Diagnostic value of STMN1, LMO2, HGAL, AID expression and 1p36 chromosomal abnormalities in primary cutaneous B cell lymphomas

Histopathology. 2017 Oct;71(4):648-660. doi: 10.1111/his.13279. Epub 2017 Jul 19.

Abstract

Aims: Distinction between primary cutaneous follicular lymphoma (PCFL) and primary cutaneous marginal zone lymphoma (PCMZL) is challenging, as clear-cut immunophenotypical and cytogenetic criteria to segregate both entities are lacking.

Methods and results: To characterize PCFL and PCMZL more clearly and to define criteria helpful for the differential diagnosis, we compared expression of immunohistochemical markers [LIM-only transcription factor 2 (LMO2), human germinal centre-associated lymphoma (HGAL), stathmin 1 (STMN1), activation-induced cytidine deaminase (AID), myeloid cell nuclear differentiation antigen (MNDA)] and the presence of cytogenetic abnormalities described previously in nodal follicular lymphoma [B cell lymphoma 2 (BCL2) and BCL6 breaks, 1p36 chromosomal region deletion (del 1p36)] in a series of 48 cutaneous follicular and marginal zone lymphomas [cutaneous follicular lymphoma (CFL) and cutaneous marginal zone lymphoma (CMZL)]. Immunostaining for STMN1, LMO2, HGAL and AID allowed the distinction between CFL and CMZL, and STMN1 was the most sensitive marker (100% CFL, 0% CMZL). LMO2, HGAL and AID were positive in 93.2%, 82.1% and 86.2% CFL (all CMZL-negative). MNDA was expressed in both entities without significant difference (10.3% CFL, 30.8% CMZL, P = 0.18). BCL2, BCL6 breaks and the del 1p36 were present in 16.7%, 10.7% and 18.5% CFL and no CMZL. Finally, three and 29 CFL were reclassified as secondary cutaneous follicular lymphomas (SCFL) and PCFL without significant differences concerning phenotypical and cytogenetic features. BCL2, BCL6 breaks and the del 1p36 were present in 11.1%, 8% and 16.7% PCFL and did not impact the prognosis.

Conclusion: LMO2, HGAL, STMN1 and AID, but not MNDA, are discriminant for the recognition between CFL and CMZL. BCL2, BCL6 rearrangements and the del 1p36 have a role in the pathogenesis of PCFL, the latest being the most common alteration.

Keywords: 1p36 chromosomal deletion; STMN1; cutaneous lymphoma; cytogenetic alteration.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 1 / genetics*
  • Cytidine Deaminase / genetics
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins / genetics
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell, Marginal Zone / genetics*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoma, Follicular / genetics*
  • Lymphoma, Follicular / pathology
  • Male
  • Microfilament Proteins
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Stathmin / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • BCL2 protein, human
  • BCL6 protein, human
  • Biomarkers, Tumor
  • GCSAM protein, human
  • Intracellular Signaling Peptides and Proteins
  • LIM Domain Proteins
  • LMO2 protein, human
  • Microfilament Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • STMN1 protein, human
  • Stathmin
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase