Common clonal origin of an acute B-lymphoblastic leukemia and a Langerhans' cell sarcoma: evidence for hematopoietic plasticity

Abstract

BackgroundThe hierarchical organization of hematopoiesis with unidirectional lineage determination has become a questionable tenet in view of the experimental evidence of reprogramming and transdifferentiation of lineage-determined cells. Clinical examples of hematopoietic lineage plasticity are rare. Here we report on a patient who presented with an acute B-lymphoblastic leukemia and developed a Langerhans' cell sarcoma 9 years later. We provide evidence that the second neoplasm is the result of transdifferentiation. Design and MethodsB-cell acute lymphoblastic leukemia was diagnosed in an 11-year old boy in 1996. Treatment according to the ALL-BFM-1995 protocol resulted in a complete remission. Nine years later, in 2005, Langerhans' cell sarcoma was diagnosed in a supraclavicular lymph node. Despite treatment with different chemotherapy protocols the patient had progressive disease. Finally, he received an allogeneic peripheral blood stem cell transplant and achieved a continuous remission. Molecular studies of IGH-and TCRG-gene rearrangements were performed with DNA from the Langerhans' cell sarcoma and the cryopreserved cells from the acute B-lymphoblastic leukemia. The expression of PAX5 and ID2 was analyzed with real-time reverse transcriptase polymerase chain reaction. ResultsIdentical IGH-rearrangements were demonstrated in the acute B-lymphoblastic leukemia and the Langerhans' cell sarcoma. The key factors required for B-cell and dendritic cell development, PAX5 and ID2, were differentially expressed, with a strong PAX5 signal in the acute Blymphoblastic leukemia and only a weak expression in the Langerhans' cell sarcoma, whereas ID2 showed an opposite pattern. ConclusionsThe identical IGH-rearrangement in both neoplasms indicates transdifferentiation of the acute B-lymphoblastic leukemia into a Langerhans' cell sarcoma. Loss of PAX5 and the acquisition of ID2 suggest that these key factors are involved in the transdifferentiation from a B-cell phenotype into a Langerhans'/dendritic cell phenotype. Haematologica 2010;95(9):1461-1466. doi:10.3324/haematol.2009 This is an open-access paper.

Cutaneous T-Cell/Histiocyte-Rich B-Cell Lymphoma: A Case Report and Review of the Literature

“…This suggests potential evolution from one process to the other, as stressed by some authors [22], although cutaneous involvement is exceedingly rare in this disease. Another possible explanation is hypothesized on the basis of tumor progression from lymphocyte-predominant Hodgkin’s disease, sharing common morphological features and supporting the recent evidence of hematopoietic plasticity in a single case of an acute B-lymphoblastic leukemia and Langerhans’ cell sarcoma [2,23]. Usually, lymphocyte-predominant Hodgkin’s lymphoma can also be differentiated by the lack of nodularity of the infiltrate, the absence of typical lymphohistiocytic cells, the large number of small B lymphocytes composing the nodules, the absence of CD57+ cells in the reactive infiltrate and the coexpression of CD15 and EMA in the blasts [2,11,17].…”

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.…”

Cytological findings of langerhans cell sarcoma in a case of quintuple cancer

“…However, KRAS and BRAF gene mutations were not detected in our case. There have been several reports on LCS arising from other tumors of hematopoietic and lymphoid tissues 13, 14, 15, 16. However, there has been no report on LCS related to T‐cell/histiocyte‐rich large B‐cell lymphoma.…”