Bone Marrow Infiltration of Angioimmunoblastic T-Cell Lymphoma: Identification and Prognostic Impact of Histologic Patterns and Diagnostic Application of Ancillary Phenotypic and Molecular Analyses

Arch Pathol Lab Med. 2020 May;144(5):602-611. doi: 10.5858/arpa.2019-0007-OA. Epub 2019 Sep 26.

Abstract

Context.—: Angioimmunoblastic T-cell lymphomas originate from T follicular helper cells and express respective markers (BCL6, CD10, CXCL13, ICOS, and PD-1). Although commonly present, bone marrow involvement by angioimmunoblastic T-cell lymphoma can be diagnostically challenging. Additionally, only little is known about the distribution of T follicular helper cells in healthy and reactively changed bone marrows or in samples affected by other lymphomas.

Objective.—: To establish a diagnostic approach to reliably identify bone marrow infiltration of angioimmunoblastic T-cell lymphoma.

Design.—: We analyzed the morphologic infiltration pattern and the expression of T follicular helper-cell markers in 42 matched paired lymph node and bone marrow samples and applied comparative clonality testing. Furthermore, we studied the expression of BCL6 and PD-1 in a control cohort of healthy, reactively changed, and otherwise affected bone marrows.

Results.—: We identified 3 different bone marrow infiltration patterns correlating with overall survival (interstitial/micronodular infiltration with or without eosinophilia and diffuse infiltration with eosinophilia). The matched pairs showed a consistent (co)expression of PD-1 and BCL6 with a generally weaker expression in the bone marrow than in the lymph nodes. Comparative clonality testing was helpful in only a minority of cases. Infiltrates of the most important differential diagnoses contained either PD-1- or BCL6-positive tumor-infiltrating cells, but no coexpressing cells.

Conclusions.—: Bone marrow infiltration by angioimmunoblastic T-cell lymphoma displays 3 different patterns that correlate with prognosis. BCL6 and PD-1 can be reliably used to identify lymphoma infiltrates and to help rule out several differential diagnoses. Comparative clonality testing rarely provides additional value and cannot replace morphologic and phenotypic analyses.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Bone Marrow / pathology
  • Chemokine CXCL13 / metabolism
  • Female
  • Humans
  • Immunoblastic Lymphadenopathy / diagnosis*
  • Immunoblastic Lymphadenopathy / metabolism
  • Immunoblastic Lymphadenopathy / pathology
  • Lymph Nodes / pathology
  • Lymphoma, Follicular / diagnosis*
  • Lymphoma, Follicular / metabolism
  • Lymphoma, Follicular / pathology
  • Lymphoma, T-Cell / diagnosis*
  • Lymphoma, T-Cell / metabolism
  • Lymphoma, T-Cell / pathology
  • Male
  • Middle Aged
  • Neprilysin / metabolism
  • Phenotype
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Switzerland
  • T-Lymphocytes, Helper-Inducer / pathology

Substances

  • BCL6 protein, human
  • Biomarkers, Tumor
  • CXCL13 protein, human
  • Chemokine CXCL13
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • Neprilysin