Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity.
The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77-year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours.
Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. maradot@libero.it.
Maria Raffaella
MR
Ambrosio
Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy.|School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
Giulia
G
De Falco
Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy.|Pathology Unit, Ospedale di Circolo di Busto Arsizio, Busto Arsizio, Italy.
Bruno Jim
BJ
Rocca
Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy.
Aurora
A
Barone
Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy.
Teresa
T
Amato
Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy.
Cristiana
C
Bellan
Section of Pathology, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
Stefano
S
Lazzi
Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy.
Lorenzo
L
Leoncini
D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology*; D000066670:Cell Plasticity; D019175:DNA Methylation; D006801:Humans; D016130:Immunophenotyping; D054752:Langerhans Cell Sarcoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D051757:PAX5 Transcription Factor / Q000235:genetics
D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human
Array comparative genomic hybridization; GeneScan; Langerhans cell sarcoma; Marginal zone lymphoma; Trans-differentiation