Clonally Related Follicular Lymphoma and Langerhans Cell Neoplasm: A Study of 2 Cases
Dava S West, Ahmet Dogan, Rhett P Ketterling, Mark E Law, Ellen D McPhail, David S Viswanatha, Paul J Kurtin, Linda N Dao, Ryan D Ritzer, Grzegorz S Nowakowski, Andrew L Feldman. Mayo Clinic, Rochester, MN
Background: The traditional model of hematopoiesis was based on unidirectional maturation into lineage-committed cells. However, recent studies indicate mature B lymphocytes have the potential for significant lineage plasticity. We and others have reported follicular lymphomas (FLs) transdifferentiating into clonally related histiocytic/dendritic cell neoplasms. These occasionally have shown focal expression of markers associated with Langerhans cells, but transdifferentiation of FL to tumors with characteristic features of Langerhans cell neoplasms has not been reported.
Design: Two patients with FL developed Langerhans cell neoplasms. We studied the morphologic, immunophenotypic, and genetic features of both neoplasms in the 2 patients. Presence of t(14;18) was tested using dual-fusion fluorescence in situ hybridization (FISH) or combined immuno-FISH for IGH/BCL2. Clonality was assessed by immunoglobulin gene rearrangement (IGR) studies using BIOMED-2 primers with microdissection where indicated.
Results: A 52-year-old man presented with lymphadenopathy. A right inguinal lymph node showed morphologically and phenotypically typical FL, grade 1. The patient received immunochemotherapy and had persistent, stable disease for 8 years. He then presented with increasing lymphadenopathy and lymph node biopsy showed Langerhans cell sarcoma (LCS) with no evidence of FL. The same clonal IGR was present in FL and LCS specimens. FISH showed IGH/BCL2 fusion in both tumors, and immuno-FISH confirmed IGH/BCL2 in the langerin-positive cells of the LCS nuclei. The patient's condition deteriorated rapidly and he died 3 months later. A 77-year-old woman presented with lymphadenopathy, an abdominal mass, and pulmonary nodules. Lymph node biopsy showed Langerhans cell histiocytosis (LCH) and minimal involvement by FL, grade 1. Both components showed typical immunophenotype. FISH showed IGH/BCL2 fusion in nuclei of both FL and LCH components. A clonal IGR was detected in the micro-dissected LCH component. Following diagnosis, the patient transferred care to another facility.
Conclusions: These cases provide striking samples of neoplastic transdifferentiation and expand the histologic spectrum of lesions clonally identical to otherwise typical follicular lymphoma. The genetic events underlying transdifferentiation are unknown and represent a rich area of potential research. Awareness of this phenomenon may aid in diagnosis when histologically dissimilar tumors arise in a patient with synchronous or metachronous lymphoma.
Monday, March 19, 2012 1:00 PM
Poster Session II # 214, Monday Afternoon