Follicular Helper T-Cell-derived Nodal Lymphomas: Study of Histomorphologic, Immunophenotypic, Clinical, and RHOA G17V Mutational Profile.

The study was designed to review the demographic, clinical, and pathologic characteristics of follicular helper T cells (TFH)-derived nodal PTCL in India including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL) with follicular helper T cell phenotype (P-TFH), and follicular T-cell lymphoma with additional immunohistochemistry (IHC) and RHOAG17V mutational analysis, as well as their impact on survival. This retrospective study included 88 cases of PTCL that were reclassified using IHC for TFH markers (PD1, ICOS, BCL6, and CD10) and dendritic-meshwork markers (CD21, CD23). Cases of TFH cell origin were evaluated for RHOAG17V mutation using Sanger sequencing and amplification-refractory mutation system-polymerase chain reaction (PCR) (validated using cloning and quantitative PCR) with detailed clinicopathologic correlation. Extensive re-evaluation with added IHC panel resulted in a total of 19 cases being reclassified, and the final subtypes were AITL (37 cases, 42%), PTCL-not otherwise specified (44, 50%), P-TFH (6, 7%), and follicular T-cell lymphoma (1, 1%). The presence of at least 2 TFH markers (>20% immunopositivity) determined the TFH origin. AITL patients tended to be male and showed increased presence of B-symptoms and hepatosplenomegaly. Histomorphology revealed that 92% of AITL cases had pattern 3 involvement. Sanger sequencing with conventional PCR did not yield any mutation, while RHOAG17V was detected by amplification-refractory mutation system-PCR in AITL (51%, P =0.027) and P-TFH (17%), which was validated with cloning followed by sequencing. Cases of RHOAG17V-mutant AITL had a worse Eastern Cooperative Oncology Group performance status initially but fared better in terms of overall outcome ( P =0.029). Although not specific for AITL, RHOAG17V mutation shows an association with diagnosis and requires sensitive methods for detection due to low-tumor burden. The mutant status of AITL could have prognostic implications and translational relevance.

Differential expression of miRNA in histological subtype of Wilms tumor.

INTRODUCTION: Wilms tumor is the most common renal malignancy in children and difficult to differentiate from other paediatric abdominal tumors radiologically, necessitating an invasive procedure for diagnosis. Previous studies have shown the potential role of miRNA as biomarkers for diagnosis, histological subtyping and prognosis. In this study, we are exploring the role of miRNA in the histological subtyping of Wilms tumor in the Indian population. MATERIALS AND METHODS: A total of 15 cases of Wilms tumor were evaluated for global miRNA expression analysis by microarray. Total RNA was extracted from fresh frozen tumor and miRNA expression analysis was performed using Agilent platform. Unsupervised clustering was done to analyse the data. RESULTS: Using unpaired student T test, top 10 significantly differentially expressed miRNA were selected which could differentiate among different histological subtypes by unsupervised hierarchical clustering and principal component analysis. The presence of necrosis, heterologous differentiation led to change in miRNA expression profile and led to a distinct cluster formation. CONCLUSIONS: A panel of 5 miRNAs (miR1, 133b, 299-3p, 499a-5p, 491-3p) could differentiate among different histological subtypes of Wilms tumor, thus avoiding an invasive procedure in children, however, further confirmation using real time PCR analysis will be needed.

Lymphoma subtypes in India: a tertiary care center review.

Lymphomas are a group of neoplasm arising from immune cells with varied clinical presentation, molecular profile, morphology and immunophenotype. The epidemiology and response to treatment varies among patients from different geographical locations. We analyze the demographic characteristics of lymphomas in a tertiary care center of India over a period of five years. This was a retrospective study including cases from 2015 to 2019 which were classified according to WHO classification 2017. A total of 4115 lymphoma cases were diagnosed. Hodgkin lymphomas (HL) comprised 30.35% (n = 1249), and non-Hodgkin lymphoma (NHL) was 69.65% (n = 2866). Site of presentation was nodal in 64.76% cases, and 35.23% were extranodal. There was an overall male predominance. Among the NHLs, B-cell type comprised of 84.08% and 15.38% was T- and NK cell lymphomas. Mature B cell lymphomas comprised 82.41% with predominant being diffuse large B cell lymphoma type (42.53%) followed by follicular lymphoma (10.81%) and small lymphocytic lymphoma (6.10%). Among the T-cell type, PTCL NOS (2.65%) was the predominant subtype followed by ALK positive anaplastic large cell lymphoma (ALCL-ALK+) (2.44%), extranodal NK-T cell lymphoma (2.02%) and others. Classical type was predominant type (97.91%) among HL, and 2.08% were nodular lymphocyte predominant type. Among the classical HL, nodular sclerosis (28.1%) and mixed cellularity (32.18%) co-dominated. Our study indicates that the Indian population differs in the prevalence, presentation and the subtyping among various lymphomas. Higher prevalence of Hodgkin lymphoma, DLBCL, ALK + ALCL and immature cell neoplasm was noted.