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Background: The serum tryptase level is used as a diagnostic marker in mastocytosis and is considered to reflect the burden of (neoplastic) mast cells (MC). Methods: In the present study, serum tryptase levels were measured in patients with mastocytosis by fluoroenzyme immunoassay and compared with the extent of infiltration of the bone marrow (BM) by neoplastic MC, determined by tryptase immunohistochemistry. Sixteen patients with cutaneous mastocytosis (CM) and 43 patients with systemic mastocytosis (SM) were examined. Results: In most patients with CM (defined by the absence of dense compact MC infiltrates in tryptase-stained BM sections), normal or near-normal serum tryptase levels (median 10 ng/ml, range 2–23 ng/ml) were measured. By contrast, in the vast majority of patients with SM, elevated serum tryptase levels (median 67 ng/ml) were found. In addition, there was a significant correlation between the grade of infiltration of the BM by neoplastic MC and tryptase levels in patients with SM (r = 0.8). Moreover, enzyme levels differed significantly among the groups of patients with different types of SM. The highest levels (>900 ng/ml) were detected in the patient with MC leukemia, 2 patients with slowly progressing SM and high MC burden (smoldering SM) and 1 patient with indolent SM. In contrast, in all 3 patients with isolated BM mastocytosis (no skin lesions and no signs of multiorgan involvement), serum tryptase levels were <20 ng/ml. Conclusions: In summary, our data suggest that the measurement of serum tryptase is a reliable noninvasive diagnostic approach to estimate the burden of MC in patients with mastocytosis and to distinguish between categories of disease.

The proto‐oncogene C‐KIT encodes a tyrosine kinase receptor that is expressed on mast cells and haematopoietic stem cells and can show somatic mutations in patients with mastocytosis. Only scattered information is available about mutations in C‐KIT in patients with other myeloid neoplasms. Moreover, the prevalence of mutations in C‐KIT in bone marrow specimens of individuals with systemic mastocytosis is largely unknown. Using sequence analysis, we have screened cDNAs of the C‐KIT domain encompassing codon 510–626 and codon 763–858 in bone marrow (BM) mononuclear cells (MNCs) of patients with myelodysplastic syndromes (n = 28) and patients with systemic mastocytosis (n = 12) for the presence of mutations. Furthermore, restriction fragment length polymorphism analysis was applied for identification of the C‐KIT 2468A→T and the C‐KIT 1700T→G mutation, as well as the C‐KIT 1642A→C polymorphism. All 11 patients with systemic indolent mastocytosis tested positive for C‐KIT 2468A→T. In contrast, no mutation was identified in the case of aggressive mastocytosis. Among patients with myelodysplastic syndromes, no patient showed a somatic mutation in C‐KIT. The allele frequency for C‐KIT 1642A→C among the entire patient population was 0·038 and was 0·125 among age‐ and sex‐matched healthy controls. Our data demonstrate that myelodysplastic syndromes without histological or cytological evidence of mastocytosis do not exhibit somatic mutations in exons 10, 11, 12, 16, 17 and 18 of C‐KIT. In contrast, BM MNCs of patients with systemic indolent mastocytosis were all positive for C‐KIT 2468A→T and negative for additional mutations in these exons. The C‐KIT 1642A→C polymorphism is not associated with myelodysplastic syndrome or systemic mastocytosis.

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