Cutaneous Carcinoma Research Articles

Primary Cutaneous NUT Carcinoma: Clinicopathologic and Genetic Study of 4 Cases.

WHO Classification of Skin Tumors, fifth edition (2023) has newly described primary cutaneous NUT carcinoma; however, information on this cancer type remains scarce. Herein, we performed clinicopathologic and genetic analyses of 4 cases. Four elderly women (median age 77y, range: 68 to 82y) were included. The median tumor size was 12.5 (10 to 40mm). Tumors were located on the scalp, temple, thigh, and palm. Two (50%) patients presented with regional lymph node metastases. Neither distant metastasis nor mortality was observed during patient follow-up of 10.5 (3 to 15) months. Sanger, panel DNA and whole-exome RNA sequencing revealed BRD3::NUTM1 (n=2) and BRD4::NUTM1 (n=2) fusions. Histology of BRD3-rearranged tumors revealed an epidermal connection, relatively small tumor nests, and ductal or intracytoplasmic luminal formation, whereas that of BRD4-rearranged tumors revealed large solid nests comprising discohesive tumor cells. NUT, cytokeratins, p63, EMA, TRPS1, c-MYB, CD56, and INSM1 were immunoexpressed to varying degrees in all (100%) tumors. Furthermore, diffuse SOX10 expression was common (3/4, 75%). The literature review of five previously described cases revealed women predominance, no recurrence, frequent BRD3::NUTM1 fusions, and histology of ductoglandular structures. Our study findings and literature suggest elderly women predominance, relatively frequent BRD3::NUTM1 fusions, histopathologic ductoglandular differentiation, absence of abrupt keratinisation, and a characteristic immunoprofile in primary cutaneous NUT carcinoma, unlike in that of other organ. No distant metastasis or disease-associated mortality was seen in all cases with limited follow-up.

Apical Abscess on a Zygomaticus Implant Initially Diagnosed as a Cutaneous Carcinoma.

We present a case of an infection on a zygomaticus implant presenting on the skin, mimicking a cutaneous carcinoma, and presenting to a head and neck tumor board. The clinical findings were an intermittently discharging lesion over the zygomatic bone, which resolved upon removing the offending zygomaticus implant. It is essential to be aware that infections on a zygomaticus implant can occur well away from the normal tooth-bearing areas, and having a dentist with knowledge of these implants on a tumor board can prevent misdiagnosis and treatment.

The Immune Response of Cutaneous Basosquamous- and Squamous-Cell Carcinoma Associated with Sun Exposure

In recent years, there has been an observed increase in the frequency of cutaneous carcinoma, which correlates with sun exposure. This study aims to explore the variances of tumor characteristics and immune response markers among patients diagnosed with cutaneous squamous-cell carcinoma (SCC) and basosquamous-cell carcinoma (BSC) with varying levels of sun exposure. The objective is to elucidate the potential influence of sun exposure on tumor progression and immune response in these types of carcinomas. We conducted a retrospective observational study that included 132 patients diagnosed with SCC and BSC. Participants were separated into high- and low-sun exposure groups. Tumor characteristics and immune response markers, including lymphocyte percentage (LY%), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), were assessed using the Mann–Whitney U test. Our findings revealed the interplay between sun exposure, inflammation, aging, and immune response. In 80% of cases, it was found that individuals had high sun exposure throughout their lifetime. Patients in the high sun exposure category had a significantly higher LY% than those with low sun exposure (24.22 ± 7.64 vs. 20.71 ± 8.10, p = 0.041). Also, the NLR was lower in patients with high sun exposure (3.08 ± 1.47 vs. 3.94 ± 2.43, p = 0.023). Regarding inflammatory markers, the erythrocyte sedimentation rate (ESR), LY%, NLR, and LMR showed significant differences between the two groups. Patients who were diagnosed with SCC had higher ESR values (p = 0.041), higher LY% (p = 0.037), higher NLR (p = 0.041), and lower LMR (p = 0.025). This study provides evidence supporting distinct tumor characteristics and immune response patterns in patients diagnosed with SCC and BSC with a high sun exposure history. These findings imply that sun exposure may contribute to tumor progression and influence the immune response in individuals with SCC and BSC.

Successful Treatment of Metastatic Primary Cutaneous Adnexal Carcinoma With a PD-1 Inhibitor.

Standard of care treatment for metastatic cutaneous adnexal carcinomas is not well established. In this case report, we highlight the successful use of anti-programmed cell death protein 1 (anti-PD-1) therapy in treating a patient with low tumor mutation burden, microsatellite stable, high programmed death-ligand 1 (PD-L1) gene expression, metastatic primary cutaneous adnexal carcinoma with significant radiographic, and circulating tumor DNA response with durable benefit. Immune checkpoint inhibitors hold promise as a future treatment option in rare instances of metastatic disease from primary skin adnexal carcinoma. Further studies are needed to identify better immune checkpoint inhibitor predictive biomarkers for rare, advanced-stage non-melanoma skin cancers.

GATA3 Positively Correlates with BCL2 Expression in Indolent and Aggressive Histological Types of Cutaneous Basal Cell Carcinoma.

Some histological basal cell carcinoma (BCC) types demonstrate more aggressive behavior than others. They are known as high-risk BCC and are more challenging in therapy, contrary to indolent (low-risk) BCC types. Identifying novel protein markers to predict aggressiveness and potential therapeutic targets in challenging cases is recommended. GATA3 is a transcription factor critical for epithelial and lymphocytic differentiation. This study investigated the immunohistochemical expression of GATA3 in indolent and aggressive BCC and its association with BCL2 expression. Retrospectively collected indolent and aggressive BCC groups (24 cases each) were immunohistochemically stained with anti-GATA3 and BCL2 antibodies. The mean expression score (by area percentage) and TIL counts were determined and compared using ImageJ analysis. Stromal tumor-infiltrating lymphocytes (TIL) were counted per high-power field (HPF) on hematoxylin and eosin (H&E) staining. GATA3 and BCL2 expressions were significantly higher in the indolent group than in the aggressive group. GATA3 expression significantly correlated with BCL2 score and TIL counts. Higher GATA3 expression was significantly associated with a more indolent BCC histological type, higher BCL2 expression, and higher TIL count. GATA3 is a possible target for immunomodulation experiments to improve BCC immunotherapy outcomes.

Cetuximab for the treatment of cutaneous squamous-cell carcinoma in kidney transplant recipients – A retrospective cohort study

Background: Kidney transplant recipients are at high risk of developing cutaneous squamous cell carcinoma (cSCC) due to prolonged immunosuppression. While most lesions can be managed with local therapy, a subset of patients develop advanced cSCC that is unresectable, recurrent or metastatic. Immune check point inhibitors (ICI) and chemotherapy may jeopardize the transplanted kidney. Cetuximab, an anti-epidermal growth factor receptor antibody, has demonstrated efficacy in advanced cSCC, but data regarding efficacy and safety in solid organ transplant recipients is lacking. Methods: This retrospective cohort study analyzed kidney transplant recipients diagnosed with locally advanced or metastatic cSCC who were treated with cetuximab. Results: Seventeen patients were included in the analysis. The median age was 57 years at the time of kidney transplantation and 62 years at diagnosis of index lesion. Cetuximab was administered with radiation therapy as a radiosensitizer in 58.8% of patients, as monotherapy in 17.6% of patients, and with chemotherapy in 23.5% of patients. Importantly, no detrimental impacts on kidney graft function were observed. The main toxicites were grade 1–2 skin reactions and electrolyte imbalance. Of the 10 patients receiving cetuximab with chemoradiotherapy as a radiosesnitizer, 2 were treated with definitive intent, 7 of them in the adjuvantsetting, and 1 for palliative pourpose. Over half of these patients achieved a complete response (37.29%) or no recurrence after resection (23.5%). Median time to disease progression was 10 months. Conclusions: This novel study suggests cetuximab has a reasonable safety profile and potential efficacy in kidney transplant recipients with advanced cSCC, without impairing allograft function. Further prospective research with larger sample sizes is warranted to confirm these findings. Cetuximab should be investigated as a systemic treatment option for this high-risk population of solid organ transplant recipientss with recurrent, metastatic, or unresectable cSCC.

Radiation Therapy for Non-Melanoma Skin Cancer: A Study of 63 Cases

Cutaneous carcinomas are the most common skin cancers. Our work aims to identify the epidemiological and clinicopathological characteristics of cutaneous carcinomas, especially squamous cell carcinomas and basal cell carcinomas, treated and monitored at the Oncoradiotherapy Department of the Mohammed VI University Hospital of MARRAKECH, treated with radiotherapy, and to evaluate their efficacy and tolerance. Our study is retrospective and descriptive. We collected data from 63 patients treated and monitored between 2019 and 2022 at the Marrakech University Oncohematology Hospital. For each patient, we collected epidemiological, clinicopathological, therapeutic, and evolutionary data using an exploitation form. The age of the patients ranged from 27 to 95 years, with a peak between 61 and 70 years and a median of 64.32. Males predominated (74.6%). The matte skin phenotype was the most common, present in more than half of the patients. Among 63 patients surveyed, 69.8% had a history of prolonged sun exposure. Tumors of the head and neck were found in 65% of cases, with clinical appearance varying: 36.5% ulcerative-budding, 31.7% budding, 22.2% nodular, 6.4% sclerodermiform, and 3.2% ulcerated. Recurrences accounted for only 27% of consultations, and precancerous lesions were found in only 16% of patients. Most patients consulted at locally advanced stages (68.2%). Histologically, squamous cell carcinoma was confirmed in 63.5% of patients. External radiotherapy was performed in all patients, using three-dimensional conformal technique, adjuvant in 77.7% of cases, exclusive definitive in 19%, and palliative in 3.2% of cases. No patient received brachytherapy. Acute complications were observed in 52% of cases and late complications in 8%. After an average follow-up of 2 years, 76% of patients are still being followed in good disease control status with a complete response in 83% of them, 11% local recurrence, and 6% distant metastases. The incidence of cutaneous ........

Using optical coherence tomography to optimize Mohs micrographic surgery

Mohs micrographic surgery (MMS) is considered the gold standard for treating high-risk cutaneous basal cell carcinoma (BCC), but is expensive, time-consuming, and can be unpredictable as to how many stages will be required or how large the final lesion and corresponding surgical defect will be. This study is meant to investigate whether optical coherence tomography (OCT), a highly researched modality in dermatology, can be used preoperatively to map out the borders of BCC, resulting in fewer stages of MMS or a smaller final defect. In this prospective study, 22 patients with BCC undergoing surgical excision were enrolled at a single institution. All patients had previously received a diagnostic biopsy providing confirmation of BCC and had been referred to our center for excision with MMS. Immediately prior to performing MMS, OCT was used to map the borders of the lesion. MMS then proceeded according to standard protocol. OCT images were compared to histopathology for agreement. Histopathologic analysis of 7 of 22 MMS specimens (32%) revealed a total absence of BCC, indicating resolution of BCC after previous diagnostic biopsy. This outcome was correctly predicted by OCT imaging in 6 of 7 cases (86%). Nine tumors (9/22, 41%) had true BCC and required a single MMS stage, which was successfully predicted by pre-operative OCT analysis in 7 of 9 cases (78%). The final six tumors (27%) had true BCC and required two MMS stages for complete excision; preoperative OCT successfully predicted the need for a second stage in five cases (5/6, 83.3%). Overall, OCT diagnosed BCC with 95.5% accuracy (Cohen’s kappa, κ = 0.89 (p-value =  < 0.01) in the center of the lesion. Following a diagnostic biopsy, OCT can be used to verify the existence or absence of residual basal cell carcinoma. When residual tumor is present that requires excision with MMS, OCT can be used to predict tumor borders, optimize surgery and minimize the need for additional surgical stages.

Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation.

Cutaneous squamous carcinoma is the second most common epithelial malignancy, associated with significant morbidity, mortality, and economic burden. However, the mechanisms underlying cSCC remain poorly understood. In this study, we identified TGM3 as a novel cSCC tumor suppressor that acts via the PI3K-AKT axis. RT-qPCR, IHC and western blotting were employed to assess TGM3 levels. TGM3-overexpression/knockdown cSCC cell lines were utilized to detect TGM3's impact on epithelial differentiation as well as tumor cell proliferation, migration, and invasion in vitro. Additionally, subcutaneous xenograft tumor models were employed to examine the effect of TGM3 knockdown on tumor growth in vivo. Finally, molecular and biochemical approaches were employed to gain insight into the tumor-suppressing mechanisms of TGM3. TGM3 expression was increased in well-differentiated cSCC tumors, whereas it was decreased in poor-differentiated cSCC tumors. Loss of TGM3 is associated with poor differentiation and a high recurrence rate in patients with cSCC. TGM3 exhibited tumor-suppressing activity by regulating cell proliferation, migration, and invasion both in vitro and in vivo. As a novel cSCC tumor differentiation marker, TGM3 expression was positively correlated with cell differentiation. In addition, our results demonstrated an interaction between TGM3 and KRT14 that aids in the degradation of KRT14. TGM3 deficiency disrupts keratinocytes differentiation, and ultimately leads to tumorigenesis. Furthermore, RNA-sequence analysis revealed that loss of TGM3 enhanced EMT via the PI3K-AKT signaling pathway. Deguelin, a PI3K-AKT inhibitor, blocked cSCC tumor growth induced by TGM3 knockdown in vivo. Taken together, TGM3 inhibits cSCC tumor growth via PI3K-AKT signaling, which could also serve as a tumor differentiation marker and a potential therapeutic target for cSCC. Proposed model depicted the mechanism by which TGM3 suppress cSCC development. TGM3 reduces the phosphorylation level of AKT and degrades KRT14. In the epithelial cell layer, TGM3 exhibits a characteristic pattern of increasing expression from bottom to top, while KRT14 and pAKT are the opposite. Loss of TGM3 leads to reduced degradation of KRT14 and activation of pAKT, disrupting keratinocyte differentiation, and eventually resulting in the occurrence of low-differentiated cSCC.

Primary Cutaneous Apocrine Carcinoma of the Thigh: A Rare Case Report

Primary Cutaneous Apocrine Carcinoma of the Thigh: A Rare Case Report

No difference in overall survival for primary cutaneous Merkel cell carcinoma after Mohs surgery and wide local excision: A multicenter cohort analysis

No difference in overall survival for primary cutaneous Merkel cell carcinoma after Mohs surgery and wide local excision: A multicenter cohort analysis

Difficult Airway in a Patient with Well-Differentiated Epidermoid Carcinoma: A Case Report

Introduction: Cutaneous epidermoid carcinoma (SCC) is a common skin tumor that can arise from precursor lesions or de novo. It is the second leading cause of death from skin cancer and its incidence is expected to double by 2030. Risk factors include gender, ionizing radiation, alcohol and tobacco use, and HPV infection. SCC can be classified into five types according to the Peniche classification, with the ulcerative form being the most frequent. Anesthesia management for head and neck cancers is challenging due to airway complications. Case presentation: An 82-year-old female with a history of biomass combustion smoke exposure and hypertension presented with a painful papular lesion on the left nasal wing. Biopsy revealed well-differentiated epidermoid cancer. Despite treatment, the lesion progressed rapidly, leading to a request for surgical resection. The patient had predictors of difficult intubation and ventilation, and initial intubation attempts were unsuccessful. After aspiration of secretions and intracavitary bleeding, successful intubation was achieved on the second attempt. Controlled ventilation was initiated with specific settings. Clinical discussion: A difficult airway can pose challenges for anesthesiologists, especially in patients with head and neck cancer. Pre-anesthetic evaluation and preparation for rescue devices or maneuvers are crucial. In this case, the patient had a difficult Intubation Prediction Index. General anesthesia allowed for invasive monitoring, venous access, and reliable mechanical ventilation. Direct laryngoscopy was performed due to retro nasal bleeding, with equipment available for difficult airway management and aspiration. Conclusion: Anesthetic management for patients with head cancer presents challenges in airway management and carries the risk of complications. Pre-anesthetic and airway assessment are crucial to prevent complications and ensure successful intubation.

Unveiling the Therapeutic Horizon: HPV Vaccines and Their Impact on Cutaneous Diseases-A Comprehensive Review.

Human papillomavirus (HPV) encompasses a diverse array of viruses, comprising approximately 200 serotypes that affect humans. While the majority of HPV strains are associated with benign skin or mucous membrane growths, a subset is implicated in severe health conditions, such as cervical, anal, vulvar, and vaginal cancers. Despite the established effectiveness of HPV vaccines in preventing cervical and anal carcinomas in particular, their therapeutic potential in addressing cutaneous diseases linked to diverse HPV strains remains an intriguing area of investigation. This narrative review critically examines the existing literature to assess the viability of HPV immunization as a therapeutic intervention for prevalent cutaneous conditions. These include genital and extragenital cutaneous warts, epidermodysplasia verruciformis, and keratinocyte carcinomas. The findings suggest a promising dual role for HPV vaccines in preventing and treating dermatologic conditions while emphasizing future research directions, including the immunization perspective against β-HPVs. Moreover, the presence of conflicting study outcomes underscores the imperative for larger-scale, randomized trials with well-matched control groups to validate the efficacy of HPV immunization in the dermatologic context. This review contributes valuable insights into the evolving landscape of HPV-vaccine applications in the field of dermatology.

Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary.

Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP. A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations. We identified 14HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations. The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.

Comparative Analysis of US Guidelines for the Management of Cutaneous Squamous Cell and Basal Cell Carcinoma.

This study presents a comparative analysis of recently published guidelines to manage cutaneous squamous cell carcinoma (cSCC) and cutaneous basal cell carcinoma (cBCC) within the United States (US). A PubMed database search was performed for the time period between June 1, 2016, and December 1, 2022. A comprehensive comparison was performed in the following clinical interest areas: staging and risk stratification, management of primary tumor and regional nodes with curative intent, and palliative treatment. Guidelines from 3 organizations were analyzed: the American Academy of Dermatology (AAD), the National Comprehensive Cancer Network (NCCN), and the American Society for Radiation Oncology (ASTRO). The guidelines used different methodologies to grade evidence, making comparison difficult. There was agreement that surgery is the preferred treatment for curative cBCC and cSCC. For patients ineligible for surgery, there was a consensus to recommend definitive radiation. AAD and NCCN recommended consideration of other topical modalities in selected low-risk cBCC. Postoperative radiation therapy (PORT) was uniformly recommended in patients with positive margins that could not be cleared with surgery and in patients with nerve invasion. The definition and extent of nerve invasion varied. All guidelines recommended surgery as the primary treatment in patients with lymph node metastases in a curative setting. The criteria used for PORT varied; NCCN and ASTRO used lymph node size, number of nodes, and extracapsular extension for recommending PORT. Both NCCN and ASTRO recommend consideration of systemic treatment along with PORT in patients with extracapsular extension. Conclusion: US guidelines provide contemporary and complementary information on the management of cBCC and cSCC. There are opportunities for research, particularly in the areas of staging, indications for adjuvant treatment in curative settings, extent of nerve invasion and prognosis, and the role of systemic treatments in curative and palliative settings.

Detection of α-papillomaviruses in extragenital cutaneous squamous cell carcinomas.

Previous studies have demonstrated that human papillomaviruses (HPVs) of the beta genus can contribute to the onset of cutaneous carcinomas in organ transplant recipients. In contrast, there are limited data related to the oncogenicity of alpha (α)-HPVs in the skin. Herein, we explore the characteristics of three cutaneous squamous cell carcinomas presenting α-HPV infection occurring in patients with HIV, in order to determine the role of α-HPV in these skin cancers.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study

Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous-cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. Of 514 SOTRs who presented with 623 primary cSCCs, 37 developed metastases with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size >2cm, clinical ulceration, poor differentiation grade, perineural invasion and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9% - 68.4%). SOTRs have a high risk of cSCC metastases and well-established clinical and histological risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Cutaneous apocrine carcinoma

Cutaneous apocrine carcinoma

Primary cutaneous mucoepidermoid carcinoma: a case series

Primary cutaneous mucoepidermoid carcinoma: a case series

DERMATOFIBROSARCOMA PROTUBERANS: THE EXPERIENCES OF DIAGNOSIS AND TREATMENT THROUGH A RARE CASE REPORT

Background: Dermatofibrosarcoma protuberans (DFSP) is classified as a soft tissue sarcoma, representing a rare form of skin cancer. Despite its rarity, DFSP is acknowledged as the most common skin sarcoma. The clinical features of DFSP are highly varied, making early-stage diagnosis challenging. Treatment initiated at an advanced stage significantly increases the risk of DFSP recurrence. Case Report: A 65-year-old female patient sought medical attention at our hospital due to a giant tumor on her central back. The lesion had initially appeared two years prior and had been initially misdiagnosed as keloids. Subsequently, the patient underwent intralesional steroid injections and surgery at a private clinic, but the lesion exhibited no improvement and relapsed within two months. Upon presenting to the National Hospital of Dermatology and Venereology, the patient displayed a brown-red raised tumor measuring approximately 8x4cm on her back. Given the suspicion of a cutaneous carcinoma, a biopsy was conducted. The histopathology and immunohistochemistry tests confirmed the diagnosis of DFSP. Consequently, the patient underwent wide excision of the lesion, including 3 cm of normal skin around it and deep into the fascia. No recurrence was recorded after one year of follow-up. Conclusion: DFSP, a rare form of skin carcinoma, can be challenging to differentiate from various other conditions, including keloids. In cases where conventional treatments such as intralesional triamcinolone acetonide injection show poor improvement for suspected keloids, DFSP should be considered and confirmed through histopathology and immunohistochemistry tests. Received 28 June 2023Revised 26 September 2023Accepted 29 November 2023