Tumor budding as a risk factor for lymph node metastases in cutaneous squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Current staging systems have limitations in stratifying high-risk cases of cutaneous squamous cell carcinoma (cSCC). Tumor budding (TB) has emerged as a potential prognostic factor in various cancers. OBJECTIVES: This systematic review and meta-analysis aimed 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 cut-off 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 cSCC patients were included. The random-effects analysis showed a significant association between high TB (≥5 buds) and NM (OR = 13.29, 95% CI = 5.55; 31.86). DISCUSSION: Tumor budding is a promising histopathologic 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 high-risk cases and guide optimal management strategies for each patient. However, further investigation is needed to determine standardized reporting guidelines for TB in cSCC.

Breslow density ability to predict melanoma survival: should it be used in clinical practice?

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.

Comparative clinicopathological study of the main anatomic locations of oral squamous cell carcinoma.

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.

Oral Trichogranuloma in an Asian 12-Year-Old Female With Trichotillomania.

Pilonidal sinus is an acquired chronic inflammatory condition associated with the penetration of hair fragments into the skin. In the pathogenesis of most of these cases, a traumatic event initiates the process allowing the introduction of the hairs into the skin. We report an unusual case of acquired pilonidal sinus as a consequence of the unconscious habit of chewing on the hairs in a 12-year-old girl. Although most commonly located in the gluteal cleft, it has been reported in several areas of the body (including face), but to the best of our knowledge, this is the first report in the oral cavity. Our case presented as a palatal and vestibular fistula in a patient who suffered from an undiagnosed peculiar form of hair pulling disorder that involved hair chewing but not trichophagia.

Regeneration of periodontal intrabony defects using platelet-rich fibrin (PRF): a systematic review and network meta-analysis.

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.

Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma.

The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients' prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45-1.24; p = 0.251); HR = 0.82 (0.51-1.33; p = 0.425); and HR = 0.79 (0.49-1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.

Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry.

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.

Silicone Granulomas at the Peripheral Intravenous Cannula Puncture Site.

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.

Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

Head and neck cancer (HNC) is an ascending and agressive disease. The search for new molecular markers is emerging to solve difficulties in diagnosis, risk management, prognosis and effectiveness of treatments. Proteins related to apoptotic machinery have been identified as potential biomarkers. Caspase 3 is the main effector caspase and has a key role in apoptosis. The objective of this systematic review and meta-analysis is to review studies that analyze changes in Caspase 3 and Cleaved Caspase 3 expression both in oral premalignant disorders (OPMD) as well as in head and neck cancer (HNC). This study also proposes to review the prognostic values associated with HNC according to the expression of Caspase 3. Medline (via PubMed), EMBASE, Scopus, Cochrane, Web of Science and Grey Literature Database were screened from inception to june of 2022 and 18 studies were selected and 8 were included in the prognostic meta-analysis. Results related to the comparison of Caspase 3 expression demonstrated similar expression of Caspase 3 in HNC, with an average of 51.9% (9.5-98.1) showing high/moderate expression compared to 45.7% (14.6-84.7) in OPMD. Of interest, Cleaved Caspase 3 resulted incresed in HNC when compared with OPMD, being 73.3% (38.6-88.3) versus 22.9% (7.1-38.7). Pooled Fixed effect of HR values (95% CI) for OS related to Caspase 3 IHC expression in HNC patients was 1.48 (95% CI 0.95-2.28); also, the rate of heterogeneity was low, as revealed by I2 = 31%. For DFS was 1.07 (95% CI 0.79-1.45) with I2 = 0% and DSS showed a HR of 0.88 (95% CI 0.69-1.12) with I2 = 37%. Caspase 3 and Cleaved Caspase 3 expression could be linked with malignancy progression, but the expression of Caspase 3 did not influence the prognosis of patients with HNC.

Acral Calcified Vascular Leiomyoma: Report of 3 Cases and Literature Review.

ABSTRACT: Angioleiomyomas are benign neoplasms, which usually present as solitary, slow-growing nodules on the skin of lower extremities, but acral location on the hands or feet is unusual. Yet, microscopically, they may show many histopathological variants, focal calcification is uncommon. Extensive calcification masquerading the real nature of the tumor has been rarely reported, the term acral calcified leiomyoma having been proposed for this entity. This change is more often in distal locations and has been interpreted as degenerative in nature, probably related to repetitive minor trauma. We report 3 examples of this unusual condition on the feet of 2 male and one female subjects (aged, 68, 69, and 80 years) and make a review of the 31 cases available in the literature. Two of our cases are associated with highly uncommon features, such as transepidermal calcium elimination and concomitant calcaneal spur.

Cutaneous Polymer-Coating Embolism After Endovascular Procedures: Report of Two Cases and a Literature Review.

ABSTRACT: Different hydrophilic and hydrophobic polymers are used as lubricious coatings to reduce vascular traumas in minimally invasive percutaneous procedures. Although they are usually very safe, there is still a risk of serious complications in patients undergoing such procedures, mostly derived from the devices' coating detachment and systemic embolization. The lungs are the most common organ involved, followed by the central nervous system. Yet, cutaneous embolization is unusual, and only 19 cases are available in the literature. Most commonly, they present as asymptomatic retiform purpura on the lower legs, which tends to involve spontaneously. Correct clinical diagnosis is not suspected in most cases, being cholesterol emboly or vasculitis the preferred options. Time interval since surgical procedure and appearance of lesions vary widely but they generally start in the first few days. Histopathological identification of the embolus as bluish, amorphous intraluminal material in dermal vessels is diagnostic, but vasculitic signs are not present. We report 2 cases of skin lesions as the main manifestation of polymer embolization after endovascular surgical procedures. In both cases, biopsy allowed identification of embolized foreign material and lesions resolved without specific treatment.

Analysis of the Efficiency and Prognostic Value of the Sentinel Node Technique in Oral Squamous Cell Carcinoma after Seven Years.

Background and objectives: The purpose of this study was to analyse the diagnostic and prognostic efficiency of the sentinel lymph node biopsy technique (SLNB). Materials and Methods: This is a prospective observational study performed by the Hospital Complex in Santiago de Compostela (CHUS) in Spain, between February 2013 and June 2020. The study included 60 patients, who had been diagnosed with OSCC in stage T1/T2N0M0. Results: 10 patients (16.7%) presented with SN+ (sentinel node positive). The majority (80%) only presented subcapsular affection, however one case also presented with extracapsular affection. Using the Kaplan-Meier curves, we determined that the average survival estimation for SN- patients was 74.0 months (CI95% 67.6-80.5) and it was 45.4 months (CI95% 10.9-24.0) for SN+ patients (p = 0.002). SN+ patients presented an OR = 11.000 (CI95% 2.393-50.589, p = 0.002) for cancer-related mortality. In terms of the diagnostic performance of the SN (sentinel node) test, a 55% sensitivity, a 100% specificity, 100% PPV and a 84% NPV were obtained. The analysis using ROC (receiver operating characteristic) curves revealed an AUC = 0.671 (CI95% 0.492-0.850, p = 0.046). Conclusions: SLNB seems to be an adequate technique for the detection of hidden metastases.

Expression of Connexin 43 in 32 Cases of Merkel Cell Carcinoma.

INTRODUCTION: Connexins (Cxs) are channel proteins that allow direct connection among cells and between cells and the extracellular space. There is very little information in the literature on the expression of Cxs by Merkel cell carcinoma (MCC). MATERIALS AND METHODS: Thirty-two cases of MCC were recovered from our archives and studied immunohistochemically for Cx43. RESULTS: All our cases expressed several neuroendocrine markers. Most cases showed nonimmunohistochemically perceptible staining for Cx43. There was no difference between Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative cases. One case could not be evaluated. Only 2 cases showed a focal (10% of the tumor) membranous staining of Cx43. One of these cases was MCPyV-negative and, in the other, CM2B4 could not be evaluated. CM2B4 was positive in 18 cases and negative in 13 cases, and it could not be evaluated in 1 case. CONCLUSIONS: MCC shows a low Cx43 level, with no differences between MCPyV-positive and MCPyV-negative cases. Therefore, this opens the door for Cx43 targeting in therapeutic approaches to MCC.

Mucinous Metaplasia of the Vulva in Zoon Vulvitis and Lichen Sclerosus et Atrophicus. Description of 3 Additional Cases of a Rarely Reported Histopathologic Finding.

Mucinous metaplasia of the vulva (MMV) is a histopathologic finding that has been reported previously in only 3 patients and needs to be distinguished from vulvar extramammary Paget disease. We report 3 additional instances of MMV associated to Zoon vulvitis and vulvar lichen sclerosus et atrophicus. Histochemical and immunohistochemical studies were performed on biopsies from erythematous and erosive vulvar lesions of 3 women aged 64, 80 and 84 years, with features of Zoon vulvitis (2 cases) and lichen sclerosus et atrophicus (1 case). Mucin-containing epithelial cells were present on the uppermost layers of the squamous epithelium. On immunohistochemical study the metaplastic cells were positive for cytokeratin 7, epithelial membrane antigen and carcinoembryonic antigen, thus mimicking the phenotype of Paget disease. MMV is most likely related to chronic inflammation. Cytological and architectural features allow for distinction from Paget disease because the mucin-containing cells of mucinous metaplasia of the vulva lack atypia and are predominantly located on the most superficial layers of the surface epithelium.

Resolution of acenocoumarol-associated calciphylaxis with drug withdrawal.

Calciphylaxis is a syndrome of cutaneous ischaemic necrosis and ulceration due to arteriolar calcification with subsequent thrombosis, which rarely presents in patients without terminal kidney disease. Recently, several reports of coumarins-associated calciphylaxis have stressed the relevance of anticoagulant therapy as an important risk factor for the development of this condition. We report five cases of acenocoumarol-associated, biopsy-proven calciphylaxis in women aged between 64 and 92 years. The drug had been prescribed for atrial fibrillation and was taken without interruption from 14 to 224 months. Lesions were present for months in all cases and were resistant to multiple therapeutic options, but they resolved only with simple wound care measures 6-14 months after changing the anticoagulant therapy.