Clonally Related Follicular Lymphomas and Langerhans Cell Neoplasms

Abstract

The traditional model of hematopoiesis is based on unidirectional maturation of hematopoietic precursors into lineage-committed cells. However, recent studies indicate that mature B lymphocytes may demonstrate significant lineage plasticity. We and others have reported transdifferentiation of follicular lymphomas (FLs) into clonally related histiocytic/dendritic cell neoplasms. Here, we describe 2 patients with FL who developed clonally related Langerhans cell neoplasms. The first was a 52-year-old man diagnosed with FL, grade 1. He received immunochemotherapy and had stable disease for 8 years. He then developed increasing lymphadenopathy, and lymph node biopsy showed Langerhans cell sarcoma with no evidence of FL. The second patient was a 77-year-old woman who presented with lymphadenopathy, an abdominal mass, and pulmonary nodules. Lymph node biopsy showed both Langerhans cell histiocytosis and minimal involvement by FL, grade 1. In each case, a combination of immunoglobulin gene rearrangement and fluorescence in situ hybridization studies provided evidence to support a clonal relationship between the FL and Langerhans cell neoplasm. These cases provide striking examples of neoplastic transdifferentiation and expand the spectrum of lesions clonally identical to otherwise typical FL. Awareness of this phenomenon may aid in diagnosis when histologically dissimilar tumors arise synchronously or metachronously in patients with lymphoma.

Lymphoblastic transformation of follicular lymphoma: a clinicopathologic and molecular analysis of 7 patients

“…Loss of transcription factor Pax5 allows mature B cells to dedifferentiate to uncommitted hematopoietic progenitors and develop into progenitor cell lymphomas [24]. In vivo, cases of low-grade B cell lymphoma and B-ALL transformation to clonally related histiocytic sarcoma, interdigitating cell sarcoma and Langerhans cell tumors have been reported [33][34][35]. Thus, dedifferentiation to a B cell precursor level is another, although less plausible, way to explain lymphoblastic transformation of FL.…”

High prevalence of myeloid neoplasms in adults with non–Langerhans cell histiocytosis

“…12 This is largely based on several case reports describing individual patients with lymphoid neoplasms and a clonally related secondary malignant histiocytosis. [33][34][35][36][37] However, the high frequency of myeloid neoplasms in patients with ECD or MH suggests a nonfortuitous biological association of both conditions. Although it is well established that myeloid neoplasms such as classic MPNs, MDS, and AML originate from hematopoietic stem cells, 38-41 the cell(s) of origin of LCH and non-LCH conditions are far less clearly delineated.…”

Activating mutations of the oncogene EZH2 in cutaneous melanoma revealed by next generation sequencing

“…In contrast, the patient's follicular lymphoma demonstrated neither EZH2 (Y641) nor BRAF (V600) mutations. Transdifferentiation of lymphoma into Langerhans cell neoplasms, histiocytic sarcomas and dendritic cell sarcomas has been reported [29,30]. However, the expression of melanocytic markers including Melan-A in the index case, together with the lack of shared EZH2 and BRAF mutations between the melanoma and lymphoma, makes transdifferentiation unlikely in this case.…”