Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology.

Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma in situ (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.

Characterizing the cutaneous late effects of allogeneic hematopoietic stem cell transplantation: A systematic review.

BACKGROUND: There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139). Studies reporting cutaneous cancer outcomes were included if the age at transplant was ≤19 years. Titles, abstracts, and full-text articles were screened in duplicate. RESULTS: Out of 824 citations that were screened, 12 articles were selected for analysis. The final sample included 67 pediatric HSCT recipients, comprising 65 allogeneic transplant recipients and 2 cases of HSCT with an unknown donor type. The median age at transplant and skin cancer diagnosis were 7.4 and 13 years, respectively. Out of the 67 pediatric HSCT recipients, some patients developed more than one lesion, resulting in 71 lesions. The most common skin cancer type was cutaneous squamous cell carcinoma (32 lesions), followed by basal cell carcinoma (25 lesions). The median latency period between HSCT and skin cancer diagnosis ranged from 0 to 29 years. Identified risk factors for skin cancers included younger age at the time of transplant, exposure to total body irradiation, prolonged post-transplant immunosuppression, graft versus host disease, and sunburn. CONCLUSION: Skin cancers are reported in pediatric allogeneic HSCT recipients, and the risk appears to be increased. More data are needed to better characterize this risk.

Concomitant vs Staged Therapeutic Inguinal Lymphadenectomy in Clinically Node Positive Penile Squamous Cell Carcinoma: Does It Make a Difference?

PURPOSE: Inguinal lymph node dissection within 3 months of primary tumor resection in penile cancer has been associated with longer recurrence-free and cancer-specific survival. However, the optimal timing and effect of lymphadenectomy performed concurrently at the time of primary lesion management on oncologic outcomes in clinically lymph node positive penile squamous cell carcinoma remains unknown. MATERIALS AND METHODS: An international, multicenter cohort of 966 penile cancer cases was queried for penile squamous cell carcinoma management after the year 2000, clinically lymph node positive status, and performance of penile surgery and inguinal lymph node dissection. Cohorts were stratified as concomitant if inguinal lymph node dissection and penile surgery occurred on the same date or staged when inguinal lymph node dissection was performed after penile resection. Rates and patterns of penile squamous cell carcinoma recurrence were reported. Distant recurrence-free, cancer-specific, and overall survival were estimated using Kaplan-Meier analyses and groups compared with log-rank testing. RESULTS: Of 253 contemporary men with clinically lymph node positive penile squamous cell carcinoma, 96 (38%) underwent concomitant inguinal lymph node dissection and 157 (62%) had inguinal lymph node dissection performed in a staged manner. Penile cancer was most likely to recur distantly (19%) followed by in the groin (14%) or pelvis (5%). There were no differences in distant recurrence-free, cancer-specific, or overall survival between management strategies. Multivariable analysis adjusting for stage, treatment center, and perioperative chemoradiation also demonstrated no recurrence-free, cancer-specific, or overall survival benefit between management strategies. CONCLUSIONS: Inguinal lymph node dissection performed concurrently with excision of the penile tumor for clinically node positive penile squamous cell carcinoma is not associated with differences in recurrence-free, cancer-specific, or overall survival compared to staged lymph node dissection.

Diffusion-weighted imaging complements T2-weighted MRI for tumour response assessment in squamous anal carcinoma.

OBJECTIVES: A published tumour regression grade (TRG) score for squamous anal carcinoma treated with definitive chemoradiotherapy based on T2-weighted MRI yields a high proportion of indeterminate responses (TRG-3). We investigate whether the addition of diffusion-weighted imaging (DWI) improves tumour response assessment in the early post treatment period. MATERIALS AND METHODS: This retrospective observational study included squamous anal carcinoma patients undergoing MRI before and within 3 months of completing chemoradiotherapy from 2009 to 2020. Four independent radiologists (1-20 years' experience) scored MRI studies using a 5-point TRG system (1 = complete response; 5 = no response) based on T2-weighted sequences alone, and then after a 12-week washout period, using a 5-point DWI-TRG system based on T2-weighted and DWI. Scoring confidence was recorded on a 5-point scale (1 = low; 5 = high) for each reading and compared using the Wilcoxon test. Indeterminate scores (TRG-3) from each reading session were compared using the McNemar test. Interobserver agreement was assessed using kappa statistics. RESULTS: Eighty-five patients were included (mean age, 59 years ± 12 [SD]; 55 women). T2-weighted TRG-3 scores from all readers combined halved from 24% (82/340) to 12% (41/340) with DWI (p < 0.001). TRG-3 scores changed most frequently (41%, 34/82) to DWI-TRG-2 (excellent response). Complete tumour response was recorded clinically in 77/85 patients (91%). Scoring confidence increased using DWI (p < 0.001), with scores of 4 or 5 in 84% (287/340). Interobserver agreement remained fair to moderate (kappa range, 0.28-0.58). CONCLUSION: DWI complements T2-weighted MRI by reducing the number of indeterminate tumour responses (TRG-3). DWI increases radiologist's scoring confidence. CLINICAL RELEVANCE STATEMENT: Diffusion-weighted imaging improves T2-weighted tumour response assessment in squamous anal cancer, halving the number of indeterminate responses in the early post treatment period, and increases radiologists' confidence. KEY POINTS: Tumour response based on T2-weighted MRI is often indeterminate in squamous anal carcinoma. Diffusion-weighted imaging alongside T2-weighted MRI halved indeterminate tumour regression grade scores assigned by four radiologists from 24 to 12%. Scoring confidence of expert and non-expert radiologists increased with the inclusion of diffusion-weighted imaging.

Need for adjuvant radiotherapy in oral cancer: depth of invasion rather than tumor diameter.

PURPOSE: The 8th edition of the TNM Cancer Staging Manual incorporates depth of invasion (DOI) into the pathologic tumor classification for oral squamous cell carcinoma (OSSC). While deep invading tumors with small tumor diameters (TD) have been categorized as early stage tumors in the 7th edition, they are now upstaged, potentially influencing the decision to initiate adjuvant radiotherapy (RT). METHODS: OSCC patients surgically treated with curative intent between 2010 and 2019 were consecutively included. Tumors were staged based on TD only (according to the 7th edition TNM Cancer Staging Manual), then restaged based solely on DOI. RESULTS: Of the 133 included patients, 58 patients (43.6%) had a different pT-stage when using DOI instead of TD for staging (upstaging in 23.3%). Overall survival (OS) was significantly worse in patients who were upstaged with DOI. In addition, stratification by adjuvant RT showed significant worse OS in upstaged patients without receiving adjuvant RT. CONCLUSIONS: DOI seems to be an import indicator for adjuvant RT in OSCC-patients.

[Diagnostics and treatment of secondary malignancies of the parotid gland-An overview]. / Diagnostik und Therapie sekundärer Malignome der Ohrspeicheldrüse ­ eine Übersicht.

BACKGROUND: Secondary malignancies of the parotid gland frequently have a cutaneous origin and the incidence in central Europe is increasing. OBJECTIVE: The aim of this review article was to present the epidemiology, (differential) diagnostics and treatment of secondary malignancies of the parotid gland. MATERIAL AND METHODS: A literature search of the current guidelines and evidence was carried out in the web-based databank PubMed. RESULTS: The incidence of secondary malignancies of the parotid gland seems to be increasing in Europe, mainly due to a rising incidence of metastases of cutaneous squamous cell carcinomas. Except for malignant lymphomas, parotidectomy is the treatment of choice in the curative situation. In the absence of clear evidence, in the case of an intact facial nerve lateral or total parotidectomy with ipsilateral neck dissection seems to be indicated, depending on the entity of the secondary malignancy. CONCLUSION: The differential diagnostics of squamous cell carcinoma (in) of the parotid gland can be complicated. When a squamous cell carcinoma of the parotid gland is diagnosed for the first time, a dermatological full body examination and a detailed medical history should be taken with respect to skin tumors of the head and neck region. In addition to surgical treatment of the parotid gland and neck, adjuvant radiotherapy is usually indicated.

[Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma].

OBJECTIVE: To explore the significance and feasibility of whole exon sequencing and immune related indexes in personalized precision treatment of oral squamous cell carcinoma (OSCC). METHODS: We retrospectively screened the patients who underwent surgery for oral cancer in Peking University Hospital of Stomatology and underwent genetic and immune biomarkers tests between January 2021 and June 2022. Combined with the clinicopathological characteristics of patients, potential targeted drugs and immunotherapy drugs were screened to evaluate the possibility of gene testing benefiting OSCC. The main evaluation indicators included the number of gene mutations, combined positive score (CPS), tumor mutation burden (TMB), microsatellite sequence status and human leukocyte antigen B (HLA-B) locus. Excel was used for statistical analysis. RESULTS: A total of 10 patients were enrolled and 9 were included in this study, including 6 males and 3 females, with an average age of (55.44±9.59) years. The tumor location was buccal (5 cases), tongue (3 cases) and gingival (1 case). The results of genetic testing showed that 3 (33.3%) patients had no gene mutations in the tumor tissue, 5 (55.6%) patients had unique TP53 gene mutations, and 1 (11.1%) patient had TP53 and CHEK1 mutations. However, no drugs were available for targeted therapy of the mutated genes. The genetic tumor gene testing results showed that no genetic tumor gene was found in all the patients, suggesting that OSCC had a low possibi-lity of hereditary tumor. In terms of immune efficacy related markers, CPS test results showed that 8 patients had CPS≥1. TMB detection results showed that the median value of TMB value was 0.72 mutations/Mb, and the range was 0 to 4.32 mutations/Mb. The negative and positive control results of microsatellite sequence status were consistent, indicating that all the tumor tissues detected were microsatellite stability. The results of HLA-B detection showed that only one patient had B62 gene mutation, suggesting that the B44 and B62 related genotypes of HLA-B in OSCC tissue samples were low. CONCLUSION: The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.

Diagnostic Accuracy Of Fine Needle Aspiration Cytology In Comparison To Open Biopsy For Lesions Of Oral Cavity In COVID-19 Era.

Objective: To compare the diagnostic accuracy and uses of fine needle aspiration cytology with histopathology in the diagnosis of lesions of oral cavity. METHODS: The single-centre, prospective, non-randomised controlled trial was conducted at the departments of Oral and Maxillofacial Surgery and Pathology of Allama Iqbal Medical College/Jinnah Hospital, Lahore, Pakistan, from January 10 to August 10, 2021, and comprised patients of either gender aged >10 years having superficial or deep well- established mass, palpable, nodular, ulcerative lesions, swellings of the oral cavity or of major or minor salivary glands having intraoral presence or manifestation with size >1 cm. Data was analysed using SPSS 20. RESULTS: Of the 43 patients, 22(51.2%) were males and 21(48.8%) were females. The overall mean age was 40.5±15 years (range 13-70 years). On cytological examination, 6(14%) samples were excluded for being insufficient aspirate. Of the remaining 37(86%) samples, 20(51.4%) were detected with malignancy on histopathology. The accuracy of fine needle aspiration cytology was 33(89.19%). Conclusion: Fine needle aspiration was found to be a reliable and cost-effective technique in the diagnosis of oral cavity lesions.

Diagnostic and prognostic role of cancer stem cell biomarkers in oral squamous cell carcinoma; A Systematic Review.

Objectives: To evaluate the role of cancer stem cell biomarkers in diagnosis and prognosis of OSCC patients. METHODS: The search strategy was entered into PubMed NLM, EBSCO CINAHL, EBSCO Dentistry & Oral Sciences Source, Wiley Cochrane Library, and Scopus. The full text eligible studies (n=7) were assessed for their quality using the JBI Critical Appraisal Checklist to evaluates the methodological quality of the studies based on possibility of bias in its design, conduct, and analysis. Selected studies were further analysed based on different parameters such as publication year, sample size, and outcomes. RESULTS: A total of 432 studies were identified through the search strategy. A total of 306 records were removed before screening either because of duplication or marked ineligible by the automation tools. The screened records were 126 out of which 104 were removed as they were not conducted on OSCC. Twenty-two reports were sought for retrieval, however, we could not find the full text of 3 studies and12 studies were excluded because the biomarkers were not associated with cancer stem cells. The most common cancer stem cell biomarkers associated with OSCC were MCT1,VEGF-A, GD15, HIF1 α, Ki67, Hsp 70, Cyclin D1, and CD44. CONCLUSIONS: Various stem cell biomarkers have been found to have diagnostic and prognostic role in oral squamous cell carcinoma such as Cyclin D1, VEGF-A, GD15, and CD44. They can be used to predict the overall survival rate, local progression-free survival rate, and distant metastasis-free survival rate in Head and Neck cancer patients.

External Auditory Canal Carcinoma With An Unusually Extensive Invasion.

External auditory canal carcinoma, while starting out as a seemingly benign condition, if left untreated can have an aggressive course of disease and involve multiple lower cranial nerves. Squamous cell carcinoma remains the most frequent histological type of malignant neoplasm of the external auditory canal and temporal bone. Here we describe a patient with a history of chronic suppurative otitis media with an extensive spread, the tumour was reaching from the skull base to the oropharynx involving neurovasculature along with soft tissues and bones, as well as the cerebellum. The involvement of the recurrent laryngeal and hypoglossal nerves were the most unusual presentation here. The case differed from all previous reported cases as the spinal accessory nerve was to spared. Surgery and radiotherapy are the treatment options but for the inoperable cases presenting with an already poor prognosis, concomitant radiotherapy is the only choice.

Therapy Failure and Resistance Mechanism in Eyelid and Ocular Surface Tumors.

Malignant tumors of the eyelids and ocular surface are common ocular malignancies. At present, surgical treatment is mostly the first choice for these types of tumors. However, postoperative tumor recurrence and metastasis are still regarded as failures in the treatment of such malignancies. Based on this, malignant tumors of the eyelid and ocular surface are sometimes accompanied by local adjuvant chemotherapy and systemic chemotherapy to treat patients with relapse, invasion of adjacent tissues, and systemic metastases. Still, drug resistance greatly affects the treatment effect. This review lists several mechanisms of recurrence and metastasis of ocular surface and eyelid tumors after surgery, as well as mechanisms that may lead to non-surgical treatment or drug resistance.

Combined PET-CT and MRI for response evaluation in patients with squamous cell anal carcinoma treated with curative-intent chemoradiotherapy.

OBJECTIVES: To assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for response assessment post curative-intent chemoradiotherapy (CRT) in anal squamous cell carcinoma (ASCC). METHODS: Consecutive ASCC patients treated with curative-intent CRT at a single centre between January 2018 and April 2020 were retrospectively identified. Clinical meta-data including progression-free survival (PFS) and overall survival (OS) outcomes were collated. Three radiologists evaluated PET-CT and MRI using qualitative response assessment criteria and agreed in consensus. Two-proportion z test was used to compare diagnostic performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy). Kaplan-Meier analysis (Mantel-Cox log-rank) was performed. RESULTS: MRI (accuracy 76%, PPV 44.8%, NPV 95.7%) and PET-CT (accuracy 69.3%, PPV 36.7%, NPV 91.1%) performance metrics were similar; when combined, there were statistically significant improvements (accuracy 94.7%, PPV 78.9%, NPV 100%). Kaplan-Meier analysis demonstrated significant differences in PFS between responders and non-responders at PET-CT (p = 0.007), MRI (p = 0.005), and consensus evaluation (p < 0.001). Cox regression analysis of PFS demonstrated a lower hazard ratio (HR) and narrower 95% confidence intervals for consensus findings (HR = 0.093, p < 0.001). Seventy-five patients, of which 52 (69.3%) were females, with median follow-up of 17.8 months (range 5-32.6) were included. Fifteen of the 75 (20%) had persistent anorectal and/or nodal disease after CRT. Three patients died, median time to death 6.2 months (range 5-18.3). CONCLUSION: Combined PET-CT and MRI response assessment post-CRT better predicts subsequent outcome than either modality alone. This could have valuable clinical benefits by guiding personalised risk-adapted patient follow-up. KEY POINTS: • MRI and PET-CT performance metrics for assessing response following chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC) were similar. • Combined MRI and PET-CT treatment response assessment 3 months after CRT in patients with ASCC was demonstrated to be superior to either modality alone. • A combined MRI and PET-CT assessment 3 months after CRT in patients with ASCC has the potential to improve accuracy and guide optimal patient management with a greater ability to predict outcome than either modality alone.

Hydrochlorothiazide use is associated with the risk of cutaneous and lip squamous cell carcinoma: A systematic review and meta-analysis.

PURPOSE: The aim of this study is to investigate the association between hydrochlorothiazide (HCTZ) use and the risk of cutaneous and lip squamous cell carcinoma development. METHODOLOGY: We performed a systematic review and meta-analysis of case-control studies. We searched the Cochrane Library, PubMed, Scopus, Web of Science and LILACS. This study was registered in PROSPERO under protocol CRD42019129710. The meta-analysis was performed using the software Stata (version 12.0). RESULTS: A total of 2181 published studies referring to the theme were identified, from which six were included in this systematic review. Men were more frequently affected by cutaneous and lip squamous cell carcinoma than women, with a 1.42:1 ratio. The mean age for cutaneous and lip squamous cell carcinoma development was 73.7 years. This meta-analysis demonstrated a chance of developing cutaneous and lip squamous cell carcinoma in any region of the body in hydrochlorothiazide users of 1.76-fold higher than in non-users. In addition, a risk factor of 1.80 higher (CI 95% = 1.71-1.89) of cutaneous squamous cell carcinoma in the head and neck region was observed in HCTZ users. Moreover, in the analysis of the dose used, the chance of developing squamous cell carcinoma was 3.37-fold lower when the concentration of HCTZ used was less than 50,000 mg. CONCLUSIONS: Our results confirm the association between the use of hydrochlorothiazide and the cutaneous and lip squamous cell carcinoma development.

Treatment Options in Early Stage (Stage I and II) of Oropharyngeal Cancer: A Narrative Review.

OBJECTIVE: to show an overview on the treatments' options for stage I and II oropharyngeal carcinomasquamous cell carcinoma (OPSCC). BACKGROUND: The traditional primary treatment modality of OPSCC at early stages is intensity modulated radiation therapy (IMRT). Trans-oral robotic surgery (TORS) has offered as an alternative, less invasive surgical option. Patients with human papilloma virus (HPV)-positive OPSCC have distinct staging with better overall survival in comparison with HPV-negative OPSCC patients. METHODS: a comprehensive review of the English language literature was performed using PubMed, EMBASE, the Cochrane Library, and CENTRAL electronic databases. CONCLUSIONS: Many trials started examining the role of TORS in de-escalating treatment to optimize functional consequences while maintaining oncologic outcome. The head-neck surgeon has to know the current role of TORS in HPV-positive and negative OPSCC and the ongoing trials that will influence its future implementation. The feasibility of this treatment, the outcomes ensured, and the side effects are key factors to consider for each patient. The variables reported in this narrative review are pieces of a bigger puzzle called tailored, evidence-based driven medicine. Future evidence will help in the construction of robust and adaptive algorithms in order to ensure the adequate treatment for the OPSCC at early stages.

Validation of the American Joint Committee on Cancer Staging in Squamous Cell Carcinoma of the Vermilion Lip.

BACKGROUND: The vermilion lip is a unique anatomical junction between cutaneous and mucosal surfaces. Squamous cell carcinoma (SCC) of the vermilion lip (vlSCC) was previously classified as oral SCC (oSCC) under the American Joint Committee on Cancer (AJCC) 7th edition (AJCC7), but has been recategorized as a cutaneous SCC of the head and neck (HNcSCC) in the AJCC 8th edition (AJCC8). We investigated the locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for the various pathological T categories and disease stages of vlSCC as per AJCC8. METHODS: We performed a retrospective cohort study of 297 patients diagnosed with vlSCC between January 2004 and February 2019. For this study, vlSCC cases were staged according to both AJCC7 and AJCC8. Kaplan-Meier survival curves and Cox regression models were used to analyze differences in LRC, DFS, and OS between each pT category and disease stage, and log-rank tests were performed for subgroup analysis. RESULTS: Restaging of vlSCC using the AJCC8 resulted in 19% of patients being upstaged to pT3, and 16% being upstaged to stage III. No patients were downstaged in pT stage or overall stage. CONCLUSIONS: Our study shows that when the AJCC8 HNcSCC staging system is applied to vlSCC, there are important aberrations leading to unwarranted upstaging of pT1 and redundancy of pT2. Understanding of these limitations are important in considering treatment escalation.

Correlation of anal cytology with follow-up histology and Human Papillomavirus genotyping: A 10-year experience from an academic medical center.

BACKGROUND: Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status. METHODS: 377 ACs from 169 patients (151 males and 18 females) from 2008 to 2017 were included. HPV genotyping (n = 47) and SP within one year of AC (n = 58) were reviewed. RESULTS: AC/SP was discrepant in 22 cases (37.9%), with a tendency towards AC underestimating the degree of dysplasia. Specifically, any abnormality on AC was 93.8% sensitive for detecting high-grade dysplasia (HGD). However, when requiring a high-grade AC diagnosis, the sensitivity decreases to 12.5%. "Other high-risk HPV" was the most common genotype (57.4%). When considered with all AC with a high-grade diagnosis, co-testing with HPV improved the sensitivity for HGD to 56.3%. Sensitivity improved further to 87.5% when only considering cases with both AC and HPV testing, and were high-risk HPV positive. Furthermore, following review and consensus diagnosis, 8 cases changed from "Discrepant" to "Agreed", reducing the discrepancy rate to 24.1%. Remaining discrepancies were explained by sampling error. CONCLUSION: Given the enhanced sensitivity of AC and HPV testing together, and sampling error seen with AC leading to underestimating dysplasia, we recommend AC and HPV co-testing, as well as describing confounding factors in AC reports and obtaining consensus opinion in equivocal cases.

The value of CT, MRI, and PET-CT in detecting retropharyngeal lymph node metastasis of head and neck squamous cell carcinoma.

BACKGROUND: The diagnostic accuracies of the imaging studies should be clearly acknowledged in managing head and neck cancer patients; however, the accuracies of preoperative imaging studies in detecting retropharyngeal lymph node (RPLN) metastasis are still not clarified. This study was to evaluate diagnostic accuracies of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) in detecting RPLN metastasis of head and neck squamous cell carcinomas. METHODS: For 123 patients who had performed RPLN dissection during the surgery of their squamous cell carcinoma of the head and neck, preoperative CT, MRI, and/or PET-CT were reviewed for RPLN metastasis in a blinded fashion by one experienced radiologist. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of each imaging modality were assessed, by comparing with the histopathologic findings of the resected RPLNs that served as the standard of reference. RESULTS: RPLNs were pathologically positive for metastasis in 43 of the 123 patients (35%). Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in detecting metastasis to RPLN were 65, 94, 85, 83, and 84% for CT; 74, 94, 87, 87 and 87% for MRI; 83, 93, 89, 89 and 89% for PET-CT, respectively. When all the three imaging modalities were considered together (n = 74), they offered sensitivity of 90%, specificity of 91%, positive predictive value of 87%, negative predictive value of 93%, and accuracy of 91%. CONCLUSIONS: The preoperative imaging studies offered relatively high specificity rates, but rather low sensitivity rates. The three imaging modalities altogether increased diagnostic accuracies, which highlights the potential of the three studies when used altogether can minimize missed diagnoses of RPLN metastasis.

[AMG-102 inhibits proliferation and induces apoptosis of laryngeal squamous cell carcinoma cells by regulating c-Met/PI3K/Akt pathway].

Objective: To investigate the effects of c-Met inhibitor AMG-102 on the proliferation and apoptosis of laryngeal squamous carcinoma Hep-2 cells and the underlying mechanism. Methods: Laryngeal squamous carcinoma cell line Hep-2 cells were treated with 2.5, 5 and 10 µmol/L AMG-102, respectively. The proliferation activities of Hep-2 cells were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT). The apoptotic rate of Hep-2 cells was detected by flow cytometry analysis and Hoechst staining. The mRNA expression levels of apoptosis-related genes were detected by real-time quantitative polymerase Chain reaction (RT-qPCR), and the protein expressions of c-Met/PI3K/AKT pathway were detected by western blot. Results: Compared with the control group, the proliferation rates of Hep-2 cells treated with 2.5, 5 and 10 µmol/L AMG-102 for 24 hours were (89.8±1.1)%, (79.8±1.0)% and (69.1±1.2)%, respectively; for 48 hours were (76.8±2.0)%, (60.2±1.1)% and (49.8±1.2)%, respectively; for 72 hours were (50.1±2.0)%, (41.5±1.1)% and (33.6±1.0), respectively, with significant differences (all P<0.05). The apoptotic rates of Hep-2 cells treated with 2.5, 5 and 10 µmol/L AMG-102 for 48 hours were (16.09±1.53)%, (27.51±2.02)% and (36.57±1.42)%, respectively, which were significantly higher than (3.62±0.10) % in the control group (all P<0.05). After treated with 2.5, 5 and 10 µmol/L AMG-102 for 48 hours, the relative expression levels of Bcl-2 mRNA in Hep-2 cells were 0.58±0.13, 0.38±0.12 and 0.20±0.13, respectively; the relative protein expression of p-Met were 80.0±3.8, 50.6±4.2 and 28.5±1.3, respectively; the relative protein expression of p-PI3K were 87.1±0.9, 54.2±1.2 and 21.0±1.2, respectively; the relative protein expression of p-AKT were 98.7±5.6, 56.9±3.2 and 32.2±4.3, respectively; which were significantly lower than those in the control group (all P<0.05). The relative expression levels of Bax mRNA were 1.78±0.13, 2.37±0.14 and 3.05±0.13, respectively, and the relative expression levels of caspase-3 mRNA were 1.98±0.14, 2.47±0.14 and 3.15±0.13, respectively, which were significantly higher than those in the control group (all P<0.05). Conclusion: c-Met inhibitor AMG-102 could inhibit the proliferation and induce apoptosis of laryngeal squamous carcinoma Hep-2 cells by regulating the c-Met/PI3K/Akt pathway.

[MicroRNA-140-5p suppresses cell proliferation and invasion in esophageal squamous cell carcinoma by targeting Glut1].

Objective: To investigate the expression of microRNA-140-5p (miR-140-5p) in esophageal squamous cell carcinoma (ESCC) and its role in cell proliferation and invasion of ESCC. Methods: Real-time quantitative PCR (qPCR) was used to detect the expression levels of miR-140-5p in ESCC tissues and cells. Negative control and miR-140-5p mimic were transfected into Eca109 and KYSE70 cells. CCK-8 kit and Transwell assay were employed to examine the changes of cell proliferation and invasion ability after transfection, respectively. The dual-luciferase reporter assay was used to assess the interaction of miR-140-5p with Glut1. Western blot was utilized to detect the Glut1 protein expression after transfection. Results: Analysis of the related GEO datasets revealed that the expression of miR-140-5p in ESCC tissues was significantly lower than that in normal tissues (P<0.01). The qPCR testing demonstrated that the expression of miR-140-5p in ESCC tissues and cells was markedly lower than that in normal tissues and normal esophageal epithelial cell Het-1A (P<0.01). The miR-140-5p expression was closely associated with tumor differentiation, TNM staging and lymph node metastasis in ESCC patients. The survival rate of ESCC patients with high miR-140-5p level was higher than those with low miR-140-5p level (P<0.05). Besides, addition of miR-140-5p mimic significantly upregulated the expression of miR-140-5p in Eca109 and KYSE70 cells, and suppressed cell proliferation and invasion in Eca109 and KYSE70 cells. The dual-luciferase reporter assay showed that Glut1 was a direct target of miR-140-5p in ESCC cells, and its expression was upregulated in ESCC tissues. Glut1 expression was inversely associated with miR-140-5p expression in ESCC tissues. MiR-140-5p mimic dramatically inhibited the expression of Glut1 in Eca109 and KYSE70 cells. Conclusions: MiR-140-5p plays an essential role in ESCC development and progression. Targeting at miR-140-5p/Glut1 may be a novel therapeutic strategy for ESCC patients.

[Clinical and pathological analysis of 64 patients with primary neoplasms of the lacrimal drainage system].

Objective: To analyze the pathological classification and age distribution of primary neoplasms of the lacrimal drainage system. Methods: Retrospective case series study. A total of 64 patients (65 eyes) were diagnosed with primary neoplasms of the lacrimal drainage system and received surgery at Tianjin Eye Hospital from January 2006 to December 2016. All the clinical data of the patients were analyzed, including gender, diseased eye, age, clinical manifestations, composition of benign and malignant masses, and prognosis. The histopathological composition and age distribution of patients with primary lacrimal mass, lacrimal duct mass and lacrimal sac mass were analyzed according to the different diseased sites. Results: Twenty-three patients (24 eyes) were male, and 41 patients (41 eyes) were female. The right eye was involved in 36 patients, the left eye in 27 patients, and both eyes in one patient. The age at diagnosis ranged from 12 to 78 years old [mean, (46±4) years]. The course of disease was (13.1±4.2) months, ranging from 1 month to 7 years. The chief complaint was tear discharge in 43 patients, tumor in 19 patients, and abscess discharge in 2 patients. There were 29 patients with angular displacement and 21 patients with swelling pain. There were 51 patients with benign lesions, 4 with borderline lesions, and 9 with malignantlesions. These neoplasms consisted of primary peripunctal neoplasms in 17 patients, primary canalicular neoplasms in 2 patients, and primary lacrimal sac neoplasms in 45 patients. All primary peripunctal neoplasms (17 cases) were benign, among which nevi (10 cases) occupied the first place. All primary canalicular neoplasms (2 cases) were benign, there were 1 case of epidermoid cysts and 1 case of degenerative disease. Among the primary benign lacrimal sac masses (32 cases), mucous epithelial cysts (9 cases), dermoid cysts (6 cases), and epidermoid cysts (6 cases) occupied the first three places. Among the primary borderlin lacrimal sac masses (4 cases), there were 2 cases of giant cell tumor of soft tissue, 1 case of solitary fibrous tumor, and 1 case of inflammatory myofibroblastic tumor. The primary malignant mass of lacrimal sac (9 cases) was dominated by squamous cell carcinoma (3 cases). In terms of age distribution, the patients with primary peripunctal mass were mainly in the group of 40-59 years old (14 cases). The primary benign mass of lacrimal sac mainly occurred in the group of less than 40 years old (15 cases) and the group of 40-59 years old (11 cases). The patients with primary lacrimal sac borderline and malignant masses were all in the groups of over 40 years old. A total of 49 patients were followed up for 27 months to 16 years. The average follow-up time was (57.2±3.8) months. Lacrimal sac transitional cell carcinoma relapsed 7 months after surgery in one patient, and lacrimal sac melanoma relapsed 1 year after surgery in one patient. The patients did not relapse in 24 months and 38 months after surgery respectively. There were no recurrence of other cases. Conclusions: Primary peripunctal neoplasms are mostly characterized with benign lesions, among which nevi are most common. Mucous epithelial cysts, epidermoid cysts, and dermoid cysts are the major benign lacrimal sac neoplasms. Squamous cell carcinomas are the most common malignant lacrimal sac neoplasms. The malignant tumor of lacrimal sac often occurs in the middle-aged and elderly patients. (Chin J Ophthalmol, 2020, 56: 364-369).