Background: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM. Methods: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM. Results: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly. Conclusion: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.

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Different genes related to alveolar stability have been associated with familial interstitial pneumonia (FIP). Here, we report a novel, rare SFTPA1 variant in a family with idiopathic interstitial pneumonia (IIP). We performed whole-exome sequencing on germline DNA samples from four members of one family; three of them showed signs of pulmonary fibrosis (idiopathic interstitial pneumonia) with autosomal-dominant inheritance. A heterozygous single nucleotide variant c.532 G > A in the SFTPA1 gene has been identified. This variant encodes the substitution p.(Val178Met), localized within the carbohydrate recognition domain of surfactant protein A and segregates with the genes causing idiopathic interstitial pneumonia. This rare variant has not been previously reported. We also analyzed the detected sequence variant in the protein structure in silico . The replacement of valine by the larger methionine inside the protein may cause a disruption in the protein structure. The c.532 G > A variant was further validated using Sanger sequencing of the amplicons, confirming the diagnosis in all symptomatic family members. Moreover, this variant was also found by Sanger sequencing in one other symptomatic family member and one young asymptomatic family member. The autosomal-dominant inheritance, the family history of IIP, and the evidence of a mutation occurring in part of the SFTPA1 gene all suggest a novel variant that causes FIP.