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.