Somatic D816V KIT mutation in a case of adult-onset familial mastocytosis

Letter to the editor.-- et al.Peer Reviewe

Familial occurrence of systemic and cutaneous mastocytosis in an adult multicentre series

n/

Multiple large osteolytic lesions in a patient with systemic mastocytosis: a challenging diagnosis

Patients with advanced variants of Systemic Mastocytosis may develop destructive bone lesions when massive mast cell (MC) infiltrates are present. Finding of large osteolyses in indolent systemic mastocytosis, typically characterized by low MC burden, should prompt investigations for an alternative explanation

Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM

Spanish Network on Mastocytosis (REMA): et al.[Background]: Indolent systemic mastocytosis (ISM) without skin lesions (ISMs-) shows a higher prevalence in males, lower serum baseline tryptase levels, and KIT mutation more frequently restricted to bone marrow (BM) mast cells (MCs) than ISM with skin lesions (ISMs+). Interestingly, in almost one-half of ISMs- patients, MC-mediator release episodes are triggered exclusively by insects. [Objective]: We aimed to determine the clinical and laboratory features of ISMs- associated with insect-induced anaphylaxis (insectISMs-) versus other patients with ISM. [Methods]: A total of 335 patients presenting with MC activation syndrome, including 143 insectISMs-, 72 ISMs- triggered by other factors (otherISMs-), 56 ISMs+, and 64 nonclonal MC activation syndrome, were studied. [Results]: Compared with otherISMs- and ISMs+ patients, insectISMs- cases showed marked male predominance (78% vs 53% and 46%; P <.001), a distinct pattern of MC-related symptoms, and significantly lower median serum baseline tryptase levels (22.4 vs 28.7 and 45.8 μg/L; P ≤.009). Moreover, insectISMs- less frequently presented BM MC aggregates (46% vs 70% and 81%; P ≤.001), and they systematically showed MC-restricted KIT mutation. [Conclusions]: ISMs- patients with anaphylaxis triggered exclusively by insects display clinical and laboratory features that are significantly different from other ISM cases, including other ISMs- and ISMs+ patients, suggesting that they represent a unique subgroup of ISM with a particularly low BM MC burden in the absence of adverse prognostic factors.Supported by Fondo de Investigaciones Sanitarias –FIS– of the Instituto de Salud Carlos III, Ministery of Economy and Competitivity, Madrid, Spain grant PS09/00032; Fundación Sociosanitaria de Castilla-La Mancha grants 2010/008 and G-2010/ C-002; Fundacióon Española de Mastocitosis grant FEM 2011; BioB-HVS is supported by grant RETICS (Redes Temáticas de Investigación Cooperativa en Salud) RD09/ 00760074 (Toledo, Spain); RTICC (Red Temática de Investigación Cooperativa en Cáncer) grants RD09/0076/00133, RD12/0036/0048; FIS; FEDER, Ministery of Economy and Competitivity, Madrid, Spain grant PI11/02399; and Fundación Ramón Areces, Madrid, Spain grant CIVP16A1806; and by Associazione Italiana Leucemie e Linfomi of Verona (AIL-Verona) and ASIMAS (Associazione Italiana Mastocitosi). L. Escribano has been supported by one or more grants from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Fundacion Sociosanitaria de Castilla La Mancha, and from FEM. A. García-Montero has been supported by one or more grants from ISCIII. M. Mollejo and A. Orfao have been supported by one or more grants from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad. L. Sánchez-Muñoz has been supported by one or more grants from Fundacion Sociosanitaria de Castilla La Mancha.Peer Reviewe

Non-steroidal anti-inflammatory drug-induced anaphylaxis infrequent in 388 patients with mastocytosis: A two-center retrospective cohort study

BackgroundAnaphylaxis is a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. It is therefore hypothesized that mastocytosis patients may also be predisposed to severe hypersensitivity reactions to certain medications including non-steroidal anti-inflammatory drugs (NSAIDs). For this reason, these patients are usually discouraged from using these drugs. The current study aimed to determine the prevalence and evaluate the severity of NSAID-related hypersensitivity reactions among patients with mastocytosis.MethodsA retrospective study was conducted among a total of 388 (≥18 years old) consecutive patients from two independent European mastocytosis centers, in Sweden and Italy. Patients underwent a thorough allergy work-up where self-reported NSAID-hypersensitivity reactions were re-evaluated by an allergist in the first cohort (202 patients) and results were validated in the second cohort (186 patients).ResultsOverall frequency of NSAID-hypersensitivity was 11.3% in the total study cohort. Most patients reacted with cutaneous symptoms (89%), whereas severe hypersensitivity reactions were infrequent with only 11 patients (2.8%) experiencing anaphylaxis. All NSAID-related hypersensitivity reactions had occurred before mastocytosis was diagnosed. There was no difference between the groups regarding gender, baseline tryptase levels or presence of atopy, asthma/rhinitis.ConclusionOur study indicates an approximate 4-fold increased prevalence of NSAID hypersensitivity among mastocytosis patients compared to the general population. However, most NSAID reactions were limited to the skin as the prevalence of overall anaphylaxis was infrequent. Our results support that mastocytosis patients with a known tolerance to NSAIDs can continue using these medications without special precautions, whereas those with a prior reaction to NSAIDs should undergo thorough allergy work-up, including drug challenges

Personalized management strategies in mast cell disorders: ECNM-AIM User's guide for daily clinical practice

Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user’s guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice.This work was supported in part by the Austrian Science Fund (FWF; projects F4704 and P32470-B to P.V.) and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (to M.C.C. and D.D.M.). The content is solely the responsibility of the authors and does not represent the official views of the NIH

Early stability and late random tumor progression of a HER2-positive primary breast cancer patient-derived xenograft

We established patient-derived xenografts (PDX) from human primary breast cancers and studied whether stability or progressive events occurred during long-term in vivo passages (up to 4&nbsp;years) in severely immunodeficient mice. While most PDX showed stable biomarker expression and growth phenotype, a HER2-positive PDX (PDX-BRB4) originated a subline (out of 6 studied in parallel) that progressively acquired a significantly increased tumor growth rate, resistance to cell senescence of in vitro cultures, increased stem cell marker expression and high lung metastatic ability, along with a strong decrease of BCL2 expression. RNAseq analysis of the progressed subline showed that BCL2 was connected to three main hub genes also down-regulated (CDKN2A, STAT5A and WT1). Gene expression of progressed subline suggested a partial epithelial-to-mesenchymal transition. PDX-BRB4 with its progressed subline is a preclinical model mirroring the clinical paradox of high level-BCL2 as a good prognostic factor in breast cancer. Sequential in vivo passages of PDX-BRB4 chronically treated with trastuzumab developed progressive loss of sensitivity to trastuzumab while HER2 expression and sensitivity to the pan-HER tyrosine kinase inhibitor neratinib were maintained. Long-term PDX studies, even though demanding, can originate new preclinical models, suitable to investigate the mechanisms of breast cancer progression and new therapeutic approaches

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial

The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance

Spectroscopic and Morphological Studies of Metal-Organic and Metal-Free Dyes onto Titania Films for Dye-Sensitized Solar Cells

We have investigated the spectroscopic behavior of three different sensitizers adsorbed onto titania thin films in order to gain information both on the electron transfer process from dye to titania and on the anchorage of the chromophore onto the semiconductor. We have examined by UV-Vis and fluorescence spectroscopy the widely used ruthenium complex cis-di(thiocyanato)bis(2,2′-bipyridyl-4,4′-dicarboxylato)ruthenium(II) (N719), the more recently developed organic molecular 3-(5-(4-(diphenylamino)styryl)thiophen-2-yl)-2-cyanoacrylic acid (D5), and a push-pull zinc phthalocyanine sensitizer (ZnPc). Three type of titania films with different morphology, characterized by SEM and FT-IR measurement, were considered: a mesoporous transparent film deposited by spin-coating (TiMS), a semiopaque film deposited by doctor-blade from mesoporous titania (TiMS_DB) and a semiopaque film deposited by doctor-blade form commercial P25 titania (P25_DB). The use of TiMS is responsible for the adsorption of a higher amount of dye since the mesoporous structure allows increasing the interfacial area between dye and titania. Moreover, the fluorescence emission peak is weaker when the sensitizers are adsorbed onto TiMS. These findings suggest that mesostructured films could be considered the most promising substrates to realize photoanodes with a fast electron transfer process

Risk and management of patients with mastocytosis and MCAS in the SARS-CoV-2 (COVID-19) pandemic:Expert opinions

The COVID-19 (SARS-CoV-2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase and patients at risk can only be protected to a degree, since the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here within, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. As no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Whereas the overall risk to acquire the SARS-CoV-2 virus may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain co-morbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. By contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.P.V. was supported by the Austrian Science Fund (FWF), projects P32470-B and 46 F4704-B20. J.G. is supported by the Charles and Ann Johnson Foundation. 47 D.D.M. is supported by the Division of Intramural Research, NIAID.Peer reviewe