Type Of Squamous Cell Carcinoma Research Articles

Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer

Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.

Endoglin and squamous cell carcinomas.

Despite the fact that the role of endoglin on endothelial cells has been extensively described, its expression and biological role on (epithelial) cancer cells is still debatable. Especially its function on squamous cell carcinoma (SCC) cells is largely unknown. Therefore, we investigated SCC endoglin expression and function in three types of SCCs; head and neck (HNSCC), esophageal (ESCC) and vulvar (VSCC) cancers. Endoglin expression was evaluated in tumor specimens and 14 patient-derived cell lines. Next to being expressed on angiogenic endothelial cells, endoglin is selectively expressed by individual SCC cells in tumor nests. Patient derived HNSCC, ESCC and VSCC cell lines express varying levels of endoglin with high interpatient variation. To assess the function of endoglin in signaling of TGF-β ligands, endoglin was overexpressed or knocked out or the signaling was blocked using TRC105, an endoglin neutralizing antibody. The endoglin ligand BMP-9 induced strong phosphorylation of SMAD1 independent of expression of the type-I receptor ALK1. Interestingly, we observed that endoglin overexpression leads to strongly increased soluble endoglin levels, which in turn decreases BMP-9 signaling. On the functional level, endoglin, both in a ligand dependent and independent manner, did not influence proliferation or migration of the SCC cells. In conclusion, these data show endoglin expression on individual cells in the tumor nests in SCCs and a role for (soluble) endoglin in paracrine signaling, without directly affecting proliferation or migration in an autocrine manner.

PO-01-107 INTRA-CARDIAC SPINDLE CELL CARCINOMA FOLLOWING CATHETER ABLATION OF ATRIAL FIBRILLATION AND LEFT ATRIAL APPENDAGE CLOSURE

Spindle cell carcinoma (SpCC), a type of squamous cell carcinoma (SCC), is a rare tumor with features similar to sarcoma that often arises from the respiratory system. Myocardial involvement of these tumors has not been described. We present a case of metastatic SpCC diagnosed through routine transesophageal echocardiography (TEE) following left atrial appendage occlusion (LAAO). To describe a rare occurrence of metastatic SpCC diagnosed through routine TEE following LAA occlusion. NA A 61 year old male with a history of coronary artery disease and heart failure presented with persistent symptomatic atrial fibrillation (AF) despite anti-arrhythmic therapy. We performed pulmonary vein isolation (PVI) and during intubation a laryngeal mass was noted. He was diagnosed with T2N0M0 sarcomatoid SCC and had surgery, radiation and chemotherapy (cisplatin). At that time, he was felt to have a favorable 5 year survival prognosis. Six months later he represented with symptomatic AF and underwent repeat PVI. Due to concerns regarding bleeding risk, LAAO was later performed. During follow up TEE at day 45, a new cystic lesion arising from the posterior left atrium and a 2x3cm heterogenous mass associated with the interatrial septum was noted (Figure 1 A-D). CT scan showed new mediastinal masses with extension into the left atrium in the region treated with radiofrequency ablation (Figure 1 E-H). Biopsy revealed SpCC consistent with the initial laryngeal mass. Tumor extending from the perihilar mass and in the fossa ovalis, given the proximity of prior work and prior transseptal puncture, raises the concern for inadvertent iatrogenic spread of tumor and that catheter manipulation facilitated invasion into the LA with the pedunculated mass and seeded the septum. The patient unfortunately continued to decline clinically and shortly thereafter transitioned to comfort care and passed away. We present a case of persistent symptomatic AF in which laryngeal SpCC was diagnosed during initial PVI and rapidly progressive metastatic SpCC diagnosed via TEE in follow up after LAAO. This presentation is concerning for inadvertent iatrogenic spread of tumor from an extracardiac source through PVI. SpCC is more aggressive than typical SCC, however rapid invasion through the chest wall, lung and myocardium within 1.5 months is extremely rare. While primary spindle cell sarcoma of the myocardium has been reported, to our knowledge we report the first case of metastatic SpCC to the heart.

Basaloid Squamous Cell Carcinoma of Cervix – A Rare Case Report

Basaloid squamous carcinoma of the uterine cervix is a rare tumor type characterized by an ulcerated, infiltrating growth pattern; nests or cords of small basaloid cells; prominent peripheral palisading of cells in the tumor cell nests; and the absence of significant stromal reaction. The characteristic microscopic features are nests, lobules, trabeculae and groups of round to oval basaloid tumor cells. These tumor cells are small with high nuclear cytoplasmic ratio and shows peripheral palisading. There may be areas of comedo type necrosis and areas showing typical squamous cell carcinoma differentiation.

Comparison of Recurrence Patterns between Adenocarcinoma and Squamous Cell Carcinoma after Stereotactic Body Radiotherapy for Early-Stage Lung Cancer.

We compared recurrence patterns between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) after stereotactic body radiotherapy (SBRT) for early-stage lung cancer. Patients with ADC and SCC histology, who were treated with SBRT for clinical stage IA1-IIA lung cancer at our institution, were included in the analysis. The rates of disease-free survival (DFS), overall survival (OS), local recurrence (LR), lymph node metastasis (LNM), and distant metastasis (DM) were calculated using the Kaplan-Meier method or the cumulative incidence function. Among the 204 patients analyzed, 138 and 66 were in the ADC and SCC groups, respectively. The median follow-up period was 60 months. The five-year DFS and OS rates were 57% vs. 41% and 69% vs. 48% in the ADC and SCC groups, respectively (p = 0.015 and 0.019, respectively). In the multivariate analysis, the histological type was not associated with DFS or OS. Five-year LR, LNM, and DM rates were 10% vs. 24%, 12% vs. 20%, and 25% vs. 27% in the ADC and SCC groups, respectively (p = 0.0067, 0.074, and 0.67, respectively). The multivariate analysis identified the histological type of SCC as an independent factor for LR (hazard ratio, 2.41; 95% confidence interval, 1.21-4.77; p = 0.012). The present results suggest that the risk of LR after SBRT is higher for SCC than for ADC.

Venous thrombosis, multiple carcinomatous foci and differences in metastatic pathways of penile carcinoma.

The aim of the present study was to explore the life-threatening complications and metastatic pathways of penile squamous cell carcinoma (SCC), as numerous patients with penile cancer are relatively young, are of good general health and have no visceral metastasis, yet have poor survival rates. A total of 94 patients with SCC of the penis who were surgically treated were included in the current study. The coagulation parameters, including prothrombin time (PT), fibrinogen and D-dimer, were analyzed. The patients' age ranged from 25 to 95 years (mean ± standard deviation, 53.3±1.4 years). A total of 77 patients (81.9%) underwent partial penectomy and 17 (18.1%) underwent radical penectomy. The PT was significantly different between patients whose tumour invaded the corpora cavenosum and those whose tumour had not invaded, and between patients with and without pelvic lymph node metastasis. A negative correlation was obtained between PT and pelvic lymph node metastasis. In addition, six typical SCC cases and one metastatic penile carcinoma case manifested with multiple carcinomatous foci, embolisms and evidence of a metastatic pathway occurring simultaneously with tumour progression were presented. The present study indicated that venous thrombosis is one of the life-threatening complications of advanced penile cancer. Furthermore, multiple carcinomatous foci were detected in histological images. Of note, direct clinical evidence for different metastatic pathways of primary and secondary penile carcinoma was provided.

Towards non-invasive monitoring of non-melanoma skin cancer using spatially offset Raman spectroscopy.

BCC (basal cell carcinoma) and SCC (squamous cell carcinoma) account for the vast majority of cases of non-melanoma skin cancer (NMSC). The gold standard for the diagnosis remains biopsy, which, however, is an invasive and time-consuming procedure. In this study, we employed spatially offset Raman spectroscopy (SORS), a non-invasive approach, allowing the assessment of deeper skin tissue levels and collection of Raman photons with a bias towards the different layers of epidermis, where the non-melanoma cancers are initially formed and expand. Ex vivo Raman measurements were acquired from 22 skin biopsies using conventional back-scattering and a defocused modality (with and without a spatial offset). The spectral data were assessed against corresponding histopathological data to determine potential prognostic factors for lesion detection. The results revealed a positive correlation of protein and lipid content with the SCC and BCC types, respectively. By further correlating with patient data, multiple factor analysis (MFA) demonstrated a strong clustering of variables based on sex and age in all modalities. Specifically for the defocused modality (zero and 2 mm offset), further clustering occurred based on pathology. This study demonstrates the utility of the SORS technology in NMSC diagnosis prior to histopathological examination on the same tissue.

WHO 2022 classification of penile and scrotal cancers: updates and evolution.

Squamous cell carcinoma (SCC) is the most common malignant tumour of the penis. The 2022 WHO classification reinforces the 2016 classification and subclassifies precursor lesions and tumours into human papillomavirus (HPV)-associated and HPV-independent types. HPV-associated penile intraepithelial neoplasia (PeIN) is a precursor lesion of invasive HPV- associated SCC, whereas differentiated PeIN is a precursor lesion of HPV-independent SCC. Block-type positivity of p16 immunohistochemistry is the most practical daily utilised method to separate HPVassociated from HPVindependent penile SCC. If this is not feasible, the term SCC, not otherwise specified (NOS) is appropriate. Certain histologies that were previously classified as"subtypes" are now grouped, and coalesced as "patterns", under the rubric of usual type SCC and verrucous carcinoma (e.g. usual-type SCC includes pseudohyperplastic and acantholytic/pseudoglandular carcinoma, and carcinoma cuniculatum is included as a pattern of verrucous carcinoma). If there is an additional component of the usual type of invasive SCC (formerly termed hybrid histology), the tumour would be a mixed carcinoma (e.g. carcinoma cuniculatum or verrucous carcinoma with usual invasive SCC); in such cases, reporting of the relative percentages in mixed tumours may be useful. The consistent use of uniform nomenclature and reporting of percentages will inform the refinement of future reporting classification schemes and guidelines/recommendations. The classification of scrotal tumours is provided for the first time in the fifth edition of the WHO Blue book, and it follows the schema of penile cancer classification for both precursor lesions and the common SCC of the scrotum. Basal cell carcinoma of the scrotum may have a variable clinical course and finds a separate mention.

Immunohistochemical Evalution of Endoglin (CD 105) as Angiogenic Endothelial Marker of Squamous Cell Carcinoma in Dogs

Back ground: Angiogenesis is the process of using existent vascular bed to form new blood vessels. Neoangiogenesis is one of the hallmarks of cancer for tumour progression and metastasis. Microvessel density (MVD) is a powerful prognostic tool in oncology for assessing the tumour vasculature. Endoglin (CD 105) is a specific marker for activated endothelium. The present research intends to investigate the prognostic and metastatic potential of Endoglin (CD 105) and immunohistochemical expression in canine squamous cell carcinoma (SCC). Method: Totally, 15 SCC were collected from the Veterinary Clinical Complex, Tirunelveli during a one year period. The tumours were histopathologically identified as different grades. Immunohistochemically analysed with Endoglin (CD 105) and Peritumoural microvessel density and intratumourl microvessel density (PTMVD and ITMVD) were calculated using the “hot spot method”. Result: All the cases were positive for CD 105 and were strongly stained with both peritumoural and intratumoural blood vessels. Among the different types of SCC, Grade III had the highest values of microvessel density. The study concluded that different grades have different MVD values within SCC cases, thereby reflecting the behaviour of neoplasms directly. Endoglin (CD 105) is one of the best endothelial markers to determine MVD because it aids to assess the prognostic and metastatic potential of tumours and it plays a significant role in the estimation of overall survival period after surgery.

MA12.08 Pagetoid Growth of Squamous Cell Carcinoma with a Subsolid Component

Squamous cell carcinoma (SCC) is a solid, frequently central tumor. In recent years, an increase of peripheral type SCC was reported, accounting for up to 55% of SCC and characterized by alveolar filling growth pattern. We describe a novel growth of SCC.

CD109 Is a Critical Determinant of EGFR Expression and Signaling, and Tumorigenicity in Squamous Cell Carcinoma Cells.

Simple SummarySquamous cell carcinoma is a type of cancer resulting from cancer of the squamous cells that line some organs of the body such as the skin, lungs, and vulva. It is one of the leading causes of cancer-related deaths worldwide. In the current study, we show that a protein called CD109 plays an important role in the progression of this type of cancer. We also show that CD109 acts by associating with another protein called the epidermal growth factor receptor (EGFR), stabilizing its levels and promoting its action, leading to increased progression of squamous cell carcinoma. Together, these findings highlight a potential clinical utility for targeting CD109 in squamous cell carcinoma.(1) Background: Squamous cell carcinoma (SCC) is one of the leading causes of cancer-related deaths worldwide. CD109 is overexpressed in many cancers including SCC. Although a pro-tumorigenic role for CD109 has been shown in non-SCC cancers, and in one type of SCC, the mechanisms and signaling pathways reported are discrepant. (2) Methods: The CD109-EGFR interaction and CD109-mediated regulation of EGFR expression, signaling, and stemness were studied using microarray, immunoblot, immunoprecipitation, qPCR, immunofluorescence, and/or spheroid formation assays. The role of CD109 in tumor progression and metastasis was studied using xenograft tumor growth and metastatic models. (3) Results: We establish the in vivo tumorigenicity of CD109 in vulvar SCC cells and demonstrate that CD109 is an essential regulator of EGFR expression at the mRNA and protein levels and of EGFR/AKT signaling in vulvar and hypopharyngeal SCC cells. Furthermore, we show that the mechanism involves EGFR-CD109 heteromerization and colocalization, leading to the stabilization of EGFR levels. Additionally, we demonstrate that the maintenance of epithelial morphology and in vitro tumorigenicity of SCC cells require CD109 localization to the cell surface. (4) Conclusions: Our study identifies an essential role for CD109 in vulvar SCC progression. We demonstrate that CD109 regulates SCC cellular stemness and epithelial morphology via a cell-surface CD109-EGFR interaction, stabilization of EGFR levels and EGFR/AKT signaling.

Clinicopathological Characteristics of Cervical Squamous Cell Carcinoma and Correlation with Tumor-Associated Neutrophil

BackgroundCervical carcinoma is one of the most common cancers in women, according to data from World Health Organization (WHO).Cervical carcinoma ranks the fourth most deadly type of cancer. Squamous cell carcinoma is the most common type of this cervicalcancer and it is generally caused by Human Papilloma Virus (HPV) types 16 and 18. Tumor-Associated Neutrophil (TAN) are foundin various types of cancer, the density of TAN can determine the prognostic type of tumor or cancer in each individual. This studywas aimed to identify correlation between clinicopathological characteristics of cervical squamous cell carcinoma (SCC) and TAN incervical SCC patients registered at RSUP Dr. Mohammad Hoesin Palembang.MethodsThis type of research is analytic with a cross-sectional method. Data collection in this study used a 37 slides archive which werediagnosed as cervical squamous cell carcinoma in Anatomic Pathology in RSUP Dr. Mohammad Hoesin Palembang for the periodof 2017-2019.ResultsFrom 37 cervical SCC patients, the clinicopathological characteristics of the majority of cervical SCC patients occurred in the agegroup of 51 year-old (51.4%), with histopathological type of non-keratinizing SCC (75,7%) and the most frequent differentiationdegree was moderately differentiated (75,7%). The TAN density was mostly found at low TAN densities (73%). There wassignificant correlation between age and TAN density (p=0.035) and there was no significant correlation between age and TANdensity (p=0.269).ConclusionIt was explained that the higher the degree of differentiation, the lower the density value, however the neutrophils in this studycannot be ascertained whether the neutrophils of anti-tumor (N1) or pro-tumor (N2) characteristic

Preoperative MRI of breast squamous cell carcinoma: diagnostic value of distinguishing between two subtypes

To retrospectively analyse the clinical and MRI data of primary squamous cell carcinoma (SCC), particularly pure squamous cell carcinoma (PSCC) and mixed squamous cell carcinoma (MSCC). The MRI data and clinicopathological characteristics of 20 patients with histopathologically confirmed SCC of the breast, including eight PSCC patients and 12 MSCC patients, from multiple centres between January 2013 and December 2020 were analysed retrospectively. Nine of 12 patients in the MSCC group showed hyperintensity on T1-weighted imaging (WI), while this feature was not observed in the PSCC group (p=0.001). Most of the PSCC group showed rim enhancement, whereas most of the MSCC group showed heterogeneous enhancement (p=0.007). In addition, there was no significant difference in the thickness of the rim enhancement and the percentage of necrotic components in the tumours between the two types of SCCs of the breast (p=0.545 and p=0.662, respectively). Four patients (4/12) in the MSCC group had sentinel lymph node metastasis, while only one patient (1/8) in the PSCC group showed lymph node metastasis (p=0.603). Metastatic disease occurred in 25% of patients with PSCC and in approximately 41.7% of patients with MSCC. The signal on T1WI and internal enhancement characteristics were the key features for differentiating PSCC and MSCC. Therefore, MRI phenotypes may provide additional information for the pathological classification of breast SCC.

Comparative study of genomic, immunological and functional features of squamous cell carcinomas in five anatomical locations

Squamous cell carcinomas (SCCs) are the most common human solid tumors and a major cause of cancer mortality. They are a group of aggressive, genetically complex neoplasms with a high risk of recurrence and metastasis. In the Republic of Moldova in 2018 the incidence of head, neck, esophagus, lung, skin and cervical cancers constituted 3242 cases of which about 50% represented the histopathological form of Squamous Cell Carcinoma. Early diagnosis, improving the outcomes of disease management and adaptation of therapies are current and necessary requirements for reducing mortality. Genetic changes, alteration of intracellular signaling pathways, and immune system response in these cancers may be influenced by various factors such as: oncogenic viruses (HPV), local microbiome, tumor localization, etc. In order to extend the understanding and the area of knowledge about these malignancies, to highlight the biological similarities and differences between certain types of SCCs, are required complex, comparative studies of genomic, epigenomic, proteomic, metabolomic, imunological and microbiome events. This complex, comparative approach has not been widely applied in previous studies and will allow the identification of similarities and differences between the multi-omics and non-omics features, the determination of individual and common biomarkers in 5 types of Squamous Cell Carcinomas: skin, head-neck, esophagus, lung and cervical. The goal of the research is the comparative study of SCCs from different anatomical locations in order to improve the screening, early diagnosis, disease management and treatment of these tumors.

Human papillomavirus immunohistochemistry in high grade squamous cell lesions of esophagus

Background: Over the past decade, the cause–effect relationship between human papillomavirus (HPV) and squamous cell carcinoma (SCC) of the esophagus has been worked over. A few reports in the literature have demonstrated HPV protein within premalignant and malignant cells of SCC of the esophagus. Aims and Objectives: The aim was to study the high-grade squamous cell lesions and its relation with high-risk HPV infection to be evident on immunohistochemistry for high-risk HPV on biopsies of esophageal lesions. Materials and Methods: Biopsy from 20 esophageal growth processed conventionally, and histological section is stained by hematoxylin and eosin stains; paraffin-embedded tissue of esophageal lesions is processed and stained for immunohistochemistry in the detection of HPV by cocktail HPV16 and HPV18 antibodies by the standard procedure. Results: The present poster describes the results of immunohistochemistry for high-risk HPV on 20 cases of esophagus premalignant squamous cell lesions along with the SCC types and its grade. It has been observed that five cases have been demonstrated for positive results of immunohistochemistry for high-risk HPV. Conclusions: It may be postulated that HPV plays an important role in the pathogenesis of SCC esophagus.

Comparative Analysis of Clinicopathological Characteristics, Survival Features, and Protein Expression Between Basaloid and Squamous Cell Carcinoma of the Esophagus.

BackgroundBasaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma (SCC) of the esophagus. This study aimed to assess the discrepancy in clinicopathological characteristics and protein expression between esophageal BSCC and typical esophageal SCC.Study DesignWe reviewed 40 cases of esophageal BSCC. As controls, 63 well-differentiated SCC (WSCC) patients, 70 moderately differentiated SCC (MSCC) patients, and 51 poorly differentiated SCC (PSCC) patients were selected. The clinicopathologic characteristics and immunoreactivity of Ki-67, p53, p63, and epidermal growth factor receptor (EGFR) were then evaluated in the BSCC and typical SCC patients.ResultsThe 5-year survival rates for the BSCC patients were 27.5%. The prognostic outcomes of the BSCC group were similar to those of the PSCC and MSCC groups but worse than that of the WSCC group, with a significant difference (P=0.045). Ki-67 expression was significantly higher in the BSCC group than that in the WSCC group (P < 0.05). Meanwhile, there were no significant differences in the expression of the other molecular markers (p53, p63, and EGFR) between the typical SCC and BSCC groups (P > 0.05). The median survival time of esophageal the BSCC patients with low p53 expression was significantly longer than that of the patients with high p53 expression (P=0.026). Further, the median survival time of the esophageal BSCC patients with high p63 expression was significantly longer than that of the patients with low p63 expression (P=0.041). Meanwhile, Ki-67 and EGFR expressions were not correlated with OS in the BSCC group.ConclusionEsophageal BSCC has a more clinically virulent course. Notably, p53 and p63 expression are associated with prognosis in BSCC. These findings conject that evaluation of multiple cancer biomarkers might be a promising auxiliary diagnostic indicator in BSCC.

Nonsmoking and Nondrinking Oral Squamous Cell Carcinoma Patients: A Different Entity.

ObjectiveOur goal was to analyze the demographic and pathologic characteristics as well as prognosis in nonsmoking and nondrinking (NSND) oral squamous cell carcinoma (SCC) patients compared with typical oral SCC patients.Patients and MethodsA total of 353 patients were retrospectively enrolled and divided into two groups: the NSND group and the current smoking/current drinking (CSCD) group. Demographic, pathologic, and molecular data were compared between the two groups. The main research endpoints were locoregional control (LRC) and disease-specific survival (DSS).ResultsIn the NSND group, 16.3%, 41.9%, and 53.5% of patients were aged no more than 40 years, were female, and had an educational background of high school or above compared to 3.7%, 6.0%, and 38.2% of patients in the CSCD group, respectively. A total of 15.1% of the NSND patients had SCC of the lower gingiva and floor of the mouth, which was lower than the 35.6% of patients in the CSCD group. CSCD patients were likely to have an advanced disease stage (48.7% vs 32.5%, p=0.042) and poorly differentiated cancer (26.6% vs 16.3%, p=0.042). The NSND patients had a mean Ki-67 index of 24.5%, which was lower than the mean of 35.7% in the CSCD patients. The two groups had no HPV infection and similar p16 expression (4.7% vs 10.1%, p=0.132), but there was higher expression of p53 (38.6% vs 17.4%, p<0.001) and p63 (59.9% vs 29.1%, p<0.001) in the CSCD group. The 5-year LRC rates for NSND patients and CSCD patients were 48% and 38%, respectively, and the difference was significant (p=0.048). The 5-year DSS rates for NSND patients and CSCD patients were 56% and 39%, respectively, and the difference was significant (p=0.047). Further, a Cox model confirmed the independence of smoking and drinking status for affecting LRC and DSS.ConclusionNSND oral SCC patients are a different entity. HPV infection has a limited role in carcinogenesis in NSND patients, and p16 expression is associated with worse locoregional control.

Clinicopathological features of basal cell type dysplasia of esophagus

Objective: To investigate the clinicpathological features of basal cell type dysplasia of the esophagus. Methods: The clinicopathological data of 71 cases of basal cell type dysplasia of esophagus were collected at the People's Liberation Army Joint Logistics Support Force 989 Hospital, from 2009 to 2019, and the histomorphologic characteristics and immunophenotype were evaluated. The relevant literature was reviewed. Results: The ratio of male to female patients was 1.6∶1.0, and the median age was 65 years (range 48-81 years). The tumors were located in the upper segment of the esophagus in four cases (5.6%), the middle segment in 54 cases (76.1%), and the lower segment in 13 cases (18.3%).The median maximal tumor diameter was 12.0 mm (range 3-42 mm). According to Paris Classification, 0-Ⅱb accounted for 42.3% (30/71) of the cases. Under endoscope, the lesions were reddish with abnormal mucosal microvessels. Histologically, the neoplastic cells were small, with a high nuclear-cytoplasmic ratio, similar to basal cells, and uniform in morphology. The structural atypia was characterized by dense and disordered tumor cells, loss of basal cell polarity, and absence of normal squamous differentiation gradient. In 10 cases, the tumors were confined to the lower part of the epithelium. The tumor cells were smaller and more uniform in shape, and extend to the superficial lamina propria. Sixty-one tumors involved at least the entire layer of the upper cortex. There were 31 cases of neoplasms with superficial invasive carcinoma. The types of neoplasms included typical squamous cell carcinoma, basaloid squamous cell carcinoma, small cell neuroendocrine carcinoma, squamous cell carcinoma with sebaceous adenoid carcinoma, and differentiation of glandular/ductal epithelioid carcinoma. Immunohistochemical staining showed that the mutant expression rate of p53 protein was 41.5% (17/41). All 41 cases (100.0%) showed abnormal distribution pattern of Ki-67. According to the initial pathologic diagnosis, there were 18 cases of low grade dysplasia, 12 cases of atypical epithelial cells, and 41 cases of high grade dysplasia and superficially invasive carcinoma. Conclusions: Basal cell type dysplasia has unique morphologic characteristics and represents a tumor subtype in the morphologic lineage of esophageal squamous dysplasia. Tumor cells of basal cell type dysplasia, especially those distributed only in the lower part of the stratified squamous epithelium, may be tumor stem cells at the earliest stage of esophageal carcinogenesis and have multidirectional differentiation potential. When the tumor is confined to the lower part of the stratified squamous epithelium, it does not meet the diagnostic criteria for esophageal squamous dysplasia as defined by the current WHO classification.

Differences in the mitochondrial microsatellite instability of Keratoacanthoma and cutaneous squamous cell carcinoma

Keratoacanthoma (KA) is a common cutaneous neoplasm which often resembles typical squamous cell carcinoma (SCC) in both its clinical and historical presentation. Several studies have attempted to identify methods for distinguishing between KA and SCC, however, none of these have proven to play any obvious roles in these tumors. Given this we went on to evaluate mitochondrial microsatellite instability (mtMSI) in KA and SCC in an effort to understand these tumors better. DNA was isolated from paired normal and tumoral tissues donated by 57 KA patients and 43 SCC patients. MtMSI was then analyzed using eight microsatellite markers and was observed in 2 (3.5%) of the 57 KA patients and 8 (18.6%) of the 43 SCC patients, respectively. MtMSI was also shown to affect different locations depending on tumor type. In KA patients, mtMSI was detected at mitochondrial D514 D-loop and presented with (CA) n repeats, in contrast, all of the SCC patient experienced mtMSI at the D310 with (C)n repeats of the D-loop region. These differences in location were found to be significant, which may support the hypothesis that KA and SCC have different pathogenetic pathways. Our results also suggest that mtMSI may be a candidate for developing novel differential diagnostic methods for KA and SCC.

Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages.

Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation betweenthe type of HPV, the HPV 16 lineage or sublineage, andany of the histologic features or morphologic SCC subtypes.