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1.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675086

RESUMO

Canonical and non-canonical Wnt signaling pathways are involved in cell differentiation and homeostasis, but also in tumorigenesis. In fact, an exaggerated activation of Wnt signaling may promote tumor growth and invasion. We summarize the most intriguing evidence about the role of Wnt signaling in cutaneous carcinogenesis, in particular in the pathogenesis of non-melanoma skin cancer (NMSC). Wnt signaling is involved in several ways in the development of skin tumors: it may modulate the inflammatory tumor microenvironment, synergize with Sonic Hedgehog pathway in the onset of basal cell carcinoma, and contribute to the progression from precancerous to malignant lesions and promote the epithelial-mesenchymal transition in squamous cell carcinoma. Targeting Wnt pathways may represent an additional efficient approach in the management of patients with NMSC.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Via de Sinalização Wnt , Proteínas Hedgehog , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/genética , Carcinoma Basocelular/patologia , Inflamação , Carcinogênese , Microambiente Tumoral
3.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36674553

RESUMO

TRPCs (transient receptor potential classical or cation channels) play a crucial role in tumor biology, especially in the Ca2+ homeostasis in cancer cells. TRPC4 is a pH-sensitive member of this family of proteins. As solid tumors exhibit an inversed pH-gradient with lowered extracellular and increased intracellular pH, both contributing to tumor progression, TRPC4 might be a signaling molecule in the altered tumor microenvironment. This is the first study to investigate the expression profiles of TRPC4 in common skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM) and nevus cell nevi (NCN). We found that all SCCs, NCNs, and MMs show positive TRPC4-expression, while BCCs do only in about half of the analyzed samples. These data render TRPC4 an immunohistochemical marker to distinguish SCC and BCC, and this also gives rise to future studies investigating the role of TRPC4 in tumor progression, and especially metastasis as BCCs very rarely spread and are mostly negative for TRPC4.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/patologia , Melanoma/genética , Melanoma/patologia , Carcinoma de Células Escamosas/patologia , Concentração de Íons de Hidrogênio , Microambiente Tumoral/genética
4.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674836

RESUMO

Hedgehog-GLI (HH) signaling plays an essential role in embryogenesis and tissue homeostasis. Aberrant activation of the pathway through mutations or other mechanisms is involved in the development and progression of numerous types of cancer, including basal cell carcinoma, medulloblastoma, melanoma, breast, prostate, hepatocellular and pancreatic carcinomas. Activation of HH signaling sustains proliferation, suppresses cell death signals, enhances invasion and metastasis, deregulates cellular metabolism and promotes angiogenesis and tumor inflammation. Targeted inhibition of the HH pathway has therefore emerged as an attractive therapeutic strategy for the treatment of a wide range of cancers. Currently, the Smoothened (SMO) receptor and the downstream GLI transcriptional factors have been investigated for the development of targeted drugs. Recent studies have revealed that the HH signaling is also involved in tumor immune evasion and poor responses to cancer immunotherapy. Here we focus on the effects of HH signaling on the major cellular components of the adaptive and innate immune systems, and we present recent discoveries elucidating how the immunosuppressive function of the HH pathway is engaged by cancer cells to prevent immune surveillance. In addition, we discuss the future prospect of therapeutic options combining the HH pathway and immune checkpoint inhibitors.


Assuntos
Carcinoma Basocelular , Neoplasias Cerebelares , Neoplasias Cutâneas , Masculino , Humanos , Proteínas Hedgehog/metabolismo , Transdução de Sinais , Carcinoma Basocelular/patologia , Receptor Smoothened/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo
5.
BMJ Case Rep ; 16(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599494

RESUMO

A man in his 50s presented with an ulcerative lesion within the left axillary fold that had progressively worsened over 18 months. Biopsy revealed an ulcerative basal cell carcinoma (BCC), which was surgically managed. CT chest scans done 7 months later assessed post-treatment of radiotherapy. This revealed pulmonary lesions, which were biopsy-proven metastatic BCC. Sonidegib, a hedgehog signalling inhibitor, was used for first-line treatment. Due to progressive disease, sonidegib was ceased. Cemiplimab, a checkpoint inhibitor, was used as second-line treatment based on a phase II trial demonstrating efficacy in the setting of metastatic BCC. CT reports were initially consistent with response but after 6 months of cemiplimab treatment, repeat CT chest scans revealed a decrease in size of the previously cited pulmonary lesions.This is a rare case of BCC metastases which has limited treatment options. This case provides insight of the patient experience on such treatment.


Assuntos
Carcinoma Basocelular , Neoplasias Pulmonares , Neoplasias Cutâneas , Masculino , Humanos , Neoplasias Cutâneas/patologia , Proteínas Hedgehog , Carcinoma Basocelular/patologia , Piridinas , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário
6.
Acta Derm Venereol ; 103: adv00841, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36600530

RESUMO

Basal cell carcinoma is the most prevalent cancer in Caucasians worldwide. The aim of this study was to examine the overall risk of melanoma among patients diagnosed with basal cell carcinoma. This population-based retrospective cohort study included data from January 2010 to December 2018 from the databases of the Clalit Health Maintenance Organization and 2 major pathology laboratories in North District, Israel. The incidence and hazard ratio of melanoma in patients with a diagnosis of basal cell carcinoma were determined. Of 466,700 participants, 51% were women and the mean (standard deviation) follow-up was 6.7 (2.9; range 1-9) years. A total of 3,338 patients were diagnosed with basal cell carcinoma during the study period, 82 of whom subsequently developed melanoma. Patients with basal cell carcinoma had a significantly higher incidence of melanoma than patients without basal cell carcinoma (2.46% vs 0.37%; p < 0.0001). Univariate Cox regression analysis revealed a hazard ratio of 6.6 (95% confidence interval: 3.6-12.1; p < 0.0001) for melanoma in patients with a diagnosis of basal cell carcinoma. In conclusion, a diagnosis of basal cell carcinoma confers a significant risk of melanoma.


Assuntos
Carcinoma Basocelular , Melanoma , Neoplasias Cutâneas , Humanos , Feminino , Masculino , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Estudos de Coortes , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Melanoma/epidemiologia , Melanoma/patologia , Incidência , Fatores de Risco
7.
Expert Rev Anticancer Ther ; 23(1): 43-56, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36579630

RESUMO

INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant tumor in adult white populations. If BCCs are not treated for years, if they cause massive destruction of the surrounding tissues, if they are considered unresectable or not eligible for radiotherapy they become progressively 'locally advanced' (laBCC) or metastatic (mBCC). These tumors are defined as 'difficult-to-treat BCC.' AREAS COVERED: A comprehensive search on PubMed was conducted to identify relevant literature about the several approved and recommended treatment options for the management of difficult-to-treat BCC published from January 2012 to July 2022. Surgical options, radiotherapy, hedgehog inhibitors, immunotherapy, and combined treatments are discussed. The keywords used were basal cell carcinoma; difficult-to-treat BCC; management of difficult-to-treat BCC; surgical therapy; radiotherapy; hedgehog inhibitors; immunotherapy. EXPERT OPINION: Identifying the best approach to DTT BCCs is one of the main challenges for the dermato-oncologist. The introduction of HHI for the treatment of advanced BCCs has revolutionized the clinical management of DTT BCCs. The immune checkpoint inhibitor cemiplimab has been approved for the treatment of locally advanced or metastatic BCC refractory to HHI therapy or in patients intolerant to HHI therapy. Multidisciplinary teams (MDTs) play a key role in managing these complex patients.


Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Adulto , Humanos , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Terapia Combinada , Proteínas Hedgehog , Neoplasias Cutâneas/patologia
8.
Med Image Anal ; 84: 102702, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36516556

RESUMO

Although deep learning (DL) has demonstrated impressive diagnostic performance for a variety of computational pathology tasks, this performance often markedly deteriorates on whole slide images (WSI) generated at external test sites. This phenomenon is due in part to domain shift, wherein differences in test-site pre-analytical variables (e.g., slide scanner, staining procedure) result in WSI with notably different visual presentations compared to training data. To ameliorate pre-analytic variances, approaches such as CycleGAN can be used to calibrate visual properties of images between sites, with the intent of improving DL classifier generalizability. In this work, we present a new approach termed Multi-Site Cross-Organ Calibration based Deep Learning (MuSClD) that employs WSIs of an off-target organ for calibration created at the same site as the on-target organ, based off the assumption that cross-organ slides are subjected to a common set of pre-analytical sources of variance. We demonstrate that by using an off-target organ from the test site to calibrate training data, the domain shift between training and testing data can be mitigated. Importantly, this strategy uniquely guards against potential data leakage introduced during calibration, wherein information only available in the testing data is imparted on the training data. We evaluate MuSClD in the context of the automated diagnosis of non-melanoma skin cancer (NMSC). Specifically, we evaluated MuSClD for identifying and distinguishing (a) basal cell carcinoma (BCC), (b) in-situ squamous cell carcinomas (SCC-In Situ), and (c) invasive squamous cell carcinomas (SCC-Invasive), using an Australian (training, n = 85) and a Swiss (held-out testing, n = 352) cohort. Our experiments reveal that MuSCID reduces the Wasserstein distances between sites in terms of color, contrast, and brightness metrics, without imparting noticeable artifacts to training data. The NMSC-subtyping performance is statistically improved as a result of MuSCID in terms of one-vs. rest AUC: BCC (0.92 vs 0.87, p = 0.01), SCC-In Situ (0.87 vs 0.73, p = 0.15) and SCC-Invasive (0.92 vs 0.82, p = 1e-5). Compared to baseline NMSC-subtyping with no calibration, the internal validation results of MuSClD (BCC (0.98), SCC-In Situ (0.92), and SCC-Invasive (0.97)) suggest that while domain shift indeed degrades classification performance, our on-target calibration using off-target tissue can safely compensate for pre-analytical variabilities, while improving the robustness of the model.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Aprendizado Profundo , Neoplasias Cutâneas , Humanos , Austrália , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia
9.
Dermatol Surg ; 49(1): 13-16, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36533789

RESUMO

BACKGROUND: There are limited data on the etiology, clinical characteristics, and optimal treatment of vulvar basal cell carcinoma (BCC). OBJECTIVE: This retrospective review may aid in treatment decisions for vulvar BCC. MATERIALS AND METHODS: A retrospective review of our institutional CoPath database was performed, using search terms to identify cases of vulvar BCCs from 2000 to 2018. RESULTS: A total of 35 cases of vulvar BCC were included. Patient age ranged from 33 to 97 years with a mean age of 70 years. Of the 35 cases, 28 (80%) involved the cutaneous vulva, 6 (17%) involved the suprapubic area, and 1 (3%) involved the clitoris. Most vulvar BCCs were treated by wide local excision (46%) and vulvectomies (37%), with 3 cases treated with Mohs (11%) and 2 with electrodesiccation and curettage (6%). Preoperative tumor sizes were 0.86 cm2 for Mohs, 0.94 cm2 for excision, and 1.54 cm2 for vulvectomy. The mean margins were 3 mm for Mohs, 4.4 mm for wide local excision, and 6 mm for vulvectomy. Most cases (77%) were identified and treated by gynecology. CONCLUSION: Mohs micrographic surgery should be considered for the advantages of being tissue sparing, evaluating the complete peripheral and deep margin, and avoiding the costs and risks of general anesthesia.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Neoplasias Vulvares , Feminino , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/cirurgia , Carcinoma Basocelular/patologia , Cirurgia de Mohs , Vulva/cirurgia , Vulva/patologia , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/patologia
10.
Dermatol Surg ; 49(1): 1-7, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36533788

RESUMO

BACKGROUND: Histologic perineural invasion (PNI) in basal cell carcinomas (BCC) lacks evidence-based treatment guidelines. OBJECTIVE: Systematically review and analyze treatment outcomes of BCC with histologic PNI (PNBCC). MATERIALS AND METHODS: PubMed, Embase, and Cochrane Reviews were searched through June 25, 2021. Thirteen eligible cohort studies were meta-analyzed. RESULTS: 502 of 713 PNBCC were treated with Mohs Surgery (MMS), wide local excision (WLE), or surgery (MMS or WLE) with adjuvant radiation (Surg + RT). Overall 5-year local control (LC) was 97.2% and cancer-specific survival (CSS) was 99.6%. Surg and Surg + RT did not differ in recurrence (2.1% vs 4.7%; p-value 0.56; RR 1.51 [0.37, 6.20]), LC (97.9% vs 96.2%; p-value 0.19; RR 0.98 [0.96, 1.01]) or CSS (100% vs 99.1%; p-value 0.40; RR 0.99 [0.95, 1.02]). LIMITATIONS: No randomized controlled trials were found. Outcome data were often lacking. CONCLUSION: Overall LC and CSS were high at median 5-year follow-up for surgery alone and Surg + RT. Surgery alone and Surg + RT demonstrated statistically equivalent outcomes. We do not recommend adjuvant radiation therapy for solely histologic PNBCC if clear margins are achieved.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Radioterapia Adjuvante , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Recidiva Local de Neoplasia/cirurgia , Carcinoma Basocelular/radioterapia , Carcinoma Basocelular/cirurgia , Carcinoma Basocelular/patologia , Cirurgia de Mohs
13.
Laryngorhinootologie ; 101(12): 969-978, 2022 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-36513089

RESUMO

AIM OF STUDY: We present the current standard in diagnosis and treatment of basal cell carcinoma. Useful procedures for clinical management should be derived from this. METHODS: A systematic literature search was carried out in the PubMed online database. The collected information was analyzed and evaluated. An overall concept was created from the gained knowledge. RESULTS: Basal cell carcinoma is the most common tumor in humans and its incidence is expected to increase in the future. When managing the disease, a one-dimensional orientation towards the clinical or histological subtype is not sufficient because of the heterogeneity of the tumor. The primary implementation of risk stratification, which is decisive for the further diagnostic and therapeutic steps, is becoming increasingly important. The gold standard in treatment continues to be the surgical procedure, which should be carried out using micrographically controlled surgery if possible. In addition, there are other therapeutic methods such as radiotherapy or a number of topical therapy options (photodynamic therapy, cryotherapy, application of 5-fluorouracil or imiquimod), which can be used in certain cases. Hedgehog inhibitors are also effective drugs for advanced or metastatic basal cell carcinoma. Practitioners have gained several years of experience with regard to effectiveness and handling of adverse events. With the PD-1 inhibitor cemiplimab, another therapeutic option for inoperable or metastatic tumors has been available since June 2021. CONCLUSION: Basal cell carcinoma will continue to gain in relevance in daily dermatological practice in the coming years. A structured approach to the assessment of the existing risk category of the tumor and the subsequent determination of the optimal therapy regimen are of central importance. Advanced or metastatic tumors no longer represent a hopeless situation for the patient. With long-termhedgehog therapy, an adapted dosage scheme can avoid discontinuation of therapy due to side effects. The therapeutic potential of the PD-1 inhibitor cemiplimab can also be used with the side effect profile known from other types of skin cancer.


Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Inibidores de Checkpoint Imunológico , Antineoplásicos/uso terapêutico , Proteínas Hedgehog , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/terapia , Carcinoma Basocelular/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia
14.
Nat Commun ; 13(1): 7650, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36496446

RESUMO

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Estados Unidos , Humanos , Estudos Longitudinais , Canadá , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/patologia , Fatores de Risco
15.
Rom J Morphol Embryol ; 63(2): 383-393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36374143

RESUMO

Basal cell carcinoma (BCC) is a common, locally invasive tumor that arises within sun-damaged skin and rarely develops on the palms and soles or mucous membranes. Men generally have higher rates of BCC than women. Incidence also increases with age and the median age of diagnosis is 68 years old. Mortality from BCC is rare and cases of aggressive, local destructive, metastatic BCCs are more likely from tumors with aggressive histopathological (HP) patterns. The aim of this study was to investigate and correlate the immunohistochemical expression of p53, Ki67, alpha-smooth muscle actin (α-SMA), cluster of differentiation (CD)44 and CD31 with both aggressive and nonaggressive types of BCCs. In our study, we observed a varied staining pattern for p53, with the highest reactivity noticed in the peripheral palisading zone. The staining pattern for Ki67 was similar to p53, with a more pronounced reaction in the periphery of the tumor. We found different Ki67 and p53 expression among the various subtypes of BCC. The CD31 reactivity, mostly seen in the stroma, was positive in all BCCs and varied significantly between its different HP subtypes. Regarding stromal expression of α-SMA, the adenoid and basosquamous types had the most intense reaction in our study. The CD44 tumor expression was correlated in our study to the aggressive pattern of BCCs.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Masculino , Feminino , Idoso , Antígeno Ki-67/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Actinas/metabolismo , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/patologia , Receptores de Hialuronatos/metabolismo
16.
Am J Dermatopathol ; 44(12): 879-885, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395444

RESUMO

ABSTRACT: Patients submitted to radiotherapy for tinea capitis in childhood have an increased incidence of scalp basal cell carcinomas (BCCs) but also of other neoplasms, namely, follicular tumors. In a cohort of such patients, we also found a high incidence of infundibulocystic BCCs, an otherwise rare variant. We thus hypothesized that postradiotherapy BCCs could be more prone to display follicular differentiation. We compared the histological and immunohistochemical features of postradiotherapy BCCs [both conventional (16 cases) and infundibulocystic (16 cases)] with those of BCCs arising in sun-exposed areas (16 cases), using markers of follicular differentiation (PHLDA-1, CK15, CD34, ß-catenin, and calretinin). Postradiotherapy BCCs showed slightly higher tendency for infundibular and/or trichilemmal differentiation than BCCs from sun-exposed areas (37.5% vs. 18.8%), but this difference was not statistically significant. Nevertheless, infundibulocystic BCCs showed more frequent expression of PHLDA-1 and stronger cytoplasmic expression of CK15 compared with the other lesions. In addition, CD34 highlighted a characteristic meshwork of stromal cells surrounding the epithelial component in all infundibulocystic BCCs, in contrast to the other postradiotherapy BCCs and UV-related BCCs, in which 78.1% were negative or only focally positive. In conclusion, our study suggests a tendency for more frequent follicular differentiation in postradiotherapy BCCs compared with BCCs from sun-exposed areas. In addition, the immunohistochemical study confirms previous data from the literature regarding infundibulocystic BCCs (higher CK15 and PHLDA-1 expression) and shows a distinctive stromal positivity for CD34 that has not been previously acknowledged in these tumors.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/patologia , Couro Cabeludo/patologia , Incidência
17.
Eur J Cancer ; 177: 103-111, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36335780

RESUMO

BACKGROUND: Basal cell carcinoma (BCC) is the most common human malignancy. In most cases, BCC has slow progression and can be definitively cured by surgery or radiotherapy. However, in rare cases, it can become locally advanced or, even more rarely, metastatic. The alternative recommended treatments are Sonic Hedgehog pathway inhibitors; however, the response is often short-lived. METHODS: This was a phase 2 basket study (NCT03012581) evaluating the efficacy and safety of nivolumab in a cohort of 32 advanced BCC patients, enrolled after failure of Sonic Hedgehog inhibitors, including 29 laBCC (91%) and 3 mBCC (9%). RESULTS: Compared to previously published studies, our population consisted of severe patients with a poor prognosis because they had already received multiple lines of treatment: all patients received previous Sonic Hedgehog inhibitors, 53% of patients already had chemotherapy and 75% radiotherapy. At 12 weeks, we reported 3.1% of complete responses, 18.8% of partial responses, and 43.8% of stable diseases. The best response rate to nivolumab reached 12.5% of complete responses (four patients), 18.8% of partial responses (three patients), and 43.8% of stable diseases (14 patients). Adverse events (AE) were mostly grade 2 or 3, slightly different to the adverse events observed in the treatment of metastatic melanoma (higher rate of diabetes, no thyroid dysfunction). CONCLUSION: Nivolumab is a relevant therapeutic option for patients with advanced relapsing/refractory BCC.


Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Antineoplásicos/uso terapêutico , Carcinoma Basocelular/patologia , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Imunoterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/patologia
18.
Skin Res Technol ; 28(6): 886-888, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36325590

RESUMO

Sebaceoma is a rare benign sebaceous tumor that usually occurs on the face and scalp. We report a case of a 3-mm solitary pink papule on the nose in an elderly woman. Dermoscopic examination showed yellow-pinkish background with a central yellow homogeneous structure, peripheral branching vessels (crown vessels), and scattered gray or reddish-brown irregular areas. Reflectance confocal microscopy (RCM) revealed tumor islands with massive dendritic cells and scattered bright fine granules in the dermis, a suspicious palisading arrangement at the periphery, and there seemed to be peritumoral dark spaces. The combined dermoscopic and RCM examination were highly suspicious for the diagnosis of basal cell carcinoma (BCC), so the lesion was excised completely, but was eventually diagnosed as sebaceoma by histopathology. This case suggests that there are some overlaps in both dermoscopic and RCM features between sebaceoma and BCC. The application of dermoscopy and RCM to the diagnosis of sebaceoma is challenging, further studies are needed in this field.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Feminino , Idoso , Dermoscopia/métodos , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/patologia , Microscopia Confocal/métodos , Diagnóstico Diferencial
19.
Turk J Med Sci ; 52(3): 691-698, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36326339

RESUMO

BACKGROUND: We aimed to elucidate the causes of the increased melanisation in basal cell carcinoma (BCC) and seborrheic keratosis (SK), and the role of melanocytes in this process. METHODS: This study was a retrospective-cohort study conducted in the pathology department of a university hospital between January 2019 and October 2020. Forty-nine SK and 30 pigmented BCC were included in our study. SRY-box transcription factor 10 (SOX10), CD68, and Masson-Fontana staining was used for analysis in all samples. A representative section of each specimen was photographed under ×400 magnification to facilitate the assessments of the morphology of the melanocytes and their following morphometric parameters: density, nuclear diameter, and distribution. The density of pigmented keratinocytes in the lesional epidermis was scored. The nuclear diameters of melanocytes located in the nonlesional epidermis, the density of the melanophages, and the presence or absence of ulceration and solar elastosis were also recorded. RESULTS: The morphometric findings confirmed a statistically significant increase in melanocyte density in the BCC group compared with that in the SK group (p < 0.001). Moreover, the nuclear minor diameters in the melanocytes of the BCC sections were significantly higher than those in the SK specimens (p < 0.001). The epidermal melanocytes were distributed diffusely in almost all BCC specimens (96.7%), whereas they were mainly limited to the basal layer in the majority of the SK sections (59.2%). The number of epidermal melanised keratinocytes with a score of 3 was significantly higher in the SK group (n = 31; 63.2%) than in the BCC group (n = 6; 20%) (p = 0.001), and they were the main cells representing the pigmented appearance of the tumours. No significant difference was found between both tumour groups in terms of their melanophage density scores (p = 0.206). DISCUSSION: This study is the first step towards an objective quantification of the melanocytes in pigmented epithelial tumours and may provide a morphological background for future studies on these skin lesions.


Assuntos
Carcinoma Basocelular , Ceratose Seborreica , Neoplasias Epiteliais e Glandulares , Dermatopatias , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Estudos de Coortes , Carcinoma Basocelular/patologia , Melanócitos/patologia , Ceratose Seborreica/patologia , Neoplasias Epiteliais e Glandulares/patologia
20.
Int J Mol Sci ; 23(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36430669

RESUMO

Systemic treatment with hedgehog inhibitors (HHis) is available to treat basal cell carcinomas but their utility is limited by adverse effects. Topical delivery methods may reduce adverse effects, but successful topical treatment depends on sufficient skin uptake, biological response, and time in tumor tissue. The aim of this review was to evaluate the current status of topical HHi delivery for BCCs and discuss barriers for translating systemic HHis into topical treatments. A literature search identified 16 preclinical studies and 7 clinical trials on the topical delivery of 12 HHis that have been clinically tested on BCCs. Preclinical studies on drug uptake demonstrated that novel formulations, and delivery- and pre-treatment techniques enhanced topical HHi delivery. Murine studies showed that the topical delivery of sonidegib, itraconazole, vitamin D3 and CUR-61414 led to biological responses and tumor remission. In clinical trials, only topical patidegib and sonidegib led to at least a partial response in 26/86 BCCs and 30/34 patients, respectively. However, histological clearance was not observed in the samples analyzed. In conclusion, the incomplete clinical response could be due to poor HHi uptake, biodistribution or biological response over time. Novel topical delivery techniques may improve HHi delivery, but additional research on cutaneous pharmacokinetics and biological response is needed.


Assuntos
Administração Cutânea , Carcinoma Basocelular , Proteínas Hedgehog , Animais , Humanos , Camundongos , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Distribuição Tecidual , Itraconazol
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