Clinical implications of activation of the LIMD1-VHL-HIF1α pathway during head-&-neck squamous cell carcinoma development.

Background & objectives Given the importance of the role of hypoxia induced pathway in different cancers including head-and-neck squamous cell carcinoma (HNSCC), this study delved into elucidating the molecular mechanism of hypoxia-inducible factor-1α (HIF1α) activation in HNSCC. Additionally, it analyzes the alterations of its regulatory genes [von Hippel-Lindau (VHL) and LIM domain containing 1 (LIMD1)] and target gene vascular endothelial growth factor (VEGF) in head-and-neck lesions at different clinical stages in relation with human papillomavirus (HPV) infection. Methods Global mRNA expression profiles of HIF1α, VHL, LIMD1 and VEGF were evaluated from public datasets of HNSCC, followed by validation of their expression (mRNA/protein) in an independent set of HPV+ve/-ve HNSCC samples of different clinical stages. Results A diverse expression pattern of the HIF1α pathway genes was observed, irrespective of HPV infection, in the datasets. In validation in an independent set of HNSCC samples, high mRNA expressions of HIF1α/VEGF were observed particularly in HPV positive samples. However, VHL/LIMD1 mRNA expression was low in tumours regardless of HPV infection status. In immunohistochemical analysis, high/medium (H/M) expression of HIF1α/VEGF was observed in basal/parabasal layers of normal epithelium, with significantly higher expression in tumours, especially in HPV-positive samples. Conversely, high cytoplasmic VHL expression in these layers gradually decreased with the progression of HNSCC, regardless of HPV infection. A similar trend was noted in LIMD1 expression (nuclear/cytoplasmic) during the disease development. The methylation pattern of VHL and LIMD1 promoters in the basal/parabasal layers of normal epithelium correlated with their expression, exhibiting a gradual increase with the progression of HNSCC. The H/M expression of HIF1α/VEGF proteins and reduced VHL expression was associated with poor clinical outcomes. Interpretation & conclusions The results of this study showed differential regulation of the LIMD1-VHL-HIF1α pathway in HPV positive and negative HNSCC samples, illustrating the molecular distinctiveness of these two groups.

An Unusual Tumor: Squamous Cell Carcinoma of the Colon in Lynch Syndrome.

Primary squamous cell carcinoma of the colon and rectum is a rare malignancy. Most of the anatomical sites that are reported to be affected include the esophagus and anal canal. This report highlights the case of a 54-year-old male with a known history of Lynch syndrome and a previous diagnosis of colon cancer who was found to have a recurrence of malignancy affecting this unlikely area. The treatment strategies for this colorectal squamous cell carcinoma have not been thoroughly explored, so this report aims to highlight effective interventions, including surgical resection and neoadjuvant chemotherapy and radiation. There is a poor prognosis associated with this condition, as it does not typically present until the late stages; however, in this particular instance, early detection leads to improved outcomes.

Oral Squamous Cell Carcinoma of the Right Buccal Mucosa: A Case Report.

Oral squamous cell carcinoma (OSCC) is indeed one of the most common types of oral cancer, typically affecting individuals over the age of 50. It primarily originates from the squamous epithelial cells lining the oral cavity. While it is relatively rare in individuals under 40 years old, it can still occur, albeit less frequently in that age group. Risk factors for developing OSCC include tobacco use (smoking or chewing), excessive alcohol consumption, chronic irritation (such as from poorly fitting dentures), human papillomavirus (HPV), infection, and certain dietary foods. Early detection and treatment are crucial for improving outcomes and reducing the mortality associated with this type of cancer. This report describes a case of OSCC, staged T2 N0 M0, involving the right buccal mucosa of a 51-year-old male patient. The patient reported intense pain in an ulcer on the right side of his cheek. This report focuses on the etiological factors and a brief literature review of squamous cell carcinoma.

Platysmal Myocutaneous Flap for Intra Oral Defects:Is It an Underutilized Option? Our Experience of 10 Cases.

Various methods of reconstruction are available for reconstructing oral cancer defects, but all of them have their inherent drawbacks. The superiorly based platysma myocutaneous flap is a common reconstruction option for intra-oral defects following oral cancer resections. We present our results of using platysmal flaps in reconstructing intraoral defects following oral cavity cancer resection in our 7 patients along with resection of three cases of premalignant conditions of oral cavity. All the patients were males of age ranging from 24 to 42 years and diagnosed as squamous cell carcinoma of oral cavity stage I and II were included in this study.Of 10 patients eight had no postoperative complications. One patient developed partial skin loss of neck donor site, which was managed conservatively. Other patient had complete flap loss which healed with secondary intention. We recommend this flap as incision is always away from the face, the scars are hidden beneath collars and the patients are very comfortable with good cosmetics and functional outcomes.\.

A Case Report of Kearns-Sayre Syndrome: Not an Absolute Contraindication for Radiotherapy.

Kearns-Sayre syndrome (KSS) is a rare mitochondrial disorder, and the effects of radiotherapy on such a population group are unknown. A 60-year-old male with a history of KSS was diagnosed with locally advanced basal cell carcinoma along the left inner canthus. He was treated at our institution with curative intent radiotherapy alone and tolerated it well with no major acute or late toxicities. There was a complete clinical and radiological response of the tumor, with no evidence of recurrence 2.5 years after treatment. Further research is needed to explore the effects of ionizing radiation on patients with mitochondrial DNA defects.

Cliniciopathological Spectrum of Skin and Soft Tissue Swellings at a Tertiary Care Hospital of Lahore, Pakistan.

Background Skin and soft tissue swellings (SSTS) frequently present in dermatology, plastic surgery, and general surgery departments. While a general surgeon can take care of excisable lesions, people typically seek plastic surgery for cosmetic reasons. According to the signs and symptoms, soft tissue and skin lesions must be removed, and it is crucial to maintain cosmesis following their removal. Objective The aim of this article is to describe the clinical and histopathological types, sites, laterality, and postoperative complications of SSTS. Material and methods This retrospective study was conducted at the Department of Plastic and Reconstructive Surgery, Lahore General Hospital, Lahore, Pakistan in November 2022. We studied admitted patients from July 1, 2020 to June 30, 2022 for SSTS excision. Data on patients' demographics, associated features of SSTS, and their postoperative complications was gathered using Google Docs-generated proforma and sent to a statistician for the computation of results via a Microsoft Excel-generated spreadsheet. Results Out of the total 60 patients, 66.7% of the lesions were found in women. The mean age at presentation came out to be 34.16±17.42 years. Nevi with 16.7% were the most common SSTS in our study. The most common site of presentation of SSTS was the scalp and face in 63.3% of cases. Fever was the most frequently encountered post-excision complication in 40% of patients. Conclusion A comprehensive history, clinical examination, signs and symptoms, and the histology of the lesion, all play a crucial role in the management of such swellings. Surgery was the definitive treatment option for SSTS. There were very few major complications in a handful of patients.

Clinicopathologic Characteristics of Melanoma in Patients with Parkinson Disease.

Patients with Parkinson disease (PD) are at high risk for developing melanoma, although current literature lacks details on the associated clinicopathologic characteristics. Our retrospective case-control study aimed to guide skin cancer surveillance recommendations for patients with PD, focusing on tumor sites. Our study included 70 adults with concurrent diagnoses of PD and melanoma from January 1, 2007 to January 1, 2020 at Duke University and 102 age-, sex-, and race-matched controls. The head/neck region accounted for 39.5% of invasive melanomas in the case group compared with 25.3% in the control group as well as 48.7% of noninvasive melanomas in the case group compared with 39.1% in the control group. Of note, 50% of metastatic melanomas in patients with PD originated on the head and neck (n = 3). Logistic regression showed 2.09 times higher odds of having a head/neck melanoma in our case group compared with that in the control group (OR = 2.09, 95% confidence interval = 1.13‒3.86; P = 0.020). Our study is limited by small sample size, and our case cohort lacked diversity regarding race, ethnicity, sex, and geography. Validation of the reported trends could provide more robust guidance for melanoma surveillance in patients with PD.

Survival After Resection for Epidermoid Cyst-originated Squamous Cell Carcinoma of the Liver: Case Report and Review of the Literature.

Epidermoid cyst is a rare type of congenital hepatic cyst. Reports on squamous cell carcinoma (SCC) of the liver are very limited and mostly have poor outcomes. We present a 45-year-old woman who came to our hospital due to obstructive jaundice caused by an epidermoid cyst-originated SCC. She underwent radical resection and lived for two years without signs of recurrence. The presentation, treatment, pathological results, as well as literature review, are provided below.

Prevalence of and Associated Factors for Eyelid Cancer in the American Academy of Ophthalmology Intelligent Research in Sight Registry.

Purpose: To estimate the prevalence of eyelid cancers in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS) Registry and evaluate the associated factors. Design: Retrospective IRIS Registry database study. Participants: All patients in the IRIS Registry between December 1, 2010, and December 1, 2018, with International Classification of Disease, ninth and 10th revisions, codes for eyelid cancers (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], malignant melanoma [MM], sebaceous carcinoma/other specified malignant neoplasm [SBC], melanoma in situ [MIS], and unspecified malignant neoplasm [UMN]). Methods: The prevalence of each eyelid cancer type was estimated overall and by age group, sex, race, ethnicity, and smoking status. The associations between any eyelid cancer (AEC) or each cancer type and possible risk factors were examined using univariate and multivariate logistic regression models. Main Outcome Measures: Prevalence of and associated factors for each eyelid cancer type. Results: There were 82 136 patients with eyelid cancer identified. The prevalence of AEC was 145.1 per 100 000 population. The cancer-specific prevalence ranged from 87.9 (BCC) to 25.6 (UMN), 11.1 (SCC), 5.0 (SBC), 4.1 (MM), and 0.4 (MIS) per 100 000 population. The prevalence of AEC and each cancer type increased with increasing age (all P < 0.0001), and the prevalence of AEC, BCC, SCC, and MM was higher in males (all P < 0.0001), MIS (P = 0.02). The prevalence of BCC, SCC, MM, SBC, and AEC was highest in Whites versus that in patients of any other race (all P < 0.0001). In the multivariate logistic regression model with associated risk factors (age, sex, race, ethnicity, and smoking status), AEC was associated with older age groups ([< 20 years reference {ref.}]; odds ratio [95% confidence interval]: 20-39 years: 3.35 [1.96-5.72]; 40-65 years: 24.21 [14.80-39.59]; and > 65 years: 42.78 [26.18-69.90]), male sex (female [ref.]; 1.40 [1.33-1.48]), White race (inverse associations with African Americans [0.12 {0.09-0.16}], Asians [0.19 {0.13-0.26}], others [0.59 {0.40-0.89}]), and ethnicity (non-Hispanic [ref.]; Hispanic: 0.38 [0.33-0.45]; unknown: 0.81 [0.75-0.88]). Active smoking (never smoker [ref.]) was associated with AEC (1.11 [1.01-1.21]), BCC (1.27 [1.23-1.31]), SCC (1.59 [1.46-1.73]), and MM (1.26 [1.08-1.46]). Conclusions: This study reports the overall and cancer-specific prevalence of eyelid cancers using a large national clinical eye disease database. Smoking was found to be associated with AEC, BCC, SCC, and MM, which is a new observation. This epidemiologic profile of on-eyelid cancers is valuable for identifying patients at a higher risk of malignancy, allocating medical resources, and improving cancer care.

Endoscopic submucosal dissection of a tumor in the upper esophageal sphincter and piriform sinus.

Video 1Endoscopic submucosal dissection of a tumor in the upper esophageal sphincter and piriform sinus.

Primary endometrial squamous cell carcinoma with synchronous early stage Fallopian adenocarcinoma: A case report and review of diagnostic and treatment considerations.

Background: Primary endometrial squamous cell carcinoma (PESCC) remains a rare sub-type of endometrial cancer. This case is especially unique due to the incidental finding of early stage Fallopian adenocarcinoma. This report adds to the literature of this rare condition and discuss it's etiology, clinical course, and treatment regimen.Case: 65 year old postmenopausal female presented with postmenopausal bleeding. Dilation and curettage revealed endometrial highly atypical squamous epithelial proliferation. Staging procedure showed FIGO stage IB squamous cell carcinoma of the endometrium, without evidence of cervical involvement. A small focus of incidental poorly differentiated FIGO stage IA adenocarcinoma of the left Fallopian tube was discovered. She underwent six cycles of Paclitaxel and Cisplatin, and has remained disease free for two years. Conclusion: Primary endometrial squamous cell carcinoma is poorly understood entity. Early diagnosis is critical due to the strong correlation between initial stage and survival. Biopsy of the cervix and endometrium should be considered in cases of abnormal uterine sampling. The case presented is a prototypical example of PESCC, both in presentation, pathology, and course. It is especially unique due to synchronous high grade Fallopian adenocarcinoma.

Cholecystokinin Receptor Antagonist Suppresses Melanoma Growth by Inducing Apoptosis of Tumor Cells.

Melanoma is a malignant skin tumor with high metastatic activity. Although melanoma has been well-studied, its cellular kinetics remain elusive. The cholecystokinin (CCK) receptor is expressed in various types of tumors because CCK promotes the survival and proliferation of tumor cells. Thus, we hypothesized that the growth of melanoma was positively regulated by signals from the CCK receptor and sought to investigate whether CCK receptor antagonists affect the growth of melanoma cells expressing CCK receptor. Immunohistochemically, the CCK receptor A is expressed in the clinical specimens of melanoma. CCK receptor antagonists decreased the viability of melanoma cells by suppressing cell division and promoting apoptosis. CCK receptor antagonists also decreased the mitochondrial membrane potential through enhanced gene expression of the proapoptotic protein, Bcl2-associated X, and tumor suppressor, p53, suggesting that the antagonist induced the apoptosis of melanoma cells in a mitochondria-dependent manner. In addition, a caspase 3 inhibitor, Z-DEVD-FMK, partially blocked the antiviability of the antagonist, indicating that caspase 3 is involved in antagonist-induced apoptosis. Notably, tumor growth was attenuated when a CCK receptor antagonist was locally administered to the melanoma-bearing mice. Therefore, our study suggests the therapeutic potential of CCK receptor antagonists in the treatment of skin cancer.

Effective control of recurrent and metastatic GU SCC by employing a multimodal approach in a patient with a history of radiation and transscrotal surgery for stage I seminoma.

This 68-year-old male, with a history of treated testicular seminoma, developed scrotal SCC 30 years later, with a metastatic SCC recurrence following another interval of 10 years. He exhibited good response to multimodal therapy, though subsequently underwent orchiectomy, revealing SCC invading his solitary testicle. This case presents a unique danger of adjuvant radiation in testicular cancer survivors, demonstrates the efficacy of multimodal therapy with GU SCC, and describes a highly unusual histologic finding.