Angioimmunoblastic T-cell Lymphomas With the RHOA p.Gly17Val Mutation Have Classic Clinical and Pathologic Features

Am J Surg Pathol. 2016 Mar;40(3):335-41. doi: 10.1097/PAS.0000000000000555.

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is a nodal-based mature T-cell lymphoma with distinctive clinical symptomatology and histology. Research into its pathogenesis supports a cellular derivation from follicular helper T cells and overexpression of genes related to B cells, follicular dendritic cells, and vascular growth. Recently, a novel recurring somatic mutation in RHOA, encoding p.Gly17Val, was discovered in nearly 70% of AITLs and in a smaller proportion of peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS). We investigated a series of AITLs to compare RHOA mutated with wild-type case for clinicopathologic differences. Targeted exome and Sanger sequencing was performed on 27 AITLs and 10 PTCL-NOS. The RHOA G17V mutation was identified in 63% of the AITL cases and in none of the PTCL-NOS cases. The median variant allelic frequency was 14%, with a range of 0.4 to 50% in positive cases. RHOA G17V-mutated cases had a significantly higher incidence of splenomegaly and B symptoms at diagnosis, but there was no difference in overall survival between mutated and wild-type subgroups. Cases with the RHOA G17V mutation had a significantly higher mean microvessel density (P<0.01) and expressed a greater number of follicular helper T-cell markers (P<0.05) than wild-type cases. RHOA G17V is present in a significant proportion of angioimmunoblastic lymphomas and is associated with classic pathologic features of AITL. Additional studies are needed to provide a biological or functional link between altered RHOA function and these pathologic features.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Immunoblastic Lymphadenopathy / enzymology
  • Immunoblastic Lymphadenopathy / genetics*
  • Immunoblastic Lymphadenopathy / pathology
  • Immunohistochemistry
  • Lymphoma, T-Cell / enzymology
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / pathology
  • Male
  • Microvessels / pathology
  • Middle Aged
  • Mutation*
  • Phenotype
  • Splenomegaly / genetics
  • Splenomegaly / pathology
  • rhoA GTP-Binding Protein / genetics*

Substances

  • Biomarkers, Tumor
  • RHOA protein, human
  • rhoA GTP-Binding Protein