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Actinic keratosis (AK) is characterized by a reddish or occasionally skin-toned rough patch on sun-damaged skin, and it is regarded as a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), utilizing 5-aminolevulinic acid (ALA) along with red light, is a recognized treatment option for AK that is limited by the penetration depth of light and the distribution of the photosensitizer into the skin. Cold atmospheric plasma (CAP) is a partially ionized gas with permeability-enhancing and anti-cancer properties. This study analyzed, in vitro, whether a combined treatment of CAP and ALA-PDT may improve the efficacy of the treatment. In addition, the effect of the application sequence of ALA and CAP was investigated using in vitro assays and the molecular characterization of human oral SCC cell lines (SCC-9, SCC-15, SCC-111), human cutaneous SCC cell lines (SCL-1, SCL-2, A431), and normal human epidermal keratinocytes (HEKn). The anti-tumor effect was determined by migration, invasion, and apoptosis assays and supported the improved efficacy of ALA-PDT in combination with CAP. However, the application sequence ALA-CAP–red light seems to be more efficacious than CAP-ALA–red light, which is probably due to increased intracellular ROS levels when ALA is applied first, followed by CAP and red light treatment. Furthermore, the expression of apoptosis- and senescence-related molecules (caspase-3, -6, -9, p16INK4a, p21CIP1) was increased, and different genes of the junctional network (ZO-1, CX31, CLDN1, CTNNB1) were induced after the combined treatment of CAP plus ALA-PDT. HEKn, however, were much less affected than SCC cells. Overall, the results show that CAP may improve the anti-tumor effects of conventional ALA-PDT on SCC cells. Whether this combined application is successful in treating AK in vivo has to be carefully examined in follow-up studies. [ABSTRACT FROM AUTHOR]

Objective: Treating aggressive superficial squamous cell carcinoma (SCC) poses challenges due to invasiveness. Palliative care is recommended for inoperable cases with extensive tumors near vital organs, risking disfigurement or functional impairment. Electrochemotherapy (ECT) is an emerging cutaneous tumor treatment, but its efficacy against superficial SCC remains uncertain. This study conducts a systematic review and single-arm meta-analysis to evaluate ECT's effectiveness against superficial SCC and provide current evidence for clinical practice. Methods: Embase, PubMed and Cochrane Library were searched for studies up to May 2023. The random effects model analyzed complete response (CR) and partial response (PR), with subgroup assessment based on drug dosage, treatment response evaluation, tumor size, primary/recurrent status, and tumor location. Results: Ten studies involving 162 patients and 208 tumors were included. Pooled CR and PR rates for ECT-treated superficial SCC were 66.5% (95% CI 48.4%–82.5%; I2 = 84%) and 20.3% (95% CI 10.5%–32.3%; I2 = 70%), respectively. Subgroup analysis indicated ECT's superiority in treating primary tumors (PR: 70%, CR: 30%) and tumors ≤ 3 cm (PR: 81.3%, CR: 10.1%) compared to recurrent tumors (PR: 56.7%, CR: 36.5%) and tumors > 3 cm (PR: 45.2%, CR: 34.4%). Conclusion: This single-arm meta-analysis confirms ECT's efficacy against superficial SCC, especially in primary tumors and those ≤ 3 cm in diameter. The study highlights the impact of tumor location and response evaluation on ECT's benefits, warranting further investigation through additional research. [ABSTRACT FROM AUTHOR]

GCA, also known as Buschke-Lowenstein tumor, is a rare sexually transmitted disease associated with HPV types 6 and 111. These warts are considered histologically benign, but there is a risk of localized invasion and development of malignancy. This malignant transformation occurs most often in the perianal and vulvar areas, and involvement of other sites is relatively rare2. In this case, we report a rare case of a giant wart originating from breast skin infected with HPV and progressing to cutaneous squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Acantholytic squamous cell carcinoma (aSCC) is a rare type of skin cancer that represents about 4.9% of all squamous cell carcinoma cases. Currently, there are no standardized guidelines for diagnosing this cancer. This study aimed to compile and analyze the existing research on the clinical and molecular characteristics of aSCC. We reviewed 52 studies that included 482 patients, most of whom were older males. We found that aSCC commonly appears on the head and neck as nodules with surface changes such as thickening, erosion, or ulceration. Our review also highlights that certain molecular markers, such as cytokeratins, are commonly present, while others, like CD15 and various vascular markers, are often absent. The findings suggest that understanding both the clinical presentation and molecular features of aSCC is crucial for accurate diagnosis. Our systematic review provides data which can help doctors better identify and treat this rare form of cancer, ultimately improving patient outcomes. Introduction: Acantholytic squamous cell carcinoma (aSCC) is a rare clinicopathological subtype of cutaneous squamous cell carcinoma, accounting for approximately 4.9% of all SCC cases. However, there are currently no standardized criteria for the diagnosis of aSCC. This systematic review is the first to summarize the clinical and molecular features of aSCC. Methods: A systematic search of Medline, Embase, Scopus, and PubMed was performed. All articles in English or French were included, with no restriction of publication date. All articles with original data pertaining to clinical or molecular characteristics of aSCC were included. Two reviewers screened articles and resolved conflicts. Results: Our systematic review included 52 studies on the clinical and molecular features of aSCC, including a total of 482 patients (76% male, mean age at diagnosis 68.9 years): 430 cases assessed clinical features, while 149 cases assessed molecular features. The most common location of aSCC was the head and neck (n = 329/430; 76.5%). In terms of morphology, most lesions were described as nodules (n = 93/430, 21.6%), with common surface changes being hyperkeratosis (n = 6), erosion (n = 6), ulceration (n = 5), and crusting (n = 3). With regard to dermoscopy, only six cases were noted in the literature, including findings such as ulceration (n = 3), keratin clots (n = 2), and erosions (n = 2). Thirty-four studies discussed the molecular markers of aSCC, with the most prevalent markers being cytokeratins. CD15 negativity was noted in 23 cases, while common endothelial vascular markers such as CD34 (n = 16), CD31 (n = 15), factor VIII-related antigen (n = 10), and ERG (n = 1) were often not expressed. Finally, expression of intracellular adhesion molecules (i.e., E-cadherin, CD138) was markedly decreased compared to non-acantholytic invasive SCC. Conclusions: This systematic review summarizes the clinical characteristics and molecular features of aSCC. As clinical differentiation can be difficult, clinicopathological correlation with molecular markers may help ensure proper diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The study examined the relationship between Human Papillomavirus (HPV) and various types of skin cancer, including squamous cell carcinoma, basal cell carcinoma, and melanoma. It aimed to assess how HPV influenced the likelihood of developing these cancers, considering factors such as age, gender, urbanization, and existing health conditions. Through statistical models, the research quantified the risk of skin cancer in individuals with HPV compared to those without, underscoring how behaviors related to sun exposure and protection practices could alter these risks. The findings were crucial for guiding prevention and treatment strategies and were of significant interest to medical professionals and public health policymakers. Overall, the study enhanced our understanding of the risks associated with HPV, potentially leading to more effective health interventions. Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96–7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70–5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14–5.74), and melanoma (aHR = 4.36, 95% CI: 2.76–6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this review is to focus on the possibility of patients with squamous cell carcinoma to develop a second primary disease such as DLBCL, perhaps because of the irradiation of the head and neck area. Materials and methods: A case of an 89-year-old man is reported, who initially underwent surgical and complementary treatment for neck squamous cell carcinoma of occult primary and later for tonsillar diffuse large B-cell non-Hodgkin lymphoma. Results: The second primary was considered a recurrence in the neck of the original cancer of unknown primary, so a new surgical management was decided. The final pathology report described a diffuse large B-cell non-Hodgkin lymphoma. Conclusions: The importance of maintaining follow-ups for patients with occult primary cancers who are at an elevated risk of developing a metastasis or a second primary carcinoma outbreak is highlighted. [ABSTRACT FROM AUTHOR]

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Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this review is to focus on the possibility of patients with squamous cell carcinoma to develop a second primary disease such as DLBCL, perhaps because of the irradiation of the head and neck area. Materials and methods: A case of an 89-year-old man is reported, who initially underwent surgical and complementary treatment for neck squamous cell carcinoma of occult primary and later for tonsillar diffuse large B-cell non-Hodgkin lymphoma. Results: The second primary was considered a recurrence in the neck of the original cancer of unknown primary, so a new surgical management was decided. The final pathology report described a diffuse large B-cell non-Hodgkin lymphoma. Conclusions: The importance of maintaining follow-ups for patients with occult primary cancers who are at an elevated risk of developing a metastasis or a second primary carcinoma outbreak is highlighted.

The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003–2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (p trend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (p trend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30–39, 40–49, and 50–64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003–2006. SCC:ADC decreased from approximately 2.5:1 in 2003–2006 to 1.3:1 in 2015–2018 while the CIN3:AIS remained relatively constant, ∼10:1. Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated. • Following the introduction of 3-yearly co-testing, the detection of CIN3 and AIS increased. • Following the introduction of 3-yearly HPV and Cytology co-testing, diagnoses of cervical squamous cell carcinoma decreased. • Following the introduction of 3-yearly HPV and Cytology co-testing, diagnoses of cervical adenocarcinoma did not change. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma is the most common cancer worldwide. Most of basal cell carcinoma can be detected in the early stages and are generally well controlled with local resection. Despite the high incidence of BCC, intramucosal BCC is a very rare clinical entity. We hereby present a rare case report of pigmented BCC on soft palate and review the literature of this entity. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the clinico-ultrasound features of primary squamous cell carcinoma of the thyroid (PSCCT) and secondary SCCT (SSCCT) and evaluate the accuracy of fine needle aspiration (FNA) recommendation for SCCT with American College of Radiology-Thyroid Imaging and Reporting Data System (ACR-TIRADS) and Chinese-TIRADS (CTIRADS). Materials and methods: We retrieved 26 SCCT patients (11 PSCCT, 15 SSCCT) from our hospital's pathology database (5,718 patients with thyroid malignancy) over 23 years. Medical records and ultrasound data of the 26 patients with 27 SCCTs were analyzed retrospectively, and each SCCT focus was categorized based on the two TIRADSs. Results: For 26 patients (21 males, 5 females) with an age range of 42-81 years, rapidly enlarging thyroid/neck nodules (18/26, 69.2%), dysphagia (7/26, 26.9%), hoarseness (6/26, 23.1%), dyspnea (5/26, 19.6%), cough (4/26, 15.4%), neck pain (2/26, 7.7%), B symptoms (2/26, 7.7%), and blood in sputum (1/26, 3.8%) were presented at diagnosis. Five asymptomatic patients (5/26, 19.2%) were detected by ultrasound. Hoarseness was more common in PSCCT (5/11, 45.5%) than in SSCCT (1/15, 6.7%) (P=0.032). For 27 SCCTs with a mean size of 3.7 ± 1.3 cm, the ultrasound features consisted of solid (25/27, 92.6%) or almost completely solid composition (2/27, 7.4%), hypoechoic (17/27, 63%) and very hypoechoic echogenicity (10/27, 37%), irregular/lobulated margin with extra-thyroidal extension (27/27, 100%), taller-than-wide shape (13/27, 48.1%), punctate echogenic foci (6/27, 22.2%), hypervascularity (23/27, 85.2%) and involved neck lymph (13/26, 50.0%). A total of 27 SCCTs were evaluated as high malignancy risk stratification (=TR4 and 4B) by the two TIRADSs and recommended FNA in 96.3-100% (26/27, 27/27). Pathologically, more than half of PSCCTs (7/12, 58.3%) and a quarter of SSCCTs (4/15, 26.7%) were poorly differentiated, while moderately and well-differentiated grades were observed in 5 PSCCTs and 11 SSCCTs (P=0.007). Thirteen patients (50.0%) underwent surgery with radical operation in 5 cases (5/13, 38.5%). Conclusion: SCCT is an extremely rare and aggressive malignancy with a male predominance. PSCCT and SSCCT had similar clinical and ultrasound features except for tumor differentiation and the symptom of hoarseness. SCCT showed a high malignancy risk stratification in ACR-TIRADS and C-TIRADS, with a high rate of FNA recommendation. [ABSTRACT FROM AUTHOR]

We intended to update human papillomavirus (HPV) prevalence and p16INK4a positivity in oropharyngeal squamous cell carcinomars (SCC), and calculate HPV attributable fraction (AF) for oropharyngeal SCC by geographic region. We searched Medline, Embase, and the Cochrane Library to identify published studies of HPV prevalence and p16INK4a positivity alone or together in oropharyngeal SCC before December 28, 2021. Studies that reported type‐specific HPV DNA prevalence using broad‐spectrum PCR‐based testing methods were included. We estimated pooled HPV prevalence, type‐specific HPV prevalence, and p16INK4a positivity. AF of HPV was calculated by geographic region. One hundred and thirty‐four studies including 12 139 cases were included in our analysis. The pooled HPV prevalence estimate for oropharyngeal SCC was 48.1% (95% confidence interval [CI] 43.2‐53.0). HPV prevalence varied significantly by geographic region, and the highest HPV prevalence in oropharyngeal SCC was noted in North America (72.6%, 95% CI 63.8‐80.6). Among HPV positive cases, HPV 16 was the most common type with a prevalence of 40.2% (95% CI 35.7‐44.7). The pooled p16INK4a positivity in HPV positive and HPV16 positive oropharyngeal SCC cases was 87.2% (95% CI 81.6‐91.2) and 91.7% (84.3‐97.2). The highest AFs of HPV and HPV16 were noted in North America at 69.6% (95% CI 53.0‐91.5) and 63.0% (48.0‐82.7). [Correction added on 31 October 2023, after first online publication: the percentage symbol (%) was missing and has been added to 63.0% (48.0‐82.7) in the Abstract and Conclusion.] A significant proportion of oropharyngeal SCC was attributable to HPV. HPV16 accounts for the majority of HPV positive oropharyngeal SCC cases. These findings highlight the importance of HPV vaccination in the prevention of a substantial proportion of oropharyngeal SCC cases. [ABSTRACT FROM AUTHOR]

Introduction: Squamous cell carcinoma accounts for about 90% of head and neck cancers. The present study aimed to investigate the epidemiology and anatomical involvement pattern of squamous cell carcinoma (SCC) in the head and neck region from 2013-2021 in Imam Khomeini Hospital, Kermanshah, Iran. Material & Methods: This descriptive cross-sectional study was conducted on all the patients with SCC of the head and neck treated at Imam Khomeini Medical Center in Kermanshah over a period of 10 years. Demographic and pathological information was extracted from the patients' medical records. Then, the obtained data was analyzed in SPSS software (version 23). Findings: Out of 299 patients identified with SCC, 236 (78.9%) were male, and the remaining were female. The majority of the patients (48.8%) fell within the age group of 55-72 years, with 57.9% reporting a history of smoking and 76.9% residing in urban areas. Among those studied, the most commonly affected site was the larynx, accounting for 49.5% (148) of cases. The highest incidence of head and neck cancers in both men and women was observed in 2019, with 15.9% and 15.7% of cases, respectively. Discussion & Conclusion: The results of this study showed that most patients were older men over 50, who mostly lived in the city and smoked. The most anatomical site of involvement was the larynx. Therefore, it is recommended to pay attention to these risk factors to prevent and control these cancers.

Actinic keratosis (AK) is characterized by a reddish or occasionally skin-toned rough patch on sun-damaged skin, and it is regarded as a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), utilizing 5-aminolevulinic acid (ALA) along with red light, is a recognized treatment option for AK that is limited by the penetration depth of light and the distribution of the photosensitizer into the skin. Cold atmospheric plasma (CAP) is a partially ionized gas with permeability-enhancing and anti-cancer properties. This study analyzed, in vitro, whether a combined treatment of CAP and ALA-PDT may improve the efficacy of the treatment. In addition, the effect of the application sequence of ALA and CAP was investigated using in vitro assays and the molecular characterization of human oral SCC cell lines (SCC-9, SCC-15, SCC-111), human cutaneous SCC cell lines (SCL-1, SCL-2, A431), and normal human epidermal keratinocytes (HEKn). The anti-tumor effect was determined by migration, invasion, and apoptosis assays and supported the improved efficacy of ALA-PDT in combination with CAP. However, the application sequence ALA-CAP–red light seems to be more efficacious than CAP-ALA–red light, which is probably due to increased intracellular ROS levels when ALA is applied first, followed by CAP and red light treatment. Furthermore, the expression of apoptosis- and senescence-related molecules (caspase-3, -6, -9, p16INK4a, p21CIP1) was increased, and different genes of the junctional network (ZO-1, CX31, CLDN1, CTNNB1) were induced after the combined treatment of CAP plus ALA-PDT. HEKn, however, were much less affected than SCC cells. Overall, the results show that CAP may improve the anti-tumor effects of conventional ALA-PDT on SCC cells. Whether this combined application is successful in treating AK in vivo has to be carefully examined in follow-up studies.

Purpose: Complications of implant prostheses have direct correlation with the increased use of implants for dental rehabilitation. In this study, we present cases of peri-implant oral malignancies (PIOM) around dental implants and a retrospective analysis of patients treated for PIOM. Methods: The retrospective analysis was performed with patients treated for PIOM at the Department of Oral and Maxillofacial Surgery of the Seoul National University Dental Hospital between 2006 and 2014. The patient records were thoroughly screened for previous medical issues, human papilloma virus infections, and other clinical data with a focus on relevant information such as localization, time from implant insertion to the development of the carcinoma, implant type and prosthetic rehabilitation. Results: Twenty-one patients were diagnosed with PIOM. The male-to-female ratio was 1.625. The mean age of the patients was 60.42 ± 9.35 years old. Three patients reported ongoing alcohol/tobacco consumption. Five patients had a history of previous oral cancer surgery or exhibited mucosal lesions. The time from implant placement until carcinoma diagnosis was 49.13 ± 33.63 months on average. Most PIOM patients (95.2%) were diagnosed with SCC. All patients had previously been treated for peri-implantitis. In 85.7% of the patients, prostheses were observed on the opposing teeth where PIOM occurred. Conclusion: Based on the review of these cases, it can be deduced that there is a possibility that implant treatment and galvanic currents between prosthesis may constitute an irritant and/or inflammatory cofactor which contributes to the formation and/or development of malignant tumors. Patients at potential risk may benefit from individualized recall intervals and careful evaluations. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer is one of the most prevalent cancers worldwide. Dickkopf-1 (DKK-1) and -2 (DKK-2) are important proteins for the regulated Wnt signalling pathway. Alternations in the Wnt pathway are associated with tumour progression. The aim of the study was to analyse the concentration of DKK-1 and DKK-2 in tumour and matched non-tumour (NT) samples of 65 patients with nonsmall cell lung cancer (NSCLC), including 3 subtypes: adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Material and methods: The protein concentration was measured by enzyme- linked immunosorbent assay (ELISA) in homogenates. Results: The difference between the level of DKK-1 in tumour and NT specimens was not significant for the whole NSCLC group and SCC and LCC subtype, while in AC samples they were significantly higher (p = 0.028). The highest concentration of DKK-1 was found in the advanced NSCLC samples, with the T4 parameter as well as stage III. Significantly decreased DKK-2 concentrations were detected in all NSCLC subtypes (p < 0.05). Moreover, the DKK-2 level was higher in non-smokers than in smokers. The results indicate that concentrations of DKKs were different in relation to subtypes as well as clinical and socio- demographic parameters. The concentration of DKKs could be associated with the progression of NSCLC. Conclusions: We suggest that DKK-1 could play an oncogenic role in AC, while DKK-2 could be a tumour suppressor in all NSCLC subtypes. Dickkopf- 1 and DKK-2 proteins could have differential roles in the Wnt signalling pathway, which is important in many cellular processes, such as proliferation and apoptosis. [ABSTRACT FROM AUTHOR]

Orbital defects represent difficulties in head and neck reconstruction owing to 3-dimensional complexity of the socket with aim to restore form and function. Recommended methods of reconstruction include mucosal and skin grafts free microvascular myofascial or fasciocutaneous flaps. However, most frequently, reconstruction of orbital defects calls for measures somewhere in between. The temporoparietal fascia flap (TPFF) fits well as it provides thin, pliable coverage of defects with dependable blood supply, tolerance for a large degree of rotation and minimal donor site morbidity. We hereby present our experience and results of 10 cases using TPPF and temporalis muscle post orbital exentration defects.Ten patients (7 male and 3 females) age ranging from 25 to 64 years underwent reconstruction of orbital exenteration defects using TPPF and temporalis muscle from June 2019 to June 2020 in our department. The primary disease was squamous cell carcinoma (SCC) of orbital structures (anterior compartment) in all 10 patients. All cases were clinically N0 and M0.All patients had successful transfer of TPFF grafts and temporalis muscle transfer without flap compromise. TPPF was used in all 10 patients while Temporalis muscle flap was used to fill orbital socket in our 9 patients. Temporoparietal fascial flap showed viable option for subtle orbital and malar contour defect. All patients had intact dura with residual orbital cavity after resection reconstructed with TPPF and temporalis muscle without any additional flap usage. No frontal paralysis or orbital fistula was seen but local recurrence occurred in one patient in follow up and managed with RT. The TPFF is one of the most reliable and versatile regional flaps in the head and neck for orbital reconstruction. [ABSTRACT FROM AUTHOR]

Introduction: Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are two cutaneous conditions with morphological resemblance, which can complicate the diagnosis in some cases. Using immunohistochemistry staining of biomarkers could be beneficial in resolving this obstacle. Objectives: we investigated a variety of biomarkers assessed in different studies in order to find the most important and helpful biomarkers for differentiation between SCC and lesions capable of spontaneous regression. Methods: PubMed medical literature and Google Scholar database were used to identify relevant literature up to 15 June 2022. The aim of our analyses was to determine the capability of biomarkers to distinguish SCC from lesions capable of spontaneous regression using calculated individual and pooled OR and 95% CI and I2 tests. Results: Six potential biomarkers are CD10 with pooled OR= 0.006 (95% CI 0.001 to 0.057) and I2=0%; COX-2 with pooled OR=0.089 (95% CI 0.029 to 0.269) and I2=17.1%; Elastic Fibers with pooled OR= 6.69 (95% CI 2.928 to 15.281) and I2=0%; IMP-3 with pooled OR=0.145 (95% CI 0.021 to 1.001) and I2=44.5%; P53 with pooled OR=0.371 (95% CI 0.188 to 0.733) and I2=55.9%; AT1R with OR=0.026 (95% CI 0.006 to 0.107). Conclusions: We suggest the utilization of the following IHC biomarkers for discrimination between lesions with spontaneous regression such as KA and SCC: CD10, COX-2, and Elastic Fibers.

This study addresses the gap in understanding the prognostic relevance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression in metastatic cervical squamous cell carcinoma (SCC) patients undergoing anti-vascular endothelial growth factor-based therapy. A retrospective multicenter study (n = 34) explored HIF-1 alpha expression via immunohistochemistry in patients treated with platinum chemotherapy and bevacizumab. Median progression-free survival (PFS) was significantly lower in the HIF-1 alpha low score group compared to the high score group (4.9 vs 12.9 months, P = 0.014). Similarly, the median overall survival (OS) was significantly reduced in the HIF-1 alpha low score group (8.3 vs 20.4 months, P = 0.006). This study, the first of its kind, highlights the prognostic significance of HIF-1 alpha expression in metastatic cervical SCC patients treated with bevacizumab-based therapy.

Cutaneous squamous cell carcinoma (cSCC) arises from the abnormal proliferation of keratinocytes of the epidermis, most commonly due to UV-light-induced DNA damage. Although histopathological assessment is the gold standard for diagnosing cSCC, nascent optical imaging diagnostic modalities enable clinicians to perform “optical or virtual biopsy” in real-time. We aim to report advances in optical imaging diagnostics for cSCC, along with an updated review of the literature. A comprehensive literature review was performed using PubMed, Embase, and Cochrane databases for manuscripts published from 2008 to 2022. The search yielded a total of 9581 articles, out of which 136 relevant articles were included in the literature review after fulfilling screening and eligibility criteria. This review highlights the current optical imaging devices used for diagnosing cSCC and their diagnostic features. These devices include in vivo and ex vivo reflectance confocal microscopy, optical coherence tomography, line-field confocal optical coherence tomography, multiphoton tomography, and high-frequency ultrasonography. Although surgical excision or Mohs micrographic surgery is considered the gold standard, the latest developments in nonsurgical management of cSCC are discussed. Based on he review of the literature, we conclude that contemporary optical imaging devices such as confocal microscopy, optical coherence tomography, line-field confocal optical coherence tomography and multiphoton tomography have revolutionized real-time diagnostic imaging in dermatology, particularly within the realm of skin cancer. These devices enable rapid diagnoses and allow for a faster initiation of therapy. The application of newer imaging devices to cSCC management may benefit high-risk patients (e.g., chronic UV radiation exposure or organ transplant recipients) or patients with multifocal cSCC, for whom multiple biopsies would be impractical, thus avoiding unnecessary biopsies. Together with dermoscopy, optical imaging technologies can help to improve the efficiency of diagnosis by reducing the turnaround time and the need for extensive laboratory processing resources.

5-Fluorouracil (5-FU), a BCS class III drug, has low oral bioavailability and is cytotoxic in nature causing severe systemic side effects when administered through the intravenous route. Topical drug delivery could potentially mitigate the systemic side-effects. Microemulsions (MEs) would be an apt solution due to enhanced partitioning of the drug to the skin. However, conventional methods for preparing MEs are inefficient since they are not continuous and are very tedious and time-consuming processes hence revealing the need for the development of continuous manufacturing technology. In our study, 5-FU MEs were prepared using a continuous manufacturing Twin Screw Process (TSP) and its efficiency in the treatment of skin cancer was evaluated. Water-in-oil MEs were prepared using isopropyl myristate as the oil phase and Aerosol OT and Tween 80 as the surfactants. The average particle size was observed to be 178 nm. Transmission electron microscopy was employed to confirm the size and shape of the MEs. FTIR study proved no physical or chemical interaction between the excipients and the drug. In vitro drug release using vertical diffusion cells and ex vivo skin permeation studies showed that the drug was released sustainably and permeated across the skin, respectively. In in vitro cytotoxicity studies, 5-FU MEs were accessed in HaCat and A431 cell lines to determine percentage cell viability and IC50. Skin irritation and histopathological examination implied that the 5-FU MEs did not cause any significant irritation to the skin. In vivo pharmacodynamics studies in rats suggested that the optimised formulation was effective in treating squamous cell carcinoma (SCC). Therefore, 5-FU MEs efficiently overcame the various drawbacks faced during oral and intravenous drug delivery. Also, TSP proved to be a technique that overcomes the various problems associated with the conventional methods of preparing MEs. [ABSTRACT FROM AUTHOR]

Introduction: Squamous cell carcinoma accounts for about 90% of head and neck cancers. The present study aimed to investigate the epidemiology and anatomical involvement pattern of squamous cell carcinoma (SCC) in the head and neck region from 2013-2021 in Imam Khomeini Hospital, Kermanshah, Iran. Material & Methods: This descriptive cross-sectional study was conducted on all the patients with SCC of the head and neck treated at Imam Khomeini Medical Center in Kermanshah over a period of 10 years. Demographic and pathological information was extracted from the patients' medical records. Then, the obtained data was analyzed in SPSS software (version 23). Findings: Out of 299 patients identified with SCC, 236 (78.9%) were male, and the remaining were female. The majority of the patients (48.8%) fell within the age group of 55-72 years, with 57.9% reporting a history of smoking and 76.9% residing in urban areas. Among those studied, the most commonly affected site was the larynx, accounting for 49.5% (148) of cases. The highest incidence of head and neck cancers in both men and women was observed in 2019, with 15.9% and 15.7% of cases, respectively. Discussion & Conclusion: The results of this study showed that most patients were older men over 50, who mostly lived in the city and smoked. The most anatomical site of involvement was the larynx. Therefore, it is recommended to pay attention to these risk factors to prevent and control these cancers. [ABSTRACT FROM AUTHOR]

Malignant transformation of mature cystic teratoma (MCT) is a well-known but uncommon phenomenon seen mostly in postmenopause women. We report a case of a 65-year-old postmenopausal woman with a malignant transformation of MCT and with a low-grade squamous intraepithelial lesion in her cervix. She was treated surgically by total abdominal hysterectomy with bilateral salpingo-oophorectomy with a preoperative diagnosis of right ovarian teratoma. Her postoperative period was uneventful. On follow-up, the histopathology report revealed a right ovarian dermoid cyst with well-differentiated squamous cell carcinoma; there was no evidence of malignancy elsewhere, including the cervix. Ascitic fluid was also free of malignant cells, and the disease was at stage Ia. The patient did not receive any adjuvant chemotherapy and was followed up with clinical examination postoperatively for 1 year, and there was no evidence of any relapse clinically. Preoperative diagnosis of malignant transformation of squamous cell carcinoma (SCC) is difficult, as there is no specific screening marker and no consensus or standard guidelines available regarding the optimum management of this relatively poorly known entity. Here we emphasize the need for a high index of suspicion of malignant transformation with the presence of factors such as elderly age, the huge size of the tumor, and large solid components in the tumor. Considering the scarcity of case reports and studies about SCC arising from MCT, every experience with malignant transformation of MCT should be reported for a better understanding of the disease presentation and management. [ABSTRACT FROM AUTHOR]

The activin–follistatin system regulates several cellular processes, including differentiation and tumorigenesis. We hypothesized that the immunostaining of βA-activin and follistatin varies in neoplastic cervical lesions. Cervical paraffin-embedded tissues from 162 patients sorted in control (n = 15), cervical intraepithelial neoplasia (CIN) grade 1 (n = 38), CIN2 (n = 37), CIN3 (n = 39), and squamous cell carcinoma (SCC; n = 33) groups were examined for βA-activin and follistatin immunostaining. Human papillomavirus (HPV) detection and genotyping were performed by PCR and immunohistochemistry. Sixteen samples were inconclusive for HPV detection. In total, 93% of the specimens exhibited HPV positivity, which increased with patient age. The most detected high-risk (HR)-HPV type was HPV16 (41.2%) followed by HPV18 (16%). The immunostaining of cytoplasmatic βA-activin and follistatin was higher than nuclear immunostaining in all cervical epithelium layers of the CIN1, CIN2, CIN3, and SCC groups. A significant decrease (p < 0.05) in the cytoplasmic and nuclear immunostaining of βA-activin was detected in all cervical epithelial layers from the control to the CIN1, CIN2, CIN3, and SCC groups. Only nuclear follistatin immunostaining exhibited a significant reduction (p < 0.05) in specific epithelial layers of cervical tissues from CIN1, CIN2, CIN3, and SCC compared to the control. Decreased immunostaining of cervical βA-activin and follistatin at specific stages of CIN progression suggests that the activin–follistatin system participates in the loss of the differentiation control of pre-neoplastic and neoplastic cervical specimens predominantly positive for HPV. [ABSTRACT FROM AUTHOR]

The calcium-sensing receptor (CaSR) is an important regulator of epidermal function. We previously reported that knockdown of the CaSR or treatment with its negative allosteric modulator, NPS-2143, significantly reduced UV-induced DNA damage, a key factor in skin cancer development. We subsequently wanted to test whether topical NPS-2143 could also reduce UV-DNA damage, immune suppression, or skin tumour development in mice. In this study, topical application of NPS-2143 (228 or 2280 pmol/cm2) to Skh:hr1 female mice reduced UV-induced cyclobutane pyrimidine dimers (CPD) (p < 0.05) and oxidative DNA damage (8-OHdG) (p < 0.05) to a similar extent as the known photoprotective agent 1,25(OH)2 vitamin D3 (calcitriol, 1,25D). Topical NPS-2143 failed to rescue UV-induced immunosuppression in a contact hypersensitivity study. In a chronic UV photocarcinogenesis protocol, topical NPS-2143 reduced squamous cell carcinomas for only up to 24 weeks (p < 0.02) but had no other effect on skin tumour development. In human keratinocytes, 1,25D, which protected mice from UV-induced skin tumours, significantly reduced UV-upregulated p-CREB expression (p < 0.01), a potential early anti-tumour marker, while NPS-2143 had no effect. This result, together with the failure to reduce UV-induced immunosuppression, may explain why the reduction in UV-DNA damage in mice with NPS-2143 was not sufficient to inhibit skin tumour formation. [ABSTRACT FROM AUTHOR]

Abstract Background Reconstruction of soft tissue defects following surgical tumor resection is important for quality of life in cancer patients with oral and oropharyngeal squamous cell carcinoma (SCC). This study presents a novel computer-aided reconstruction of soft tissue (CARST) technology employed with these patients. Methods We first described the CARST technology in detail in a report of a 34-year-old male patient with locally invasive right-sided tongue SCC following a nearly total glossectomy and reported the postoperative outcomes. This digital technology was applied to construct a 3D model from CT images, which was used to delineate surgical resection boundaries and design a personalized reconstruction of the soft tissue defect. A nonuniform rational B-spline (NURBS) was generated and applied to transform the 3D model into a 2D flap-cutting guide printed out using a 3D printer. We then reported a case-series study on oral and oropharyngeal SCC patients who were randomly assigned to receive the CARST (n = 15) or a traditional soft tissue reconstruction (n = 15). Clinicopathological features and short- and long-term postoperative outcomes between the two groups were compared. Results The patient with the tongue SCC had a successful CARST following surgical tumor resection without any complications. His speech and swallowing functions recovered well after surgery and he experienced no significant changes to his appearance following recovery. There was no recurrence within a 3-year follow-up period. Results of the case-series study showed that the CARST group had significantly shorter operative and post-operation hospital-stay time, a higher flap utilization rate, and a trend of less and milder postoperative complications, and they experienced no significant difference in intraoperative blood loss and long-term outcomes compared to the traditional group. Conclusion CARST is a safer and more efficient personalized technology of soft tissue reconstruction following surgical tumor resection in patients with oral and oropharyngeal SCC.

SLC1A5, short for solute carrier family 1 member 5, is a neutral amino acid transporter whose expression has been reported to be upregulated in various cancers, including esophageal squamous cell carcinoma (ESCC). Despite this, little has been described regarding the immunological involvement of SLC1A5 expression in the tumor microenvironment of ESCC. Given this, we adopted in silico analyses together with a wet lab strategy to investigate the prognostic and clinicopathological meaning of SLC1A5 expression in ESCC. In silico analyses of SLC1A5 expression data available from The Cancer Genome Atlas (TCGA) database revealed that SLC1A5 expression was unrelated to the prognosis of ESCC, which holds true when extended to other types of squamous cell carcinoma (SCC), including head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC). Further analyses revealed that SLC1A5 expression correlated markedly with the infiltration density of effector CD8+ T cells in ESCC, and the same was true for HNSC and LUSC when extrapolated. As experimental confirmation, multiplexed immunofluorescent staining was undertaken to verify the correlation between SLC1A5 expression and infiltration of CD8+ T cells in a tissue microarray prepared from ESCC and matched normal control tissues. Our data confirmed that SLC1A5 expression was not associated with prognosis but was associated with the exclusion of CD8+ T cells. Taken together, all the data we curated strongly support the notion that SLC1A5 expression is associated with CD8+ T-cell exclusion in the tumor microenvironment of SCC.

Nonmelanoma skin cancer is the most common cancer in the world, and lung cancer is the leading cause of death from cancer. Histologically, squamous cell carcinoma (SCC) is the second most prevalent type of both skin and lung cancers. We report the case of a 38-year-old female with metastatic, poorly differentiated lung SCC detected on chest X-ray after she presented to the hospital with cough and dyspnea. She had had a 7.5 cm moderately differentiated well-circumscribed posterior scalp SCC completely excised eight years earlier. CT scan showed a large right lung mass, nodular filling defect in the left atrium (LA), and metastases to the adrenal glands and the first rib. Her pulmonary tumor extends to the LA via the right superior pulmonary vein, which is rarely reported in the literature. Ultrasoundguided biopsy of the rib mass showed poorly differentiated SCC. The patient received urgent radiotherapy, given superior vena cava and mainstem bronchus compression. Head CT showed no brain metastasis. A biopsy of the left adrenal initially reported an undifferentiated pleomorphic sarcoma; however, a second pathologist reported it as a poorly differentiated carcinoma of lung origin. At least three pathologists verified the specimen, and it had a PD-L1 test with a 1-49% score. An initial echocardiogram confirmed the LA mass. The patient received a Paclitaxel-Carboplatin-Pembrolizumab regimen as the first-line treatment for metastatic SCC. A repeat echocardiogram after cycle 1 showed a decrease in the size of the tumor in the LA. Almost five months after her initial visit, this young woman’s symptoms and performance status have improved post-palliative radiotherapy and chemo-immunotherapy. Follow-up CT showed smaller lung, nodal, adrenal, and costochondral masses, and evidence of necrosis. This case is clinically relevant because it represents a common problem presenting uncommonly. Moreover, it highlights that ultrasound-guided interventions and medical imaging are essential in directing metastatic cancer diagnosis, treatment, and follow-up, especially when pathology cannot confirm but only presume a specific diagnosis. [ABSTRACT FROM AUTHOR]

Nonmelanoma skin cancer is the most common cancer in the world, and lung cancer is the leading cause of death from cancer. Histologically, squamous cell carcinoma (SCC) is the second most prevalent type of both skin and lung cancers. We report the case of a 38-year-old female with metastatic, poorly differentiated lung SCC detected on chest X-ray after she presented to the hospital with cough and dyspnea. She had had a 7.5 cm moderately differentiated well-circumscribed posterior scalp SCC completely excised eight years earlier. CT scan showed a large right lung mass, nodular filling defect in the left atrium (LA), and metastases to the adrenal glands and the first rib. Her pulmonary tumor extends to the LA via the right superior pulmonary vein, which is rarely reported in the literature. Ultrasound-guided biopsy of the rib mass showed poorly differentiated SCC. The patient received urgent radiotherapy, given superior vena cava and mainstem bronchus compression. Head CT showed no brain metastasis. A biopsy of the left adrenal initially reported an undifferentiated pleomorphic sarcoma; however, a second pathologist reported it as a poorly differentiated carcinoma of lung origin. At least three pathologists verified the specimen, and it had a PD-L1 test with a 1-49% score. An initial echocardiogram confirmed the LA mass. The patient received a Paclitaxel-Carboplatin-Pembrolizumab regimen as the first-line treatment for metastatic SCC. A repeat echocardiogram after cycle 1 showed a decrease in the size of the tumor in the LA. Almost five months after her initial visit, this young woman’s symptoms and performance status have improved post-palliative radiotherapy and chemo-immunotherapy. Follow-up CT showed smaller lung, nodal, adrenal, and costochondral masses, and evidence of necrosis. This case is clinically relevant because it represents a common problem presenting uncommonly. Moreover, it highlights that ultrasound-guided interventions and medical imaging are essential in directing metastatic cancer diagnosis, treatment, and follow-up, especially when pathology cannot confirm but only presume a specific diagnosis.

Objective: To compare the expression of CD-10 in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Study Design: Comparative cross-sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from Jun 2016 to Jun 2017. Methodology: After taking ethics approval from the ethical review committee AFIP, previously diagnosed, thirty-eight cases of each basal cell carcinoma and squamous cell carcinoma were taken from the histopathology department of Armed Forces Institute of Pathology, Rawalpindi. CD-10 was applied according to standard protocol. The intensity of the CD-10 expression is assessed and categorized into three groups. CD-10 expression less than 10% in the tumour cell was taken as negative (-), 10 to 50% staining was taken as positive (+) and greater than 50% staining in tumour cells was taken as strong positive (++). Results: Out of the total 76 cases included in the study, 9 (24%) were strongly positive (++) whereas 20 (52.6%) were positive (+) and 9 (23.7%) were negative (-) for CD-10 expression. Out of the total 38 cases of SCC 4 (11%) cases showed positive CD-10 expression and 34 (89%) showed negative (-) results. A significant association (p-value

Although the carcinogenesis of SCC with EM is not understood,[5] EM is closely related to alcohol intake and tobacco smoking.[[1], [3], [5]] Then, we examined genetic characteristics using next-generation sequencing (NGS). Keywords: endoscopic submucosal dissection (ESD); epidermalization; epidermoid metaplasia; squamous cell carcinoma (SCC) EN endoscopic submucosal dissection (ESD) epidermalization epidermoid metaplasia squamous cell carcinoma (SCC) 327 329 3 07/27/23 20230701 NES 230701 Abbreviations CNV copy number variations ESD endoscopic submucosal dissection EM epidermoid metaplasia IPCL intra-papillary capillary vessels NGS next-generation sequencing SCC squamous cell carcinoma Epidermoid metaplasia (EM) is relatively common in the oral cavity, but rare in the esophagus.[1] It is defined by a well-developed granular layer and overlying hyperorthokeratosis close to the epidermis.[1] EM is principally benign, but is sometimes associated with dysplasia but seldom associated with carcinoma in and around the EM.[[2], [4]] We want to report a very rare case with esophageal squamous cell carcinoma (SCC) resembling EM and we analyzed molecular characteristics of this lesion. EM is characterized by a well-developed granular layer and overlying hyperorthokeratosis resembling the epidermis.[1] EM is essentially benign, but is seldom associated with SCC in and around the EM.[[2], [4]] Therefore, he underwent ESD and the resected whitish tumor measured 23 × 22 mm after formalin fixation. [Extracted from the article]

Skin diseases and disorders have a significant impact on people's health and quality of life. Current medical practice suggests different methodologies for detecting and diagnosing skin diseases and conditions. Most of these require medical tests, laboratory analyses, images, and healthcare professionals to assess the results. This consumes time, money, and effort, and the waiting time is stressful for the patient. Therefore, it is an essential requirement to develop a new automatic method for the non-invasive diagnosis of skin diseases and disorders without the need for healthcare professionals or being in a medical clinic. This research proposes millimeter-wave (MMW) radiometry as a non-contact sensor for the non-invasive diagnosis of skin diseases and conditions. Reflectance measurements performed using 90 GHz radiometry were conducted on two samples of participants; sample 1 consisted of 60 participants (30 males and 30 females) with healthy skin, and sample 2 contained 60 participants (30 males and 30 females) suffering from skin diseases and conditions, which were: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), burn wounds, and eczema. Radiometric measurements show substantial differences in reflectance in the range of 0.02–0.27 between healthy and unhealthy regions of the skin on the same person. These results indicate that radiometry, as a non-contact sensor, can identify and distinguish between healthy and diseased regions of the skin. This indicates the potential of using radiometry as a non-invasive technique for the early detection of skin diseases and disorders. [ABSTRACT FROM AUTHOR]

Primary Intraosseous Carcinoma (PIOC) is a rare and aggressive squamous cell carcinoma (SCC) derived from remnants of odontogenic epithelium with no initial connection to oral mucosa. Due to the rarity of the disease, etiology and epidemiology are not clearly defined. The most affected site is the posterior mandible, and clinical features include swelling of the jaw, jaw pain, and sensory disturbances. Given the similarities of PIOC to other odontogenic carcinomas, diagnosis is often difficult, resulting in delays in intervention. Treatment of PIOC of the mandible includes surgery alone, surgery with adjuvant radiotherapy or chemotherapy, and free flap reconstruction. PIOC prognosis is poor, with the lymph nodal status acting as an important indicator. We present a case of a 60-year-old female who presented with a left submandibular mass initially thought to be SCC of unknown primary origin. Further investigation led to a final diagnosis of PIOC of the mandible. Clinical, radiological, and histological features of PIOC will be discussed., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, McDonald et al.)

Bowen's disease (BD), also known as squamous cell carcinoma (SCC) in situ, is a precancerous skin condition that can potentially progress to invasive tumors. Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor typically found in sun-exposed areas of elderly Caucasians. The coexistence of BD and MCC is extremely rare, particularly when MCC is located in subcutaneous tissue rather than its typical epidermal or dermal layers. This case report presents an unusual instance of BD coexisting with subcutaneous MCC on the dorsum of the hand in an elderly Japanese male. An 87-year-old Japanese male with over 30 years of sun exposure presented with a progressively enlarging red tumor on the dorsum of his left hand. A biopsy confirmed BD, and the tumor was excised with a 5 mm margin followed by skin grafting. Histopathological examination revealed subcutaneous MCC along with BD, with MCC cells forming small nests in the dermal papillary layer. Immunohistochemistry showed positive staining for synaptophysin and CK20 in a perinuclear dot pattern, confirming the MCC diagnosis. Given the patient's advanced age and the absence of positive surgical margins, a watch-and-wait approach was adopted. The patient has been under close outpatient monitoring, and no recurrence has been observed after six months. This case highlights the rarity of subcutaneous MCC coexisting with BD, with only a few reported cases of such coexistence. The unusual subcutaneous presentation and the presence of multiple micro-nodules instead of large atypical cell clusters suggest an early-stage MCC beneath BD. The pathogenesis of this coexistence remains unclear but raises important questions regarding the relationship between sun exposure and viral factors like Merkel cell polyomavirus (MCPyV), which was not tested in this case. The findings underscore the need for comprehensive diagnostic evaluation when encountering complex or atypical skin lesions. This report emphasizes the rarity of subcutaneous MCC coexisting with BD and underscores the importance of comprehensive diagnostic assessment in unusual cases. Further research is warranted to better understand the underlying mechanisms and to guide optimal management strategies for such rare and challenging presentations., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ishihara et al.)

Abstract Hypothesis Squamous cell carcinomas (SCC) of the external auditory canal (EAC) may harbor unique genomic alterations that may explain aggressive behavior and differentiate these tumors from cutaneous SCCs of other subsites. Background EAC SCCs arise in a non‐ultraviolet‐exposed region of the head and neck, are often locally aggressive and may metastasize to lymph nodes or distant sites. The genomic alterations underlying cutaneous SCC of other sites are well‐documented; however, mutational profiles of EAC SCC are less well characterized and may contribute to the unique anatomic site, high rates of recurrence and tumor spread. We performed targeted sequencing of a cohort of primary EAC SCCs to identify recurring and potentially targetable genomic alterations. Methods Genomic DNA was extracted from formalin‐fixed paraffin‐embedded specimens of 7 EAC SCCs and subjected to targeted DNA sequencing using a 227‐gene panel. Somatic alterations and gene copy number alterations were annotated using our validated, in‐house bioinformatics pipelines. Results In our EAC SCCs, we found recurrent alterations in TP53 and genes of receptor tyrosine kinase (eg, EGFR, FGFR) and PI3K pathways (eg, PIK3CA), similar to cutaneous SCCs of other head and neck sites. We also observed a high frequency of telomerase reverse transcriptase amplification and DNA methyltransferase 1 alterations, both of which are rarely observed in cutaneous SCCs of other sites. Conclusion These data represent the first step toward precise molecular characterization of EAC SCCs that may lead to an enhanced understanding of tumor biology and modernized precision medicine approaches for unique tumors. Level of Evidence: NA