The KIT D816V allele burden predicts survival in patients with mastocytosis and correlates with the WHO type of the disease

KIT D816V is present in a majority of patients with systemic mastocytosis (SM). We determined the KIT D816V allele burden by quantitative real‐time PCR in bone marrow and peripheral blood of 105 patients with mastocytosis. KIT D816V was detected in 92/105 patients (88%). Significant differences in the median allele burden were observed between disease subgroups: cutaneous mastocytosis (0.042%), indolent SM (0.285%), smoldering SM (5.991%), aggressive SM (9.346%), and SM with associated hematologic non‐mast cell lineage disease (3.761%) (P < 0.001). The KIT D816V burden also correlated with serum tryptase (R = 0.5, P < 0.005) but not with mast cell infiltration in bone marrow or mediator symptoms. Moreover, the allele burden was of prognostic significance regarding survival (P < 0.01). Patients responding to cytoreductive therapy showed a significant decrease in KIT D816V (P < 0.05). To conclude, the KIT D816V burden correlates with the variant of mastocytosis, predicts survival, and is a valuable follow‐up parameter in SM.     

Systemic mastocytosis presenting with a prominent B lymphocyte proliferation in the bone marrow and extensive fibrosis of the spleen

Systemic mastocytosis is a disease characterized by multifocal mast cell proliferation in the bone marrow or other extracutaneous organs. Because of loosely scattered and hypo-/agranular mast cells, the diagnosis is sometimes very difficult. In the bone marrow, mast cell infiltration may be associated with prominent lymphoid infiltration leading to a misdiagnosis of a low grade non-Hodgkin lymphoma. A 49-year-old woman presented with right arm and leg pain, psychiatric symptoms, and diarrhea for four years. Physical examination and laboratory investigation revealed hepatosplenomegaly, anemia, mild thrombocytosis, mild leucocytosis and lymphocytosis. In the bone marrow biopsy, there was a prominent B lymphocyte proliferation reminiscent of a low grade non-Hodgkin lymphoma/leukemia and there were some spindle cells aggregates in paratrabecular location. The consecutive bone marrow biopsies were similar to the first. The subsequent splenectomy specimen exhibited striking fibrosis. In the lymph node sections, there was marginal zone hyperplasia. Multifocal accumulations of mast cells were strongly positive with mast cell tryptase and CD117 on immunohistochemical staining, though no metachromasia was identified in Giemsa and Toluidine Blue stained aspirates and tissue sections, probably due to hypo-/agranulation of mast cells. The case was presented to emphasize the importance of the antibody to mast cell tryptase in the diagnosis of mastocytosis and to discuss problems of differential diagnosis of systemic mastocytosis.     

The Expression of Melanoma Inhibitory Activity on Mast Cells in Child Patients with Cutaneous Mastocytosis

Background

Cutaneous mastocytosis is a disorder characterized by the proliferation of mast cells in the skin. Melanoma inhibitory activity (MIA) is a serum marker for malignant melanoma. However, it has not been known on MIA expression of cutaneous mastocytosis.

Methods

We investigated the expression of MIA in 4 child patients with cutaneous mastocytosis immunohistochemically and serum MIA level in 1 patient by enzyme-linked immunosorbent assay.

Results

Histopathological examination revealed diffuse mast cell infiltration in the dermis. MIA was positive for infiltrating mast cells in all patients. Serum level of MIA was elevated in 1 patient.

Conclusion

Although it was difficult to assess the significance of elevated serum levels of MIA in child patients, MIA was expressed on infiltrating mast cells in our study. Based on our findings, mast cell-derived MIA might be related to the formation of pigmented regions in cutaneous mastocytosis.     

Mast cell subpopulations in the synovial tissue of patients with osteoarthritis: selective increase in numbers of tryptase-positive,chymase-negative mast cells

Although there is relatively little evidence of inflammation in osteoarthritis (OA), increases in mast cell numbers and mast cell activation are prominent features of the synovial tissue. As little is known of the types of mast cells which may be involved, the numbers and distribution of mast cell subpopulations have been investigated as defined according to their content of proteases. Tissue was obtained from patients with OA undergoing total knee replacement surgery (n=14) and from control subjects either post-mortem (n=11) or following leg amputation for peripheral vascular disease (n=3); a double-labelling immunocytochemical procedure with monoclonal antibodies specific for tryptase and chymase was applied to identify those mast cells which contain both tryptase and chymase (MC_TC) and those with tryptase but not chymase (MC_T). There was considerable variation between individual tissues and between sites of tissue sampling, but cells of the MC_TC subset were predominant in the synovial layer of both groups of subjects without joint disease, accounting for some 60 per cent of all mast cells present. In tissue from OA patients, however, there appeared to have been a striking shift in the relative proportions of mast cells from the MC_TC to the MC_T phenotype, with many more MC_T cells present in the synovial tissues of OA patients (median 53 MC_T/mm²) than in tissue from post-mortem (7·5 MC_T/mm², P<0·0001) or amputation controls (12 MC_T/mm²). In contrast, numbers of synovial MC_TC cells in the synovium of OA patients (20 MC_TC/mm²) differed little from those in either of the control groups (both 12 MC_TC/mm²). In several other conditions, the MC_T cells have been linked with inflammatory events, but it seems that in OA, other factors may be operating to induce a selective expansion of this subpopulation.     

Serum concentration of baseline mast cell tryptase: evidence for a decline during long‐term immunotherapy for Hymenoptera venom allergy

Background Baseline serum mast cell tryptase concentration (BTC) is thought to reflect the constitutive mast cell load or activity of an individual patient. Little is known about the individual stability of BTC during long‐term venom immunotherapy (VIT). Objective To investigate the intra‐individual stability of BTC over time in patients with Hymenoptera venom allergy. Methods Three hundred and two patients were studied. BTC was measured before and at least twice during VIT. At least 4 weeks lay between BTC measurements and the most recent field sting, in‐hospital sting, or preceding venom injection. Multifactorial mixed linear models were used to analyse BTC changes over time. Results Median observation time was 4.2 years (range 2–12 years). Before VIT, the median BTC was 6.8 μg/L (range 1.14–177 μg/L). The median coefficient of variation (CV) over time was 15.3% (range 1.9–63.8%). The median CV was significantly smaller in patients presenting with an elevated BTC (>11.4 μg/L) than in patients with a normal BTC (11.4%, range 2.6–39.5%; vs. 17.6%, range 1.9– 63.8%; P<0.001). During VIT and after adjusting for age and gender, we found a slight but significant decrease of BTC over time (2.5% per year, 95% confidence interval 2.0–3.0%, P<0.001). Conclusion Individual variation of BTC during VIT does not rise when BTC is increased before therapy. VIT is associated with a small, but continuous decrease of BTC over time possibly indicating a dampened mast cell function or a decline in mast cell burden. Cite this as: S. Dugas‐Breit, B. Przybilla, M. Dugas, A. Arnold, G. Pfundstein, H. Küchenhoff and F. Ruëff, Clinical & Experimental Allergy, 2010 (40) 643–649.     

Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric patients with mastocytosis in Spain: a study of the Spanish network on mastocytosis (REMA)

BACKGROUND: Mast cells (MCs) play a key role in allergic diseases through the release of inflammatory mediators, which are responsible of allergic symptoms. Mastocytosis is characterized by an abnormal proliferation and accumulation of mast cells, in which mediators are released intermittingly or continuously. Despite these clinical similarities, few studies have addressed the presence of allergic symptoms in mastocytosis patients, including anaphylaxis. OBJECTIVE: A prospective evaluation was carried out to study the prevalence of allergic diseases in patients with mastocytosis and their impact on the natural history of mastocytosis. METHODS: A questionnaire was given to 210 patients with mastocytosis to evaluate the history of asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria and anaphylaxis. Patients underwent total IgE, Phadiatop infant (aeroallergens and food allergens), specific IgE to latex and to Anisakis simplex determinations. Skin tests were done to 72 patients. RESULTS: The prevalence of allergy, as defined by clinical symptoms associated to specific IgE, was 23.9%. Total IgE level was significantly higher in patients with allergy as compared with patients without allergy (median 58 vs. 16.5 kU/L, P<0.0001). Anaphylactic symptoms were present in 36 patients (22%), in nine the allergen was identified. Males had more allergy and anaphylactic symptoms than females (61.5% vs. 38.5% and 72% vs. 28%, respectively). CONCLUSIONS: Allergic diseases coexist in patients with mastocytosis with similar frequency as compared with the general population. Anaphylactic symptoms are more prevalent in males with mastocytosis and in patients with elevated IgE. CAPSULE SUMMARY: The prevalence of allergy in mastocytosis is similar to the general population. Anaphylactic symptoms are more prevalent in males and in patients with elevated IgE. The coexistence of atopy does not influence mastocytosis-associated symptoms.