Poly(ADP-ribose) polymerase inhibitors (PARPis) have demonstrated remarkable efficacy in tumors carrying BRCA1/2 pathogenic variants (PVs) through the mechanism of synthetic lethality. PVs in other homologous recombination (HR) genes may also impair homologous recombination repair and confer sensitivity to PARPis; however, their predictive value remains uncertain and appears to vary according to the affected gene and tumor type. We review and critically discuss the current evidence regarding the predictive value of non-BRCA HR gene pathogenic variants as biomarkers of PARPi sensitivity across ovarian, breast, prostate, and pancreatic cancers. A narrative review was conducted between October 2023 and December 2025, first identifying pivotal clinical trials of PARP inhibitors across ovarian, breast, prostate, and pancreatic cancers, followed by a targeted search of PubMed, Embase, Web of Science, and Google Scholar for relevant preclinical and clinical studies. Seventeen clinical studies and multiple preclinical reports were analyzed regarding genomic frequency, HRD association, and treatment response. Preclinical studies consistently demonstrated increased PARPi sensitivity in models with alterations in several non-BRCA HR genes. Clinical evidence, however, was heterogeneous. PALB2 demonstrated the strongest and most consistent association with PARPi benefit across tumor types, while RAD51C and RAD51D also showed clinically meaningful activity, particularly in ovarian cancer. In contrast, evidence supporting PARPi sensitivity in tumors harboring ATM, CHEK2, CDK12, and several other HR gene alterations remained limited or inconsistent. Differences in gene function, biallelic inactivation, variant type, and current limitations of HRD companion diagnostic assays likely contribute to the observed variability in clinical response. Non-BRCA HR gene alterations represent promising predictive biomarkers for PARPi therapy but should not be considered a homogeneous group. Future biomarker-driven studies integrating comprehensive genomic profiling and functional assessment of homologous recombination deficiency are needed to refine patient selection and optimize the clinical application of PARPis beyond BRCA1/2-associated cancers.

A COVID-19 é a doença infecciosa cujo agente etiológico é um betacoronavirus, o SARS-CoV-2. Sua emergência se deu em uma província chinesa em dezembro de 2019, tornando-se uma pandemia que desafia a saúde pública global. Habitualmente, apresenta-se como uma síndrome gripal, com possibilidade de evolução para síndrome respiratória aguda grave. Além disso, pode provocar alterações na coagulação e resposta inflamatória do indivíduo, levando a complicações tromboembólicas. Este artigo relata o caso de um paciente de 58 anos, diagnosticado com COVID-19, que seguia em isolamento domiciliar e, evoluiu com dispneia e hemoptise no quarto dia de doença. O diagnóstico do tromboembolismo pulmonar (TEP) foi confirmado através de tomografia contrastada de tórax. O paciente foi internado para tratamento clínico, necessitando de acompanhamento em Unidade de Terapia Intensiva (UTI) entre o terceiro e quinto dia de internação. Após alta da UTI, o paciente evoluiu sem demais intercorrências, recebendo alta no décimo dia de internação hospitalar.

Lymphomatoid granulomatosis (LG) is a rare B-cell lymphoproliferative disease associated with Epstein-Barr virus (EBV). Characteristic for this disease is angiocentric and angiodestructive lymphoid infiltration with atypical EBV-positive В-cells, among which the reactive T lymphocytes predominate, often necrosis is identified. LG is mainly diagnosed in middle and old age, more often in immunocompromised subjects. Morphological grading depends on the proportion of EBV-positive В lymphocytes with different grades of atypia and coagulative necrosis severity. In most cases, lung tissue lesions are identified, other extranodal areas of involvement include CNS, kidney, liver, and skin. The clinical course of LG varies from indolent to aggressive. With a low-grade disease, spontaneous regression is possible, whereas Grade 3 requires treatment and differential diagnosis with diffuse large B-cell lymphoma. This paper reports a case of a 85-year-old prostate cancer patient with LG Grade 3 and lung tissue involvement. As the patient was free of any clinical manifestations, surveillance approach seemed to be reasonable. A series of control CT scans showed a gradual reduction of tumor mass in the left lung with its complete spontaneous regression in 14 months. This case highlights the potential for a favorable outcome of LG Grade 3 without special therapy. This is particularly relevant for elderly patients with various comorbidities.

Secretory carcinoma of the lung is an exceptionally rare salivary gland-type malignancy, typically associated with NTRK fusions. We report a 71-year-old woman with pulmonary stage IIIA adenocarcinoma having salivary gland differentiation and solid-cribriform architecture, confirmed by S100 and Pan-TRK immunohistochemistry. Broad DNA and RNA next-generation sequencing identified an EML4-NTRK3 fusion. After adjuvant chemotherapy, maintenance larotrectinib was initiated based on proven TRK inhibitor efficacy in metastatic NTRK-fusion tumors and emerging evidence for targeted therapy benefit in driver-positive early stage lung adenocarcinoma. Our findings demonstrate the value of molecular pathology in the diagnostic journey of pulmonary malignancies, guiding rare fusion detection and supporting therapeutic decisions based on rare fusions in early stage disease.

A embolia pulmonar (EP) tardia na COVID-19 é aquela que ocorre semanas após a infecção pelo SARS-CoV-2 e vem sendo relatada mesmo nos pacientes que manifestaram síndrome gripal leve. Não há explicação fiável para sua ocorrência, mas parece envolver persistência das alterações inflamatórias virais associadas à exposição de fosfolipídios e liberação de micropartículas de membrana potencialmente trombogênicas. A trombólise com ativadores de plasminogênio, principalmente a alteplase, é bem estabelecida nos casos de EP de alto risco e considerada nos eventos de intermediário alto risco, com benefícios como reperfusão pulmonar, redução de pressão da artéria pulmonar e estabilidade do ventrículo direito (VD). Entretanto, há poucos casos relatados de trombólise na EP secundária a COVID-19. Apresentamos o caso de uma paciente feminina adulta, sem fatores de risco significativos para eventos trombogênicos diagnosticada com COVID-19 leve que no 18º dia após o início dos sintomas evoluiu com EP associada à instabilidade de VD e foi submetida à trombólise com alteplase intravenosa com sucesso.

The germline landscape of hereditary breast cancer has been characterized predominantly in populations of European ancestry, with limited evidence from populations with different demographic histories. We investigated germline diversity and genotype–phenotype associations in a single-center ambispective cohort at a tertiary referral cancer center in Brazil. Among 10,098 individuals who underwent germline genetic testing, 503 adults with invasive or microinvasive breast cancer met the predefined eligibility criteria and carried 514 pathogenic or likely pathogenic germline variants. Analyses assessed gene distribution, recurrent and founder variants, ecological diversity metrics, and associations with clinicopathological characteristics and survival outcomes. BRCA1 (31.6%) and BRCA2 (21.7%) were the most frequently altered susceptibility genes, followed by TP53 (13.1%), including the Brazilian founder variant TP53 p.R337H (10.7%). Diversity analyses indicated substantial heterogeneity beyond BRCA1/2. In exploratory unadjusted analyses, BRCA1-associated tumors more frequently exhibited triple-negative phenotype, high histological and nuclear grade, elevated Ki-67, and increased tumor-infiltrating lymphocytes, whereas tumors associated with BRCA2, ATM, CHEK2, and mismatch repair genes more frequently exhibited luminal phenotypes. Recurrent variants included alleles previously reported in different geographic and population contexts. Exploratory survival analyses detected no statistically significant differences among genetic groups within a five-year analytical horizon. These findings describe a heterogeneous germline spectrum and exploratory genotype–phenotype associations in a Brazilian cohort. Heterogeneous genetic testing coverage and the absence of individual genomic ancestry assessment limit interpretation; the findings should not be considered ancestry-specific or nationally representative. Further studies with uniform genetic testing and genomic ancestry assessment are warranted in broader Brazilian and Latin American cohorts.