Rapid advances in cancer genetics and genomics, pathophysiology, diagnostics, and therapeutics have substantially increased the complexity of clinical oncology. Integrating large and diverse data streams into timely, patient-specific decisions provides a compelling rationale for incorporating artificial intelligence (AI) into cancer care. Generative artificial intelligence (GenAI) encompasses several classes of models capable of generating new content. This clinically focused review concentrates on GenAI applications based primarily on large language models (LLMs) and vision-language models (VLMs), as well as emerging agentic systems that use these models to perform coordinated, multistep tasks. LLMs demonstrate substantial medical knowledge, strong performance on oncology-related assessments, and emerging capabilities in clinical reasoning. Guideline- and retrieval-augmented systems can improve concordance with expert recommendations and interpretation of complex treatment algorithms. LLMs and VLMs have been applied to documentation, patient communication, information extraction and summarization, clinical decision support, and multimodal data synthesis. However, performance varies substantially across tasks and clinical domains, with important limitations including incomplete or outdated information, training-data bias, automation bias, and confabulation. Agentic AI represents an emerging extension of these technologies in which LLMs or VLMs are incorporated into systems capable of multistep planning, external information retrieval, specialized tool use, and iterative evaluation and refinement. Early oncology applications include evidence synthesis, multimodal clinical decision support, radiology, pathology, surgery, and individualized treatment planning. With rigorous validation, transparent implementation, continual updating, and appropriate expert oversight, GenAI may augment oncologists' judgment, improve patient understanding and experience, streamline cancer care delivery, and advance personalized oncology.

The BRCA1 and BRCA2 tumor suppressor genes are integral to the repair of DNA double-strand breaks. Therefore, germline pathogenic variants (PVs) in either of these genes are associated with an increased risk of developing hereditary cancers. For over 30 years, studies have demonstrated a well established and markedly increased lifetime risk of female breast cancer and ovarian cancer for individuals with a PV in BRCA1 or BRCA2. Additional canonical cancers include prostate cancer, pancreatic cancer for males and females, and male breast cancer. Several noncanonical cancers have also been reported in association with BRCA1 or BRCA2, including stomach cancer and endometrial cancer. This review summarizes the established and evolving cancer risks associated with germline PVs in BRCA1 or BRCA2 as well as current clinical management recommendations. With increased uptake and diversified utility of germline genetic testing, this summary provides a current overview for clinical management of both male and female individuals with a PV in BRCA1 or BRCA2.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by abnormal accumulation of surfactant within the alveoli, leading to impaired gas exchange and progressive respiratory symptoms. We report a 40-year-old stone grinder presenting with chronic cough, dyspnea, weight loss and hypoxemia. High-resolution computed tomography showed bilateral ground-glass opacities, while bronchoalveolar lavage (BAL) yielded characteristic milky fluid. Cytological examination demonstrated PAS-positive eosinophilic material with foamy macrophages, confirming secondary PAP related to silica exposure. Lung biopsy was not feasible because of the patient's condition. Whole lung lavage resulted in marked clinical, radiological and oxygenation improvement, highlighting BAL cytology's diagnostic value.

Perivascular epithelioid cell tumours (PEComas) are rare mesenchymal neoplasms with characteristic myomelanocytic differentiation and limited descriptions in fine-needle aspiration (FNA) specimens. A woman in her 30s with a history of ALK-positive anaplastic large cell lymphoma in remission was found to have a 2.1-cm hepatic mass during evaluation of persistent liver function abnormalities. Ultrasound-guided FNA demonstrated a cellular neoplasm composed of loosely cohesive clusters and singly dispersed epithelioid to spindle cells with abundant eosinophilic cytoplasm, mild to moderate nuclear atypia and prominent nucleoli. Immunohistochemical studies showed positivity for smooth muscle actin, caldesmon, HMB-45 and Melan-A, supporting a myomelanocytic phenotype. Molecular testing identified pathogenic TSC2 splice-site mutations. Subsequent resection confirmed hepatic PEComa, epithelioid angiomyolipoma variant. This case highlights the characteristic cytomorphologic, immunophenotypic and molecular features of hepatic PEComa and demonstrates the value of FNA with ancillary testing in establishing a preoperative diagnosis and excluding morphologic mimics.

Proton therapy offers a distinct physical advantage over photon radiotherapy through the Bragg peak dose concentration in target with both lower integral dose and finite path length, and sharper penumbra as compared to photons, collectively reducing radiation exposure to surrounding normal tissues and potentially improving the therapeutic ratio. However, this advantage is tempered by uncertainties, including range uncertainty and variable relative biological effectiveness. In this review, the authors summarize contemporary evidence supporting proton therapy across pediatric, central nervous system (CNS), head and neck, thoracic, breast, gastrointestinal, genitourinary, and hematologic malignancies, as well as reirradiation. The strength of evidence varies substantially by disease site. Proton therapy is well established in pediatric cancers and selected CNS tumors, where minimizing integral dose and late toxicity is especially important. Randomized trials have demonstrated clinically meaningful benefits in selected settings, including improved disease control and survival with proton craniospinal irradiation for leptomeningeal metastases and reduced toxicity with preserved disease control and survival benefit in oropharyngeal cancer. Conversely, randomized data in localized prostate cancer have not shown improved patient reported outcomes compared with intensity modulated photon therapy. Ongoing phase 3 trials across multiple disease sites are expected to further define the role of protons by clarifying comparative effectiveness, toxicity reduction, and cost-effectiveness relative to advanced photon techniques. Future progress will depend on improved patient selection, robust treatment planning, and emerging technologies including adaptive proton therapy, proton arc therapy, and FLASH radiotherapy.