Diagnosis Of Mastocytosis Research Articles

Treatment Approaches for Diffuse Cutaneous Mastocytosis in Children: Literature Review and Actual Clinical Experience

Background. Mastocytosis is a very rare disease with various manifestations, based on abnormal clonal proliferation of mast cells in organs and tissues, such as: skin, bone marrow, lymph nodes, liver, spleen, and gastrointestinal tract. The diagnosis can be established according to clinical manifestations, laboratory, and instrumental data. Darier’s sign and histological examination are crucial for mastocytosis diagnosis. The presented clinical case describes very rare cutaneous form of mastocytosis. Clinical case description. The girl, 2.5 years old, was hospitalized with multiple erythematous papules on her body, face, and limbs. Comprehensive examination, including bone marrow biopsy and positron-emission tomography, allowed us to exclude mastocytosis systemic manifestations. Conclusion. Despite the fact that mastocytosis in children is mostly represented by skin form, it is necessary to perform complex patient examination on any systemic damage. Antihistamines in combination with topical and/or systemic glucocorticoids are often effective, but complete response does not always occur. Implementation of other therapeutic options, such as targeted drugs (tyrosine kinase inhibitors), is suggested In case of no or insufficient therapeutic effect.

Misleading Trails: Uncovering Systemic Mastocytosis Disguised as Eosinophilic Gastrointestinal Disorder - A Case Report

An uncommon class of illnesses known as mastocytosis is defined by aberrant mast cells in different tissues or organs. It encompasses mast cell sarcoma, systemic mastocytosis, and cutaneous mastocytosis. For those without advanced manifestations of the disease, the diagnosis of Systemic Mastocytosis can be protracted due to the high rate of symptom overlap with other illnesses. A 56-year-old female patient was brought to our department for a diagnosis because of her history of eosinophilia, chronic colitis, and skin allergies. The patient's eosinophilia remained in spite of treatment. The patient's blood count revealed persistent eosinophilia even after five months. An examination of the bone marrow aspirate showed a hypercellular bone marrow with a noticeable eosinophilic prominence. To our astonishment, the trephine biopsy showed sheets and nodules of mast cells, expressing strong positivity for CD117 immunostain. A review of the colonic biopsy also showed a significant mast cell presence as highlighted by CD117 immunostain. A definitive diagnosis of systemic mastocytosis was reached, indicating that, in situations of eosinophilia, a low index of suspicion and meticulous morphological examination are necessary to prevent delays in the diagnosis of mastocytosis, particularly in cases where there is no cutaneous involvement.

Epidemiology of mastocytosis: a population-based study (Sweden).

Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood. To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries. Individuals (≥ 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI). We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators. We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population. Underreporting and inconsistencies in the use of diagnostic codes.

P105 Adult-onset mastocytosis: a retrospective review

Abstract Mastocytosis is characterized by an abnormal proliferation of mast cells in different organs, with the skin being the most frequently affected site. Adult-onset mastocytosis often follows a chronic course and is more likely to have extracutaneous involvement. We undertook a retrospective case note review of adult patients with a diagnosis of mastocytosis in our dermatology department between 2021 and 2022. Fourteen patients were identified with a female-to-male ratio of 1.8 : 1. Median age at disease onset was 46 years (range 25–75). Lesions were described as maculopapular (n = 8), macular (n = 3), telangiectatic (n = 2) and urticated (n = 1). The torso was affected in 12 patients (86%). The most commonly reported symptom was pruritus (n = 9). Other complaints included flushing (n = 3), abdominal pain (n = 2), dizziness (n = 2), weight loss (n = 2), night sweats (n = 2), syncope (n = 1), musculoskeletal pain (n = 1) and symptoms of recurrent anaphylaxis (n = 1). Two patients were asymptomatic. Darier sign was elicited in five patients and negative in two (not documented in seven). Eight patients were assessed for lymphadenopathy and organomegaly, with no detected abnormality. Eleven patients had skin biopsies; 10 (91%) had mastocytosis in the skin confirmed on histology; one patient had a nondiagnostic histological finding, but mastocytosis was diagnosed on the basis of clinical presentation. Seven patients had elevated serum tryptase levels (> 20 ng mL−1) on at least one occasion. Bone densitometry was done in five patients with elevated serum tryptase: two had osteopenia and one had osteoporosis. Eleven patients underwent bone marrow examination. Mast cell infiltration of the bone marrow was detected in four patients; KIT mutations in bone marrow were subsequently identified in three patients. Twelve patients remain under long-term follow-up. Treatments prescribed included antihistamine (n = 10), epinephrine autoinjector (n = 6), topical steroids (n = 5), vitamin D (n = 5), calcium (n = 4), H2 blocker (n = 2), bisphosphonates (n = 2), phototherapy (n = 2), leukotriene antagonists (n = 2), cosmetic camouflage (n = 1), oral sodium cromoglicate (n = 1) and KIT–tyrosine kinase inhibitor (n = 1). Despite treatments, none of the patients had regression (partial or complete) of cutaneous disease, although no fatal outcome was observed. Four (29%) cases had a final diagnosis of indolent systemic mastocytosis (all had elevated serum tryptase levels, two had anaemia). Our findings were consistent with the literature, where serum tryptase levels rather than systemic symptoms were a reliable predictor of systemic mastocytosis. Interestingly, 10 (71%) patients had mastocytosis limited to the skin, which is in contrast to the published literature, where the majority of people with adult-onset mastocytosis have systemic forms of the disease.

PA17 Paediatric-onset mastocytosis: a retrospective review

Abstract Mastocytosis is characterized by an abnormal accumulation of mast cells in different organs. The skin is the most frequently affected site. Most cases of paediatric-onset mastocytosis are benign, localized to the skin and regress spontaneously. We retrospectively reviewed the case notes of paediatric patients with a diagnosis of mastocytosis in dermatology departments within our region between 2021 and 2022. Seventeen patients were identified. The disease was more prevalent in males (male-to-female ratio 1.8s : 1). The median age at onset was < 1 year (range birth–4 years). The lesions were described as solitary (n = 9), macular (n = 6) and maculopapular (n = 2). The torso was involved in 16 patients. Other body sites affected were the face (n = 2), scalp (n = 1), limbs (n = 5) and buttock (n = 2). Most patients were asymptomatic (n = 12). Symptoms, including abdominal pain (n = 3), pruritus (n = 2), musculoskeletal pain (n = 1), diarrhoea (n = 1), flushing (n = 1), headache (n = 1) and dizziness (n = 1), were reported. Darier sign was positive in 11 patients and negative in three (not documented in three). None of the patients had bone marrow examination. One patient underwent a skin biopsy, which confirmed mastocytosis in the skin; the remaining 16 patients were diagnosed with cutaneous mastocytosis based on the characteristic clinical features. The disease was classified into mastocytoma (n = 8) and urticaria pigmentosa (n = 9). Five patients with urticaria pigmentosa were assessed for lymphadenopathy and organomegaly: four had blood investigations, including serum tryptase (n = 4), full blood count (n = 2) and liver function tests (n = 2); one had an abdominal ultrasound. No abnormality was found. Patients with mastocytoma were not examined for lymphadenopathy or organomegaly, or had further investigations for systemic involvement. Eight patients were managed by watchful monitoring. Nine patients received active treatments, including topical steroids (n = 6), antihistamines (n = 6), oral sodium cromoglicate (n = 1), phototherapy (n = 1), epinephrine autoinjector (n = 1) and cosmetic camouflage (n = 1). Partial regression was observed in seven cases at a median follow-up of 3 years (range 1–14), and seven had persistent disease. Six patients remain under long-term follow-up, and eight were discharged with a median follow-up period of 1.5 years (range 1–14). Five patients were followed to adolescence (disease was persistent in three cases and there was partial regression in two cases; none had complete resolution). While serum tryptase levels do not appear to have a prognostic value in the paediatric population, we would recommend checking these in patients whose disease persists beyond adolescence as this may indicate progression to systemic mastocytosis.

Pathomorphology of cutaneous mastocytosis

Introduction. Mastocytosis as a result of mast cell infiltration of the skin and other organs develops at any age. The relevance of this work is determined by the lack of systematic data on the pathomorphological features of the clinical forms and types of cutaneous mastocytosis, defined by the Consensus European-American Mastocytosis Group and the WHO classification in 2016. The variability of dermatological clinical manifestations in children and adults, the difficulties in interpreting laboratory tests create a problem for verifying the diagnosis and further treatment. The aim. To determine the main pathohistological features of clinical forms and types of cutaneous mastocytosis. Material and methods. The article includes data from patients who were treated and monitored at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology in 2019–2022. Results. The literature and own data on the characteristic pathomorphological patterns that are important for the diagnosis of mastocytosis with skin lesions in children and adults are systematized. The pathological substrate of lesions in diffuse cutaneous mastocytosis and mastocytoma was a massive infiltrate of mast cells in the papillary and reticular layers of the dermis. The histological picture in the monomorphic type of maculopapular cutaneous mastocytosis (MPCM) in children was characterized by a relatively lower density of mast cell infiltration of the papillary dermis compared to other clinical forms of mastocytosis. Also, in children, the density of mast cells in the affected skin was significantly higher compared to adults. In addition, in adults with PPCM, the papillary dermis was less infiltrated with mast cells. This confirms the opinion that the monomorphic type of MPCM in children is phenotypically similar to MPCM in adults. Conclusions. Further prospective follow-up of patients may allow conclusions to be drawn about the prognostic value of pathological examination in mastocytosis in adults and children.

Transcriptomic profiling does dot refine mastocytosis diagnosis.

Not available.

Analisis Perbandingan Dempster Shafer dan Case Base Reasoning Dalam Diagnosis Penyakit Mastocytosis Menggunakan Metode Perbandingan Eksponensial

Diseases pose a major challenge in the medical world. Accurate and precise diagnosis is a crucial key in disease management, including the case of mastocytosis. Mastocytosis is a disorder characterized by the proliferation of mast cells that can affect various organ systems in the human body. There are various variations of mastocytosis, but they can generally be categorized into two main types: cutaneous mastocytosis, which primarily affects the skin and is the most common form, and systemic mastocytosis, which is a more severe form involving the accumulation of mast cells in organs and tissues throughout the body, not just the skin. Planning a successful course of therapy and providing a positive outlook for patients heavily relies on an accurate and timely diagnosis of mastocytosis. This study utilizes an exponential comparison strategy to compare and contrast the Dempster-Shafer (DS) and Case Based Reasoning (CBR) techniques in detecting mastocytosis. The Dempster-Shafer technique is employed in this study to gather and evaluate data from various ambiguous and inadequate sources. This method utilizes the theory of mass variability to represent uncertainty in disease diagnosis. On the other hand, Case Based Reasoning is an approach that relies on past experiences and utilizes existing knowledge in the form of previously encountered cases to make diagnoses. In this study, exponential comparison is used to assign greater weight to certain attributes considered more important in the diagnosis process. This exponential comparison method allows for more flexible attribute weighting, enabling more accurate modeling of symptoms and related factors in mastocytosis. The aim of this research is to use the exponential comparison approach to develop, analyze, and compare both strategies in detecting mastocytosis. With the lowest rate for cutaneous mastocytosis and the highest percentage for systemic mastocytosis, the research findings indicate that both approaches yield comparable results. The Dempster-Shafer approach has proven to be more accurate in mastocytosis diagnosis when comparing the calculations of these two methods with the exponential comparison method

Arachidonic acid metabolism and its use in the diagnosis of mastocytosis

<abstract> <p>Mast cells and basophils degranulate upon activation, releasing preformed mediators from intracellular granules into the extracellular environment, of which tryptase and histamine are the two most common and best characterized mediators. Despite the large number of mediators synthesized by mast cells, the non-tryptase biomarkers used to evaluate systemic mastocytosis and mast cell activation syndrome do not include the metabolites of the prestored amine histamine and the <italic>de novo</italic> synthesized phospholipids prostaglandin D2 and leukotriene C4. Currently, these markers are not used as criteria for the diagnosis of mastocytosis and mast cell activation syndrome. However, consensus groups foster the use of increases in measured baseline levels of these metabolites as potential diagnostic criteria. Metabolites of arachidonic acid such as prostaglandin D2 or leukotriene C4 play a role in the development of symptoms in systemic mastocytosis and mast cell activation syndrome. In this review, the metabolites of arachidonic acid and the detection of the metabolites of leukotrienes and prostaglandins in mastocytosis are highlighted. Measurement of these metabolites remains a major challenge because they are not widely available in daily clinical practice. However, new insights have been gained in recent years, and their application in the clinic has progressed.</p> </abstract>

Dermatoscopy for the cutaneous mastocytosis diagnosis in children

Dermatoscopy for the cutaneous mastocytosis diagnosis in children

Incorporating Tryptase Genotyping Into the Workup and Diagnosis of Mast Cell Diseases and Reactions

The measurement of mast cell tryptase levels in serum has found utility in the diagnosis and management of both clonal mast cell disorders and severe mast cell-dependent systemic reactions in the form of anaphylaxis. A more recent discovery is that a majority of individuals with elevated basal serum tryptase levels have increased germline TPSAB1 gene copy number encoding α-tryptase. This genetic trait is referred to as hereditary α-tryptasemia (HαT) and affects nearly 6% of the general population. In clinical practice, the presence or absence of HαT should thus now be determined when defining what constitutes an abnormal serum tryptase level in the diagnosis of mastocytosis. Further, as rises in serum tryptase levels are used to support the diagnosis of systemic anaphylaxis, variability in baseline serum tryptase levels should be factored into how significant a rise in serum tryptase is required to confirm the diagnosis of a systemic allergic reaction. In practicality, this dictates that symptomatic individuals undergoing evaluation for a mast cell-associated disorder or reaction with a baseline serum tryptase level exceeding 6.5 ng/mL should be considered for tryptase genotyping in order to screen for HαT. This review provides detailed information on how to use the results of such testing in the diagnosis and management of both mastocytosis and anaphylaxis.

COVID-19 vaccination in the setting of mastocytosis—Pfizer-BioNTech mRNA vaccine is safe and well tolerated

COVID-19 vaccination in the setting of mastocytosis—Pfizer-BioNTech mRNA vaccine is safe and well tolerated

Establishing diagnostic criteria for mastocytosis in skin biopsies

The diagnosis of mastocytosis in skin biopsies can be challenging - particularly in cases with very few mast cells. More diagnostic criteria are needed. We analyzed 103 skin biopsies from patients with mastocytosis and compared them with biopsies from inflammatory skin lesions and normal skin. Using CD117 immunostaining, we determined the mast cell distribution pattern, the percentage of mast cells in the inflammatory infiltrate, and the mast cell count per mm². We found that a sheet-like or subepidermal distribution of mast cells was specific for mastocytosis. The most significant feature was the percentage of mast cells and not the mast cell count. We found that a mast cell percentage above 40% was fully specific in both adults and children but lacked sensitivity, especially in adults. In children, all cases with a percentage below 40% harbored a number of mast cells above 90 per mm², allowing a straightforward diagnosis. In adults, the diagnosis was more challenging and cases with less than 40% of mast cells could be diagnosed on account of a number of mast cells above 40 per mm², with 88.5% sensitivity and 95.2% specificity. Additional signs might be useful in difficult cases. However, CD25 immunostaining was not useful. We confirmed that the criteria currently applied in the bone marrow were not appropriate for the skin. Accordingly, we developed an algorithm for the diagnosis of mastocytosis in skin biopsies with a high level of interrater reproducibility (mean kappa 0.8).

Screening for Hereditary Alpha-Tryptasemia in Subjects with Systemic Mastocytosis (SM) and Non-SM Mast Cell Activation Symptoms

▪IntroductionHereditary alpha-Tryptasemia (HαT) is a group of genetically defined traits that share increased copy number of TPSAB1 gene encoding for both the α- and β-alleles (Lyons et al 2018). Increased copy number (CN) of the α-tryptase coding sequence in TPSAB1 on one or both alleles represents the genetic base of HαT (Lyons et al 2016). HαT is characterized by mild elevation in serum tryptase levels and a variety of mast cell (MC) activation symptoms, including recurrent anaphylaxis. Prevalence in the general population is up to 5%, that increases up to 20% in systemic mastocytosis (SM); it has been suggested that HαT might be a germline variant predisposing to SM development. In SM, HαT correlated with higher incidence of mediator-related symptoms (Greiner G et al, Blood 2021). Due to its complexity, the assay for TPSAB1 CN is performed in few centers and the actual prevalence of HαT in selected subsets is still to be elucidated. To this end, we screened for HαT 2 groups of subjects, the first with MC activation symptoms and no evidence of SM, the second with diagnosis of SM according to WHO-2016.MethodsDroplet digital PCR (ddPCR) was used to measure CN variation (CNV) in TPSAB1 by adapting standard CNV ddPCR protocol to genotype for both TPSAB1 and TPSB2 (Fig.1A). The high homology between α and β encoding isoforms and the presence of paralogous genes in a single locus makes TPSAB1 CNV detection very challenging. ddPCR was performed on genomic DNA with/without BamHI, using the PrimePCR ddPCR Copy Number reference AP3B1 (BioRad). Accuracy and precision of the ddPCR protocol was assessed by analyzing 10 samples in triplicate in 3 separate experiments. Data robustness and repeatability can be appreciated in Fig 1B.ResultsWe studied 41 subjects with mediator-related symptoms and augmented basal serum tryptase (BST) (cohort 1) and 150 patients with ascertained diagnosis of mastocytosis (cohort 2). The BST threshold established for cohort 1 was equal or higher than 11 mcg/L. Median age was 64.7 yr, males 54%; median BST levels was 15.3 (range 12.3-21 mcg/L); 29% of the pts had history of anaphylaxis.In cohort 2, 134/150 (89.3%) pts had a diagnosis of SM, whereas 13/150 (8,6%) were Cutaneous Mastocytosis (CM). Among SM patients, 113(84.3%) presented with non-advanced SM variants. Advanced forms including aggressive SM (ASM) and SM with an associated hematological neoplasm (SM-AHN) were diagnosed in 6 (4.5%) and 8 (6%) respectively. In 3 pts, SM subtype was not available. Median age was 49 yr, males 55%; 41.7% of the pts had history of anaphylaxis.HαT was documented in 27 (65.9%) subjects in cohort 1, and 14 (9.3%) in cohort 2. In cohort 1, 3 α-tryptase (3α) copy number was observed more frequently (59.2% of HαT+ pts); conversely 3α and 2α-tryptase copy number were observed at a similar rate (42,8%) in cohort 2.HαT+ pts in cohort 1 presented significantly higher BST (17.1 vs 12.05 mgc/L, P<0.001), as previously reported (Greiner G et al, Blood 2021); however, occurrence of mediator related symptoms was comparable to HαT wt, 72% vs 71.4% , respectively; likewise for anaphylaxis (28% in HαT+ vs 33%).In cohort 2, BST levels were similar in HαT+ and HαT wt pts (24.6 and 24.3 mcg/L), as were anaphylaxis episodes (50% and 41%, respectively). A trend for lower MC burden in HαT+ as assessed by flow cytometry was demonstrated (% of bone marrow MC: 0.01% in HαT+ vs 0.07%) whereas no meaningful differences emerged regarding the symptom burden. In addition, a lower prevalence of KIT 816V mutation was observed in HαT+ (71.4% vs 89.5%; p=0.073).ConclusionsIn our study HαT+ was observed in around 10% of patients with SM, a prevalence lower than previously reported (Greiner et al, Blood 2021) and remarkably lower than in a selected cohort of subjects with raised BTL and history of mediator-released symptoms (66%). ddPCR represents a suitable method to investigate the presence of CNV in the α-tryptase coding sequence. Genetic testing for HαT+ should be considered in the diagnostic workout of patients presenting with anaphylaxis or MC mediator-related symptoms and no suspicion/evidence of SM. The clinical correlates of HαT in SM remain to be fully ascertained.Supported by IMH no.GR-2016-02362631 and AIRC, Mynerva project no21267 [Display omitted] DisclosuresElena: CELGENE: Other: funding for meeting participation; PFIZER: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Vannucchi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees.

Distinct plasma biomarkers confirm the diagnosis of mastocytosis and identify increased risk of anaphylaxis

Mastocytosis encompasses a heterogeneous group of disorders characterized by accumulation of clonal mast cells (MCs) in the skin and/or internal organs. Patients typically present with a broad variety of recurrent mediator-related clinical symptoms, including severe anaphylaxis. However, not all patients with mastocytosis experience anaphylactic reactions. We sought to identify disease-specific biomarkers in plasma that could be used to predict patients with mastocytosis with increased risk of anaphylaxis. Nineteen patients (≥18 years) and 2 control groups (11 subjects with allergic asthma and 13 healthy volunteers without history of atopy) were recruited. In total, 248 plasma proteins were analyzed by Proximity Extension Assay using Olink Proseek Multiplex panels. We identified 4 novel proteins, in addition to tryptase, E-selectin, adrenomedullin, T-cell immunoglobulin, and mucin domain 1, and CUB domain-containing protein 1/CD138 to be significantly increased in patients with mastocytosis compared with both patients with asthma and healthy controls. Furthermore, we investigated whether we could discriminate between patients with mastocytosis with or without anaphylaxis. In addition to tryptase, we identified 3 novel proteins, that is, allergin-1, pregnancy-associated plasma protein-A, and galectin-3, with significantly different levels in patients with mastocytosis with anaphylaxis compared with those without anaphylaxis. Newly identified proteomic biomarkers may be used to predict patients with mastocytosis with increased risk of anaphylaxis.

Protocolo diagnóstico de la mastocitosis

Mastocytosis is an emerging differential diagnosis in patients with specific mediator-related symptoms. Typical skin lesions are found in some patients, and the mastocytosis diagnosis can be achieved. However, in absence of lesions, diagnosis is a challenge. We developed a diagnostic algorithm for patients with suspected mastocytosis based on international consensus of networks of experts on this disease.

Laboratory Tests in Diagnosis of Mastocytosis: Literature Review and Case Report

Abstract Мastocytosis is a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MCs) in the skin and/or other organ systems. Mastocytosis is a rare disease. The annual incidence is 5-10 cases per 1 million people. However, the majority of cases stay undiagnosed due to the lack of specific tests and a wide variety of clinical features of the disease. In mastocytosis, somatic mutations of KIT gene lead to autocrine dysregulation and constitutive c-KIT activation in the absence of its ligand SCF. Clinical symptoms of the disease are determined by MC mediator release and/or infiltration of tissues by MCs. According to the World Health Organisation classification updated in 2016 mastocytosis is divided to cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), SM with an associated hematologic (non-MC-lineage) neoplasm (SMAHN), aggressive SM (ASM), MC leukemia (MCL) and MC sarcoma (MCS). The CM and ISM prognosis is excellent with (almost) normal life expectancy, unlike aggressive forms (ASM and MCL) with poor prognosis. In this paper the key aspects of clinical features and diagnostic criteria of mastocytosis are discussed. We present a case report of a patient with mastocytosis in the skin following psoralen plus ultraviolet A (PUVA) therapy with good response.

Dermatofibroma harboring mast cells histologically exposes systemic mastocytosis diagnosis

Dermatofibroma harboring mast cells histologically exposes systemic mastocytosis diagnosis

PS1461 FAMILIAL OCCURRENCE OF SYSTEMIC AND CUTANEOUS MASTOCYTOSIS IN AN ADULT MULTICENTER SERIES: A REPORT OF 22 CLUSTERED CASES

Background:Mastocytosis refers to a group of clonal disorders characterized by abnormal proliferation of mast cells infiltrating various tissues, especially skin and hematopoietic organs. Clinical presentation is heterogeneous and may vary from skin‐limited disease to more aggressive variants. The clonal nature of mastocytosis has been largely demonstrated by the identification of gain‐of‐function mutations in exon 17 causing constitutive activation of the c‐KIT protooncogene. In the large majority of patients with systemic disease a somatic aspartate‐to‐valine substitution in codon 816 (D816 V) of the KIT gene is demonstrable. Typically, mastocytosis is considered a non‐hereditary disease, although clustered cases were reported in pediatric series with an estimated frequency of 8–10%, in the absence or presence of c‐KIT mutations, generally located outside the exon 17. Prevalence data about familial cases in adults are lacking. To our knowledge, somatic D816 V KIT mutation was reported only in two adult clusters and in two pediatric familial cases.Aims:In this retrospective, observational, multicenter study we sought: a) to estimate the prevalence of familial disease in a series of 1541 patients with mastocytosis referred in adulthood (&gt;16 years old) to 8 Italian Institutions, and b) to describe the clinical and molecular characteristics of clustered cases.Methods:Diagnosis of mastocytosis was made according to the 2016 World Health Organization criteria. All patients were asked for the occurrence of the same disease in relatives. Clinical and molecular data were recorded in all patients and in the affected relatives, when available.Results:Familial occurrence of mastocytosis was reported in 22 patients (1.4% of the whole cohort). Clinical and molecular characteristics are reported in table I. Index cases were 12 males and 10 females, median age at diagnosis was 43 years (range 16–65 years). Diagnosis in index patients was systemic mastocytosis (SM) (n = 15), mastocytosis in the skin (MIS) (n = 3), and maculo‐papular cutaneous mastocytosis (MPCM) (n = 4). All but one SM patients harbored D816V KITmutation. Each index case reported a single affected relative: they were 14 males and 8 females, with median age at diagnosis of 20 years (range 0–70 years). Diagnosis in relatives was SM (n = 7), MIS (n = 3), MCPM (n = 6) and Mastocytoma (n = 6). The relationship between index and relatives was mainly “parent and child” (41%) and “siblings” (27%). Notably, 4 SM patients had one child who developed single or multiple mastocytoma; in other two families index and/or relatives developed an associated hematological neoplasia.Summary/Conclusion:To our knowledge, this is the largest report about the prevalence and the characteristics of familial cases in an adult population of patients with mastocytosis. Familial occurrence of mastocytosis with different clinical and molecular characteristics between indices and relatives suggests that D816 V KIT mutations may be a secondary genetic event. Further studies, including search for mutations in all patients with skin‐limited disease and genotyping of D816V‐mutated patients, are needed to confirm our hypothesis.image

Frequency of isolated cutaneous involvement in adult mastocytosis: a cohort study.

Mastocytosis is characterized by the accumulation/proliferation of abnormal mast cells. The frequency of isolated cutaneous involvement in adults with mastocytosis has not been fully determined. The main objective of our study was to assess the frequency of isolated cutaneous mastocytosis (CM) in adults with mastocytosis skin lesions. The second objective was to compare the clinical, histological, biological and imaging features in patients with isolated CM and patients with systemic mastocytosis (SM). We included all patients with histology-proven mastocytosis skin lesions between January 2009 and December 2017. The mastocytosis diagnosis was made according to the international diagnostic criteria. All data were collected from a dedicated specific case report. Among 160 patients with mastocytosis skin lesions, 25 patients had isolated CM (15.6%), 105 had SM and 30 (18.7%) patients had undetermined mastocytosis. Skin KIT mutation (OR: 51.9, 95% CI: 3.9-678, P=0.001) and high bone marrow tryptase (OR: 97.4, 95% CI: 10.3-915, P=0.001) were strong predictors of SM. The prevalence of osteoporosis was higher in the SM population than in the isolated CM population. Moreover, a decrease in bone mineral density over a short period of follow-up (1-2years) was associated with SM. There were no differences between the two groups regarding the frequency of mast cell activation symptoms, the presentation of skin lesions, the number of mast cells in the dermis and the level of serum tryptase. We propose considering the KIT mutation status and bone marrow tryptase levels to aid the diagnosis of isolated CM in adult mastocytosis patients. Only a small minority of adults with mastocytosis skin lesions has isolated cutaneous involvement. In 18.7% of mastocytosis cases, even complete workup does not allow for a precise classification of patients.