Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings
Introduction
Mast cells (MC) are a normal constituent of perivascular tissue and can be found throughout the body [1]. However, their numbers vary greatly depending on the tissue site. Although they are usually present in lymph node sinuses they are virtually absent from the normal spleen. An increase in MC numbers is either reactive (MC hyperplasia) or neoplastic (MC disease or mastocytosis). Because MC are difficult to identify in routine H and E-stained sections, an increase may easily be overlooked unless special metachromatic stains like giemsa or toluidine blue are applied [2], [3]. Hematopathologists therefore use Giemsa stains to identify MC in lymph nodes and bone marrow sections. A marked increase in diffusely distributed MC is often associated with reactive, chronic inflammatory, and fibrogenic conditions but may also occur in various hematologic malignancies such as immunocytoma, chronic lymphocytic leukemia, myelodysplasia, and acute myeloid leukemia [4], [5], [6]. However, extremely large MC numbers are encountered almost exclusively in MC neoplasia, i.e. mastocytosis/MC disease and MC leukemia. Neoplastic MC may exhibit marked cellular atypia and therefore are sometimes extremely difficult to identify [7]. However, it has recently been shown that immunohistochemical staining with antibodies against tryptase, which is one of the two highly specific MC-associated serine proteases, is a powerful tool for the recognition of very atypical or immature MC in MC leukemia and for the detection of small, even minute, dense focal MC infiltrates in staging procedures in patients with known cutaneous mastocytosis [8]. In the following, the histopathologic patterns of tissue involvement in MC proliferative disorders are described. The value of various histochemical/immunohistochemical markers for the diagnosis of mastocytosis and its discrimination from other hematologic malignancies will also be discussed.
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Patients and methods
The results of this study are based on the detailed clinical and histopathologic evaluation of more than 100 patients (mostly adults) with mastocytosis/MC disease (most cases with proven bone marrow involvement) and of more than 50 patients with a marked reactive increase in MC (mostly bone marrow trephine biopsy specimens). Serum tryptase levels were measured in certain of these patients. The length of the pre-diagnostic interval and the survival time were known for most patients. The most
General histopathological aspects
Because very little information is available about normal MC numbers at different tissue sites, the diagnosis of a slight increase in MC, i.e. mild MC hyperplasia, often seems to be made arbitrarily. In a morphometric study, we found MC numbers of <4/mm2 bone marrow in most normal/reactive states, while in myelodysplastic syndromes MC numbers usually were >5 but <100/mm2. In MC neoplasia, however, the MC count in most cases was much higher than 100/mm2, reaching a maximum of 2655/mm2. The
Discussion
A diagnosis of systemic MC disease should not, in general, be made on the basis of bone marrow aspiration cytology alone. Although the number of MC in some exceptional cases may be strikingly high [20], [21], it must be emphasized that the cytological investigation of bone marrow smears often yields false-negative results because MC numbers are small in most cases of systemic MC disease. However, the histopathological diagnosis of MC disease also has its limitations. Small samples are often
Conclusions
A diagnosis of MC disease/mastocytosis is not always easy to establish on the basis of morphology alone. According to our findings in a large series of cases the following points should be observed:
- 1.
Tissue sections should always be investigated because the cytologic evaluation of bone marrow smears may yield false-negative results.
- 2.
Bone marrow should be immunostained for tryptase in all cases of suspected primary (or secondary) MC disease because atypical (hypogranulated or even
Acknowledgements
The authors Hans-Peter Horny and Peter Valent both contributed towards study design, data interpretation, and final approval.
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