Mastocytosis is a very rare, clonal disease characterized by the accumulation of mast cells in one or more organ systems. It is characterized by the presence of multifocal compact clusters or cohesive aggregates/infiltrates of abnormal mast cells. Mastocytosis is a very heterogeneous disease, ranging from skin lesions that spontaneously regress, to highly aggressive neoplasms with short survival. Subtypes of mastocytosis are recognized mainly by the distribution of the disease and clinical manifestations [Citation1].
Systemic mastocytosis is a chronic disorder that almost always involves bone marrow. Variants of systemic mastocytosis range from indolent systemic mastocytosis with a median survival not significantly different from that of the general population, to aggressive systemic mastocytosis with a median survival of 41 months, to mast cell leukemia with a median survival of 2 months [Citation2]. In a high proportion of cases, the clonal nature of the disease can be established on the basis of the demonstration of a gain-of-function mutation involving the tyrosine kinase domain of c-kit. Typically, the A71763T substitution is detected, where aspartate is changed to valine at the codon 816 of c-kit [Citation3].
Using the flow cytometric approach, clear immunophenotypic differences have been found between mast cells from normal individuals and those from patients with mastocytosis [Citation4,Citation5]. All mast cells express CD117 and tryptase antigens; neoplastic mast cells additionally show aberrant expression of CD25 and/or CD2 antigens, which are never present in normal bone marrow mast cells and which constitute minor diagnostic criteria for the diagnosis of systemic mastocytosis. In particular, the aberrant expression of CD25 antigen is currently considered the immunophenotypic hallmark of neoplastic mast cells. Furthermore, it has been described that mast cells from patients with mastocytosis display higher reactivity for CD63 and CD69 activation-associated antigens. In addition, the expression of various complement-related cell surface antigens (CD11b/CR3, CD11c/CR4, CD35/CR1, CD55/DAF, CD59/MIRL, CD88/C5aR) on bone marrow mast cells in systemic mastocytosis is significantly higher than in control subjects [Citation6].
The expression of the activation marker CD30 has not been explored so far in systemic mastocytosis. CD30 is expressed in a subset of lymphoid neoplasms, but is rarely expressed in myeloid neoplasms. The work that Dr. Valent and colleagues have performed and review in this issue of Leukemia and Lymphoma [Citation7] is the first demonstration that the activation marker CD30 is aberrantly expressed in mastocytosis, particularly in aggressive forms of disease, such as aggressive systemic mastocytosis and mast cell leukemia. The authors found that CD30, also known as Ki-1 antigen, is expressed in neoplastic mast cells in a majority of patients with advanced systemic mastocytosis, whereas in most patients with indolent disease CD30 expression is minimal. These results were confirmed by TissueFAXS analysis and in the mast cell leukemia cell line HMC-1. In addition, CD30 mRNA expression in HMC-1 cells and in marrow biopsy samples correlated with immunohistochemical findings [Citation8].
The demonstration of differential expression of CD30 in different variants of systemic mastocytosis is an exciting finding, since currently there are no immunophenotypic markers that can be utilized during routine bone marrow biopsy evaluation to distinguish between indolent and more aggressive forms of the disease. Diagnosis of aggressive systemic mastocytosis is rendered mostly based on clinical findings of organ insufficiency due to mast cell infiltration (so called C-findings), which include osteolysis (or osteoporosis) with pathologic fractures, hepatosplenomegaly with impaired liver function and ascites, and malabsorption [Citation1]. CD30 expression in mast cells may serve as a potentially valuable screening tool and prognostic marker in the future. CD30 may also hold promise as a potential new therapeutic target in advanced forms of mast cell disease that currently represent a treatment challenge with poor prognosis.
Supplementary Material
Download Zip (977.9 KB)Potential conflict of interest:
Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.
References
- Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008.
- Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 2010;113:5727–5736.
- Garcia-Montero AC, Jara-Acevedo M, Teodosio C, et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood 2006;108:2366–2372.
- Escribano L, Díaz Agustín Beatriz, Bravo P, et al. Immunophenotype of bone marrow mast cells in indolent systemic mast cell disease in adults. Leuk Lymphoma 1999;35:227–235.
- Escribano L, Garcia Montero AC, Núñez R, et al. Flow cytometric analysis of normal and neoplastic mast cells: role in diagnosis and follow-up of mast cell disease. Immunol Allergy Clin North Am 2006;26:535–547.
- Núñez-López R, Escribano L, Schernthaner GH, et al. Overexpression of complement receptors and related antigens on the surface of bone marrow mast cells in patients with systemic mastocytosis. Br J Haematol 2003;120:257–265.
- Valent P, Sotlar K, Horny HP. Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: a differential diagnosis to consider in aggressive hematopoietic CD30-positive neoplasms. Leuk Lymphoma 2011;52:In press.
- Sotlar K, Cerny-Reiterer S, Petat-Dutter K, et al. Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis. Mod Pathol. 2010 Dec 24. [Epub ahead of print]