[Show abstract][Hide abstract] ABSTRACT: The 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.
B-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.
Identical 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 B-lymphoblastic leukemia and only a weak expression in the Langerhans' cell sarcoma, whereas ID2 showed an opposite pattern.
The 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. (Clinical trial registration at: Deutsches KrebsStudienRegister, http://www.studien.de, study-ID:8).
[Show abstract][Hide abstract] ABSTRACT: To report a case of a MALT lymphoma of the eyelid, which recurred in several sites over a time period of 14 years, and where the identical B-cell clone could be demonstrated in most samples using polymerase chain reaction (PCR) and GeneScan analysis.
Clinical, histologic, immunohistochemical, PCR and GeneScan analysis findings are presented.
A 58-year-old woman presented with a swelling of the left lower lid. Excisional biopsy of the tumour revealed a low-grade malignant B-cell Non-Hodgkin lymphoma (NHL) of MALT type. Despite localized radiochemotherapy, the patient developed recurrences occurring in the pharynx, in the right orbit, in the skin of the right foot, and in the bone marrow 1, 7, 11 and 14 years, respectively, after establishment of the first diagnosis. PCR for a rearrangement of the immunoglobulin heavy chains (IgH) and GeneScan analysis of the samples produced amplificates identical in size at most sites, indicating derivation from the same B-cell clone.
It is generally assumed that ocular adnexal MALT lymphoma is associated with an indolent clinical course. Using IgH-PCR and GeneScan analysis, we demonstrate that the current case illustrates that these lymphomas do indeed require regular control examinations following treatment, as they often recur and disseminate in some patients in an unpredictable manner.
Albrecht von Graæes Archiv für Ophthalmologie 08/2007; 245(7):1055-9. · 2.33 Impact Factor