Abstract
Synthesis of histamine in hematopoietic progenitor cells may be one of the earliest events in mast cell-development from pluripotent hematopoietic progenitor cells. In the present study, we asked whether the key enzyme involved in histamine generation, histidine decarboxylase (HDC), can be employed as an immunohistochemical marker for the detection of (neoplastic) mast cells (MC) in patients with cutaneous (CM) or systemic mastocytosis (SM). To address this question, we examined bone marrow biopsy specimens in a cohort of 101 patients (CM, n=10; indolent SM, n=46; SM with associated clonal non-MC lineage disease, n=31; aggressive SM, n=10; MC leukemia, n=3; MC sarcoma, n=1) using an antibody against HDC. Independent of the maturation stage of MC or subtype of disease, the anti-HDC antibody produced clear diagnostic staining results in all patients with bone marrow involvement examined including those with MC leukemia and MC sarcoma, in which MC are particularly immature and often escape analysis when examined by conventional stains. In these patients (MC leukemia, n=2; MC sarcoma, n=1), expression of HDC was reconfirmed at the mRNA level by RT-PCR analysis performed with RNA of highly enriched sorted CD117+ MC. In patients with CM or normal/reactive bone marrow (n=30), no HDC-positive infiltrates were detected. In these patients, only a few hematopoietic cells, presumably basophils, were found to react with the anti-HDC antibody. In summary, HDC is expressed in neoplastic bone marrow MC in patients with SM independent of the maturation stage of cells or the variant of disease. HDC should therefore be considered as a new MC marker in the screen panel of antigens employed to diagnose high grade MC malignancies.
Splenic Angiosarcoma with Bone Marrow Involvement Initially Diagnosed as Systemic Mastocytosis: A Case Report
