Oncocytic Thyroid Tumours With Pathogenic FLCN Mutations Mimic Oncocytic Papillary Thyroid Carcinoma on Fine-Needle Aspiration.

Background: Thyroid tumours occur in patients with Birt-Hogg-Dubé syndrome (BHD), a condition caused by germline alterations in the FLCN gene that confers an increased cancer risk. Somatic FLCN mutations may also contribute to tumorigenesis. In this study, we present the first description of the cytopathology of two thyroid tumours evaluated by fine-needle aspiration (FNA) and harbouring pathogenic FLCN mutations.

mTORC1-Dependent Regulation of the CCL24-CCR3 Axis Controls Granuloma Formation and Maintenance in Sarcoidosis.

Sarcoidosis is a chronic granulomatous disease marked by persistent inflammation and immune cell aggregation, yet its molecular underpinnings remain incompletely understood, hindering the development of effective targeted therapies. Here, we report that deletion of TSC1 or TSC2 in mice using a Fsp1-Cre leads to spontaneous formation of sarcoid-like granulomas, driven by hyperactivation of the mTORC1 pathway in fibroblasts and interstitial macrophages. Through inflammatory cytokine/chemokine array, we identified CCL24, a chemokine ligand for CCR3, as a key immunoregulatory molecule downregulated in both our murine model and sarcoid cohort plasma.

Rag GTPases Suppress Renal Cystic Disease by Inhibiting TFEB Independently of mTORC1.

Aberrant mTORC1 activation in renal tubular epithelial cells (rTECs) is implicated as a critical driver of renal cystic diseases (RCDs), including autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis (TSC), yet its precise role remains unclear. Rag GTPases recruit mTORC1 to lysosomes, its intracellular activation site. Unexpectedly, we found that deleting in rTECs, despite inhibiting mTORC1, triggers renal cystogenesis and kidney failure.

Diagnostic challenges in urinary cytology: Practical insights from The Paris System for Reporting Urinary Cytology.

Urinary cytology is an important tool for diagnosing high-grade urothelial carcinoma (HGUC) and plays a vital role in monitoring for disease recurrence. However, its diagnostic utility is often complicated by interpretive challenges, particularly when degenerative artifacts, sparse cellularity, or reactive atypia obscure key cytologic features. The Paris System for Reporting Urinary Cytology has significantly enhanced diagnostic reproducibility by establishing standardized criteria for the diagnosis of HGUC, but misclassification remains a risk, especially when evaluating subtle atypia, tissue fragments, or confounding factors like degenerative changes.

PLK1-mediated PDHA1 phosphorylation drives mitochondrial dysfunction, mitophagy, and cancer progression in Cr(VI)-associated lung cancer.

Hexavalent chromium (Cr(VI)) is a class I environmental carcinogen that induces lung epithelial cell transformation and promotes lung cancer progression by altering cell cycle regulation and cellular energy metabolism. In this study, we investigated the role of polo-like kinase 1 (PLK1) in Cr(VI)-transformed (CrT) bronchial epithelial cells (BEAS-2B) and found that PLK1 expression was significantly upregulated in these cells, leading to impaired mitochondrial function and enhanced mitophagy, which in turn stimulated cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that PLK1 directly phosphorylates the pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) at Thr57, leading to its destabilization and disruption of pyruvate dehydrogenase complex (PDHc) integrity.

RSK1-driven TRIM28/E2F1 feedback loop promotes castration-resistant prostate cancer progression.

Castration-resistant prostate cancer (CRPC) marks the advanced and lethal stage of prostate cancer (PCa). TRIM28, also known as KAP1, is a transcriptional regulator recently shown to promote CRPC cell proliferation and xenograft tumor growth. Nonetheless, knowledge gaps persist regarding the mechanisms underlying TRIM28 upregulation in CRPC as well as the genomic targets regulated by TRIM28.

PLK1-mediated phosphorylation of PHGDH reprograms serine metabolism in advanced prostate cancer.

Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet their increased biosynthetic and energetic demands. While cells possess the capacity for de novo serine biosynthesis, most transformed cancer cells heavily depend on exogenous serine uptake to sustain their growth, yet the regulatory mechanisms driving this metabolic dependency remain poorly understood. Here, we uncover a novel mechanism by which Polo-like kinase 1 (PLK1), often overexpressed in prostate cancer, orchestrates a metabolic shift in serine and lipid metabolism through the phosphorylation of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme of the serine synthesis pathway (SSP).

Left Recurrent Laryngeal Nerve Vocal Fold Paralysis in Pediatric Patient Secondary to Mediastinal Histoplasmosis Infection.

is a dimorphic soil-based fungus endemic to the Ohio and Mississippi River valleys and southeastern United States. An extremely rare presentation is the involvement of the mediastinum leading to vocal fold paralysis, with only 2 reported cases in the literature. This report presents the youngest patient to whom this pathology has been described and the third overall patient.

Presence of an Artificial Intelligence-powered Predictive Biomarker Is Associated with a Poor Response to Intravesical Bacillus Calmette-Guerin but Not to Intravesical Sequential Gemcitabine/Docetaxel in Patients with High-grade Non-muscle-invasive Bladder Cancer.

Intravesical bacillus Calmette-Guerin (BCG) is considered first-line adjuvant therapy for high-risk or high-grade non-muscle-invasive bladder cancer (NMIBC). Recently, sequential intravesical gemcitabine and docetaxel (Gem/Doce) has emerged as a promising alternative to intravesical BCG. Biomarkers to select the optimal treatment regimen could facilitate clinical decision-making.

() in Thyroid Tumors: Incidence, Significance, and Role as a Driver Gene and Secondary Alteration.

Thyroid carcinomas are driven by diverse molecular alterations, but the tumor suppressor gene folliculin (), best known for its role in Birt-Hogg-Dubé (BHD) syndrome, has received limited attention in thyroid tumors. Here, we describe two thyroid tumors with pathogenic alterations-one germline and one somatic-and analyze the broader prevalence and significance of in thyroid carcinomas using multiple large sequencing datasets, including ORIEN-AVATAR. Patient 1, with a germline mutation and a history of BHD syndrome, presented with a well-circumscribed oncocytic adenoma.

Glycogen drives tumour initiation and progression in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is an aggressive cancer defined by oncogenic drivers and metabolic reprogramming. Here we leverage next-generation spatial screens to identify glycogen as a critical and previously underexplored oncogenic metabolite. High-throughput spatial analysis of human LUAD samples revealed that glycogen accumulation correlates with increased tumour grade and poor survival.

GDP-mannose 4,6-dehydratase is a key driver of MYCN-amplified neuroblastoma core fucosylation and tumorigenesis.

MYCN-amplification is a genetic hallmark of ~40% of high-risk neuroblastomas (NBs). Altered glycosylation is a common feature of adult cancer progression, but little is known about how genetic signatures such as MYCN-amplification alter glycosylation profiles. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased core fucosylated glycan abundance within neuroblast-rich regions of human MYCN-amplified NB tumors.

Metformin in overcoming enzalutamide resistance in castration-resistant prostate cancer.

Androgen deprivation is the standard treatment for patients with prostate cancer. However, the disease eventually progresses as castration-resistant prostate cancer (CRPC). Enzalutamide, an androgen receptor inhibitor, is a typical drug for treating CRPC and with continuous reliance on the drug, can lead to enzalutamide resistance.

Precision Medicine in Cytopathology.

Over the last decade, cancer diagnostics has undergone a notable transformation with increasing complexity. Minimally invasive diagnostic tests, driven by advanced imaging and early detection protocols, are redefining patient care and reducing the need for more invasive procedures. Modern cytopathologists now safeguard patient samples for vital biomarker and molecular testing.

Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis.

Bromodomain-containing protein 4 (BRD4) has emerged as a promising therapeutic target in prostate cancer (PCa). Understanding the mechanisms of BRD4 stability could enhance the clinical response to BRD4-targeted therapy. In this study, we report that BRD4 protein levels are significantly decreased during mitosis in a PLK1-dependent manner.

Single-cell analysis identifies PLK1 as a driver of immunosuppressive tumor microenvironment in LUAD.

PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete.

Concurrent loss of LKB1 and KEAP1 enhances SHMT-mediated antioxidant defence in KRAS-mutant lung cancer.

Non-small-cell lung cancer (NSCLC) with concurrent mutations in KRAS and the tumour suppressor LKB1 (KL NSCLC) is refractory to most therapies and has one of the worst predicted outcomes. Here we describe a KL-induced metabolic vulnerability associated with serine-glycine-one-carbon (SGOC) metabolism. Using RNA-seq and metabolomics data from human NSCLC, we uncovered that LKB1 loss enhanced SGOC metabolism via serine hydroxymethyltransferase (SHMT).

Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection.

Unlabelled: Nontuberculous mycobacteria (NTM) are environmentally ubiquitous organisms that predominately cause NTM pulmonary disease (NTMPD) in individuals over the age of 65. The incidence of NTMPD has increased in the U.S.

An isolated sacral promyelocytic sarcoma in a child: A rare case report with emphasis on cytomorphology.

Myeloid sarcoma (MS) is an uncommon localized extramedullary tumor composed of immature myeloid precursor cells that can affect any organ. Promyelocytic sarcoma (PS), an extremely rare subtype of MS, is characterized by immature myeloid cells with features of acute promyelocytic leukemia (APL). We describe a case of pediatric PS that presented as a solitary sacral mass without any evidence of systemic or bone marrow involvement.

Case report: Enfortumab vedotin induced refractory DKA and multi organ failure - a rare fatal adverse event.

There are very few therapeutic options to treat patients with locally advanced or metastatic Urothelial Cancer (UC). Enfortumab vedotin (EV) was recently approved by the FDA and has become a new therapeutic option for patients previously managed with conventional treatments. Despite its efficacy, EV carries the potential for infrequent yet severe adverse effects.

TRPS1 expression in primary and metastatic prostatic adenocarcinoma, muscle invasive bladder urothelial carcinoma, and breast carcinoma: Is TRPS1 truly specific and sensitive for a breast primary?

Trichorhinophalangeal syndrome type 1 (TRPS1) has been reported to be a sensitive and specific immunohistochemical (IHC) marker for breast carcinomas, especially when determining primary site of origin. However, there is limited data on TRPS1 expression in prostate and bladder cancers. A two-phase study was performed with 1) an exploratory cohort analyzing TRPS1 gene alterations in prostate, bladder, and breast carcinoma and TPRS1 mRNA expression data in prostate and bladder carcinoma; and 2) TRPS1 and GATA3 IHC in a confirmatory cohort in prostate, bladder, and breast carcinoma samples.

Phosphorylation of AHR by PLK1 promotes metastasis of LUAD via DIO2-TH signaling.

Metastasis of lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR), an important transcription factor, is involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, acts as an oncogene promoting the malignancy of multiple cancer types.

Urinary tract cytology showing variant morphology and divergent differentiation.

Urothelial carcinoma represents a diverse group of tumours with distinct histologic subtypes, each exhibiting unique cytomorphologic features, architectural growth patterns, and/or well-developed aberrant differentiation. In fact, there are more than 13 subtypes of urothelial carcinoma recognized in the 2022 WHO classification of tumours in the urinary tract. The identification of these subtypes is crucial for an accurate diagnosis of urothelial carcinoma, and many have important clinical implications.

Locally advanced solitary fibrous tumour of the prostate.

Solitary fibrous tumours (SFTs) are rare mesenchymal neoplasms composed of spindle cells, most often occurring in the pleura. SFTs arising from the prostate are exceptionally rare, with only around 40 cases reported in literature to date. We report a man in his 60s who was referred to our clinic for elevated prostate-specific antigen and presented with mild obstructive lower urinary tract and defecatory symptoms.

Primary mediastinal seminoma presenting with paraneoplastic anti-Hu encephalitis: a case report and literature review.

Primary mediastinal seminomas are exceedingly rare tumors, often localized to the anterior mediastinum. They may present with numerous complications, including superior vena cava syndrome, chylothorax, and pericardial effusions. Less commonly, they may present with paraneoplastic encephalitis.