Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations

Autor: Sitharthan Kamalakaran, Russell K. Brynes, Keegan Barry-Holson, Imran Siddiqi, Lizalynn M. Dias, Kevin R. Kelly, Charles Ma, Irene Kang, Venkata Thodima, Jane Houldsworth, Julia Friedman, Raghavendra Padmanabhan
Rok vydání: 2015
Předmět:
0301 basic medicine
Adult
Male
medicine.medical_specialty
Pathology
Genes
Immunoglobulin Heavy Chain
DNA Mutational Analysis
Follicular lymphoma
Chromosome Disorders
Biology
Translocation
Genetic
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
immune system diseases
hemic and lymphatic diseases
medicine
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
Phosphorylation
Lymphoma
Follicular
In Situ Hybridization
Fluorescence
Aged
80 and over
Chromosomes
Human
Pair 14
medicine.diagnostic_test
Receptors
IgE
CD23
Cytogenetics
Germinal center
High-Throughput Nucleotide Sequencing
Middle Aged
medicine.disease
Immunohistochemistry
Lymphoma
030104 developmental biology
Phenotype
Proto-Oncogene Proteins c-bcl-2
Cytopathology
Chromosomes
Human
Pair 1
030220 oncology & carcinogenesis
Mutation
Female
Chromosome Deletion
Hematopathology
Chromosomes
Human
Pair 18
STAT6 Transcription Factor
Receptors
Tumor Necrosis Factor
Member 14
Fluorescence in situ hybridization
Zdroj: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 29(6)
ISSN: 1530-0285
Popis: A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2 translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al. Along with pertinent clinical information, we detail their histopathology, IGH/BCL2 translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well- to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situ hybridization analysis, the vast majority lacked IGH/BCL2 translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14 mutations were identified in three, highlighting the strong association of 1p36/TNFRSF14 abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6 mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6 mutations is higher than recently reported in conventional follicular lymphoma (11%). These findings lend support for a clinicopathologic variant of t(14;18) negative nodal follicular lymphoma and suggests importance of the interleukin (IL)-4/JAK/STAT6 pathway in this variant.
Databáze: OpenAIRE
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