus 8-latency-associated nuclear antigen (HHV8-LANA), and Epstein-Barr virus-encoded ribonucleic acid (EBER) studies via in situ hybridization (EBER-ISH). Materials and Methods: We present the morphological patterns of 13 cases of human immunodeficiency virus (HIV)-reactive lymph nodes and their clinical, hematological, biochemical and radiological parameters with special emphasis on the presence or absence of viral markers, including HHV8 and EBV. Results: Common patterns included follicular hyperplasia only (five cases), mixed pattern of follicular hyperplasia with burnt-out germinal centres (four cases), completely atretic follicle (two cases), folliculolysis (11 cases), dumbbell-shaped follicles (three each), progressive transformation of germinal centers (four cases), T-zone expansion (two cases), Reed Sternberg (RS) cells like immunoblasts (two cases), Castleman's-like features with lollipop-like follicles (three cases) and a spindle cell prominence (one case). CD8+ T-cells were predominant in 12 cases. CD8+ T-cells were prominent in germinal centers (eight cases). Plasmablasts were seen in four cases within the perigerminal center area. Immunohistochemistry for HHV8, i.e. HHV8-LANA were negative in all cases while EBER was detected in 11 cases in the centrocyte-like B cells. Two cases of multicentric Castleman's disease expressed EBER; however, they did not express HHV8. Conclusion: The wide spectrum of histological changes in HIV-associated lymphadenopathy requires recognition. The histological changes can mimic those of other infective lymphadenitis, follicular lymphoma, Castleman's disease, progressive transformation of germinal center, Hodgkin's disease and spindle cell neoplasms. Presence of EBV is common while HHV8 was not seen.