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BACKGROUND: Several cathepsins have been identified as being involved in the development of cancer. Nevertheless, the connection between cathepsins and skin cancers remained highly elusive.
METHODS: A bidirectional Mendelian randomization (MR) analysis was performed to investigate the causal association between cathepsins and skin malignancies. The genome-wide association studies (GWAS) data for cathepsins, malignant melanoma (MM), and basal cell carcinoma (BCC) were obtained from European research. The primary method employed was inverse variance weighted. In addition, MR-Egger, weighted median, weighted mode, and simple mode were also executed. Sensitivity analysis was performed using Cochran\'s Q test, MR-Egger, and MR-PRESSO.
RESULTS: From univariable MR (UVMR), cathepsin H, and S were determined to have a causal relationship with BCC. Additionally, cathepsin H was identified as associated with MM. Multivariable MR (MVMR) showed that after correcting for risk factors of skin carcinoma, cathepsin H was detected to be protective against BCC, whereas cathepsin S has been observed as a risk factor for BCC. No substantial pleiotropy and heterogeneity were identified in the sensitivity analysis.
CONCLUSIONS: This study was the first to establish a direct link between cathepsins and skin malignancies. Cathepsin H and S have the potential to serve as new biomarkers for BCC, offering valuable assistance in the prompt identification, treatment, and prevention of the disease. Nevertheless, additional clinical trials are required to validate our findings.

The keratinocyte carcinomas, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs, assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for both onset and spread. A potential correlation between the onset of BCC and a dysembryogenetic process has long been hypothesised. A selective investigation of PubMed-indexed publications supporting this theory retrieved 64 selected articles published between 1901 and 2024. From our analysis of the literature review, five main research domains on the dysembryogenetic pathogenesis of BCC were identified: (1) The correlation between the topographic distribution of BCC and the macroscopic embryology, (2) the correlation between BCC and the microscopic embryology, (3) the genetic BCC, (4) the correlation between BCC and the hair follicle and (5) the correlation between BCC and the molecular embryology with a specific focus on the Hedgehog signalling pathway. A large amount of data from microscopic and molecular research consistently supports the hypothesis of a dysembryogenetic pathogenesis of BCC. Such evidence is promoting advances in the clinical management of this disease, with innovative targeted molecular therapies on an immune modulating basis being developed.

BACKGROUND: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. The aim of the current study was to analyze the ultraviolet-enhanced fluorescence dermoscopy (UVFD) characteristics of BCCs.
METHODS: BCCs were evaluated under polarized dermoscopy (PD) and UVFD. The findings in PD were described using predefined parameters for dermoscopic evaluation in dermato-oncology. UVFD characteristics were determined based on personal observations, and included interrupted follicle pattern, absence of pink-orange or blue-green fluorescence, well-demarcated borders, and dark silhouettes.
RESULTS: In total, 163 BCCs were analyzed. Under UVFD, the interrupted follicle pattern (p < 0.001), absence of pink-orange fluorescence (p = 0.005) and well-demarcated borders (p = 0.031) were more frequently noted in BCCs < 5 mm than in bigger tumors. Lesions on the face showed clearly defined borders (p = 0.031) and interrupted follicle pattern (p < 0.001) more frequently than tumors located beyond the face. Nodular BCCs displayed interrupted follicle pattern (p = 0.001) and absence of pink-orange fluorescence (p < 0.001) more commonly than superficial subtypes. Non-pigmented BCCs more frequently showed lack of blue-green fluorescence (p = 0.007) and interrupted follicle pattern (p = 0.018) compared to pigmented variants.
CONCLUSIONS: UVFD may be a valuable, complementary to PD, tool in the diagnosis of BCC, particularly in small tumors, lesions located on the face and nodular or non-pigmented subtypes.

UNASSIGNED: Basal cell carcinoma (BCC) cases exhibit variations in tumour number, location, and growth patterns. While some patients develop only one BCC, approximately one-third of patients later develop one or more additional lesions.
UNASSIGNED: The aim of the study was to identify risk factors for further BCC lesions in patients with different phenotypic presentations.
UNASSIGNED: We retrospectively evaluated 1052 histopathologically diagnosed tumours of 861 patients, who were divided into four phenotypic presentation groups according to tumour number at initial diagnosis and during follow-up. Age, sex, tumour characteristics, surgical margins, re-excision and residual tumour rates were compared. Univariate and multivariate logistic regression analyses were performed to determine risk factors for multiple tumour development.
UNASSIGNED: There were 723 patients in the single presentation phenotype 1 (SPP1) group, 19 in the SPP-more group, 114 in the multiple presentation phenotype (MPP)-cluster initial group, and five patients in the MPP-cluster later group. Male sex was more common in the MPP-cluster later group (P = 0.028). The mean age was lower in the SPP1 and SPP-more groups (P = 0.002). Ear involvement was more common in the MPP-cluster later group (P < 0.05). Superficial and basosquamous subtypes were more common in the SPP-more and MPP-cluster later groups (P < 0.05). Re-excision and residual tumour rates were lowest in the SPP1 group (P < 0.05). Age over 69 years, male sex, and periorbital or upper extremity location were significant risk factors for multiple tumour development (P < 0.05).
UNASSIGNED: The limitations of our study include the inability to evaluate environmental risk factors, phenotypic and ethnic characteristics, and the short follow-up period for newly added patients.
UNASSIGNED: Predicting different phenotypic presentations by taking the age, gender, and tumour characteristics (localization, histopathological subtype) of the patients into account may allow new tumours to be detected at an early stage.

BACKGROUND: Hypertension affects 25-30% of the world population. Hydrochlorothiazide (HCTZ) is among the most used and cheapest medications but was in 2018 labeled with a warning stating increased risk of non-melanoma skin cancer (NMSC). This study describes geographical differences in the association between HCTZ and NMSC in a perspective of hypertensive heart disease (HHD).
METHODS: We conducted a systematic literature search (PubMed, Embase, Clinicaltrial.gov, and Clinicaltrial.eu) using PICO/PECO acronyms including case-control, cohort, and randomized controlled trials. We constructed a rate ratio of disability-adjusted life years (DALY) for HHD/NMSC in global burden of disease (GBD) regions.
RESULTS: No increased risk of NMSC with use of HCTZ was found in Taiwan, India, and Brazil. A small (hazard ratio (HR)/odds ratio (OR) ≤ 1.5) but significantly increased risk was seen in Canada, USA, and Korea. An increased risk (1.5 < HR/OR ≤ 2.5) in Iceland, Spain, and Japan and a highly increased risk (HR/OR > 2.5 in UK, Denmark, Netherlands, and Australia. HHD is associated with a more than 10-fold DALY rate compared with NMSC in 13 of 21 GBD regions corresponding 77.2% of the global population. In none of these 13 regions were there an increased risk of HCTZ-associated NMSC.
CONCLUSIONS: Despite limited information from many countries, our data point to large geographical differences in the association between HCTZ and NMSC. In all GBD regions, except Australasia, HHD constitutes a more than 5-fold DALY rate compared to NMSC. This disproportionate risk should be considered before avoiding HCTZ as part of the antihypertensive treatment.

BACKGROUND: Squamous cell carcinoma (SCC) is one of the most commonly diagnosed neoplastic disorders in reptiles. Recently, however, it has been demonstrated that basal cell carcinomas (BCCs) are frequently misclassified as SCCs. Several histological SCC and BCC variants have been characterised and their classification may allow the establishment of appropriate prognosis estimation and treatment approaches.
OBJECTIVE: To describe the clinical features and surgical outcomes of SCCs and BCCs diagnosed between 2010 and 2022 in reptiles.
METHODS: Thirty-three captive reptiles (21 squamates and 12 chelonians).
METHODS: Detailed clinical history, including staging and surgical outcomes, were performed. Statistical analysis assessed significant factors using Prism (v8.2.1).
RESULTS: While SCC was predominantly diagnosed in lizards, BCC was most commonly diagnosed in chelonians, and both neoplasms mainly occurred in adult to aged, male individuals. Although the gross pathological findings were highly comparable between SCC and BCC, considerable variation could be seen according to the primary location (oral, cutaneous or epidermis of the shell). Humane euthanasia or noncurative intent surgeries were performed in a minority of the cases. Curative intent surgeries were successful in 19 of 27 cases during a 1- to 7-year follow-up period, yet recurrence was seen in 8 cases. The results of this study allowed the identification of significant high-risk prognostic factors for SCC and BCC in reptiles.
CONCLUSIONS: This study contributes to predicting the clinical behaviour and prognosis of distinct SCC and BCC histological variants, and selecting the most appropriate treatment protocol.

OBJECTIVE: Traditionally, locally advanced scalp malignancies have been managed through composite, full-thickness calvarial resection. The aim of this study is to explore the oncologic outcomes of partial calvarial resection for locally invasive scalp malignancies without medullary space invasion, employing a burr-down approach.
METHODS: Retrospective case series.
METHODS: Tertiary referral center.
METHODS: This study analyzed records of 26 adult patients diagnosed with scalp cancer that spread to the calvarial region. Data collected included demographics, medical history, adjuvant therapy details, imaging, surgical outcomes, and postoperative oncological results.
RESULTS: 26 patients with cancerous scalp lesions necessitating calvarial resection for deep margin control were identified in 22 men and 4 women. Mean age at diagnosis was 72.7 years. The most common histopathological diagnosis was Squamous cell carcinoma (n = 16). Partial removal of the calvarial lesions was achieved in all patients without any intraoperative complications. Twelve patients received adjuvant therapy consisting of the following modalities: radiation (6), chemotherapy (1), immunotherapy (1), a combination of immunotherapy and radiation (2), and a combination of chemotherapy and radiotherapy (2). There was a total of 7 recurrences: local (n = 3,11.5 %), regional (n = 3,11.5 %), distal (n = 1,3.8 %). Long term local control was achieved in (n = 23,88.4 %) of patients. The mean time of follow-up was 19.1 months, and the mean time to recurrence was 15.1 months.
CONCLUSIONS: Partial calvarial resection represents a viable, safe, and effective surgical technique for cancerous tissue removal, reducing risks associated with full thickness calvarial resection, and enhancing soft tissue healing when compared to the established gold standard.

The identification of benign prostatic tissue within ovarian and testicular mature teratomas is an unusual occurrence. While a few documented reports exist in the literature regarding the emergence of benign prostatic tissue within teratomas, the occurrence of prostatic-type adenocarcinoma in a mature ovarian teratoma is an exceptionally rare phenomenon. To date, only two prior reports have documented such instances, and no tumors have been previously reported with prostate-type tissue with morphologically two different malignancies. We outline our experience with two tumors involving prostatic-type carcinoma, both arising in ovarian mature teratomas. Microscopic examination of the first tumor revealed small areas of infiltrative atypical glandular proliferation within the mature teratoma. In the second tumor, prostate-type tissue exhibited a low-grade basal cell carcinoma. Additionally, adjacent minute foci of adenocarcinoma of the prostate (Gleason score 3 + 4 = 7, <5% pattern 4) were identified. Goblet cell adenocarcinoma of appendiceal type was also evident in the latter tumor. In both tumors, immunostains (NKX3.1, PSA) were performed to establish the prostatic origin of these atypical glands and PIN4 was performed to document the absence of basal cell in the atypical glands. On clinical follow-up, both patients have no signs of recurrence at 14 and 11 months after the surgery. Further reports on such neoplasms would contribute to a better understanding of the prognosis and management of such occurrences.