Potential genetic mechanisms driving B/myeloid conversion in patients with follicular lymphoma and Langerhans cell neoplasms

Abstract

Transformation of follicular lymphoma (FL) to a Langerhans cell (LC) neoplasm is extremely uncommon. The shared IGH::BCL2 rearrangement is a robust finding in most transformed tumors underscoring that the cell of origin is perhaps a pre-B cell harboring IGH::BCL2 with the propensity to undergo further genetic alterations in the germinal centers of lymph nodes: does IGH::BCL2 in pre-B cells set off a plasticity cell state? Do FL and LC neoplasms develop separately through a common progenitor or via a multistep process of transdifferentiation or dedifferentiation/redifferentiation? Here, we review the literature and relevant cases presented in the Society for Hematopathology/European Association of Haematopathology 2021 Workshop to better understand this rare and complex phenomenon. We discuss clinical data, clonal relationship, and the mutational profile of these tumors and review proposed mechanisms of B/myeloid conversion based on in vitro and in vivo models.

Keywords:

• Follicular lymphoma
• Langerhans cell sarcoma
• transdifferentiation
• dedifferentiation
• lineage conversion

Authors’ contributions

M.T. and L.J.M. wrote and reviewed the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.