Breast cancer (BC) is the most prevalent malignancy in women with Li-Fraumeni syndrome (LFS). The literature on BC in LFS is limited due to its rarity worldwide. A TP53 founder pathogenic variant (c.1010G>A; p.R337H) is responsible for the higher prevalence of this syndrome among women of Brazilian ancestry.PurposeThe aim of the study was to describe the BC phenotype expressed by Brazilian female LFS carriers and compare the data between p.R337H and other TP53 germline pathogenic/likely pathogenic variants (non-p.R337H carriers).MethodsWe searched for cases of TP53 germline pathogenic/likely pathogenic variant carriers affected by BC included between 2015 and 2020 in the BLiSS (Brazilian Li-Fraumeni Study) registry at the Sírio-Libanês Hospital.ResultsAmong 163 adult female carriers from the registry, 91 (56%) had received a BC diagnosis, including 72 p.R337H carriers. BC was the first cancer diagnosed in 90% of cases. Early onset BC (age ≤45 years) was diagnosed in 78.2% of cases (11.5% <31 years; 66.7% 31–45 years; 21.8% >45 years). The median age of BC diagnosis for p.R337H carriers was 39.5 years (range 20–69 years) compared to 34 years (range 21–63 years) for non-p.R337H carriers (p = 0.009). In total, 104 breast tumors were observed in 87 women. Bilateral BC was observed in 29.3% of cases. Histology was available for 96 tumors, comprising 69 invasive breast carcinomas, which were mostly invasive ductal carcinomas (95.6%), 25 ductal in situ carcinomas and 2 soft-tissue sarcomas. Overall, 90.5% of invasive breast carcinomas were hormone receptor (HR)-positive, 39.5% were human epidermal growth factor receptor 2 (HER2)-positive, and 32.8% showed HR and HER2 co-expression. In addition, 55.4% of patients opted for contralateral prophylactic mastectomy after a first BC diagnosis. There were no significant differences in the risk of developing contralateral BC or in the immunohistochemical profile between p.R337H and non-p.R337H groups.ConclusionsThe expressed phenotype of p.R337H is similar to that of other TP53 pathogenic/likely pathogenic variants, except for an average older age at the onset of disease; however, this is still younger than the general population.

CONTEXT: Non-small cell lung cancer (NSCLC) progresses to distant metastases in most cases. The most frequent sites for distant metastases are the bones, central nervous system, adrenal glands and liver. Dissemination to the skin, myocardium, thyroid gland and intestine may occur, but is rare. CASE REPORT:We describe a case of squamous cell carcinoma in the lungs, with metastases in the colon and thyroid, in a 66-year-old female patient.The lesion was unresectable and chemotherapy was started. The patient evolved with intestinal subocclusion, and colonoscopy showed the presence of a polyp. Biopsy and immunohistochemical analysis on the polyp showed that it was compatible with squamous cell carcinoma of pulmonary origin.At a follow-up consultation, the patient presented a thyroid nodule. A aspiration biopsy and cellblock immunohistochemistry confirmed the squamous cell carcinoma of pulmonary origin. After third-line chemotherapy, the patient progressed with acute obstructive abdomen due to a retroperitoneal mass. She underwent exploratory laparotomy and died due to surgical complications. Metastases to the thyroid and colon are rarely reported in cases of epidermoid carcinoma of the lungs. Gastrointestinal involvement in pulmonary metastases may affect the stomach, small intestine and colon, and cases of bleeding and perforation have already been reported. Although richly vascularized, the thyroid is an infrequent site for metastases. Such sites reflect poor prognoses for the clinical evolution. We did not find any previous reports in the literature, on lung cancer with metastases concomitantly in the colon and thyroid, in a single patient. RESUMOCONTEXTO: O câncer de pulmão de células não pequenas evolui, na maioria dos casos, com metástases a distância. Ossos, sistema nervoso central, glândula adrenal e fígado são os sítios mais frequentes de metástases. Disseminação para pele, miocárdio, tireoide e intestino pode ocorrer, entretanto é rara. RELATO DE CASO:Descrevemos um caso de carcinoma espinocelular (CEC) de pulmão com metástase em cólon e tireoide, em mulher de 66 anos.A lesão era irressecável, e foi iniciada quimioterapia. A paciente evoluiu com suboclusão intestinal e a colonoscopia evidenciou pólipo colônico cuja biópsia e imunoistoquímica (IHQ) foram compatíveis com CEC de origem pulmonar. Em consulta de acompanhamento, detectou-se nódulo tireoidiano cuja punção aspirativa e IHQ de cellblock confirmaram CEC de origem pulmonar. Após quimioterapia de terceira linha, a paciente evoluiu com abdome agudo obstrutivo por massa retroperitoneal, sendo submetida a laparotomia exploradora, vindo a falecer por complicações da cirurgia.Metástases para tireoide e cólon são raramente reportadas em carcinomas epidermoides de pulmão. O envolvimento gastrointestinal por metástases de pulmão pode acometer estômago, intestino delgado e cólon, e casos de sangramento e perfuração já foram reportados. Embora ricamente vascularizada, a tireoide é sítio infrequente de metástases. Os sítios refletem prognósticos reservad...

Introduction: Hypercalcemia is well described in various granulomatous disorders, such as sarcoidosis, tuberculosis, berylliosis, leprosy and fungal infections. However, the association of Paracoccidioides brasiliensis and hypercalcemia is rare: to the best of our knowledge, only two cases have previously been reported, and neither had a clear documentation of the etiology of the hypercalcemia.

ObjectiveThe objective of this study was to assess the clinical value of 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) after the first cycle of induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LASCCHN).Methods and findingsA prospective, single-arm, single center study was performed, with patients enrolled between February 2010 and July 2013.Patients (n = 49) with stage III/IVA–B LASCCHN who underwent IC with taxanes, cisplatin, and fluorouracil were recruited. Staging procedures included loco-regional and chest imaging, endoscopic examination, and PET/CT scan. On day 14 of the first cycle, a second PET/CT scan was performed. Patients with no early increase in regional lymph node maximum 18F-FDG standard uptake value (SUV), detected using 18F-FDG PET/CT after first IC had better progression-free survival (hazard ratio (HR) = 0.18, 95%, confidence interval (CI) 0.056–0.585; p = 0.004) and overall survival (HR = 0.14, 95% CI 0.040–0.498; p = 0.002), and were considered responders. In this subgroup, patients who achieved a reduction of ≥ 45% maximum primary tumor SUV experienced improved progression-free (HR = 0.23, 95% CI 0.062–0.854; p = 0.028) and overall (HR = 0.11, 95% CI 0.013–0.96; p = 0.046) survival.ConclusionsThese results suggest a potential role for early response evaluation with PET/CT examination in patients with LASCCHN undergoing IC. Increased regional lymph node maximum SUV and insufficient decrease in primary tumor uptake predict poorer outcomes.

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