Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma

Mod Pathol. 2008 Jun;21(6):653-9. doi: 10.1038/modpathol.2008.30. Epub 2008 Feb 8.

Abstract

The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • DNA-Binding Proteins / biosynthesis
  • Female
  • Germinal Center / metabolism
  • Germinal Center / pathology*
  • Humans
  • Immunohistochemistry
  • Interferon Regulatory Factors / biosynthesis
  • Intracellular Signaling Peptides and Proteins
  • Kaplan-Meier Estimate
  • Lymphoma, Follicular / classification*
  • Lymphoma, Follicular / metabolism
  • Lymphoma, Follicular / pathology
  • Lymphoma, Large B-Cell, Diffuse / classification*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Microfilament Proteins
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neprilysin / biosynthesis*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-6
  • Skin Neoplasms / classification*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology

Substances

  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • GCSAM protein, human
  • Interferon Regulatory Factors
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • interferon regulatory factor-4
  • Neprilysin