Association of both BCL2 positive and negative follicular lymphoma to clasical Hodgkin lymphoma and/or gray zone lymphoma

Hum Pathol. 2024 Oct:152:105639. doi: 10.1016/j.humpath.2024.105639. Epub 2024 Aug 14.

Abstract

We present a series of 9 follicular lymphomas that progressed/transformed into classical Hodgkin lymphoma (CHL). Three cases of CHL showed a syncytial pattern (SCHL) making the differential diagnosis to Gray zone lymphoma (GZL) challenging. None of these three cases presented in the mediastinum. Based in all molecular data analyzed (BCL2/BCL6 FISH studies, IgH PCR and TNGS with a customized gene panel) we did find clonal relationship between the BCL2-positive FL cases and their CHL components in all cases. The three SCHL/GZL cases showed an activated phenotype according to Hans algorithm, presented the t(14; 18)(q32; q21), two out of three showed B cell markers and all expressed CD30 and p53. Interestingly, we identified three BCL2-negative FL cases with a further diagnosis of CHL expanding the spectrum of these association. In one of these three cases a different mutational profile was found in both the FL and the CHL components. All this data together suggests that CHL associated to BCL2-positive FL could be originated in a common progenitor cell (CPC) that give rise to both FL and CHL, acquiring this last component further genetic events in a linear fashion. On the other hand, no clonal relationship between CHL and BCL2-negative FL could be found, suggesting a fortuity association. Nevertheless, ample series of cases studied with more sensitive techniques are needed to confirm our hypothesis.

Keywords: BCL2-Negative; Classical hodgkin lymphoma (CHL); Follicular lymphoma (FL); Nonthymic gray zone lymphomas (GZL).

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Diagnosis, Differential
  • Female
  • Hodgkin Disease* / diagnosis
  • Hodgkin Disease* / genetics
  • Hodgkin Disease* / metabolism
  • Hodgkin Disease* / pathology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Follicular* / diagnosis
  • Lymphoma, Follicular* / genetics
  • Lymphoma, Follicular* / pathology
  • Male
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins c-bcl-2* / genetics
  • Proto-Oncogene Proteins c-bcl-2* / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • BCL2 protein, human
  • Biomarkers, Tumor