Endocrine gland tumors are characterized by a wide spectrum of pathologic, clinical, and molecular features. Next-generation sequencing technologies have greatly improved our knowledge of this group of neoplasms, showing robust genotype-phenotype correlation. This review summarizes the main molecular changes found in endocrine gland tumors, highlighting the interplay between tumor-specific somatic or germline genetic changes, pathology, and clinical features. The aim of the article is to provide essential information about the role of molecular pathology in defining diagnosis, prognosis, and identification of biomarkers for molecular targeted therapy.

In this article, the authors review the types of molecular alterations present in cancer and molecular methods used commonly in clinical diagnostic laboratories, including technologies such as next-generation sequencing and digital polymerase chain reaction. Additionally, the authors discuss considerations for test design, incorporating factors such as specimen type and biomarker type, to design a molecular test menu that delivers accurate and timely results in an efficient and cost-effective manner.

To carry out clinical and genetic analysis for a fetus with absent kidneys and bladder.

Clinical data of the fetus were collected. Whole exome sequencing (WES) and Sanger sequencing were carried out on fetal tissue and peripheral blood samples from its family members. A RDDC online tool was used to predict the impact of the variant on the GREB1L gene splicing, which was further validated by in vitro minigene assays. Long-range PCR was employed to verify the exonic deletional variant. An I-TASSER server was used to predict the three-dimensional structure of the mutant protein. A systematic search of Chinese and English databases was conducted using "GREB1L gene" as the keyword to summarize the clinical phenotypic spectrum associated with GREB1L gene mutations. This study was approved by the Medical Ethics Committee of the Pearl River Hospital of South Medical University (Ethics No.: 2023-KY-016).

The fetus was confirmed to have bilateral renal agenesis by autopsy. WES and Sanger sequencing revealed that the fetus, its father and grandfather have all carried a heterozygous c.4369-3_4375del variant of the GREB1L gene (NM_001142966.3), whilst its mother and grandmother did not carry the same variant. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was rated as "pathogenic". As predicted by bioinformatics analysis and confirmed by the minigene assay, this deletional variant may lead to aberrant splicing of exon 26 and result in alteration in the protein's three-dimensional structure. Literature review indicated that GREB1L gene mutations mainly cause renal dysplasia with significant clinical heterogeneity.

The heterozygous c.4369-3_4375del variant of the GREB1L gene probably underlay the pathogenesis of renal dysplasia/hypoplasia in this fetus. Discovery of this novel splicing site variant has enriched the mutational spectrum of the GREB1L gene and provided a basis for clinical diagnosis and genetic counseling.

Diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping is widely available on modern magnetic resonance imaging platforms and is increasingly embedded in head and neck oncological pathways. The technique can refine lesion characterisation, support nodal assessment, and strengthen post-treatment surveillance when it is applied to specific clinical questions. In this narrative review, we synthesise practical applications of DWI/ADC across major head and neck malignancies, including lymphoma, squamous cell carcinoma (SCC), sinonasal tumours, and salivary gland neoplasms, with emphasis on common diagnostic pitfalls and the limits of cross-study threshold transferability. We also summarise evidence relevant to treatment monitoring, adaptive radiotherapy strategies, and the technical repeatability needed for longitudinal ADC interpretation. Across the literature, markedly low ADC values favour lymphoma, whereas substantial overlap constrains benign-malignant separation in salivary and sinonasal lesions. In the post-treatment setting, meta-analytic evidence supports lower ADC values in recurrent disease than in treatment-related change, with a commonly cited recurrence threshold near 1.10 x 10-3 mm2/s. Overall, DWI is best treated as a probability-modifying biomarker that complements morphology, endoscopy, pathology, and clinical trajectory rather than replacing them.

The premetastatic niche is a specialized microenvironment established by tumor cells prior to the formation of metastatic foci in distant organs. This niche provides an optimal landing site for circulating tumor cells. As key mediators of intercellular communication, exosomes play a pivotal role in shaping the premetastatic niche. This review analyzes the effects of exosomes on premetastatic niche formation from multiple perspectives, including angiogenesis, metabolic reprogramming, matrix remodeling, immune response, organicity, and epithelial-mesenchymal transition (EMT). Their value in tumor diagnosis, prognosis, and treatment, as well as the challenges and opportunities for future clinical transformation are discussed. This article presents a narrative review conducted in accordance with the SANRA guidelines.

NTRK gene fusions are oncogenic drivers for a variety of adult and pediatric tumors, making them a target for tumor-agnostic precision medicine. Tropomyosin receptor kinase (TRK) inhibitors are approved by the US Food and Drug Administration for cancers driven by TRK fusions. However, NTRK genes can fuse with many different partner genes, leading to diverse TRK fusion proteins, highlighting the importance of identifying the specific fusion partner with optimal pan-cancer diagnostics. This analysis aims to provide an updated descriptive compendium of NTRK gene fusions.

NTRK gene fusions were identified via literature searches (PubMed), a search of a clinical trials database (larotrectinib), and searches of two genomic databases (Memorial Sloan Kettering and Children's Hospital of Philadelphia).

In total, 358 distinct NTRK gene fusion-tumor pairings were identified across 25 tumor types. Primary CNS tumors were observed to harbor 86 distinct NTRK gene fusions, followed by sarcomas (n = 73). Overall, 229 different fusion partners were identified across tumor types (regardless of NTRK gene). Twenty-three fusion partners were found to fuse with >1 NTRK gene across tumor types, while 183 fusion partners were associated with only a single NTRK gene in one tumor type. ETV6::NTRK3 was found in the highest number of different tumor types.

This analysis illustrates the diversity of NTRK gene fusion partners across various tumor types and highlights the importance of selecting a pan-tumor fusion-partner agnostic test that can identify both known and novel fusion partners to identify patients who may benefit from treatment with TRK inhibitors.

Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection has become a strong prognostic stratification factor in postoperation non-small cell lung cancer (NSCLC). Here, we sought to investigate the guiding potential of MRD in informing adjuvant therapy (AT) decisions.

Patients with stage IA to IIIB NSCLC who had undergone confirmed R0 resection were enrolled. Blood samples were collected 1 month after surgery before initiation of AT (landmark) and longitudinally every 3-6 months since surgery. Postoperative AT was conducted according to the guideline recommendations, and regular radiographical examinations were recommended for relapse surveillance. MRD detection was conducted using the MinerVa platform (Genecast Precision Diagnostic Co., Ltd. Wuhan, China) using a tumor-informed strategy based on a fixed next-generation sequencing panel spanning 769 cancer-related genes.

One hundred sixty-five patients were included in this study, with 35 (21.2%) relapses. At landmark, positive MRD was associated with shorter disease-free survival (DFS) than negative MRD (P < .001, hazard ratio, 12.0). MRD was an independent risk factor for shorter DFS, irrespective of the disease stage and high-risk factors. In the case of negative landmark MRD, there was no significant difference between the DFS of (1) those who received AT and those who did not in stage IB patients with high-risk factors (P = .974), (2) epidermal growth factor receptor (EGFR)-mutant patients with or without adjuvant chemotherapy before adjuvant targeted therapy (P = .502), and (3) EGFR/ALK wild-type with or without adjuvant immunotherapy (P = .534). Clearance of ctDNA during AT was associated with a better prognosis than persistently detected ctDNA (P < .001).

ctDNA-based MRD stratifies prognosis after curative resection in NSCLC, with MRD negativity indicating limited benefit from treatment in selected patients and ctDNA clearance reflecting improved outcomes. These findings support the clinical utility of MRD-guided adjuvant treatment strategies.

Clinical genomic profiling of tumors identifies therapeutic targets, while germline pharmacogenomics (PGx) guides drug dosing and toxicity avoidance. However, the combined clinical landscape of both somatic and germline actionable variants across cancers has not been comprehensively defined.

Tumor and matched germline whole-exome sequencing data were analyzed for 10,302 patients in The Cancer Genome Atlas. Somatic mutations with therapeutic relevance were mapped to US Food and Drug Administration (FDA)-approved targeted drugs using the Oncology Knowledge Base database (levels 1-4). Germline PGx variants were identified using PyPGx and cross-referenced with drug-gene interactions in PharmGKB (levels of clinical annotation 1-2). This enabled construction of an integrated germline-somatic PGx profile per patient.

All 10,302 patients (100%) harbored at least one actionable germline PGx variant (median = 3; range = 1-9), including 7,520 (73%) with variants relevant to chemotherapy toxicity or supportive care medications (DPYD, UGT1A1, CYP2C9, and CYP2C19). Somatic profiling revealed 4,312 patients (42%) with at least one actionable mutation matched to an FDA-approved targeted therapy (eg, PIK3CA, KRAS). Across the cohort, 5,275 (51%) patients had more actionable germline variants than somatic mutations, whereas 1,988 (19%) had more actionable somatic mutations.

Integrating germline PGx with somatic profiling reveals that actionable germline variants are nearly universal among patients with cancer in our cohort, extending beyond tumor-specific therapy to encompass toxicity and supportive care management. Routine implementation of combined germline and somatic sequencing in oncology could enhance therapeutic precision, minimize adverse effects, and inform individualized treatment decisions.

Breast cancer (BC) is the most frequent neoplasm. As a consequence of the oncologic treatment, there are diverse adverse effects, as the emotional ones. Treatment options for emotional symptoms like anxiety, depression or stress are limited.

To analyze the effectiveness of psychoeducational workshops among women with BC over the anxiety and depression symptoms.

A randomized clinical trial by blocks with 42 BC patients in stages II and III of the disease, distributed into 2 groups of 21 cases (intervention) and 21 controls. There were 9 psychoeducational workshops performed weekly. It was carried out an initial and final measurement according to the Hospital Anxiety and Depression Scale (HADS).

For the intervention group, the median score for anxiety was 9.09 at the beginning of the study and 5.85 at the end (p = 0.0005). In the control group, the median for anxiety was 8.7 and 6.7 at the end (p = 0.0494). According to the depression symptoms, the median for the intervention group was 5 at the beginning and 3.2 at the end (p = 0.0216). For the control group, the median was 4.7 at the beginning and 4.6 at the end (p = 0.6359).

The psychoeducational workshops demonstrated effectiveness to decrease the symptom burden for anxiety and depression. Early education and counselling for recently diagnosed BC patients should be considered part of the treatment to prevent and decrease these symptoms.

Uncontrolled proliferation is not the only factor driving tumor growth; the tumor microenvironment (TME) has a significant impact. Tissue homeostasis and pathogen removal depend on macrophages, which are important innate immune effector cells. Nevertheless, there is growing evidence that tumor-associated macrophages (TAMs) do not consistently suppress cancer and are functionally diverse. Specifically, M2-polarized TAMs (M2-TAMs) build up in multiple solid tumors, where they promote angiogenesis, metastasis, and immunosuppression, hastening the course of the disease. Here, we critically assess the clinical translatability of TAM-targeted treatment approaches, outline the molecular circuits underpinning M2-TAMs-tumor cell interaction, and extensively explore the phenotypic spectrum and functional diversity of macrophages in cancer. Our objective is to offer a theoretical foundation for upcoming immunotherapeutic interventions.