Radiotherapy-Associated Cutaneous Mastocytosis in a Patient With Breast Carcinoma. Case Report and Review of the Literature.

ABSTRACT: Mast cell skin disease is rarely described after external beam radiation therapy in patients with breast carcinoma, with only 7 previous reports in the literature. Skin changes typically occur within (but are not limited to) the radiation field. We present a 64-year-old woman with postradiotherapy cutaneous mastocytosis on the left breast and adjacent chest wall. The clinical and laboratory findings in all reported patients, including the current case, are reviewed. No clear mechanism has been presented to explain disease pathogenesis; although, mast cell accumulation secondary to local mediators produced in response to radiation damage and/or koebnerization phenomenon have been proposed. Cutaneous/systemic mastocytosis is not widely recognized and may be underdiagnosed in the setting of postradiation for breast cancer. It is important for clinicians and pathologists to be aware of this diagnosis for patients presenting with rashes after radiotherapy.

Pediatric cutaneous mastocytosis and c-KIT mutation screening.

Background: Cutaneous mastocytosis (CM) is a heterogeneous disease that commonly presents with skin lesions in childhood. Objective: In this study, we aimed to evaluate the clinical and laboratory test results of our patients with CM to ascertain prognostic factors by using patients' long-term follow-up results and to determine c-KIT (receptor tyrosine kinase) mutation from peripheral blood samples, which might be responsible for the etiopathogenesis of pediatric mastocytosis. Methods: The clinical observation data of 32 children who had been diagnosed with CM were retrospectively researched. Exon 8, 9, 11, 13, and 17 c-KIT gene locations were analyzed from DNA material that was obtained from peripheral blood samples of all the patients by using polymerase chain reaction analysis and automatic DNA sequencing. Results: The tryptase level was higher in patients with familial cases and in cases of patients who had gastrointestinal mediator releasing symptoms (p = 0.017, p = 0.038, respectively). The use of clarithromycin and the use of vitamin D were determined as triggers for mediator release. Hypogammaglobulinemia was found in six patients (18.8%). Indoor tobacco exposure was seen to be higher in patients not in remission than in patients in remission (59.1% and 20%, respectively) (p = 0.040). Allergic diseases were observed in 80% of patients in complete remission and 22.7% of patients not in remission (p = 0.002). Concomitant allergic diseases were found to be good prognosis markers among pediatric patients with CM. No c-KIT mutation was discovered in any of the patients. Conclusion: In this study, tobacco exposure would seem to be a barrier for remission, and concomitant allergic diseases were seen to be a good prognosis marker. Evaluation of peripheral c-KIT mutation had no diagnostic contribution among pediatric patients with CM in contrast to adults.

Association of breed and histopathological grade in canine mast cell tumours.

The aim of this study was to evaluate the relationship between breed and the histopathological grade of canine mast cell tumours (MCTs). A retrospective survey of pathology data of 9375 histopathologically confirmed diagnoses of cutaneous MCTs in the US was evaluated in the context of breed prevalence in over two million registered purebred dogs. Association of histopathological grade with breed, age, sex and spay/neuter status was assessed. The data indicate that the proportion of high-grade tumours increases with advancing age, and that male and intact dogs have increased odds of developing high-grade tumours. A significant difference in the proportion of high-grade tumours between breeds was detected. The Pug was at significantly increased risk of developing low/intermediate-grade tumours, but not high-grade tumours, resulting in preponderance of less aggressive MCTs in this breed. The results of this study suggest a genetic association for the development of high-grade MCTs.

Canine cutaneous mast cell tumors: A combined clinical and pathologic approach to diagnosis, prognosis, and treatment selection.

In view of the varied biologic behavior and the costs of treatment for canine cutaneous mast cell tumors, development of appropriate treatment plans for individual affected dogs can be difficult, but decisions regarding treatment should be made using a systematic, evidence-based approach. This manuscript reviews the current state of diagnostics and prognostication of canine cutaneous mast cell tumors, and suggests a combined approach based on clinical and pathologic assessment for decision making regarding treatment choices. The current state of histologic grading, evaluation of proliferation indices, evaluation of mutations in the c-kit gene and KIT expression, evaluation of excision and clinical staging are examined. On the basis of the current understanding of prognostication and treatment response, algorithms for selection of local and systemic therapy are presented.

[Mastocytosis: revisited with new cytogenetic data]. / La mastocytose: une maladie revisitée a la lumière des nouvelles données génétiques.

Mastocytosis is a heterogenous disorder due to abnormal proliferation and infiltration of mast cells in different tissues, primarily the skin and the bone marrow. Cutaneous mastocytosis is often benign and regresses spontaneously. Systemic mastocytosis is a chronic disease in which some types are indolent but other types such as mast cell leukemia are very aggressive. Pathogenesis of systemic mastocytosis involves a somatic mutation of the gene coding for the c-kit receptor, the most frequent mutation being D816V. Diagnostic criteria have been established by the WHO using histopathological, molecular and biochemical parameters. Treatment of systemic mastocytosis remains a challenge for the clinician due to variability and complexity of the disease. There is, in addition, a lack of a standard and efficient treatment. New targeted therapies with tyrosine kinase inhibitors directed against the c-kit receptor are currently being studied, with the purpose to act specifically on the " primum movens "of the disease. The current review provides an overview of pathogenesis, clinical presentation, diagnosis and classification of cutaneous and systemic mastocytosis. We also discuss the prognosis and the different treatments currently available according to the sub-type of mastocytosis.

Mastocitosis en edad pediátrica / Mastocytosis in children

Las mastocitosis incluyen un amplio espectro de patologías que tienen en común la infiltración anormal de mastocitos en diversos órganos, siendo la piel el más frecuentemente comprometido. Se reconocen dos variantes principales de la enfermedad: la mastocitosis cutánea (MC), que sólo compromete la piel, y la mastocítosis sistémica (M S), donde hay compromiso de órganos extracutáneos. La sintomatología de ambas variantes es causada por la infiltración celular y daño directo sobre los tejidos, así como por la liberación de mediadores químicos a la circulación sistémica, lo que hace que su presentación clínica sea altamente variable. Las mastocitosis en niños se presentan generalmente como MC, son de buen pronóstico y evolucionan con remisión de las lesiones en la mayoría de los casos. Las MS son muy poco frecuentes en este grupo etario; sin embargo, su curso crónico y la agresividad que pueden adquirir ponen en relieve la importancia de considerarlas en el diagnóstico diferencial de estos cuadros. En la actualidad no existe tratamiento curativo para las mastocitosis y el manejo es fundamentalmente sintomático.

Mastocytosis is a heterogeneous group of diseases characterized by the abnormal infiltration of mast cells (MCs) in one or more organ systems, being the skin the most common organ affected. Two main variants of the disease are recognized: cutaneous mastocytosis (CM), if abnormal infiltrates are confined to the skin, and systemic mastocytosis (SM) , if extra-cutaneous tissues are involved. Symptoms are extremely variable and result from MC-derived mediators and from destructive infiltration of MCs. The typical presentation of pediatric-onset mastocytosis consists of cutaneous manifestations, and usually regresses spontaneously. SM is a chronic disease with variable clinical course ranging from asymptomatic to highly aggressive and rapidly devastating. SM is rare in children but should be considered in the differential diagnosis. No curative treatment has been yet reported for mastocytosis and only symptomatic therapy is available.

Possible circadian variation of serum mast cell tryptase concentration.

BACKGROUND: A temporarily elevated level of serum mast cell tryptase (ST) indicates mast cell activation and occurs in systemic anaphylactic reactions (SAR). We measured ST following a sting challenge in vespid venom-allergic patients treated with venom immunotherapy (VIT) and in healthy controls, respectively. AIM OF THE STUDY: To assess changes of ST over time in vespid venom-allergic patients at the occasion of a re-sting and in healthy controls. METHODS: A sting challenge was performed in 20 patients on vespid VIT to monitor efficacy of VIT. ST was measured between 9.00 and 10.00 a.m. (baseline). Sting challenge was performed at 2.00 p.m., and ST was determined again 20 min, 90 min and 18 h later. Measurements at corresponding times of the day were done in nine healthy controls. RESULTS: One patient developed a mild SAR to the sting challenge which was associated with a temporary increase of ST. In the other 19 patients who tolerated the sting challenge without SAR ST decreased significantly by 18.0% (median, range 8.3-36.7%). Twenty minutes after the sting when compared with baseline levels (P < 0.001), a significant decrease of ST was still present after 90 min (median 13.7%) (P < 0.001), but not after 18 h (P = 0.57). A comparably significant temporary decline was found in controls. CONCLUSIONS: The temporary decline of ST in patients and in controls suggests a circadian variation of ST concentration. A normal diurnal pattern of ST concentration after sting challenge is associated with successful treatment.

Telangiectasia macularis eruptiva perstans with an associated myeloproliferative disorder.

Telangiectasia macularis eruptiva perstans (TMEP) is a cutaneous form of mastocytosis. It has been rarely associated with an underlying myeloproliferative disorder. We report the case of a patient, while receiving treatment for thrombocytosis, with both platelet production and function inhibitors presented with TMEP. TMEP is often refractory to therapy; however, our patient responded to treatment with PUVA.

The skin in mastocytosis.

The most frequent site of organ involvement in patients with any form of mastocytosis is the skin. Cutaneous expressions include urticaria pigmentosa, mastocytoma, diffuse and erythrodermic cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. The cutaneous lesions tend to appear early in life. Although urticaria pigmentosa has been reported in 12 pairs of twins and one set of triplets, the majority of affected individuals have no familial association. Most patients with systemic mastocytosis have skin lesions; however, an occasional patient will have systemic disease with no other skin features than flushing. In lesional cutaneous sites and in non-lesional skin, there is an increase in the number of mast cells. Electron microscopy shows quantitative differences between lesional skin mast cells from patients with and without systemic disease. The mast cells from adult patients with systemic disease have a larger mean cytoplasmic area, nuclear size, and granule diameter. The granules contain predominantly grating/lattice structures. The cutaneous mast cells contain tryptase and chymase. They retain their functional reactivities to relevant secretory stimuli, such as C3a, morphine sulfate, and calcium ionophore A23187. Lesional skin contains histamine, leukotriene B4, prostaglandin D2, 5-hydroxyeicosatetraenoic acid, platelet-activating factor, and heparin. Treatment of the cutaneous manifestations includes the use of H1 and H2 antihistamines, oral disodium cromoglycate, psoralens plus ultraviolet A photochemotherapy, and potent topical corticosteroid preparations.