Squamous Cell Carcinoma Lesions Research Articles

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for the treatment of vulvar squamous intraepithelial lesion

BackgroundVulvar squamous intraepithelial lesion (SIL) is a precursor lesion of vulvar squamous cell carcinoma. The current clinical treatments for vulvar SIL cause damage to the vulvar structure, chronic pain and psychological distress. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive therapy for intraepithelial lesions. The objective of this study was to compare the clinical efficacy and safety of ALA-PDT with local surgical resection for vulvar SIL. MethodsA total of 56 patients with vulvar SIL were enrolled in this retrospective study. Among them, 16 patients received local resection and 40 patients received ALA-PDT. HPV genotyping and ThinPrep cytologic test (TCT) were used to evaluate treatment efficacy. In addition, colposcopy-directed biopsy was performed in all patients at 3-month follow-up and in patients with positive high-risk human papillomavirus (HR-HPV) and/or abnormal TCT results during the follow-up. ResultsAt 3-month follow-up and in HSIL group the complete remission (CR) rate of the ALA-PDT group and surgery group was 90.6% (29/32) and 87.5% (14/16) (P = 1.000), respectively. The HPV clearance rate of the ALA-PDT group and surgery group was 45.2% (14/31) and 43.8% (7/16) (P = 0.927), respectively. The average numbers of ALA-PDT treatments were 5.34 for HSIL patients and 4.88 for LSIL patients, respectively. The CR rate of HSIL patients and LSIL patients was 90.6% (29/32) and 75.0% (6/8) (P = 0.550), respectively. The HPV clearance rate of HSIL patients and LSIL patients was 45.2% (14/31) and 37.5% (3/8) (P = 1.000), respectively. The ALA-PDT group showed similar clinical efficacy and milder adverse effects compared with the surgical group. ConclusionALA-PDT showed similar clinical efficacy as surgery in the treatment of vulvar SIL, but with milder adverse effects and maintaining the integrity of the vulvar structure.

PRF Lysates Enhance the Proliferation and Migration of Oral Squamous Carcinoma Cell Lines.

Platelet-rich fibrin (PRF) is an autologous fibrin-rich matrix where activated platelets and leucocytes accumulate. PRF has a wide spectrum of clinical indications with the overall aim of supporting tissue regeneration which in dentistry includes the healing of healthy oral mucosa with epithelial cells. In oral squamous cell carcinoma lesions, however, epithelial cells undergo malignant transformation, indicated by their unrestricted proliferation and migration potential, which should not be further enhanced by a wound-healing formula. Yet, little is known about how oral squamous cell carcinomas respond to PRF lysates. The aim of the present study was, therefore, to test the capacity of PRF lysates to change the transcriptome of HSC2 oral squamous carcinoma cells and perform bioassays to support the findings. Based on the RNAseq analysis, PRF lysates caused an increase in the genes functionally linked to cell replication and migration. In support of this screening approach, PRF lysates enhanced the proliferation of HSC2 oral squamous carcinoma cells, as indicated by 3[H]-thymidine incorporation, cell counting, and the expression of proliferation-related genes. Moreover, PRF lysates sped up cell migration in a scratch assay requiring actin polymerization. Taken together, our data showing that PRF lysates are mitogenic and stimulate motility of oral squamous carcinoma cell lines could be an indication that treatment with PRF in cases of oral carcinoma should be carefully considered.

Classification of Skin Lesion Images Using Artificial Intelligence Methodologies through Radial Fourier–Mellin and Hilbert Transform Signatures

This manuscript proposes the possibility of concatenated signatures (instead of images) obtained from different integral transforms, such as Fourier, Mellin, and Hilbert, to classify skin lesions. Eight lesions were analyzed using some algorithms of artificial intelligence: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (MEL), actinic keratosis (AK), benign keratosis (BKL), dermatofibromas (DF), melanocytic nevi (NV), and vascular lesions (VASCs). Eleven artificial intelligence models were applied so that eight skin lesions could be classified by analyzing the signatures of each lesion. The database was randomly divided into 80% and 20% for the training and test dataset images, respectively. The metrics that are reported are accuracy, sensitivity, specificity, and precision. Each process was repeated 30 times to avoid bias, according to the central limit theorem in this work, and the averages and ± standard deviations were reported for each metric. Although all the results were very satisfactory, the highest average score for the eight lesions analyzed was obtained using the subspace k-NN model, where the test metrics were 99.98% accuracy, 99.96% sensitivity, 99.99% specificity, and 99.95% precision.

Expression of p53 in toluidine blue positive oral squamous cell carcinoma lesions and expression of Ki67 in vinegar positive oral squamous cell carcinoma lesions.

The aims of this study were to investigate the sensitivity and specificity of toluidine blue and/or vinegar in oral cancer screening and to examine the correlation between clinical screening using toluidine blue and vinegar and the expression of the tumor marker p53 and proliferation marker Ki67, respectively. The study consisted of 87 patients with suspected oral squamous cell carcinoma lesions. Toluidine blue and/or vinegar were applied to the lesions, followed by biopsies. The tissues were diagnosed histopathologically and underwent immunohistochemical process for p53 or Ki67. The results revealed that the sensitivity and specificity of oral cancer screening using toluidine blue were 93% and 46%, respectively; whereas the sensitivity and specificity using vinegar were 85% and 81%, respectively. A statistically significant correlation between the use of vinegar and the expression of Ki67 (p = 0.019) was observed. Although there was a difference in the expression of p53 between specimens that were positive and negative to toluidine blue, the correlation did not reach a significant level. Based on the results from this study, vinegar has a lower sensitivity than toluidine blue but a higher specificity for oral cancer screening. The results of the clinical screening using vinegar correlated with the expression of Ki67 at the cellular level.

Role of multiple dual-phase 18F-FDG PET/CT metabolic parameters in differentiating adenocarcinomas from squamous cell carcinomas of the lung

PurposeTo evaluate the ability of multiple dual-phase 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters to distinguish the histological subtypes of non-small cell lung cancer (NSCLC). MethodsData from 127 patients with non-small cell lung cancer who underwent preoperative dual-phase 18F-FDG PET/CT scanning at the PET-CT center of our hospital from December 2020 to October 2021 were collected, and the metabolic parameters of their primary lesions were measured and analyzed retrospectively. Intraclass correlation coefficients (ICC) were calculated for consistency between readers. Metabolic parameters in the early (SUVpeak, SUVmean, SUVmin, SUVmax, MTV, and TLG) and delayed phases (dpSUVpeak, dpSUVmean, dpSUVmin, dpSUVmax, dpMTV, and dpTLG) were calculated. We drew receiver operating characteristic (ROC) curves to compare the differences in different metabolic parameters between the adenocarcinoma (AC) and squamous cell carcinoma (SCC) groups and evaluated the ability of different metabolic parameters to distinguish AC from SCC. ResultsInter-reader agreement, as assessed by the intraclass correlation coefficient (ICC), was good (ICC = 0.71, 95% CI:0.60–0.79). The mean MTV, SUVmax, TLG, SUVpeak, SUVmean, dpSUVmax, dpTLG, dpSUVpeak, dpSUVmean, and dpSUVmin of the tumors were significantly higher in SCC lesions than in AC lesions (P = 0.049, < 0.001, 0.016, < 0.001, 0.001, < 0.001, 0.018, < 0.001, 0.001, and 0.001, respectively). The diagnostic efficacy of the metabolic parameters in 18F-FDG PET/CT for differentiating adenocarcinoma from squamous cell carcinoma ranged from high to low as follows: SUVpeak (AUC = 0.727), SUVmax (AUC = 0.708), dpSUVmax (AUC = 0.699), dpSUVpeak (AUC = 0.698), TLG (AUC = 0.695), and dpTLG (AUC = 0.692), SUVmean (AUC = 0.690), dpSUVmean (AUC = 0.687), dpSUVmin (AUC = 0.680), SUVmin (AUC = 0.676), and MTV (AUC = 0.657). ConclusionsSquamous cell carcinoma of the lung had higher mean MTV, SUVmax, TLG, SUVpeak, SUVmean, SUVmin, dpSUVpeak, dpSUVmean, dpSUVmin, dpSUVmax, and dpTLG than AC, which can be helpful tools in differentiating between the two. The metabolic parameters of the delayed phase (2 h after injection) 18F-FDG PET/CT did not improve the diagnostic efficacy in distinguishing lung AC from SCC. Conventional dual-phase 18F-FDG PET/CT is not recommended.

Contact Endoscopic Surface Vascular and Epithelial Morphology in Leukoplakia and Carcinoma of the Vocal Cords

Purpose Leukoplakia is a macroscopic morphological term for thick white or grey mucosal patches that can represent various histologic diagnostic entities ranging from hyperplasia to malignancy. Aim was the study morphology of the superficial mucosa and microvascular network of the vocal cords in patients with suspected glottic squamous cell carcinoma (SCC) using contact endoscopy (CE). Material and Methods Seventy-nine patients (21 female, 58 male), with a mean age of 57.5 years ± 7.12 (range, 32–73 years), were prospectively enrolled and evaluated. Of these patients, 58 had leukoplakia (Group A/41 males and 17 females, with a mean age of 53.7 years ± 6.65), and 21 (Group B/ 17males and 4 females/ with a mean age of 60.5 years ± 6.04) had malignant lesions (pT1, n = 6; p T2, n = 8; pT3, n = 8; Group B), as proven by the results of the histological examination. Further, 79 non-smokers (control group—group C) were studied. CE imaging findings were classified into five types (I to V) based on the features of the mucosal intra-epithelial capillary loops. CE findings were correlated to the histologic findings. A separate analysis involving smoking status was done. Results The CE-based intraepithelial papillary capillary loop classification score was strongly correlated with the histological findings. Age was strongly associated with both malignancy and bilateral involvement. Smoking habits didn’t significantly differ between patients with unilateral and bilateral SCC. Conclusions CE imaging of the vocal cord mucosal capillaries may be useful for the early detection of glottic SCC and pre-cancerous lesions.

Antioxidant and photoprotective role of latex C-serum from Hevea brasiliensis during 15-week UVB irradiation in male hairless SKH-1 mice

ABSTRACT It is known that UVB radiation induces several adverse skin alterations starting from simple photoaging to skin cancer. In addition, it was demonstrated that reactive oxygen species (ROS) were found to be related to cancer development and progression. The aim of study was to examine whether male hairless (SKH-1) mice (Mus musculus) that were subchronically exposed to UVB radiation presented with actinic keratosis (AK) and squamous cell carcinoma lesions, and that treatment with latex C-serum cream significantly prevented abnormal skin development. Data demonstrated for the first time the photoprotective activity of latex C-serum extracted from the rubber tree Hevea brasiliensis var. subconcolor Ducke. Latex C-serum prevented the progression of AK to squamous cell carcinoma in SKH-1 mice, indicating that mice topically treated with latex C-serum presented only AK lesions and treatment with the highest concentration (10%) significantly reduced epidermal thickness, suggesting diminished cell proliferation. Latex C-serum protected the skin of mice against oxidative stress damage, increasing catalase (CAT) activity, regenerating glutathione (GSH) levels, lowering thiobarbituric acid-reactive species (TBARS) production and regenerating the total antioxidant capacity (TAC) of the skin. Evidence that UV radiation in skin induced systemic alterations and erythrocytic analysis indicated that latex C-serum increased CAT activity and GSH levels. Taken together these data indicate that latex C-serum plays an important antioxidant and photoprotective role, preventing serious damage to the skin following exposure to UVB radiation.

Synchronous High-Grade Squamous Intraepithelial Lesion of the Fimbria of the Fallopian Tube in a 51-Year-Old Woman with Invasive Squamous Cell Carcinoma of the Uterine Cervix.

Primary squamous cell carcinoma or squamous intraepithelial lesion of the fallopian tube is a very rare finding with only a small number of cases worldwide. We describe the case of a 51-year-old woman, undergoing an abdominal hysterectomy after the diagnosis of an HPV-associated invasive squamous cell carcinoma of the uterine cervix with the unexpected detection of an HPV16-positive high-grade squamous intraepithelial lesion of the fimbria of the right fallopian tube in the resection specimen. The finding of an isolated, HPV-associated squamous intraepithelial lesion in the fallopian tube raises the question of a de novo development in this body compartment (after exclusion of a continuous metastatic spread from the uterine cervix) by taking a virus-associated field effect into account and should encourage the inclusion of this possibility when examining the fallopian tube in a routine setting.

274. ROBOTIC-ASSISTED THORACOSCOPIC ESOPHAGECTOMY WITH MEDIASTINAL LYMPH NODE DISSECTION: DOES IT FEASIBLE FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA SURGERY?

Abstract Background Esophageal cancer is sixth leading cause of cancer-related mortality globally in 2020. Esophageal squamous cell carcinoma is one of most aggressive and need extensive operative treatment for radical and oncologic purpose. Conventional thoracotomy is highly invasive, conventional video-assisted is quite technical difficulty related with deep and narrow angle of exposure. Robotic-assisted procedure is new challenging to beat this limitation. This is descriptive report of initial robotic-assisted experiences regard to feasibility, safety and oncologic outcome. Methods We conducted a retrospective analysis of a single-center database from March 2012 to February 2023, including patients aged 45–85 years with resectable lesions of the esophageal squamous cell carcinoma who underwent robotic-assisted thoracoscopic esophagectomy using the Da Vinci Robotic surgery system. Patient data, surgical procedures, interventions, and early outcomes (within 30 days postoperation) were collected and analyzed to assess postoperative variables and adequacy of cancer clearance. The study included 12 patients, and the primary outcome was the incidence of pulmonary complications during the hospital stay. Results The overall incidence of postoperative pulmonary complications was 4cases (33.3%), with mild pulmonary infection occurring in 2cases (16.7%) without 30-day mortality in robotic-assisted thoracoscopic esophagectomy. The median admission period were 2 days and 15 days for ICU and hospital stay, respectively. The median time for the thoracic phase of operation was 210 minutes (150-445 minutes), and the median blood loss volume was 55 mL (20–300 mL). Pathological results showed that overall proximal and distal margins were uninvolved by tumor, and the median number of lymph nodes retrieval in the thoracic region was 22.5lymph nodes (14-73lymph nodes). 41.7% of patients were classified in pathological stage I. Conclusion Robotic-assisted thoracoscopic esophagectomy has shown promising early postoperative outcomes, low blood loss volume, short ICU and hospital stay, a low rate of pulmonary complications and including adequate lymph node retrieval and pathological results. These findings support the feasibility and safety of robotic-assisted thoracoscopic esophagectomy, which enhance postoperative recovery and improve surgical outcomes for the treatment of esophageal squamous cell carcinoma.

Lymph Node Metastases from Non-Melanoma Skin Cancer of the Head and Neck.

Non-melanoma skin cancer (NMSC) represents the most common malignancy in the world, comprising exceedingly common lesions such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) and rare lesions such as Merkel cell carcinoma. Risk factors are widely recognized and include ultraviolet (UV) light exposure, radiation exposure, immunosuppression, and many others. As a whole, survival and functional outcomes are favorable, but each histopathological subtype of NMSC behaves differently. Treatment regimens for the primary site usually include wide surgical excision and neck dissection in cases of clinically involved metastatic lymph nodes. The elective management of draining nodal basins, however, is a contested topic. Nearly all subtypes, excluding BCC, have a significant risk of lymphatic metastases, and have been studied with regard to sentinel lymph node biopsy (SLNB) and elective neck dissection. To date, no studies have definitively established a true single standard of care, as exists for melanoma, for any of the NMSCs. As a result, the authors have sought to summarize the current literature and identify indications and management options for the management of the cervical lymphatics for each major subtype of NMSC. Further research remains critically necessary in order to develop complete treatment algorithms.

Programmed death-ligand 1 (PD-L1) expression in cervical intraepithelial neoplasia and cervical squamous cell carcinoma of HIV-infected and non-infected patients

Programmed death-ligand 1 (PD-L1) is overexpressed in cervical carcinoma, hindering tumor destruction. The aim of this study was to assess PD-L1 expression by immunohistochemistry in cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SILs) from human immunodeficiency virus–positive (HIV+) and human immunodeficiency virus-negative (HIV-) patients. A total of 166 SCC and SIL samples of HIV+ and HIV- patients were included and analyzed for PD-L1 expression through tumor proportion score (TPS), and results were stratified in five TPS groups using SP263 antibody and, combined positive score (CPS) using 22C3 antibody. In cohort 1 (SP263 clone), all HIV+ patients were negative for intraepithelial lesion or malignancy (NILM), and low-grade squamous intraepithelial lesions (LSILs) scored < 1; and 87.5% of high-grade squamous intraepithelial lesions (HSILs) adjacent to SCC, 19% of HSILs non-adjacent to SCC, and 69% of SCCs scored ≥ 1 (15.4% scored 5). In HIV- patients, all NILM, LSILs, HSILs adjacent to SCC, and two HSILs non-adjacent to SCC scored < 1. SCC: 88.2% scored ≥ 1 and 5.9% scored 5. In cohort 2 (SP263 and 22C3 clones), 16.7% of HIV+ patients with SCC were positive with both clones, CPS ≥ 1 (22C3) or score 5 (≥ 50%) (SP263), showing no significant differences in positivity between both clones. These results indicate that a relatively low percentage of SCCs (16.7%; both in HIV+ and in HIV- patients) express PD-L1 (TPS ≥ 50% and CPS > 1), which may be due to some samples being archival material, sample characteristics, or use of different methodologies, highlighting the need for standardization of PD-L1 assessment in SCC of the cervix. The fact that PD-L1 is overexpressed in SILs of HIV+ patients suggests potential additional applications for immunotherapy in this disease.

Pulmonary microbiota signatures adjacent to adenocarcinoma, squamous cell carcinoma and benign lesion.

The occurrence and progression of lung cancer are influenced by pulmonary microbiota, yet the relationship between changes in the pulmonary microbiota and lung cancer remains unclear. To investigate the correlation between pulmonary microbiota and the signature of lung lesions, we analyzed the microbial composition at sites adjacent to the stage 1 adenocarcinoma, squamous carcinoma and benign lesion tissues in 49 patients by using 16S ribosomal RNA gene sequencing. We then conducted Linear discriminant analysis, receiver operating characteristic (ROC) curve analysis and PICRUSt prediction based on 16S sequencing results. Overall, the microbiota composition at sites close to lung lesions showed significant differences between different lesion types. Based on the results of LEfSe analysis, Ralstonia, Acinetobacter and Microbacterium are the dominant genera of lung adenocarcinoma (LUAD), lung squamous carcinoma (LUSC) and benign lesions (BENL), respectively. Furthermore, we determined the diagnostic value of the abundance ratio of Ralstonia to Acinetobacter in adenocarcinoma patients through ROC curve analysis. The PICRUSt analysis revealed 15 remarkably different metabolic pathways in these lesion types. In LUAD patients, the increase of the pathway associated with xenobiotic biodegradation may be due to the continuous proliferation of microbe with degradation ability of xenobiotics, which implied that LUAD patients are often exposed to harmful environment. The abundance of Ralstonia was related to the development of lung cancer. By measuring the abundance of microbiota in diseased tissues, we can distinguish between different types of lesions. The differences in pulmonary microbiota between lesion types are significant in understanding the occurrence and development of lung lesions.

Clinical validation of methylation biomarkers for optimal detection of high-grade vulvar intraepithelial neoplasia.

The precursor lesions of vulvar squamous cell carcinoma (VSCC) include human papillomavirus (HPV)-associated and HPV-independent squamous neoplasia with a varying cancer risk. Our study aimed to validate the accuracy of previously identified DNA methylation markers for detection of such high-grade vulvar intraepithelial neoplasia (VIN). A large clinical series of 751 vulvar lesions, originally diagnosed as high-grade VIN, were reassessed and categorized into HPV-associated or HPV-independent vulvar disease categories. Together with 113 healthy vulvar controls, all samples were tested for 12 methylation markers with quantitative multiplex methylation-specific PCR (qMSP). Performance of individual markers and selection of an optimal marker panel for detection of high-grade VIN was determined by logistic regression analysis. SST was the best-performing individual marker (AUC 0.90), detecting 80% of high-grade VIN cases, with excellent detection of HPV-independent VIN (95%), known to have the highest cancer risk. Merely 2% of controls tested methylation positive for SST. Selection of a marker panel, including ZNF582, SST and miR124-2, resulted in a comparably high accuracy for detection of high-grade VIN (AUC 0.89). In conclusion, we clinically validated the accuracy of 12 DNA methylation markers for detection of high-grade VIN. SST, as a sole marker or in a panel, provides an optimal diagnostic tool to distinguish high-grade VIN in need of treatment, particularly HPV-independent VIN, from low-grade or reactive vulvar lesions. These findings warrant further prognostic validation of methylation biomarkers for cancer risk stratification of patients with VIN.

Microbial and epidemiological factors in early detection of esophageal squamous cell carcinoma and precancerous lesions.

Microbial and epidemiological factors in early detection of esophageal squamous cell carcinoma and precancerous lesions.

Abstract 2422: In vivo pilot study of the effect of EGCG in photodynamic therapy on non melanoma skin cancer

Abstract Non-melanoma skin cancer (NSCLC) is the most frequent cancer in humans worldwide. Solar UV radiation is main risk factor to NSCLC developing in areas such as the face, neck, arms, etc. Basal cell carcinoma and precursor lesions of squamous cell carcinoma (SCC), such as actinic keratosis, Bowen’s disease, etc. can be treated with Photodynamic Therapy (PDT). PDT consists of applying a cream containing a photosensitizer on the skin lesion, to then being irradiated with light at a specific wavelength. The most used PS in skin cancer is methyl aminolevulinate (MAL). Light excites the photosensitizer, which interacts with intracellular O2, producing reactive oxygen species (ROS), triggering cancer cell death. One of the main advantages of PDT is that it offers satisfactory cosmetic results. However, its effectiveness is variable. Our previous results, using a PDT-resistant SCC cell model, showed that the addition of epigallocatechin gallate (EGCG) to PDT has a potentiated effect, killing 100% of these cells. Therefore, the aim of this work was to evaluate the effect of an EGCG-enhanced cream for PDT on squamous cell carcinoma lesions in an animal model.A two-step chemical carcinogenesis protocol (DMBA/TPA) was used in male and female mice of the Balb/c strain (21 animals). Once the animals developed the desired lesions, they were randomly separated into three groups. The first group received conventional cream (MAL 20%), the second group cream A (MAL 20% + EGCG 1%) and the third group B cream (MAL 20% + EGCG 3%). PDT was performed as follows: cream was applied for 4 hours on the lesion and then protected from the light with a patch. Subsequently, the excess cream was removed and the lesions were irradiated with 630 nm red light. The lesions were followed up for one month, measuring the size of the tumor and taking a final biopsy.We successfully develop an in vivo model of NSCLC using chemical inducers. Mice develops two kind of lesions: plane and/or papillar. All mice were treated with PDT using the three different formulations. Lesions reduced its size until a 50% more when treated with PDT plus EGCG. Formulation B (MAL 20% + EGCG 3%), was the most effective, given it had a greater on the relative reduction of the volume of the lesion. In conclusion, this in vivo pilot study evidences the enhancing effect of EGCG on PDT, encouraging the pursue to continue with the investigations on this matter, in order to improve the PDT and the quality of life of skin cancer patients. Citation Format: Carmen Gloria Ili, Daniela Leon, Maria Elena Reyes, Kurt Buchegger, Francisca Acevedo-Canala, Pablo Guzman, Claudia Nicklas, Cecicia Orlandi, Priscilla Brebi. In vivo pilot study of the effect of EGCG in photodynamic therapy on non melanoma skin cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2422.

Diagnostic accuracy of combined optical- and radio-guided SNB for neck staging of oral squamous cell carcinoma lesions in the anterior oral cavity

PurposeThe purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity.MethodsProspective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up.ResultsIn all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%.ConclusionOptical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injection.

Human β-Defensins in Diagnosis of Head and Neck Cancers

Head and neck cancers are malignant growths with high death rates, which makes the early diagnosis of the affected patients of utmost importance. Over 90% of oral cavity cancers come from squamous cells, and the tongue, oral cavity, and salivary glands are the most common locations for oral squamous cell carcinoma lesions. Human β-defensins (hBDs), which are mainly produced by epithelial cells, are cationic peptides with a wide antimicrobial spectrum. In addition to their role in antimicrobial defense, these peptides also take part in the regulation of the immune response. Recent studies produced evidence that these small antimicrobial peptides are related to the gene and protein expression profiles of tumors. While the suppression of hBDs is a common finding in head and neck cancer studies, opposite findings were also presented. In the present narrative review, the aim will be to discuss the changes in the hBD expression profile during the onset and progression of head and neck cancers. The final aim will be to discuss the use of hBDs as diagnostic markers of head and neck cancers.

Stathmin 1 and p53 Expression in Cutaneous Squamous Cell Carcinoma and Precursor Lesions.

Studies on the relationship between stathmin 1 (STMN1) and cutaneous squamous cell carcinoma (cSCC) are limited. We aimed to evaluate the relationship between clinicopathological factors and STMN1 and p53 expressions in cSCC and compare them with those in the precursor lesions of cSCC and normal tissue. A total of 195 patients, followed between January 2014 and December 2021, with diagnoses of primary cSCC (n = 129), in situ cSCC (n = 20), or actinic keratosis (n = 46), as well as 29 histopathologically normal tissue samples, were included in the study. Immunohistochemical staining for STMN1 and p53 was performed. In the cSCC group, STMN1 scores were higher in poorly differentiated ( P = 0.001) and ulcerated ( P < 0.001) tumors. A linear relationship between STMN1 score and tumor area, tumor thickness, and mitosis was found ( P = 0.001, P = 0.003, and P < 0.001, respectively). There was no statistically significant correlation between STMN1 and p53 scores. Our results support the previous view that STMN1 may be associated with some adverse clinicopathological and high-risk features of cSCC. To the best of our knowledge, this is the first and largest study to investigate STMN1 expression in cSCC, precancerous lesions of cSCC, and normal tissues.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions by p16 and p53 Immunohistochemistry: Considerations, Caveats, and an Algorithmic Approach

There is emerging evidence that vulvar squamous cell carcinoma (VSCC) can be prognostically subclassified into 3 groups based on human papillomavirus (HPV) and p53 status: HPV-associated (HPV+), HPV-independent/p53 wild-type (HPV−/p53wt), or HPV-independent/p53 abnormal (HPV−/p53abn). Our goal was to assess the feasibility of separating VSCC and its precursors into these 3 groups using p16 and p53 immunohistochemistry (IHC). A tissue microarray containing 225 VSCC, 43 usual vulvar intraepithelial neoplasia (uVIN/HSIL), 10 verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN), and 34 differentiated VIN (dVIN), was stained for p16 and p53. Noncomplementary p16 and p53 patterns were resolved by repeating p53 IHC and HPV RNA in situ hybridization (ISH) on whole sections, and sequencing for TP53. Of 82 p16-positive VSCC, 73 (89%) had complementary p16 and p53 patterns and were classified into the HPV+ group, 4 (4.9%) had wild-type p53 staining, positive HPV ISH and were classified into the HPV+ group, whereas 5 (6.1%) had p53 abnormal IHC patterns (1 null, 4 overexpression), negativity for HPV ISH, and harbored TP53 mutations (1 splice site, 4 missense); they were classified as HPV−/p53abn. Of 143 p16-negative VSCC, 142 (99.3%) had complementary p53 and p16 patterns: 115 (80.4%) HPV−/p53abn and 27 (18.9%) HPV−/p53wt. One had a basal-sparing p53 pattern, positivity for HPV ISH and was negative for TP53 mutations—HPV+ category. The use of IHC also led to revised diagnoses—HSIL to dVIN (3/43), dVIN to vaVIN (8/34), and dVIN to HSIL (3/34). Overall, 215/225 VSCC (95.6%) could be easily classifiable into 3 groups with p16 and p53 IHC. We identified several caveats, with the major caveat being that “double-positive” p16/p53 should be classified as HPV−/p53abn. We propose an algorithm that will facilitate the application of p16 and p53 IHC to classify VSCC in pathology practice.