Sebaceous carcinoma (SC) is a malignant neoplasm arising from the sebaceous glands. Its periocular location, originating from the meibomian or Zeis glands, can clinically mimic benign lesions such as chalazion or chronic blepharitis, which may delay diagnosis. We present a case of an elderly male patient with a history of nodular basal cell carcinoma, type 2 diabetes mellitus, and systemic arterial hypertension, who presented to the dermatology clinic with an asymmetric neoformation on the right lower eyelid, reddish in color with whitish-yellow areas and ulceration with a hematic crust. Dermoscopy showed polymorphic vessels and structureless yellowish areas. Histopathological examination revealed a malignant epithelial tumor with clear-cytoplasm cells, pleomorphic nuclei, and focal necrosis, with sebaceous differentiation confirmed by immunohistochemistry positive for epithelial membrane antigen (EMA). Surgical resection with a wide safety margin and reconstruction using a Mustardé flap were performed, achieving tumor-free histological margins. Clinical and imaging follow-up showed no evidence of recurrence or metastasis. In this patient, wide local excision with complete histopathological evaluation confirmed complete removal of the lesion with clear surgical margins, with no evidence of recurrence during follow-up.

Advanced cutaneous malignancies with basaloid morphology can present diagnostic and therapeutic challenges, particularly when pathological interpretations differ and disease progresses during systemic treatment. We describe the clinical course of a 53-year-old woman with an extensive, unresectable cutaneous tumor involving the posterior neck and occipital region, accompanied by bilateral cervical lymphadenopathy and additional clinically suspected cutaneous deposits. The initial diagnosis was trichoblastic carcinoma, whereas expert pathological review favored basal cell carcinoma. The extent of disease precluded surgery and definitive radiotherapy. First-line vismodegib was initiated, and palliative radiotherapy delivering 30 Gy in 10 fractions to the occipital lesions and bilateral cervical lymph nodes was completed one year later. Clinical progression was documented three months after completion of radiotherapy; one month after this, MRI demonstrated extensive infiltration involving the left parotid gland and adjacent pharyngeal spaces. Second-line cisplatin and 5-fluorouracil were subsequently administered. Follow-up MRI six months after the earlier MRI demonstrated substantial tumor volume reduction. PET/CT three months later showed a heterogeneous response compared with a year earlier, including regression at several previously involved sites and newly apparent metabolically active right axillary lymph nodes. A subsequent biopsy was reported as basaloid carcinoma. The patient later experienced clinical deterioration, received one cycle of cemiplimab, and died before further treatment or response assessment. This case illustrates the importance of pathological clarification, longitudinal imaging, and careful interpretation of treatment response during sequential systemic therapy for advanced basal cell carcinoma.

Mild basal calcitonin elevation represents a diagnostic gray zone in patients undergoing thyroid surgery for non-medullary thyroid carcinoma (MTC) indications. We evaluated calcium-stimulated calcitonin and procalcitonin kinetics according to final histopathology and nodal status in this setting. This retrospective study included 37 adults with reproducible borderline basal calcitonin elevation (< 50 pg/mL) selected from 577 patients who underwent total thyroidectomy for non-MTC indications between 2021 and 2024. All patients underwent calcium stimulation testing with measurement of calcitonin and procalcitonin at baseline and after stimulation. Biochemical responses were compared with final histopathology. Median basal calcitonin was 13.1 [11.0-16.8] pg/mL and median peak stimulated calcitonin (psCT) was 480 [320-790] pg/mL. Final histopathology showed MTC in seven patients (18.9%), all microcarcinomas, C-cell hyperplasia (CCH) without MTC in nine, and no C-cell pathology in 21. Median psCT was highest in MTC, intermediate in CCH without MTC, and lower in patients without C-cell pathology (820 [640-1040], 460 [310-670], and 360 [270-540] pg/mL, respectively; nominal p = 0.047 for MTC vs CCH). psCT values ≥ 500 pg/mL were observed in 6 of 7 MTC cases compared with 1 of 9 CCH cases without MTC. Central lymph-node metastasis was documented in 3 of 7 MTC patients and was accompanied by numerically higher psCT and fold-rise values. wf45g6 Procalcitonin increment and fold-rise were greater in MTC than in CCH without MTC, but no stable procalcitonin-based threshold or combined rule was identified. Occult micro-MTC may show marked calcium-stimulated calcitonin responses despite mild basal hypercalcitoninemia. These findings are exploratory and do not validate diagnostic or surgical thresholds.

Ionizing radiation (IR) induces oxidative stress and lipid peroxidation with ferroptosis contributing to radiation-induced cancer cell death. Peroxiredoxin 6 (PRDX6), a multifunctional enzyme involved in phospholipid repair and redox regulation, has been implicated in ferroptosis regulation, but its role in the radiosensitivity of cancer cells remains unclear. Here, we show that PRDX6 depletion enhances radiosensitivity in A549 lung cancer cells. PRDX6-silenced A549 cells exhibited elevated lipid peroxidation and labile iron levels, indicating a ferroptosis-prone state that was amplified by radiation. To identify the underlying drivers of ferroptosis sensitivity in the PRDX6 background, we performed global proteomic profiling of PRDX6-silenced A549 cells, with and without radiation. Basal PRDX6-deficient cells displayed increased levels of ACSL4 and DHCR7. ACSL4 activates peroxidation-prone polyunsaturated fatty acids for incorporation into membrane phospholipids, and DHCR7 depletes the antiferroptotic moiety, 7-dehydrocholesterol. MPST, an antioxidant protein, was downregulated. These changes were accentuated upon IR exposure with further suppression of GINS4, a negative regulator of ferroptosis. Functional rescue by oleic acid suggested the role of ACSL4 in the observed phenotypes. Radiosensitization via ferroptosis induction was additionally demonstrated in another human lung cancer cell line under the PRDX6-silenced state. Collectively, PRDX6 loss remodels the cellular proteome to establish a presensitized redox and lipid compositional state, which favors ferroptosis-driven radiosensitivity.

Mast cells (MCs) display phenotypic heterogeneity across tissues and disease contexts, yet their relevance in melanoma remains unclear. Here, we investigated MC phenotypic programs associated with melanoma progression using high-dimensional phenotyping of MCs co-cultured with melanoma spheroids, trajectory inference, and transcriptomic analyzes. Human melanoma tissues showed differences in MC phenotypic composition despite comparable abundance between outcome groups, with metastatic melanomas enriched for Tryptase[+] Chymase[-] MCs. Melanoma exposure induced MC phenotypic remodeling, characterized by loss of lineage- and effector-associated features and increased PD-1 expression, with more pronounced changes following metastatic melanoma co-culture. Trajectory analysis was consistent with a continuum toward a PD-1[+] Chymase[-] phenotype, which was detected in melanoma tissues and enriched within intratumoral regions of metastatic melanomas. Experimentally defined protein changes were used to derive two MC-associated transcriptomic signatures with opposing clinical associations, reflecting lineage- and effector-enriched versus melanoma-remodeled programs. The MC-LE signature was associated with favorable survival and interferon-responsive pathways, whereas the MC-MR signature was associated with poorer survival and tumor-associated pathways. These transcriptomic associations extended beyond melanoma across multiple TCGA cancer cohorts, and independent analysis of MCs from healthy skin, basal cell carcinoma, and melanoma showed corresponding differences in MC-LE-related features. Together, these findings support distinct mast cell phenotypic programs associated with melanoma progression and identify a PD-1[+] Chymase[-] MC phenotype enriched in metastatic disease and linked to transcriptomic features of poor survival.

The non-invasive skin cancer, especially that of the basal cell carcinoma and squamous cell carcinoma, is an increasing global health burden. Traditional methods of treatment, such as surgery, cryotherapy, and topical chemotherapeutics, are all limited by poor penetration into the skin, non-specific drug delivery, cosmetic destruction, and tumour reappearance. Moreover, the tumour microenvironment (TME) significantly contributes to disease progression through inflammation, angiogenesis, immunosuppression, and therapeutic resistance, underscoring the need for more advanced, targeted treatment methods. The purpose of this review is to critically analyse the applications of the ethosome-based drug delivery system in the precision targeting and reprogramming of the TME in the treatment of non-invasive skin cancer. Ethosomes have better skin permeability and local drug delivery than standard topical systems. They also facilitate easy access to a wide variety of therapeutic agents, allowing specific interactions with tumour tissue and other critical components of the TME, leading to better therapeutic effects with fewer off-target effects. The ethosome-based drug delivery system is an attractive non-invasive therapeutic platform for managing skin cancer by efficiently reprogramming the TME via transdermal delivery. Although they have preclinical evidence supporting their potential, they need additional clinical validation and regulatory standardisation to be successfully translated into clinical use.

Gynaecological malignancies account for over 1.4 million new diagnoses, with outcomes constrained by late-stage presentation and chemoresistance. Dysregulated redox homeostasis is a hallmark of tumourigenesis. Tumour cells maintain elevated basal reactive oxygen species (ROS), which support proliferative signalling but may also increase susceptibility to further oxidative stress. Vitamin D, acting through the vitamin D receptor (VDR), has antiproliferative and pro-apoptotic effects across cancer models, but its ability to amplify ROS beyond an apoptotic threshold in gynaecological malignancies remains unresolved. We conducted a narrative literature search of PubMed/MEDLINE, ClinicalTrials.gov and the Surveillance, Epidemiology and End Results databases, using terms related to vitamin D and its metabolites, ROS/oxidative stress, apoptosis and gynaecological malignancies. Preclinical evidence indicates that calcitriol and related compounds can induce ROS-mediated mitochondrial apoptosis, modulate autophagy and arrest the cell cycle. In ovarian cancer, non-HGSOC cell data suggest that mutant TP53 may alter calcitriol responses, requiring validation in high-grade serous ovarian carcinoma models. In cervical cancer, calcitriol radiosensitises human papillomavirus-positive cell lines through autophagy suppression, whilst an in vivo calcitriol-cisplatin study reported improved survival. In endometrial cancer, thioredoxin-interacting protein induction is a candidate mechanism for selective ROS-mediated apoptosis, although this remains context-dependent. Clinical evidence is heterogeneous: higher 25-hydroxyvitamin D status has shown modest inverse associations with ovarian cancer mortality; small trials report regression or reduced recurrence of cervical intraepithelial neoplasia; no randomised controlled trial evidence supports efficacy in invasive cervical cancer; and associations with endometrial cancer incidence are largely null. Current evidence does not support vitamin D supplementation as an oncology-specific intervention. Future research should prioritise biomarker-stratified trials incorporating VDR genotype, CYP24A1 profiling, pre-specified 25(OH)D targets and pharmacokinetically informed dosing.