Aggressive Basal Cell Carcinoma Research Articles

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.

Basal cell carcinoma-a clinical indicator of immunosuppression.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are skin-derived carcinomas. The literature strongly connects SCC with acquired immunosuppression. Current data regarding BCC's association with immunosuppressive comorbidities are vague. The primary objective of this study was to establish the correlations between BCC and immunosuppressive comorbidities of patients. Materials and methods: We conducted a retrospective cohort study on 275 patients with a histopathological proven diagnosis of BCC from October 2019 to October 2023. Demographic data, BCC characteristics, and patients' comorbidities were analyzed. Comorbidities were classified as non-immunosuppressant and immunosuppressant (primary and secondary immunodeficiencies). We recorded 292 BCCs from 275 patients (142 females, 133 males), with equally distributed skin phototypes. 66.44% of the BCCs were detected in patients with various comorbidities (p < 0.001), of which 81.44% had immunosuppressive comorbidities (p < 0.001). All the immunosuppressive comorbidities were secondary and included diabetes mellitus (47.55%), history of solid or hematogenous cancer in the last 5 years (26.57%), chronic kidney disease (8.39%), chronic infections (9.09%), and antirheumatic immunosuppressive therapies (8.39%) (p < 0.001). BCC patients with immunosuppressive comorbidities did not develop larger BCCs (p = 0.2577) or more aggressive subtypes (p = 0.4269) and BCC did not arise earlier in their life (p < 0.001). BCC on the nasal pyramid was frequent in cancer history patients (p = 0.008). The ulcerated form of BCC is more confined to patients with chronic kidney disease (p = 0.006). Multiple BCCs are more frequent in patients with secondary immunodeficiencies (p = 0.027). BCC represents a clinical indicator of secondary immunodeficiency. Further research should establish if cancer screening campaigns may be beneficial in BCC patients.

Optically Guided High-Frequency Ultrasound to Differentiate High-Risk Basal Cell Carcinoma Subtypes: A Single-Centre Prospective Study.

Basal cell carcinoma (BCC) is the most common type of skin cancer in the Caucasian population. Currently, invasive biopsy is the only way of establishing the histological subtype (HST) that determines the treatment options. Our study aimed to evaluate whether optically guided high-frequency ultrasound (OG-HFUS) imaging could differentiate aggressive HST BCCs from low-risk tumors. We conducted prospective clinical and dermoscopic examinations of BCCs, followed by 33 MHz OG-HFUS imaging, surgical excision, and a histological analysis. We enrolled 75 patients with 78 BCCs. In total, 63 BCCs were utilized to establish a novel OG-HFUS risk classification algorithm, while 15 were employed for the validation of this algorithm. The mean age of the patients was 72.9 ± 11.2 years. Histology identified 16 lesions as aggressive HST (infiltrative or micronodular subtypes) and 47 as low-risk HST (superficial or nodular subtypes). To assess the data, we used a one-sided Fisher's exact test for a categorical analysis and a Receiver Operating Characteristic (ROC) curve analysis to evaluate the diagnostic accuracy. OG-HFUS distinguished aggressive BCC HSTs by their irregular shape (p < 0.0001), ill-defined margins (p < 0.0001), and non-homogeneous internal echoes (p = 0.004). We developed a risk-categorizing algorithm that differentiated aggressive HSTs from low-risk HSTs with a higher sensitivity (82.4%) and specificity (91.3%) than a combined macroscopic and dermoscopic evaluation (sensitivity: 40.1% and specificity: 73.1%). The positive and negative predictive values (PPV and NPV, respectively) for dermoscopy were 30.2% and 76.8%, respectively. In comparison, the OG-HFUS-based algorithm demonstrated a PPV of 94.7% and an NPV of 78.6%. We verified the algorithm using an independent image set, n = 15, including 12 low-risk and 3 high-risk (high-risk) with two blinded evaluators, where we found a sensitivity of 83.33% and specificity of 91.66%. Our study shows that OG-HFUS can identify aggressive BCC HSTs based on easily identifiable morphological parameters, supporting early therapeutic decision making.

The Importance of Basal Cell Carcinoma Risk Stratification and Potential Future Pathways.

Basal cell carcinoma (BCC) is the most common human cancer. Although there are surgical and topical treatments available, surgery remains the mainstay of treatment, leading to higher costs. What is needed is an accurate risk assessment of BCC so that treatments can be planned in a patient-centered manner. In this study, we will review the literature about guidelines for the management of BCC and analyze the potential indicators of high-risk BCC. Using this risk assessment approach, we will propose pathways that will be able to optimize treatments more efficiently. This paper presents a perspective from a skin cancer expert and clinic involved in the treatment of both simple and complex cases of BCC. It addresses the key challenges associated with accurate risk stratification prior to any treatment or procedure. Different immunohistochemical and angiogenic markers for high-risk BCC were reviewed in this study. The expression of interleukin-6, vascular endothelial growth factor, and mast cells within BCC correlates with its aggressiveness. Other immunohistochemical markers, such as Cyclin D1 and Bcl-2, also play a significant role-Cyclin D1 is higher in the aggressive BCC, while Bcl-2 is lower in the aggressive BCC, compared to the nonaggressive variants. Based on our research, we will conclude that using immunohistochemical and angiogenic markers for risk assessment and stratification of BCC can help optimize treatment, ensuring that surgical procedures are used only when necessary.

Recurrence or de novo? Intradermal Basal Cell Carcinoma of the Scrotum: A Report of Two Cases

Basal cell carcinoma (BCC) is the most common cutaneous malignancy, usually occurring in sun-exposed areas. Although BCC in the scrotal region is uncommon, it carries a higher risk of metastasis than BCC at other sites. Here, we report two cases of BCC that developed in the scrotal region: Case 1 presented as a superficial nodule and Case 2 as a subcutaneous nodule. Histopathologically, both tumors lacked continuity with the surface epidermis and formed an intradermal nodule. In Case 1, BCC occurred for the first time and presumably developed de novo. Case 2 underwent excision of a scrotal BCC 5 years previously, and the histopathological diagnosis at that time was nodular BCC. However, when the original specimen was re-examined, it was determined that, although the tumor had been completely resected, part of the lesion had moved away from the nodular area to represent a micronodular phenotype, an aggressive BCC subtype. We hypothesized that partial evolution from a nodular to a micronodular phenotype may have contributed to the recurrence of BCC in Case 2.

Basal cell carcinoma of the medial canthus: resection and reconstruction by glabellar flap

The inner canthus is the site of aggressive basal cell carcinomas. The management of these tumors requires knowledge of the basic principles of reconstruction in reconstructive surgery. Surgical resection with exhaustive control of the excision margins should be performed. Even when the tumor is small, the need for healthy margins often results in a moderate to a large palpebral defect that cannot be repaired with direct sutures. The goal of reconstruction is to achieve a mobile eyelid, good corneal protection, and a good aesthetic result with acceptable donor site sequelae. In this manuscript, we describe a case of basal cell carcinoma of the medial canthus that underwent resection followed by reconstruction with a glabellar flap.

Comparison of the Basal Cell Carcinoma (BCC) Tumour Microenvironment to Other Solid Malignancies

Basal cell carcinoma (BCC) is the most common form of skin cancer, contributing to nearly a third of new cancer cases in Western countries. Most BCCs are considered low risk "routine" lesions that can either be excised through surgery or treated with chemotherapeutic agents. However, around 1-2% of BCC cases are locally aggressive, present a high risk of metastasis, and often develop chemoresistance, termed advanced BCC. There currently exists no animal model or cell line that can recapitulate advanced BCC, let alone intermediate-risk and high-risk early BCC. We previously found that aggressive BCC tumours presented a Th2 cytokine inflammation profile, mesenchymal stem cell properties, and macrophage-induced tumoral inflammation. In this study, we aimed to identify potential BCC "relatives" among solid-organ malignancies who present similar immune cell proportions in their microenvironment compositions. Using immune cell type deconvolution by CIBERSORTx, and cell type enrichment by xCell, we determined three cancers with the most similar tumour microenvironments as compared to BCC. Specifically, chromophobe renal cell carcinoma, sarcoma, and skin cutaneous melanoma presented significance in multiple cell types, namely in CD4+ T lymphocytes, gammadelta T lymphocytes, and NK cell populations. Consequently, further literature analysis was conducted to understand similarities between BCC and its "relatives", as well as investigating novel treatment targets. By identifying cancers most like BCC, we hope to propose prospective druggable pathways, as well as to gain insight on developing a reliable animal or cell line model to represent advanced BCC.

Dermoscopic and Histopathologic Analysis of the Correlation between the Pigmentation of Basal Cell Carcinoma and Tumor Aggressiveness.

Basal cell carcinoma (BCC) is the most common type of skin cancer. In patients with darker skin, most BCCs are pigmented. Studies suggest that increased pigmentation in BCC may be inversely associated with tumor aggressiveness. This study analyzed the dermoscopic features and histopathologic patterns of BCCs to evaluate the correlation between BCC pigmentation and tumor aggressiveness. A total of 76 BCC lesions were included in this retrospective study. The Mohs micrographic surgery (MMS) stage and tumor depth were measured as indices of tumor aggressiveness. The Fontana-Masson stain was performed for the identification of melanin, and immunohistochemical analysis was performed using Melan-A and HMB-45 to identify melanocytes. In MMS stage 1, the dermoscopic pigmentation value was 34.48%±14.22% (mean±standard deviation). In MMS stages 2 and 3, dermoscopic pigmentations were 13.72%±7.54% and 15.50%±17.52%, respectively. In the logistic regression model, higher dermoscopic pigmentation (95% confidence interval [CI], 0.68~0.99), melanin (95% CI, 0.63~0.89), and melanocyte-stained areas (95% CI, 0.70~0.92) were associated with a lower possibility of BCC tumor infiltration over the middle and lower layers. We found an inverse correlation between the pigmentation and aggressiveness of BCCs. Clinicians can predict the subclinical infiltration depth of BCC on the basis of the pigmentation observed on dermoscopy. Pigmentation can be considered a favorable prognostic factor for BCC.

Serum Vitamin D Levels Explored in the Latvian Cohort of Patients with Basal Cell Carcinoma Linked to the Sonic Hedgehog and Vitamin D Binding Protein Cutaneous Tissue Indices.

Ultraviolet radiation is known as one of the major contributors to skin malignancies, including basal cell carcinoma (BCC), which is the most common type of skin cancer. It is a heterogeneous tumor, which presents with various types that are stratified into low- and high-risk tumors. Sunlight is important for overall health and vitamin D synthesis in the skin, whereas deviations from the optimal level of vitamin D are shown to be associated with the risk of the development of BCC. The accumulating evidence suggests the ability of vitamin D to antagonize the Sonic Hedgehog (SHH) signaling, the key tumor pathway, and play a protective role in the development of BCC. Additionally, a vitamin D binding protein (DBP) is shown to be implicated in the complex regulation of vitamin D. Here, we aimed to explore serum vitamin D in patients with different primary and recurrent BCC of the head and neck and investigate cutaneous DBP and SHH indices, confirmed immunohistochemically in these subjects. According to the results, 94.9% of the Latvian cohort of BCC patients were found to be deficient in vitamin D. No significant differences in serum vitamin D levels were found between genders, primary and recurrent tumors, and different types of BCC. Serum vitamin D was inversely associated with tumor size. Susceptible male individuals with low blood vitamin D levels were recognized at risk of developing aggressive and recurrent BCC confirmed by the use of hierarchical clustering analysis. In smaller tumors with a favorable course, such as superficial and nodular BCC, the association between high DBP and low SHH tissue expression was found, providing supportive evidence of the existence of a link between vitamin D, proteins involved in its metabolism, as exemplified by the DBP and SHH signaling pathway. The assumption of a deficiency in the protective effect of vitamin D in patients with high-risk BCCs was proposed in low DBP and high SHH tissue indices. New extensions to existing knowledge and characterization of the BCC signaling pathways and their cross-talk with vitamin D are warranted when searching for a preferential effect of vitamin D on skin cancer.

047 Pro-dysfunction and weak anti-cancer tumor infiltrating lymphocytes associated with more aggressive BCC subtype

Background: Immune response is key in defense against basal cell carcinoma (BCC). We aim to better define the immune tumor microenvironment in this cancer. Methods: CD8+ tumor infiltrating lymphocytes (TILs) obtained from fresh BCC tumor specimens from nodular subtype (“nBCC”, n=6) versus infiltrative subtype (“iBCC”, n=6) were subject to single-cell RNA profiling. Data were analyzed using iCellR. Results: CD8+ TILs were clustered based on gene expression as follows: cytotoxic (GZMA, GZMB, IFN-γ, PRF1); naïve (CCR7, LEF1, TCF7, IL7R, OX40); exhausted (BTLA, CTLA4, PDCD1, TIM3, LAG3, STAT3, 4-1BB); and regulatory (FOXP3, TIM3, OX40); additional subtypes were observed for naïve, exhausted, and regulatory T cells.

Clinical observations of generalized and inoperable locally advanced forms of basal cell carcinoma

Background. Basal cell carcinoma (BCC) occupies around 80% of all the cases of diagnosed skin cancer (according to American Cancer Society). In various countries of the world the morbidity rate of BCC differs due to the main predisposing factor of BCC development – ultraviolet radiation. In Ukraine, according to National Cancer Registry, 15882 new cases of non-melanoma skin cancer were registered in 2019–2020. Standardized morbidity rate of this pathology increased by 2,6% compared to 2018. Basal cell cancer commonly recurs (according to different experts, the rate varies from 10% to 80%), at the same time, distant metastases are diagnosed quite rarely. Understanding contribution of Hedgehog (Hh) signaling pathway to carcinogenesis of BCC has become a serious achievement in molecular biology. In spite of relatively benign course of BCC and variety of treatment methods of this disease, there is a high risk of recurrence, and in some patients, lesions may progress to such extent that they become unsuitable for local therapy which makes it urgent to search for alternatives to surgery and radiation therapy.&#x0D; Purpose – to study the peculiarities of course, treatment, development of complications of recurrent, locally advanced, metastatic inoperable BCC by the example of clinical cases. Materials and methods. Clinical observation of female patient K., 73 years old, who was undergoing treatment in the Department of Clinical Oncology and Hematology by reason of multiple BCC lesions (observation time 14 years) and female patient D., 42 years old, who was undergoing treatment in the Department of Radiation Pathology and Palliative Care by reason of aggressive course of locally advanced form of basalioma (observation time 29 years). Observation and treatment were performed in the State Organization «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine».&#x0D; Results. The clinical cases of observation and different stages of treatment of patients with constantly recurring aggressive BCC over a long period of time, 14 and 29 years, are demonstrated. Metastasing of BCC is confirmed in both cases, local advancement is shown, various methods of treatment were used: surgery, radiation therapy, cryodestruction, chemotherapy. Difficulty of patients' management is shown, especially when all available methods are used up. Treatment of complications of special therapy methods, multistage restoring plastic surgeries using different methods of plastic repair are described.&#x0D; Conclusions. Treating recurrent, metastatic, and locally advanced inoperable forms of BCC when one runs out of possibilities of the main treatment methods – surgery, radiation therapy, chemotherapy is a difficult task which requires further development of modern technology and treatment methods.

Periocular basal cell carcinoma results and surgical outcome during a 5-year period in a larger Danish population

BackgroundTo report tumour pathology, surgical procedure, complication rates and overall outcome of periocular basal cell carcinoma (BCC) in the Department of Ophthalmology at Sygehus Lillebaelt, Southern Denmark Region over a 5-year period.MethodsMedical records for all patients who underwent surgery for periocular BCC between January 2016 and December 2020 were reviewed. All tumours were excised with a 3 mm margin beyond the clinically apparent delimitation of the tumour and analysed by frozen section histological examination. Paraffin sections were subsequently examined for a final histopathological diagnosis. Patient age, gender, date of resection, former cancer history, referring unit and follow-up time were recorded. Furthermore, histological subtypes identified from biopsy and resection, lesion location, lesion diameter, free margin after the first operation, lacrimal punctum involvement, reconstructive techniques and complications were also recorded.ResultsA total of 242 surgical excisions from 237 patients were recorded. The mean age was 69.7 ± 12.6 with women significantly predominant compared to men (1.8:1, p < 0.0001, binomial test). The mean tumour diameter was 4.29 mm (range 0.5–20 mm). The most common location and histological subtype was the lower eyelid and nodular BCC respectively (64.9% and 74.0% of cases). In 17.4% of the patients, the initial resection margin on the frozen section histology was not free of tumour cells and the risk was significantly greater for BCC subtypes considered aggressive in terms of growth pattern (morphea form, infiltrative and micronodular features) as compared to non-aggressive BCC subtypes (nodular and superficial) (p = 0.002, X2). In 239 (98.8%) of the patients, the BCC was found to be radically removed after final histopathological examination.The sensitivity of identification of aggressive subtypes of periocular BCC in biopsies was 47.7%. No recurrences were found during the 5-year period.ConclusionThis study demonstrated a tendency towards more women than men being diagnosed with periocular BCC. The initial biopsy performed for all patients underestimated the aggressiveness of BCC in almost half of the cases while aggressive BCC subtypes were more likely to need further resection after frozen section compared to non-aggressive subtypes.

Basal cell carcinoma – Pathology

Basal cell carcinoma (BCC) that originates from the basal cells of the interfollicular epidermis and/or hair follicle is a locally aggressive neoplasm. The mutations that activate the hedgehog signaling pathway play an important pathogenic role. BCC can also occur in conjunction with familial cancer syndromes. A better understanding of the intricate molecular pathogenesis has opened up therapeutic options that are found useful in patients with aggressive or metastatic BCC. Apart from the morphological features, histopathology is crucial in assessing the prognosis of BCC and deciding the best treatment option.

Incidence and trends of basal cell carcinoma in Sweden: a population‐based registry study*

Basal cell carcinoma (BCC) is the most common skin cancer. Incidence is largely unknown because of incomplete, or lack of, registration in most countries. To assess current incidence rates and recent trends for BCC in the Swedish population. Patient- and tumour-related features of all histologically confirmed BCC tumours diagnosed in Sweden from 2004 to 2017 were extracted from the population-based Swedish BCC Registry. Incidence rates were standardized to the 2013 European Standard Population and trends were analysed using Poisson regression models. The age-standardized person-based incidence rate of BCC in Sweden was 405 per 100 000 in 2017, rising from 308 per 100 000 in 2004, corresponding to an annual relative increase of 1·8% (women, 2·1%; men, 1·4%). Incidence was highest in elderly people and the most common tumour site was the head and neck. In 2017, the most common BCC subtypes were nodular and micronodular/infiltrative BCC (each 31%). Incidence of aggressive BCC subtypes increased faster than other subtypes. BCC incidence rates in Sweden are relatively high and increasing. The increasing trends were more pronounced in women and for aggressive BCC subtypes. What is already known about this topic? Basal cell carcinoma (BCC) is the most common skin cancer in white populations and its incidence is increasing. BCC is seldom registered in national population-based cancer registries, therefore incidence estimates are extrapolated from small studies or incomplete registers. BCC occurs more often in men than in women and occurs most commonly on the head and neck, followed by the trunk. What does this study add? This study provides current BCC incidence rates for an entire European population. Sex-specific trends show that BCC incidence is increasing faster in women in Sweden. Aggressive BCC subtypes appear to be increasing faster than other subtypes.

Gorlin-Goltz syndrome (GGS): A rare case report

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant inherited disorder characterized by the presence of multiple keratocystic odontogenic tumors (KCOT) in the jaws, multiple basal cell nevi carcinomas, and skeletal abnormalities. Early diagnosis of Gorlin-Goltz syndrome is essential as it may progress to aggressive basal cell carcinomas and neoplasias. In this paper, a case of GGS in a 19 year old male is reported and the literature is reviewed.

The use of dermoscopy in distinguishing the histopathological subtypes of basal cell carcinoma: A retrospective, morphological study.

Background The role of dermoscopy in distinguishing the histopathological subtypes of basal cell carcinoma (BCC) is not fully elucidated. Aims To determine the accuracy of dermoscopy in diagnosing different BCC subtypes. Methods The dermoscopic features of 102 histopathologically verified BCCs were studied retrospectively. The tumours were classified as superficial (n=33,32.3%), nodular (n=46,45.1%) and aggressive (n=23,22.6%) BCCs by histopathology. Statistical analysis included Cohen's kappa test, proportion of correlation, measures of diagnostic accuracy, diagnostic odds ratio and the credibility ratio of positive (LR+) and negative (LR-) tests. Results The highest value in all performed tests was seen in superficial BCCs (kappa 0.85; proportion of correlation 93%; diagnostic accuracy 93.1%), good correlation was noted in nodular BCCs (kappa 0.62, proportion of correlation 80%; diagnostic accuracy 80.4%) but dermoscopic correlation with histopathology was low for aggressive BCCs (kappa 0.13; proportion of correlation 79%; diagnostic accuracy 78.4%). Short, fine telangiectasias (83.3%) showed the greatest importance for the diagnosis of superficial BCCs, blue-grey ovoid nests (61.8%) had the highest diagnostic accuracy in nodular BCCs, while arborising vessels (79.4%) was the most significant dermoscopic feature for the diagnosis of aggressive BCCs. Limitations This was a retrospective analysis and included only Caucasian patients from a single centre. Conclusion The highest agreement of dermoscopic features with the histologic type was found in superficial BCCs. We did not find any specific dermoscopic structure that could indicate a diagnosis of aggressive BCC. The presence of relevant dermoscopic features in the evaluated cases was determined by the depth of tumour invasion and not by its histology.

Superficial basal cell carcinoma, think deeper: Step sectioning of skin biopsy specimens yields 14% more aggressive subtypes.

IntroductionBecause of different therapeutic regimens for superficial and non-superficial basal cell carcinomas (BCCs), accurate histopathological examination of a punch biopsy to determine its subtype is essential. The aim of the current study was to evaluate the additional yield of a more extensive step-section method to that of a standard histologic examination at 4 levels.Material and methodsData for this prospective study was obtained from the Pathology department of a Dutch tertiary hospital. Biopsy specimens of subsequent patients from March 2019 to June 2020 were sectioned to 8-levels instead of the regular 4-levels. Only patients with a superficial BCC subtype in the first 4-levels of sectioning were included (n = 100). After 8-level sectioning, it was recorded in which level (5–8) a more aggressive BCC component was found (i.e. nodular, infiltrative, or micronodular). Patients were followed-up to evaluate further treatment, and in case of excision, the excision specimen was reviewed to determine the BCC subtype. A logistic regression was performed to assess characteristics associated with a more aggressive BCC component in levels 5–8.ResultsIn 14 patients (14%) a more aggressive component was found in levels 5–8, all with a nodular component. Thirteen of these patients underwent excision, confirming a more aggressive BCC subtype. Of the 86 patients that had no deeper BCC component in levels 5–8, 26 (30.2%) underwent excision; In 4 patients no residual BCC was found, in 15 patients superficial BCC, and in 7 a more aggressive BCC subtype (1 nodular and 6 a combination of superficial/nodular/infiltrative). In multivariable analysis, head&neck localization was associated with finding a more aggressive BCC subtype in levels 5–8 (OR 6.41 (95%CI 1.56–26.30), p = 0.01)).ConclusionsMore extensive sectioning of superficial BCC biopsy specimens, especially in the head&neck area, leads to a more accurate BCC subtype diagnosis requiring different clinical management strategies.

Patidegib in Dermatology: A Current Review.

Background: Basal cell carcinoma is one of the most common types of non-melanoma skin cancers, which can be locally destructive despite low-rate metastasis. Surgery is the treatment of choice, but it lacks of efficacy on advanced cases. Hedgehog pathway inhibitors are a class of drugs providing a new therapeutic option for patients affected by advanced disease. Besides systemic therapy, such as vismodegib and sonidegib, also topical inhibitors have been developed. Patidegib is able to decrease tumor burden, reducing the adverse effects induced by systemic targeted therapies. Methods: We performed comprehensive research to summarize the use of patidegib in advanced and recurrent aggressive basal cell carcinomas. Only English language human studies were included in the search. Results: Seven trials reported the application of patidegib. Both topical and systemic patidegib demonstrated safety, tolerability, and efficacy in naïve patients with stage II and III basal cell carcinomas, while stage IV disease and not-naïve patients did not show any benefit. Conclusion: Unlike systemic Hedgehog pathway inhibitors, patidegib 2% gel is not associated with systemic adverse effects and allows a better patient management. Considering the multidisciplinary management of neoplasia, in the era of precision medicine, it is mandatory to confide in pharmacogenomics to obtain personalized combined or sequential therapies.

A Response to "Ariza and Colleagues How Wide Should the Excision Margins for Facial Small Aggressive Basal Cell Carcinoma Be? Experience With 306 Cases".

A Response to "Ariza and Colleagues How Wide Should the Excision Margins for Facial Small Aggressive Basal Cell Carcinoma Be? Experience With 306 Cases".

Misclassification of Aggressive Basal Cell Carcinoma Subtypes and Implications for Management.

Management of basal cell carcinoma (BCC) varies by histopathologic subtype; however, biopsies may inadequately characterize them as nonaggressive, risking potential suboptimal treatment. To characterize the rate of undetected aggressive BCC subtypes by size, location, and histopathology type. Retrospective cohort study of 928 BCCs treated with Mohs Micrographic Surgery (MMS) at a tertiary academic institution from 2015 to 2017, comparing patient and tumor characteristics and histopathologic subtype on biopsy versus Mohs. Among the 825 BCCs with known subtypes on biopsy, 68% (561/825) were classified as nonaggressive, 28% (159/561) of which were subsequently found to have aggressive subtypes on MMS. Aggressive features were more often underrepresented in biopsy samples taken from Area H compared with Area M/L (odd ratio [OR] 2.65, 95% confidence interval [CI] 1.73-4.08, p < .001) or those with nodular subtypes (OR 2.19, CI 1.08-4.45, p = .03). Of concern, these unsuspected aggressive BCCs required more Mohs stages for clearance (mean 2.37, SD 0.72, p < .001) compared with BCCs that remained nonaggressive on both biopsy and Mohs (mean 1.50, SD 0.75). Given the high percentage of BCCs with unsuspected aggressive subtypes, higher clinical suspicion for undiagnosed high-risk BCCs should be given to nodular BCCs and to BCCs on Area H.