Search

A 98-year-old woman presented with histologically confirmed locally advanced basal cell carcinoma of the face. A multidisciplinary approach excluded surgery because of the site near sensitive organs, extension, age, and comorbidities. Patient and caregivers declined radiotherapy considering the necessity of multiple hospital appointments. The patient was then placed on therapy with sonidegib, an oral inhibitor of the Hedgehog signaling pathway. There was a very rapid clinical response after only 28 days of treatment. The basal cell carcinoma improved progressively, with no adverse events reported. This case illustrates the efficacy and safety of this treatment in an advanced age patient. This treatment had a remarkably positive impact on quality of life, including that of the caregivers.

Basal cell hyperplasia is commonly observed in nasal polyp epithelium of eosinophilic chronic rhinosinusitis (eCRS). We examined the function and mechanisms of basal cell hyperplasia in the pathophysiology of eCRS. We found that normal human bronchial epithelial (NHBE) cells obtained basal cell characteristics when cultured with PneumaCult™-Ex Plus Medium. Most of the cells passaged three times expressed basal cell surface markers CD49f and CD271 by flow cytometry, and basal cell nuclear marker p63 by immunohistochemical staining. We named these NHBE cells with basal cell characteristics cultured Basal-like cells (cBC), and NHBE cells cultured with BEGM™ cultured Epithelial cells (cEC). The characteristics of cBC and cEC were examined and compared by RNA sequencing, RT-PCR, ELISA, and cell proliferation studies. RNA sequencing revealed that cBC showed higher gene expression of thymic stromal lymphopoietin (TSLP), IL-8, TLR3, and TLR4, and lower expression of PAR-2 compared with cEC. The mRNA expression of TSLP, IL-8, TLR3, and TLR4 was significantly increased in cBC, and that of PAR-2 was significantly increased in cEC by RT-PCR. Poly(I:C)-induced TSLP production and LPS-induced IL-8 production were significantly increased in cBC. IL-4 and IL-13 stimulated the proliferation of cBC. Finally, the frequency of p63-positive basal cells was increased in nasal polyp epithelium of eCRS, and Ki67-positive proliferating cells were increased in p63-positive basal cells. Type 2 cytokines IL-4 and IL-13 induce basal cell hyperplasia, and basal cells exacerbate type 2 inflammation by producing TSLP in nasal polyp of eCRS. [ABSTRACT FROM AUTHOR]

Skin cancer is a disorder marked by inappropriate skin cell proliferation, which is frequently brought on by UV radiation exposure from tanning booths or the sun. It can present as melanoma, squamous cell carcinoma, or basal cell carcinoma, with varying levels of malignancy and available therapies. Our newly developed photonic crystal fiber (PCF) has exceptional efficacy in the identification of skin cancer. The proposed US model has a heptagonal core and a clad surface with a heptagonal pattern. The PCF analyzer that has just been released shows a maximum relative sensitivity (RS) of 95.35% as well 94.29% for the basal (cancer) alongside basal (normal), respectively. For the aforementioned cells, we also looked at the confinement loss (CL) of 1.74 × 10–14 dB/m, 5.98 × 10–13 dB/m, plus the effective material loss (EML) of 0.0077 cm−1, 0.0088 cm−1. Rapid identification in skin cancer allows for improved results, tailored treatment, and prompt intervention. Early detection of cancer makes milder medications available, which lessens the need for aggressive treatment. Moreover, increasing the treatment of patients and simplifying the continual sickness monitoring process. Accurate evaluation also helps with research into developments that enhance global recognition as well as treatment options. The new PCF, with its exceptional detecting capacity, may have been instrumental in the prompt discovery of such harmful organisms. In summary, there are a lot of opportunities in the medical field. [ABSTRACT FROM AUTHOR]

[Display omitted] The integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population, and specific changes in their behavior are associated with chronic barrier disruption—mechanisms that have not been studied in detail in allergic rhinitis (AR). We aimed to study basal cell subtypes in AR and healthy controls. Single-cell RNA sequencing (scRNA-Seq) of the nasal epithelium was performed on nonallergic and house dust mite–allergic AR patients to reveal basal cell diversity and to identify allergy-related alterations. Flow cytometry, immunofluorescence staining, and in vitro experiments using primary basal cells were performed to confirm phenotypic findings at the protein level and functionally. The scRNA-Seq, flow cytometry, and immunofluorescence staining revealed that basal cells are abundantly and heterogeneously present in the nasal epithelium, suggesting specialized subtypes. The total basal cell fraction within the epithelium in AR is increased compared to controls. scRNA-Seq demonstrated that potentially beneficial basal cells are missing in AR epithelium, while an activated population of allergy-associated basal cells is more dominantly present. Furthermore, our in vitro proliferation, wound healing assay and air–liquid interface cultures show that AR-associated basal cells have altered progenitor capacity compared to nonallergic basal cells. The nasal basal cell population is abundant and diverse, and it shifts toward a diseased state in AR. The absence of potentially protective subtypes and the rise of a proinflammatory population suggest that basal cells are important players in maintaining epithelial barrier defects in AR. [ABSTRACT FROM AUTHOR]

Background: Basal cell hyperplasia is commonly observed in nasal polyp epithelium of eosinophilic chronic rhinosinusitis (eCRS). We examined the function and mechanisms of basal cell hyperplasia in the pathophysiology of eCRS. Methods: We found that normal human bronchial epithelial (NHBE) cells obtained basal cell characteristics when cultured with PneumaCult™-Ex Plus Medium. Most of the cells passaged three times expressed basal cell surface markers CD49f and CD271 by flow cytometry, and basal cell nuclear marker p63 by immunohistochemical staining. We named these NHBE cells with basal cell characteristics cultured Basal-like cells (cBC), and NHBE cells cultured with BEGM™ cultured Epithelial cells (cEC). The characteristics of cBC and cEC were examined and compared by RNA sequencing, RT-PCR, ELISA, and cell proliferation studies. Results: RNA sequencing revealed that cBC showed higher gene expression of thymic stromal lymphopoietin (TSLP), IL-8, TLR3, and TLR4, and lower expression of PAR-2 compared with cEC. The mRNA expression of TSLP, IL-8, TLR3, and TLR4 was significantly increased in cBC, and that of PAR-2 was significantly increased in cEC by RT-PCR. Poly(I:C)-induced TSLP production and LPS-induced IL-8 production were significantly increased in cBC. IL-4 and IL-13 stimulated the proliferation of cBC. Finally, the frequency of p63-positive basal cells was increased in nasal polyp epithelium of eCRS, and Ki67-positive proliferating cells were increased in p63-positive basal cells. Conclusions: Type 2 cytokines IL-4 and IL-13 induce basal cell hyperplasia, and basal cells exacerbate type 2 inflammation by producing TSLP in nasal polyp of eCRS.

Background: Xeroderma pigmentosum (XP) is a rare inherited disorder with a high incidence of malignant tumours. Literature data on dermoscopic and in vivo reflectance confocal microscopy (RCM) findings in patients with XP are very limited. Methods: Dermoscopic findings in 32 biopsy-proven BCCs and RCM findings in 10 biopsy-proven BCCs developed in seven XP patients were reviewed. Results: Of 32 BCCs, 28 were pigmented. On dermoscopy, BCCs exhibited multiple grey-blue globules/dots (81, 3%), short-fine telangiectasias/fine arborising vessels (65, 6%), multiple grey-blue ovoid nests (53, 1%), white structures (white-red structureless areas/shiny white areas/lines/strands) (56, 3%), arborising vessels (37, 5%), brown nests/globules/dots (28, 1%), spoke-wheel structures (9, 4%), leaf-like areas (9, 4%), ulceration (28, 1%), peripheral network (21, 9%), and multiple aggregated yellow-white globules (3, 1%). In 10 lesions in which further imaging with RCM was performed, RCM findings differentiated BCC from other tumours, including primary melanoma. Conclusions: Although the dominancy of pigmented structures may imitate melanoma clinically, dermoscopy is a valuable tool in the early diagnosis of BCCs in patients with XP. For suspicious lesions, RCM can help in differentiating pigmented BCC from primary melanoma.

Background Objective Materials and Methods Results Discussion and Conclusions Previous research has illustrated the role of cilia as mechanical and sensory antennae in various organs within the mammalian male reproductive system across different developmental stages. Despite their significance in both organ development and homeostasis, primary cilia in the human male reproductive excurrent duct have been overlooked due to limited access to human specimens.This study aimed to characterize the unique cellular composition of human efferent and epididymal ducts, with a focus on their association with primary cilia.Human efferent ductules/epididymides from five donors aged 32–47 years, were obtained through our local organ transplant program. Cell lineage specificity and primary cilia features were examined by immunofluorescent staining and confocal microscopy in the efferent ductules and the distinct segments of the epididymis.The epithelium of the human efferent duct exhibited estrogen receptor‐positive cells with primary cilia, FoxJ1‐positive multiciliated cells with numerous motile cilia, and non‐ciliated intraepithelial immune cells. Notably, intraluminal macrophages, identified by CD163/CD68 positivity, were observed to engage in sperm phagocytosis. In all three segments of the human epididymis, primary cilia were found on the surface of principal and basal cells.Our research indicates that the human efferent ductules create a distinct environment, characterized by the presence of two types of ciliated cells that are in contact with immune cells. The discovery of sensory primary cilia exposed on the surface of reabsorptive cells in the efferent ductules, as well as on basal and principal cells in the epididymis, lays the foundation for complementary functional studies. This research uncovers novel characteristics exclusive to human efferent ductules and epididymides, providing a basis for exploring innovative approaches to male contraception and infertility treatment. [ABSTRACT FROM AUTHOR]

The epididymis, a key reproductive organ, is crucial for sperm concentration, maturation, and storage. Despite a comprehensive understanding of many of its functions, several aspects of the complex processes within the epididymis remain obscure. Dysfunction in this organ is intricately connected to the formation of the microenvironment, disruptions in sperm maturation, and the progression of male infertility. Thus, elucidating the functional mechanisms of the epididymal epithelium is imperative. Given the variety of cell types present within the epididymal epithelium, utilizing a three-dimensional (3D) in vitro model provides a holistic and practical framework for exploring the multifaceted roles of the epididymis. Organoid cell culture, involving the co-cultivation of pluripotent or adult stem cells with growth factors on artificial matrix scaffolds, effectively recreates the in vivo cell growth microenvironment, thereby offering a promising avenue for studying the epididymis. The field of epididymal organoids is relatively new, with few studies focusing on their formation and even fewer detailing the generation of organoids that exhibit epididymis-specific structures and functions. Ongoing challenges in both clinical applications and mechanistic studies underscore the importance of this research. This review summarizes the established methodologies for inducing the in vitro cultivation of epididymal cells, outlines the various approaches for the development of epididymal organoids, and explores their potential applications in the field of male reproductive biology. [ABSTRACT FROM AUTHOR]

Summary: Background: Post-acute sequalae of COVID-19 defines a wide range of ongoing symptoms and conditions long after SARS-CoV-2 infection including respiratory diseases. The histopathological changes in the lung and underlying mechanism remain elusive. Methods: We investigated lung histopathological and transcriptional changes in SARS-CoV-2-infected male hamsters at 7, 14, 42, 84 and 120dpi, and compared with A (H1N1)pdm09 infection. Findings: We demonstrated viral residue, inflammatory and fibrotic changes in lung after SARS-CoV-2 but not H1N1 infection. The most prominent histopathological lesion was multifocal alveolar-bronchiolization observed in every SARS-CoV-2 infected hamster (31/31), from 42dpi to 120dpi. Proliferating (Ki67+) CK14+ basal cells accumulated in alveoli adjacent to bronchioles at 7dpi, where they proliferated and differentiated into SCGB1A+ club cell or Tubulin+ ciliated cells forming alveolar-bronchiolization foci. Molecularly, Notch pathway significantly upregulated with intensive Notch3 and Hes1 protein expression in alveolar-bronchiolization foci at 42 and 120dpi, suggesting Notch signaling involving the persistence of alveolar-bronchiolization. This is further demonstrated by spatial transcriptomic analysis. Intriguingly, significant upregulation of some cell-growth promoting pathways and genes such as Tubb4b, Stxbp4, Grb14 and Mlf1 were spatially overlapping with bronchiolization lesion. Interpretation: Incomplete resolution of SARS-CoV-2 infection in lung with viral residue, chronic inflammatory and fibrotic damage and alveolar-bronchiolization impaired respiratory function. Aberrant activation of CK14+ basal cells during tissue regeneration led to persistent alveolar-bronchiolization due to sustained Notch signaling. This study advances our understanding of respiratory PASC, sheds light on disease management and highlights the necessity for monitoring disease progression in people with respiratory PASC. Funding: Funding is listed in the Acknowledgements section.

Arterial pseudoaneurysm is a rare complication caused by damage to the arterial wall, resulting in a locally confined hematoma connected to the lumen of the artery. We report the case of a patient on anticoagulants who developed nodules at the surgical wound site after Mohs micrographic surgery for basal cell carcinoma. The initial clinical suspicion was the formation of a simple hematoma. However, Doppler ultrasound examination revealed the presence of pseudoaneurysms in the bilateral supratrochlear arteries. We believe this is the first reported case of supratrochlear artery pseudoaneurysm following dermatologic surgery.

The paper presents recommendations concerning the surveillance of patients after the treatment of squamous-cell carcinoma (SCC), basal-cell carcinoma (BCC) and Merkel-cell carcinoma (MCC) based on the current European and American recommendations. This overview discusses the methodology and detailed recommendations concerning the post-treatment surveillance, with special attention to the clinical examination, dermatoscopy, imaging diagnostics and patient education. The recommendations emphasise the significance of early monitoring for recurrences, and early detection of new skin cancers, adapted to individual risk factors in a patient and the characteristics of primary cancer. Also the significance of patient education, with regards to the protection against sun radiation and the role of skin self-examination are stressed. [ABSTRACT FROM AUTHOR]

Background: Xeroderma pigmentosum (XP) is a rare inherited disorder with a high incidence of malignant tumours. Literature data on dermoscopic and in vivo reflectance confocal microscopy (RCM) findings in patients with XP are very limited. Methods: Dermoscopic findings in 32 biopsy-proven BCCs and RCM findings in 10 biopsy-proven BCCs developed in seven XP patients were reviewed. Results: Of 32 BCCs, 28 were pigmented. On dermoscopy, BCCs exhibited multiple grey-blue globules/dots (81, 3%), short-fine telangiectasias/fine arborising vessels (65, 6%), multiple grey-blue ovoid nests (53, 1%), white structures (white-red structureless areas/shiny white areas/lines/strands) (56, 3%), arborising vessels (37, 5%), brown nests/globules/dots (28, 1%), spoke-wheel structures (9, 4%), leaf-like areas (9, 4%), ulceration (28, 1%), peripheral network (21, 9%), and multiple aggregated yellow-white globules (3, 1%). In 10 lesions in which further imaging with RCM was performed, RCM findings differentiated BCC from other tumours, including primary melanoma. Conclusions: Although the dominancy of pigmented structures may imitate melanoma clinically, dermoscopy is a valuable tool in the early diagnosis of BCCs in patients with XP. For suspicious lesions, RCM can help in differentiating pigmented BCC from primary melanoma. [ABSTRACT FROM AUTHOR]

We present a rare case of primary caruncle basal cell carcinoma (BCC), a condition with limited occurrences. Our patient, an 80-year-old woman without prior ocular pathological history, presented a 2x2mm pedunculated blackish nodular lesion on the caruncle of her left eye, without local conjunctival or cutaneous involvement. Histological analysis following complete excision confirmed the presence of basal cell carcinoma within the caruncle. Over a span of 30 months, no recurrence has been observed. While scant cases are documented in the literature, we conducted a review of these instances. Despite its infrequent manifestation, this condition should be taken into account when evaluating caruncular tumors, given its tendency to invade the orbit. Complete excision with free surgical margins is the treatment of choice, and adjuvant radiotherapy or chemotherapy might be considered. [ABSTRACT FROM AUTHOR]

Background: The prevalence of skin diseases varies geographically due to factors, such as etiology, environment, genetics, and lifestyle. The current study aimed to determine the incidence and distribution of skin disorders and to provide a description of the histomorphological spectrum. Methods: This retrospective study was conducted over a period of two years, from June 2021 to May 2023. A total of 202 skin biopsy samples were evaluated. The histopathological examination of the lesions categorized them into eight groups based on the site, pattern of involvement, and cytological features, according to the Lever’s Histopathology of the Skin. Group 1 consisted of diseases limited to the epidermis and stratum corneum; group 2 consisted of diseases with localized superficial epidermal or melanocytic proliferation; group 3 consisted of diseases of the superficial cutaneous reactive unit; group 4 included diseases with acantholytic, vesicular, and pustular morphology; group 5 included diseases with perivascular, diffuse, and granulomatous infiltrate of the reticular dermis; group 6 included tumors and cysts of the dermis and subcutis; group 7 consisted of inflammatory disorders of skin appendages; and group 8 consisted of disorders of the subcutis. Results: A total of 202 skin biopsies were collected from individuals aged 8-87 years. The majority of the cases belonged to the age group of 31-40 years. The male-to-female ratio was 1.2:1. The trunk was the most common site of biopsy, accounting for 40% of the cases, followed by the upper limb in 25% of the cases. Histopathological lesions were categorized into eight groups based on the site, pattern, and cytological features. Neoplastic lesions, both benign and malignant, accounted for 10.9% of the cases. The majority of the lesions were related to group 6, accounting for 38.1% of the cases, with the epidermal cyst being the most common lesion (7.92%). Basal cell carcinoma, observed in 2.97% of the cases, was the most common lesion among the neoplastic lesions. Group 5 lesions were the third most common (19.8%), with leprosy accounting for 9.4% of these cases. Conclusion: Histopathological examination of skin biopsies is considered the gold standard for diagnosis, and it is often supported by ancillary techniques. Leprosy was the most common disease identified in this study, which underscores the importance of effective preventive measures for control.

How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity-PAGA, cellular entropy, and regulon analysis in stromal cells reveals a cancer-specific rewiring of fibroblasts, where STAT1, TGF-β, and inflammatory signals induce a noncanonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, whose expression we validated in situ. Last, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro vismodegib-resistant BCC cell growth, Hedgehog signaling, and in vivo tumor growth in a BCC mouse model, validating HSP70's essential role in tumor growth and reinforcing the critical nature of tumor microenvironment cross-talk in BCC progression.

Background: The prevalence of skin diseases varies geographically due to factors, such as etiology, environment, genetics, and lifestyle. The current study aimed to determine the incidence and distribution of skin disorders and to provide a description of the histomorphological spectrum. Methods: This retrospective study was conducted over a period of two years, from June 2021 to May 2023. A total of 202 skin biopsy samples were evaluated. The histopathological examination of the lesions categorized them into eight groups based on the site, pattern of involvement, and cytological features, according to the Lever’s Histopathology of the Skin. Group 1 consisted of diseases limited to the epidermis and stratum corneum; group 2 consisted of diseases with localized superficial epidermal or melanocytic proliferation; group 3 consisted of diseases of the superficial cutaneous reactive unit; group 4 included diseases with acantholytic, vesicular, and pustular morphology; group 5 included diseases with perivascular, diffuse, and granulomatous infiltrate of the reticular dermis; group 6 included tumors and cysts of the dermis and subcutis; group 7 consisted of inflammatory disorders of skin appendages; and group 8 consisted of disorders of the subcutis. Results: A total of 202 skin biopsies were collected from individuals aged 8-87 years. The majority of the cases belonged to the age group of 31-40 years. The male-to-female ratio was 1.2:1. The trunk was the most common site of biopsy, accounting for 40% of the cases, followed by the upper limb in 25% of the cases. Histopathological lesions were categorized into eight groups based on the site, pattern, and cytological features. Neoplastic lesions, both benign and malignant, accounted for 10.9% of the cases. The majority of the lesions were related to group 6, accounting for 38.1% of the cases, with the epidermal cyst being the most common lesion (7.92%). Basal cell carcinoma, observed in 2.97% of the cases, was the most common lesion among the neoplastic lesions. Group 5 lesions were the third most common (19.8%), with leprosy accounting for 9.4% of these cases. Conclusion: Histopathological examination of skin biopsies is considered the gold standard for diagnosis, and it is often supported by ancillary techniques. Leprosy was the most common disease identified in this study, which underscores the importance of effective preventive measures for control. [ABSTRACT FROM AUTHOR]

Objectives TRPS1 is a new, sensitive marker for breast carcinoma (BC). Salivary glands and breasts are both exocrine glands; thus, their tumors may share similar morphology and immunophenotype. Among salivary gland–type BC, TRPS1 is reported to be positive in secretory carcinomas (SCs) but negative in acinic cell carcinomas (AciCCs) and most adenoid cystic carcinomas (AdCCs). A subset of salivary duct carcinomas (SDCs) is positive for TRPS1. Herein, we investigate TRPS1 immunohistochemical expression in salivary gland tumors (SGTs). Methods A retrospective search yielded 110 SGTs (97 primary and 13 metastatic). TRPS1 immunohistochemistry was scored as negative, low positive, intermediate positive, or strongly positive. Results TRPS1 was expressed in 78% (14/18) of pleomorphic adenoma (PA) cases but negative/low positive in all Warthin tumors (6/6 [100%]). In basal cell adenoma (BCA), TRPS1 expression was intermediate to strong (13/14 [92%]) in the stromal cells, whereas ductal or basal cells showed low expression. TRPS1 expression varied in malignant SGTs, with intermediate to strong staining in 100% (15/15) of AdCCs, 100% (5/5) of basal cell adenocarcinoma, 100% (3/3) of intraductal carcinoma, 89% (8/9) of polymorphous adenocarcinoma, and 89% (7/8) of SDCs; negative/low positive expression was observed in 100% (3/3) of SCs, 89% (8/9) of AciCCs, and 50% (3/3) of mucoepidermoid carcinomas. In addition, strong and intermediate TRPS1 expression was observed in metastatic SGT to the lungs, lymph nodes, and soft tissue. Conclusions Overall, TRPS1 is strongly expressed in PA as well as malignant and metastatic SGT. In addition, TRPS1 is positive in stromal cells of BCA but negative or low positive in ductal and basal cells. [ABSTRACT FROM AUTHOR]

Introduction: Basal cell carcinoma (BCC) of the vulva is a rare condition that accounts for less than 0.4% of BCC cases and 2% to 4% of vulvar neoplasms. BCC of the vulva is more common among white, multiparous, and postmenopausal women, especially in the seventh decade of life. The objective is to report a case of BCC of the vulva in which aspects of diagnosis and treatment were discussed. Case Report: A 63-year-old woman, G1P1A0, arrives at the office in January 2022 for treatment of a persistent lesion on her vulva. An incisional biopsy was performed which showed that it was likely nodular basal cell carcinoma with invasion of the dermis. The patient underwent tumor resection with free macroscopic margins and primary suture. The surgery had no complications preoperatively or postoperatively. The histopathology of the surgical specimen showed that it was a nodular basal cell carcinoma with an irregular, flat, white area, measuring 0.7x0.4cm, with the lateral margins 7.0 and 5.0mm apart and deep, 5.9mm; all free. Conclusion: The reported case is rare, with surgical resection of BCC of the vulva with margins being successful. Fourteen months after surgery, the patient has no evidence of local or regional recurrence.

A basal cell adenoma is a rare salivary gland tumor that usually occurs in the parotid gland, upper lip, palate, or sometimes the nasal septum. It rarely involves the submandibular gland. To the best of our knowledge, only 6 cases involving the submandibular gland have been described in the literature. We present a case of a 41-year-old female who presented with right submandibular swelling and was diagnosed as having a basal cell adenoma.

Over the past few years, high-resolution optical imaging technologies such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM), and multiphoton microscopy (MPM) have advanced significantly as new methodologies for clinical research and for real-time detection, diagnosis, and therapy monitoring of skin diseases. Implementation of these technologies into clinical research and practice requires clinicians to have an understanding of their capabilities, benefits, and limitations. This concise review provides insights on the application of OCT, RCM, and MPM for clinical skin imaging through images acquired in vivo from the same lesions. The presented data are limited to pigmented lesions and basal cell carcinoma.

Background/aimIt is estimated that nonmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), affects more than 3 million Americans each year. Translation of next-generation sequencing (NGS) data into identification of new potential targets for therapeutic applications may be helpful. Whole-exome sequencing (WES) is a widely used NGS method that involves sequencing the protein-coding regions of the genome.Case reportWe report a case of a 65-year-old female smoker who was found to have two 6 mm lesions in her left nasal vestibule. Biopsies demonstrated synchronous BCC and SCC. The patient underwent surgical excision of both cancers with safe margins followed by plastic reconstruction. WES was performed on both cancers and 16 alterations including BRCA2 (p.P389S), FAM5C (S420L), KMT2A (P855L), and SMO (L412F), as unique for BCC, and 4 alterations including TP53 (p.H179Q) and CDKN2A (p.P114L), as unique for SCC, were identified.ConclusionWe report the first documented case with unique genetic alterations in two distinct and synchronous skin BCC and SCC arising from the same nasal vestibule of a patient. This adds to the growing field of data regarding genetic variants in characterizing malignancies and potentially for targeted therapies.

Basal cell carcinoma (BCC) development in the context of a piercing is a rare phenomenon, reported in the literature in only six instances. We present a 55-year-old woman with nodular BCC involving her auricular piercing and extending clinically onto the posteroinferior right ear lobule and right post-auricular crease. Histological analysis revealed spread of the BCC through the piercing onto the anterior lobule, with evidence that the cancer utilized the piercing as a low resistance pathway for this microscopic invasion. This case is, to our knowledge, the first report of microscopic BCC present within an auricular piercing itself. Chronic inflammation related to repeated trauma from the embedded jewelry may have played a role in its formation. A piercing may provide a path of least resistance for BCC tumor cells to invade, providing a nidus for recurrence. Careful histological examination with possible complete excision of the piercing is prudent to prevent cancer return.

Despite the lower incidence of non-melanoma skin cancers in skin of color populations, greater morbidity and mortality have been reported. Literature describing non-melanoma skin cancers in Native Americans is scarce. We designed a retrospective review study aimed to evaluate the characteristics of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) in Native American patients treated with Mohs micrographic surgery between January 2015 and August 2020, at a single academic center. Twenty-six patients with 28 tumors were identified; 12 squamous cell carcinomas (92% well-differentiated) and 16 basal cell carcinomas (94% nodular). Most tumors were on the head and neck, with mean size of 563mm2 (squamous cell carcinomas) and 350mm2 (basal cell carcinomas). Tumor clearance was achieved in one stage for 75% of tumors. Recurrence was seen in two patients with squamous cell carcinoma. No mortality reported, although follow up was limited. Few Native Americans patients underwent Mohs micrographic surgery for non-melanoma skin cancers. Squamous cell cancers were larger, lower risk while basal cell carcinomas were predominantly nodular. Average time from biopsy to Mohs micrographic surgery was three months. Further studies are needed to better characterize non-melanoma skin cancers in Native Americans and to identify barriers to prompt care.

Mohs micrographic surgery (MMS) is a surgical technique used to remove skin tumors with a complete evaluation of the margins. The keystone flap technique is generally used to repair large surgical defects on limbs. We present a case where a modified keystone flap technique was used to close a large defect after Mohs micrographic surgery in a patient with a basal cell carcinoma on the nose. An excellent functional and aesthetic result was obtained with no complications during or after the procedure. We offer a novel indication for this technique for surgical defects in this area.

Stem-cell containing mammary basal epithelial cells exist in a quasi-mesenchymal transcriptional state characterized by simultaneous expression of typical epithelial genes and typical mesenchymal genes. Whether robust maintenance of such a transcriptional state is required for adult basal stem cells to fuel self-renewal and regeneration remains unclear. In this work, we utilized SMA-CreER to direct efficient basal cell-specific deletion of Ovol2, which encodes a transcription factor that inhibits epithelial-to-mesenchymal transition (EMT), in adult mammary gland. We identified a basal cell-intrinsic role of Ovol2 in promoting epithelial, and suppressing mesenchymal, molecular traits. Interestingly, Ovol2-deficient basal cells display minimal perturbations in their ability to support tissue homeostasis, colony formation, and transplant outgrowth. These findings underscore the ability of adult mammary basal cells to tolerate molecular perturbations associated with altered epithelia-mesenchymal plasticity without drastically compromising their self-renewal potential.

Mammary gland is an outstanding system to study the regulatory mechanisms governing adult epithelial stem cell activity. Stem cells in the basal layer of the mammary gland fuel the morphogenesis and regeneration of a complex epithelial network during development and upon transplantation. The self-renewal of basal stem/progenitor cells is subjected to regulation by both cell-intrinsic and extrinsic mechanisms. Nfatc1 is a transcription factor that regulates breast tumorigenesis and metastasis, but its role in mammary epithelial development and stem cell function has not been investigated. Here we show that Nfatc1 is expressed in a small subset of mammary basal epithelial cells and its epithelial-specific deletion results in mild defects in side branching and basal-luminal cell balance. Moreover, Nfatc1-deficient basal cells exhibit reduced colony forming ability in vitro and somewhat compromised regenerative potential upon transplantation. Thus, our study provides evidence for a detectable yet non-essential role of Nfatc1 in mammary epithelial morphogenesis and basal stem/progenitor cell self-renewal.

The epididymis, a key reproductive organ, is crucial for sperm concentration, maturation, and storage. Despite a comprehensive understanding of many of its functions, several aspects of the complex processes within the epididymis remain obscure. Dysfunction in this organ is intricately connected to the formation of the microenvironment, disruptions in sperm maturation, and the progression of male infertility. Thus, elucidating the functional mechanisms of the epididymal epithelium is imperative. Given the variety of cell types present within the epididymal epithelium, utilizing a three-dimensional (3D) in vitro model provides a holistic and practical framework for exploring the multifaceted roles of the epididymis. Organoid cell culture, involving the co-cultivation of pluripotent or adult stem cells with growth factors on artificial matrix scaffolds, effectively recreates the in vivo cell growth microenvironment, thereby offering a promising avenue for studying the epididymis. The field of epididymal organoids is relatively new, with few studies focusing on their formation and even fewer detailing the generation of organoids that exhibit epididymis-specific structures and functions. Ongoing challenges in both clinical applications and mechanistic studies underscore the importance of this research. This review summarizes the established methodologies for inducing the in vitro cultivation of epididymal cells, outlines the various approaches for the development of epididymal organoids, and explores their potential applications in the field of male reproductive biology.

Basal breast cancer subtype is the worst prognosis subtypes among all breast cancer subtypes. Recently, a new tumor stemness index-mRNAsi is found to be able to measure the degree of oncogenic differentiation of tissues. The mRNAsi involved in a variety of cancer processes is derived from the innovative application of one-class logistic regression (OCLR) machine learning algorithm to the whole genome expression of various stem cells and tumor cells. However, it is largely unknown about mRNAsi in basal breast cancer. Here, we find that basal breast cancer carries the highest mRNAsi among all four subtypes of breast cancer, especially 385 mRNAsi-related genes are positively related to the high mRNAsi value in basal breast cancer. This high mRNAsi is also closely related to active cell cycle, DNA replication, and metabolic reprogramming in basal breast cancer. Intriguingly, in the 385 genes, TRIM59, SEPT3, RAD51AP1, and EXO1 can act as independent protective prognostic factors, but CTSF and ABHD4B can serve as independent bad prognostic factors in patients with basal breast cancer. Remarkably, we establish a robust prognostic model containing the 6 mRNAsi-related genes that can effectively predict the survival rate of patients with the basal breast cancer subtype. Finally, the drug sensitivity analysis reveals that some drug combinations may be effectively against basal breast cancer via targeting the mRNAsi-related genes. Taken together, our study not only identifies novel prognostic biomarkers for basal breast cancers but also provides the drug sensitivity data by establishing an mRNAsi-related prognostic model.

Abstract Background: Achieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC). Objectives: The objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC. Methods: The medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates. Results: Statistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p = 0.004), tumor size (p = 0.023), tumor location in the H zone of the face (p = 0.005), and aggressive histopathological subtype (p = 0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone. Study limitations: Inadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study. Conclusions: Our results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.

Basal cell carcinoma (BCC) which is the most widespread malignant skin tumor around the world is an increasingly important public health problem since the incidence of BCC increases worldwide. In our study, we purposed to measure the variability of BCC invasion depth according to subtype, age, tumor diameter, gender, lymphocytic response, and anatomical localization and contribute to similar studies.100 BCC cases diagnosed in our department of pathology between January 2018 - June 2021 were included in the study. Clinicopathological parameters of the cases, such as demographic findings, tumor diameter, anatomical localization, histological type, and lymphocytic response, were obtained from the automatic data recording system of the hospital. The mean invasion depth was 3±1.87(0,5-13) mm. The relationship between depth of invasion and histopathological subtype (p=0.370), age (p=0.405), gender (p=0.937), lymphocytic response (p=0.418), and anatomical localization (p=0.118) was not significant. The depth of invasion was found to increase as the tumor diameter increases (p=0.004). A progressive increase in the incidence of BCC is noted making it an occupational and environmental disease with an obvious impact on the life quality of the patients. This puts a notable burden on the healthcare system, particularly in cases of invasive treatments and post-treatment relapses. Conducting multicenter research that investigates the efficacy of depth of invasion in different anatomical locations in a higher number of cases may help develop more effective treatments. [Med-Science 2023; 12(2.000): 569-73]

Basal cell carcinoma (BCC) is the most common skin cancer. Depending on its size and location, the reconstruction of the defect resulting can become very challenging for the dermatological surgeon. Shark Island Pedicle Flap (SIPF) technique is used for defects mainly in the alar or perialar nasal region, but we also use it in a modified way to close a large lesion defect in the cutaneous portion of the lip. We report two cases, one being the application of classic SIPF and the other a modified one, in which both results were satisfactory, both in terms of cosmetics and functionality.

Rationale: IL-33 is a proinflammatory cytokine thought to play a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). A recent clinical trial using an anti--IL-33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. Objectives: This study aimed to understand the effects of smoking status on IL-33. Methods: We investigated the association of smoking status with the level of gene expression of IL-33 in the airways in eight independent transcriptomic studies of lung airways. Additionally, we performed Western blot analysis and immunohistochemistry for IL-33 in lung tissue to assess protein levels. Measurements and Main Results: Across the bulk RNAsequencing datasets, IL-33 gene expression and its signaling pathway were significantly lower in current versus former or never-smokers and increased upon smoking cessation (P < 0.05). Single-cell sequencing showed that IL-33 is predominantly expressed in resting basal epithelial cells and decreases during the differentiation process triggered by smoke exposure.We also found a higher transitioning of this cellular subpopulation into amore differentiated cell type during chronic smoking, potentially driving the reduction of IL-33. Protein analysis demonstrated lower IL-33 levels in lung tissue from current versus former smokers with COPD and a lower proportion of IL-33--positive basal cells in current versus ex-smoking controls. Conclusions: We provide strong evidence that cigarette smoke leads to an overall reduction in IL-33 expression in transcriptomic and protein level, and this may be due to the decrease in resting basal cells. Together, these findings may explain the clinical observation that a recent antibody-based anti--IL-33 treatment is more effective in former than current smokers with COPD. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to evaluate the incidence of recurrence of non-melanoma skin cancer in Presidente Prudente; determine the epidemiological profile of these individuals and verify the agreement of the results with national data. The medical records of patients of any age, gender, or color, with a histopathological diagnosis of basal cell carcinoma or squamous cell carcinoma, treated surgically, with surgical margins free of neoplastic involvement, at the Hospital Regional de Presidente Prudente, from 2008 to 2018, were reviewed. looking for the number of recurrences in the first 5 years after surgical treatment. Of the total of 1,001 patients, 12.4% had recurrences, 55.7% were male and 92.9% were white. Chronic sun exposure was an important risk factor (97.2%), the face was the region with the greatest involvement in relation to primary lesions (87.2%) and the most common site of recurrence (56%). Recurrences were observed approximately 14 months after surgery in cases of basal cell carcinoma and 6.8 months in cases of squamous cell carcinoma. The recurrence incidence rate found (12.4%) is higher than the literature. The predominance of males, white color, sun exposure and the face as the main location of the crime agree with the literature. [ABSTRACT FROM AUTHOR]

Background: Full thickness defects of lower eyelid, following oncological resection, often pose a formidable challenge to the operating surgeon. Although a plethora of reconstructive options have been tried, the Mustardé flap has stood the test of time. Methods: Our patient, a 57-year old lady, diagnosed with basal cell carcinoma of the left lower eyelid underwent full-thickness wide local excision and reconstruction using modified Mustardé flap. The anterior part of defect was reconstructed using the flap. The posterior part was reconstructed using septal mucoperichondrial-cartilage composite graft, sutured to remnant palpebral conjunctiva. Results: The patient had an uneventful post-operative period. On serial follow-up, the patient had an acceptable scar. At 6 months follow-up, the facial scar was barely perceptible with normal lower lid disposition. Conclusion: The modified Mustardé flap is a simple and reliable reconstructive option for full-thickness lower eyelid defects following oncological resection in carefully selected cases. [ABSTRACT FROM AUTHOR]

BackgroundEpidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.MethodsWe examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsHigher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus.ConclusionThese findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.

Advanced basal cell carcinomas (BCCs) are driven by the Hedgehog (HH) pathway and often possess inherent resistance to SMO inhibitors. Identifying and targeting pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify an MTOR expression signature in BCC. Pharmacological inhibition of MTOR activity in BCC cells significantly reduces cell proliferation without affecting HH signalling. Similarly, treatment of the Ptch1 fl/fl ; Gli1-CreERT2 mouse BCC tumor model with everolimus reduces tumor growth. aPKC, a downstream target of MTOR, shows reduced activity, suggesting that MTOR promotes tumor growth by activating aPKC and demonstrating that suppressing MTOR could be a promising target for BCC patients.

Using scRNA-seq and microscopy, we describe a cell that is enriched in the lower airways of the developing human lung and identified by the unique coexpression of SCGB3A2/SFTPB/CFTR. To functionally interrogate these cells, we apply a single-cell barcode-based lineage tracing method, called CellTagging, to track the fate of SCGB3A2/SFTPB/CFTR cells during airway organoid differentiation in vitro. Lineage tracing reveals that these cells have a distinct differentiation potential from basal cells, giving rise predominantly to pulmonary neuroendocrine cells and a subset of multiciliated cells distinguished by high C6 and low MUC16 expression. Lineage tracing results are supported by studies using organoids and isolated cells from the lower noncartilaginous airway. We conclude that SCGB3A2/SFTPB/CFTR cells are enriched in the lower airways of the developing human lung and contribute to the epithelial diversity and heterogeneity in this region. [ABSTRACT FROM AUTHOR]

Objective: Various histological studies of facial pigmented spot sites such as solar lentigo have been reported, but few studies have used quantitative indices by histomorphometric analysis of the internal structure of pigmented spot sites using non‐invasive methods. In the present study, to quantitatively elucidate morphological changes in the epidermis in male, darker‐pigmented spots and female, light‐pigmented spots, indices that characterize the internal structure of the epidermis in pigmented spot sites were measured using in vivo confocal laser scanning microscopy (CLSM). Methods: The darkness of pigmented spots on the cheeks of 69 women and 43 men was analysed using image analysis software. The L* value was calculated from RGB values obtained from facial images. The internal structures of pigmented spots on the cheeks of 13 subjects were observed by CLSM. Various parameters were measured using CLSM images from the surface of the stratum corneum to the bottom of the dermal papillae, including the thickness of the epidermis, melanosome content, and shape of the dermal papillae. Results: Mean ΔL* values between pigmented spots and non‐pigmented areas of male subjects were significantly increased in the 40s and 50s compared with those of female subjects. Conspicuous pigmented spots increased in the 40s in male subjects and the 50s in female subjects. In CLSM observations, significant increases in the thickness of the epidermis and melanosome content were confirmed in pigmented spots compared with surrounding non‐pigmented areas. In particular, melanosome content in the male subject group with dark‐coloured pigmented spots increased significantly to about eight times that of non‐pigmented areas, and more than double that of the male subject group with light‐coloured pigmented spots. Conclusion: From the measurements of quantitative parameters, morphological changes in the epidermis were clearly related to the surface colour tone of pigmented spots. Darker pigmented spot sites tended to show longer rete pegs in the epidermis. Accumulation of melanosomes in epidermal basal cells could be considered to increase with the degree of elongation of rete pegs at pigmented spot sites and, thus, induce darker pigmented spots. [ABSTRACT FROM AUTHOR]

[Display omitted] Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2 (T2) inflammatory disease associated with an increased number of airway basal cells (BCs). Recent studies have identified transcriptionally distinct BCs, but the molecular pathways that support or inhibit human BC proliferation and differentiation are largely unknown. We sought to determine the role of T2 cytokines in regulating airway BCs. Single-cell and bulk RNA sequencing of sinus and lung airway epithelial cells was analyzed. Human sinus BCs were stimulated with IL-4 and IL-13 in the presence and absence of inhibitors of IL-4R signaling. Confocal analysis of human sinus tissue and murine airway was performed. Murine BC subsets were sorted for RNA sequencing and functional assays. Fate labeling was performed in a murine model of tracheal injury and regeneration. Two subsets of BCs were found in human and murine respiratory mucosa distinguished by the expression of basal cell adhesion molecule (BCAM). BCAM expression identifies airway stem cells among P63+KRT5+NGFR+ BCs. In the sinonasal mucosa, BCAMhi BCs expressing TSLP , IL33 , CCL26 , and the canonical BC transcription factor TP63 are increased in patients with CRSwNP. In cultured BCs, IL-4/IL-13 increases the expression of BCAM and TP63 through an insulin receptor substrate–dependent signaling pathway that is increased in CRSwNP. These findings establish BCAM as a marker of airway stem cells among the BC pool and demonstrate that airway epithelial remodeling in T2 inflammation extends beyond goblet cell metaplasia to the support of a BC stem state poised to perpetuate inflammation. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) which is the most widespread malignant skin tumor around the world is an increasingly important public health problem since the incidence of BCC increases worldwide. In our study, we purposed to measure the variability of BCC invasion depth according to subtype, age, tumor diameter, gender, lymphocytic response, and anatomical localization and contribute to similar studies.100 BCC cases diagnosed in our department of pathology between January 2018 - June 2021 were included in the study. Clinicopathological parameters of the cases, such as demographic findings, tumor diameter, anatomical localization, histological type, and lymphocytic response, were obtained from the automatic data recording system of the hospital. The mean invasion depth was 3±1.87(0,5-13) mm. The relationship between depth of invasion and histopathological subtype (p=0.370), age (p=0.405), gender (p=0.937), lymphocytic response (p=0.418), and anatomical localization (p=0.118) was not significant. The depth of invasion was found to increase as the tumor diameter increases (p=0.004). A progressive increase in the incidence of BCC is noted making it an occupational and environmental disease with an obvious impact on the life quality of the patients. This puts a notable burden on the healthcare system, particularly in cases of invasive treatments and post-treatment relapses. Conducting multicenter research that investigates the efficacy of depth of invasion in different anatomical locations in a higher number of cases may help develop more effective treatments. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity and lack of knowledge about resistant cell states remain a barrier to targeted cancer therapies. Basal cell carcinomas (BCCs) depend on Hedgehog (Hh)/Gli signaling, but can develop mechanisms of Smoothened (SMO) inhibitor resistance. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies noncanonical Gli1 activity, but characteristics and drivers of the nMRTF cell state remain unknown. Here, we use single cell RNA-sequencing of patient tumors to identify three prognostic surface markers (LYPD3, TACSTD2, and LY6D) which correlate with nMRTF and resistance to SMO inhibitors. The nMRTF cell state resembles transit-amplifying cells of the hair follicle matrix, with AP-1 and TGFß cooperativity driving nMRTF activation. JNK/AP-1 signaling commissions chromatin accessibility and Smad3 DNA binding leading to a transcriptional program of RhoGEFs that facilitate nMRTF activity. Importantly, small molecule AP-1 inhibitors selectively target LYPD3+/TACSTD2+/LY6D+ nMRTF human BCCs ex vivo, opening an avenue for improving combinatorial therapies.

Basal cell carcinoma (BCC) is one of the most common malignant tumors in human medicine and the most common skin malignancy, with the largest number of lesions found on exposed parts of the skin, on the face, head, and neck. The average age of the patients is 60 years, with an increasing incidence in younger ages and an increased incidence in males. The incidence of BCC is increasing and doubles every 25 years. Annually, there are approximately 1,000,000 newly diagnosed cases worldwide. The frequency of malignant skin tumors depends on the influence of external factors such as ultraviolet radiation and other biological properties of the skin with a higher incidence in fair-skinned people (Fitzpatrick type I and type II skin types). BCC is a slow-growing malignant tumor that arises from the basal layer of the epidermis, the outer layer of hair follicles, or the sebaceous glands. BCC can be locally invasive and, if neglected, can infiltrate surrounding structures (muscles and cartilage) and vital structures, which can ultimately lead to death. The clinical presentation is very diverse and dependent on the histological subtype. Prevention is the most important and effective approach towards reducing the burden of BCC. The best treatment for BCC is surgical excision with confirmation and verification of surgical margins. The therapeutic goal is oncologic radical resection of the tumor, followed by reconstruction of the affected area for structure and optimal aesthetic result.

Basal cell carcinoma (BCC) is a major non-melanoma skin cancer, and its incidence is increasing worldwide. Although the main etiology is sun exposure, BCC may develop in sun-protected areas such as the vulva. The sonic hedgehog signaling pathway mutation may explain the mechanism underlying the occurrence of vulvar BCC. Owing to the rarity of metastases, wide local excision is an appropriate treatment option. Here, we report the cases two postmenopausal women with vulvar BCC who were surgically treated. [ABSTRACT FROM AUTHOR]

While cardiovascular comorbidities can affect the outcomes of a variety of conditions, to our knowledge, few studies have evaluated their impact on non-melanoma skin cancers (NMSC). We studied the National Inpatient Sample to evaluate the impact of cardiovascular comorbidities on NMSC hospitalizations. Our findings displayed higher cost of care (Beta 5053; SE 1150; P < 0.001), length of stay (Beta 1.8; SE 0.394; P < 0.001), and mortality (aOR 2.51; CI 1.49–4.21; P < 0.001) in patients with NMSC who had an associated cardiovascular comorbidity. Specifically, patients with cerebrovascular disease (aOR 3.52; CI 1.18–10.5; P = 0.024), heart failure (aOR 4.02; CI 2.29–7.05; P < 0.001), complicated hypertension (OR 2.05; CI 1.16–3.61; P = 0.013), and pulmonary circulation disease (aOR 3.33; CI 1.13–9.78; P = 0.029) demonstrated greater odds of mortality. [ABSTRACT FROM AUTHOR]

We report a case of a 60-year-old man who was a former cigar smoker with a slow-growing, large exophytic left shoulder mass (15 cm in diameter) and later found to have left axillary lymphadenopathy. Fine needle aspirate biopsy of the left shoulder mass revealed squamous cell carcinoma (SCC). However, pathology of the enlarged left axillary lymph node was reported as metastatic adenocarcinoma. The patient underwent surgical resection of the shoulder mass which comprised of SCC (>95%) and adenoid basal cell carcinoma (BCC) as a second component of the tumour. The BCC had identical histology as the metastatic carcinoma in the left axillary lymph node. Therefore, diagnosis was revised as cutaneous collision tumour with metastatic BCC. Six months later following adjuvant radiation therapy, the patient was diagnosed with metastatic BCC in the right lung. Stereotactic body radiation therapy (SBRT) and a selective hedgehog pathway inhibitor vismodegib were given with only limited efficacy. Clinical trial registration number NCT03132636.

ObjectiveTo identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children.Study designThis was a multicenter, retrospective, case-control study of patients 12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001).ConclusionsNMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management.

Basal cell carcinomas (BCCs) rely on Hedgehog (HH) pathway growth signal amplification by the microtubule-based organelle, the primary cilium. Despite naive tumor responsiveness to Smoothened inhibitors (Smoi), resistance in advanced tumors remains common. Although the resistant BCCs usually maintain HH pathway activation, squamous cell carcinomas with Ras/MAPK pathway activation also arise, and the molecular basis of tumor type and pathway selection are still obscure. Here, we identify the primary cilium as a critical determinant controlling tumor pathway switching. Strikingly, Smoothened inhibitor-resistant BCCs have an increased mutational load in ciliome genes, resulting in reduced primary cilia and HH pathway activation compared with naive or Gorlin syndrome patient BCCs. Gene set enrichment analysis of resistant BCCs with a low HH pathway signature showed increased Ras/MAPK pathway activation. Tissue analysis confirmed an inverse relationship between primary cilia presence and Ras/MAPK activation, and primary cilia removal in BCCs potentiated Ras/MAPK pathway activation. Moreover, activating Ras in HH-responsive cell lines conferred resistance to both canonical (vismodegib) and noncanonical (atypical protein kinase C and MRTF inhibitors) HH pathway inhibitors and conferred sensitivity to MAPK inhibitors. Our results provide insights into BCC treatment and identify the primary cilium as an important lineage gatekeeper, preventing HH-to-Ras/MAPK pathway switching.