Use of Next-Generation Sequencing to Support the Diagnosis of Familial Interstitial Pneumonia.

Familial interstitial pneumonia (FIP) is defined as idiopathic interstitial lung disease (ILD) in two or more relatives. Genetic studies on familial ILD discovered variants in several genes or associations with genetic polymorphisms. The aim of this study was to describe the clinical features of patients with suspected FIP and to analyze the genetic variants detected through next-generation sequencing (NGS) genetic testing. A retrospective analysis was conducted in patients followed in an ILD outpatient clinic who had ILD and a family history of ILD in at least one first- or second-degree relative and who underwent NGS between 2017 and 2021. Only patients with at least one genetic variant were included. Genetic testing was performed on 20 patients; of these, 13 patients had a variant in at least one gene with a known association with familial ILD. Variants in genes implicated in telomere and surfactant homeostasis and MUC5B variants were detected. Most variants were classified with uncertain clinical significance. Probable usual interstitial pneumonia radiological and histological patterns were the most frequently identified. The most prevalent phenotype was idiopathic pulmonary fibrosis. Pulmonologists should be aware of familial forms of ILD and genetic diagnosis.

Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas.

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients' risk stratification.

TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Telomerase reverse transcriptase gene (TERT) promoter (TERTp) mutations have been reported as potential predictors of poor prognosis in several cancers, but the prognostic value of TERTp mutations for cutaneous squamous cell carcinoma (cSCC) has not been determined. OBJECTIVE: To evaluate the frequency of TERTp mutations and correlate it with clinicopathologic features and patient outcome. METHODS: We performed genetic profiling of TERTp mutations in a retrospective series of cSCCs. The predictive value of TERTp mutations and clinicopathologic parameters were assessed by using logistic regression models. RESULTS: A total of 152 cSCCs from 122 patients were analyzed for TERTp mutations; the mutation rate was 31.6% (48 of 152), and it was higher in invasive cSCC (42 of 121 [34.7%]) than in in situ cSCC (6 of 31 [19.4%]). Age older than 75 years (odds ratio [OR], 14.84; P = .013] and TERTp mutation (OR, 8.11; P = .002) were independent predictors of local recurrence. TERTp mutation (OR, 15.89; P = .022) was independently associated with higher risk of lymph node metastasis. LIMITATIONS: The restricted number of metastatic cases. CONCLUSION: TERTp mutations may prove to be a molecular biomarker with prognostic significance in invasive cSCC, but larger studies are needed.

Un tumor desorientador. Leiomioma benigno metastásico / A misleading tumor. Benign metastatic leiomyoma

No disponible

A Large Gastric Inflammatory Fibroid Polyp.

Inflammatory fibroid polyp (IFP) is an unusual benign gastrointestinal subepithelial tumor (SET). The endosonographic (EUS) features of IFPs were sporadically reported on imaging tips or small case series study. However, the differential diagnosis and optimal treatment of gastric IFP is still challenging. We report an unusual case of a large erosioned and prolapsing gastric submucosal lesion, presenting primarily with obstructive symptoms ("ball valve syndrome") and anemia. On EUS examination, a 50 mm SET in the distal antrum was seen, with hypoechoic but heterogeneous echo-pattern, located in the second and third sonographic layers of the gastric wall (deep mucosal and submucosal). The fourth (muscle) layer was intact; no peri-lesional adenopathies were identified. A decision was made to proceed to endoscopic treatment because of the mentioned symptoms. Histopathologic evaluation of the resected specimen with immunohistochemical staining was consistent with the diagnosis of IFP. IFP rarely reach these large dimensions or cause symptoms. Despite its benign etiology, endoscopic resection was important in both establishing a histologic diagnosis and treatment. EUS was crucial in the differential diagnosis. The literature concerning IFP is also reviewed.

O pólipo fibróide inflamatório (PFI) é uma lesão subepitelial (LSE) gastrointestinal incomum e benigna. As características dos PFIs gástricos na ultrassonografia endoscópica (EUS) foram esporadicamente descritas em relatos de casos clínicos e séries pequenas. No entanto, o diagnóstico diferencial e tratamento são frequentemente um desafio.Apresentamos um caso invulgar de uma LSE gástrica volumosa, com sintomas obstrutivos face ao seu efeito valvular sobre o piloro ("ball valve syndrome") e anemia por erosão da mucosa. Na avaliação por EUS observou-se uma LSE hipoecogénica mas heterogénea no antro distal, com 50 mm, e pedículo longo na dependência da segunda e terceira camadas (mucosa profunda e submucosa). Estava mantida a integridade da quarta camada (muscular), e não foram observadas adenopatias peri-lesionais. Optou-se pela exérese endoscópica face à sintomatologia referida. A análise histológica com estudo imuno-histoquímico foi compatível com PFI.Os PFIs raramente atingem estas dimensões ou causam sintomas. Apesar da sua etiologia benigna, a ressecção endoscópica foi importante para estabelecer um diagnóstico histológico bem como tratamento. Destaca-se a importância da EUS no diagnóstico diferencial desta lesão. A literatura sobre PFIs é revista.

Ovarian ependymomas of extra-axial type or central immunophenotypes.

We report the differential clinicopathologic and immunophenotypical features of 2 pure ovarian ependymomas of extra-axial type with a predominant microcystic, anaplastic pattern occurring in patients aged 22 and 32 years and a unique myxopapillary pigmented ependymoma that originated within an ovarian mature cystic teratoma in a 35-year-old woman. The latter had a central nervous system phenotype different from that previously reported in ovarian ependymomas of extra-axial types, being negative for estrogen and progesterone receptors, epithelial membrane antigen and cytokeratin 34ßE12, cell adhesion molecule 5.2, and cytokeratin 7. Furthermore, its benign behavior contrasted with the aggressive course of the other 2 ependymomas of extra-axial types, in which peritoneal invasion was present at the time of diagnosis. These findings illustrate that both central and extra-axial types of ependymoma show phenotypic variations that may point to either a derivation from different precursors or differentiation along diverse pathways. Thus, whereas ependymomas of extra-axial types would represent neometaplastic phenomena, those originated from the nervous tissue of teratomas resemble central nervous system ependymomas. Moreover, the dissimilarities between central and peripheral types of ependymoma would parallel the phenotypic differences present in primitive neural tumors of the female genital tract.