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The presence and degree of dysplasia are important diagnostic and prognostic criteria for oral leukoplakia, but evaluation of dysplasia is difficult and subjective. Carbonic anhydrase-IX (CA-IX) is expressed primarily in tumor cells and is considered a specific hypoxia marker. We investigated the role of CA-IX in oral leukoplakia. We investigated 30 specimens of oral leukoplakia and 35 dysplasia specimens adjacent to the tumor margin. We analyzed clinical variables including age, sex, degree of dysplasia, and smoking, clinical appearance of leukoplakia, number of lesions, location, size, clinical monitoring, malignant transformation and recurrence. For the immunohistochemical study, we used a noncommercial monoclonal antibody against human CA-IX MAb M75. We found greater CA-IX positivity in nonsmokers, erythroplakia and mottled leukoplakia, those located on the tongue, patients with multiple lesions, 2-4 cm leukoplakias and in recurrent cases, although differences were not statistically significant. All lesions in all samples without dysplasia were negative for CA-IX; however, for all other categories of dysplasia, the percentages of positivity and negativity varied. Regarding the diagnostic index values, we found a sensitivity of 32%, specificity of 100%, a positive predictive value of 100% and a negative predictive value of 13%. Leukoplakias appear mainly in females and potentially are malignant; more than 90% have some degree of dysplasia, and therefore require close clinical and histopathological monitoring. The CA-IX immunohistochemical marker may be useful for screening samples without dysplasia owing to its high specificity. [ABSTRACT FROM AUTHOR]

Carbonic anhydrase (CA) IX is a hypoxia marker located almost exclusively in tumor cells. We analyzed the expression of this marker in dysplastic lesions adjacent to the surgical resection margin in patients with oral squamous cell carcinoma. We investigated 70 archived tumors, 36 of which showed dysplasia adjacent to the surgical margin. We used tissue microarray technology to perform an immunohistochemical study of CA IX expression. We found 12 (33.3%) cases of mild dysplasia (10 negative, 2 positive for CA IX), five (13.9%) cases of moderate dysplasia (3 negative, 2 positive for CA IX), 1 (2.8%) case of severe dysplasia (negative for CA IX) and 18 (50%) cases of carcinoma in situ (10 negative, 8 positive for CA IX). In cases of intense expression of CA IX in the tumor, the same distribution of positive and negative cases was observed in all degrees of dysplasia (mild, moderate, severe), although cases of carcinoma in situ tended to be CA IX positive. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are proteases responsible for remodeling the extracellular matrix (ECM) and enabling spreading and metastasis of tumor cells, a common phenomenon in oral squamous cell carcinomas (OSCC). They are strongly blocked by several inhibitors, among which we must highlight, for their specificity and potency, the endogenous tissue inhibitors of metalloproteinases (TIMP-1, -2, -3 and -4). The goal of this paper is to describe the expression of TIMPs in OSCC, determining their relation with clinical, histological and prognostic factors, delving into OSCC regulation mechanisms and discussing the use of exogenous TIMPs to treat this type of tumors. Expression of TIMPs in OSCC is higher in tumors than in normal tissue, which correlates with an increase of metastatic risk and regional lymph node affectation. Although some metalloproteinases inhibitors (MMIs) have shown promising results in the treatment of these tumors, their use in OSCC has not been widely tested; and although some indirect MMIs, like COX-2 inhibitors, flavonoids and endostatin seem to have beneficial effects on the invasive capacity of OSCC through regulation of MMPs and TIMP levels, routine clinical use has not been accepted yet. [ABSTRACT FROM AUTHOR]

Background: Current staging systems have limitations in stratifying high-risk cutaneous squamous cell carcinoma (cSCC). Tumour budding (TB) has emerged as a potential prognostic factor in various cancers., Objectives: To evaluate the prognostic significance of TB in predicting lymph node metastases (NM) in cSCC., Methods: A comprehensive search of the PubMed, Web of Science, Embase and Cochrane databases was conducted. Studies investigating the association of TB using a 5-bud cutoff and NM in cSCC were included. A meta-analysis was performed using odds ratios (OR) to evaluate the association between TB and NM., Results: Six retrospective studies comprising 793 patients with cSCC were included. The random-effects analysis showed a significant association between high TB (≥ 5 buds) and NM (OR = 13.29, 95% confidence interval 5.55-31.86)., Discussion: TB is a promising histopathological feature for predicting NM in cSCC. The results show a strong association between high TB and NM, supporting its utility as a risk factor for NM in cSCC. Its inclusion in clinical practice and cSCC staging might be helpful in the stratification of patients with high-risk cases and to guide optimal management strategies for each patient. However, further investigation is needed to determine standardized reporting guidelines for TB in cSCC., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

One of the most promising approaches to correct periodontal bone defects and achieve periodontal regeneration is platelet-rich fibrin (PRF). This systematic review and meta-analysis aimed to evaluate the regeneration of periodontal bone defects using PRF compared to other regenerative treatments. The data search and retrieval process followed the PRISMA guidelines. An electronic search of MEDLINE, Cochrane, and PubMed databases was performed, selecting exclusively randomized clinical trials where the following were measured: probing depth reduction (PD), clinical attachment level gain (CAL), and radiographic bone fill (RBF). Out of 284 selected articles, 32 were chosen based on inclusion criteria. The use of platelet-rich fibrin (PRF) + open flap debridement (OFD), PRF + metformin, PRF + platelet-rich plasma (PRP), and PRF + OFD/bone graft (BG) significantly reduced PD and improved CAL and RBF. However, the combination of PRF + BG, PRF + metformin, and PRF + STATINS reduced CAL. The intervention of PRF combined with different treatments such as metformin, OFD, PRP, BG, and STATINS has a significant impact on improving PD and CAL. The use of PRF significantly improved the regeneration of periodontal bone defects compared to other treatments., (© 2024. The Author(s).)

Background: Breslow density (BD) is an estimation of melanoma volume, which has emerged as a novel histopathological prognostic biomarker., Objectives: Our aim was to evaluate the role of BD as predictor of patients´ survival and assess its prognostic value in relation to overall survival (OS), disease-free survival (DFS), melanoma-specific survival (MSS) and metastasis-free survival (MFS)., Methods: A retrospective observational study in a cohort of 107 patients with invasive melanoma was conducted. Kaplan-Meier and Log-rank tests were used for 10-year survival analysis. The ability of BD and Breslow thickness (BT) to predict survival was assessed using receiver operating characteristic curves., Results: The average follow-up was 115 months excluding deaths. BD ≥65% showed lower survival rates compared with the BD<65% group (log-rank test p<0.001). Area under the curve (AUC) of BD ≥65% was higher than BT's for all studied survival rates except for melanoma-specific survival, in which absolute BD showed the highest value., Conclusions: BD is proposed as a simple, valuable and inexpensive histopathological feature that could provide with valuable information to current melanoma staging, since it has proved a statistically significant prognostic value in relation to survival in melanoma patients, and comparable 10-year survival prediction ability to BT., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To analyze the clinicopathological and evolutionary profile of the main locations of oral squamous cell carcinoma (OSCC)., Materials and Methods: This is a retrospective study on 133 patients treated for OSCC. The group was composed of 48 women and 85 men, with a mean age 63.9 ± 12.73 years. Most cases involved the lingual border of tongue (63), followed by the gingiva (36) and the floor of mouth (34). A comparative analysis was performed using multinomial regression., Results: There were significant differences regarding age, sex, tobacco and alcohol consumption, liver pathology, oral potentially malignant disorders, and bone and perineural invasion. In multivariate regression, tobacco consumption, and bone invasion remained significant. There were no significant differences in relation to prognosis., Conclusion: The location of OSCC is an important factor in the clinicopathological assessment of this neoplasm. The main locations of OSCC show differential etiopathogenic and clinicopathological aspects. Tobacco consumption has a great relevance in the floor of mouth; nonetheless, it is less important in the tongue border and the gum, which suggests other pathogenic factors. It is necessary to consider the anatomical location of OSCC in preventive protocols, with the aim of reducing its high mortality., (© 2024 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones., (Copyright © 2023 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma (OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study, we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specific Spanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosis measures., Material and Methods: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospital centre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival were calculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression)., Results: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) and alcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailed the 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were 39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC cases referred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with an oral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatment., Conclusions: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prognosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights the better survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and the dental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the early diagnosis and multidisciplinary management of this malignant neoplasm.

Competing Interests: The authors declare no conflicts of interest.

Competing Interests: The authors declare no conflicts of interest.

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Nephrogenic adenoma (NA) is an infrequent reactive urothelial lesion. The expression of immunohistochemical renal tubular markers has been reported in NA, although a proximal or distal nephron phenotype has not been established. Special AT-rich sequence-binding protein 2 (SATB2) is a marker of a colorectal origin of adenocarcinomas, occasionally reported in renal samples. We have analyzed SATB2 expression in NA, with correlation with other tubular markers, as well as in the normal kidney. Fifty cases of NA were immunostained with PAX8, SATB2, proximal nephron markers [CD10, renal cell carcinoma (RCC) marker, alpha-methylacyl-CoA racemase (AMACR), and CD15], and distal markers (Ksp cadherin, cytokeratin 7, E-cadherin (E-cad), and cytokeratin 19). Ten normal kidney sections were stained with a double method combining SATB2 plus CD10, RCC marker, AMACR, Ksp cadherin, cytokeratin 7, or E-cad. All NA were immunoreactive for PAX8 and 57% for SATB2. Every case was positive for proximal and distal nephron markers: 100% for cytokeratins 7 and 19, 84.1% E-cad +, 81.6% AMACR +, 68.9% Ksp cadherin +, 63% CD15 +, 53.3% CD10 +, and 28.6 % RCC +. In the normal kidney, SATB2 was detected in the straight part of the proximal tubules and the thin descending loops of Henle. NA shows a multiphenotypic pattern with coexpression of both proximal and distal nephron markers, and constant expression of PAX8, cytokeratins 7 and 19. SATB2 is often positive in NA, which should be kept in mind to avoid a possible misdiagnosis of intestinal adenocarcinoma. SATB2 is a marker of the normal proximal nephron., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflict of interest: the authors declare that they have no conflict of interest.

Melanoma is the cutaneous neoplasm responsible for more patient deaths in all countries. BRAF mutations are the most common driver mutation and with the development of molecular targeted therapy, the precise knowledge of BRAF status has become increasingly important. Evaluation of BRAF mutation status has routinely been performed by polymerase chain reaction, a time consuming and expensive technique. Immunohistochemistry has been suggested as a cheaper alternative, but it has not gained general acceptance. A retrospective observational study in a cohort of 106 patients with invasive melanoma was conducted in order to develop and evaluate a machine learning approach to predict BRAF status using clinical and histologic variables. We compared the performance of different common machine learning algorithms and use SHapley Additive exPlanations (SHAP) to explain individual predictions and extract medical insights to define a heuristic model to estimate BRAF mutation probability. The Extreme Gradient Boosting algorithms obtained the best performance. Interpretability of models shows that the most important variables to estimate BRAF mutation probability are: age, Breslow thickness, and Breslow density. Based in this interpretation and medical knowledge, a simplify heuristic model is proposed to predict BRAF status using only 7 variables and obtain a performance of 0.878 of area under the curve. We propose a heuristic model that could be used by clinicians to obtain a good estimator of BRAF mutation probability., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Abstract: Different adverse reactions to silicone present in cosmetic fillers, implants, or medical devices have been reported. The granulomatous reaction on the injection site due to catheters' silicone coating is an infrequent complication, which may be clinically difficult to suspect. Although the definitive diagnosis requires identification of the silicone with techniques such as X-ray spectroscopy, the possibility of involvement of silicone, as well as the histopathologic demonstration of granulomas with refractile, nonpolarizable, and nonstainable material strongly suggests this diagnosis. Moreover, the use of a low-diaphragm aperture or phase-contrast microscopy could be useful to demonstrate the presence of this, otherwise almost transparent, foreign body., Competing Interests: The authors declare no conflicts of interest. The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)