Project description:BackgroundBasal cell carcinoma can simulate melanoma and specific dermoscopic criteria have not yet been defined in a large cohort.ObjectiveTo identify dermoscopic "trump" characteristics for differential diagnosis, identify cluster groups and assess the clinical impact of this study's findings.MethodsRetrospective, multicentric comparative study of atypical, non-facial basal cell carcinoma (≥1 seven-point checklist criteria) and melanoma (with at least one BCC criteria) at dermoscopy. Observed dermoscopic features were used to develop a proposed score. Lesion clusters were defined with hierarchical analysis. Clinical impact was assessed with a blinded reader study following this study's results.ResultsA total of 146 basal cell carcinoma and 76 melanoma were included. Atypical vascular pattern was common to most lesions (74.5%). Twelve trump features were included in the proposed score (sensitivity 94.1% and specificity 79.5%). Cluster analysis identified 3 basal cell carcinoma and 3 melanoma clusters. Findings improved overall diagnostic accuracy and confidence (26.8% and 13.8%, respectively; p < 0.001).ConclusionsThese findings support the notion that atypical vascular pattern should be considered a shared feature of both melanoma and atypical basal cell carcinoma. Our proposed score improves diagnostic accuracy and confidence. Absence of pigmented features was associated with lower diagnostic accuracy and confidence.
Project description:Introduction The incidence and mortality of melanoma are rising rapidly. Despite ongoing research and the introduction of new therapeutic methods, advanced melanoma is still considered incurable. Early detection and surgical excision of the tumor increases patients’ survival. Since the diagnostic protocol includes surgical excision of all suspicious lesions, it is burdened with a high rate of unnecessary excisions that cause unwanted scarring. This is why the development of accurate diagnostic techniques is crucial. The most common diagnostic tool in early diagnosis of cutaneous melanoma is dermoscopy, though there are emerging new techniques, such as reflectance confocal microscopy and optical coherence tomography. Aim To evaluate diagnostic accuracy of reflectance confocal microscopy as a secondary examination in melanocytic lesions previously diagnosed as melanomas by means of dermoscopy. Material and methods Forty-six melanocytic lesions presenting dermoscopic features of cutaneous malignant melanoma were examined by means of reflectance confocal microscopy. Results The RCM evaluation showed sensitivity at the level of 100% and specificity at 62%. Conclusions It can be estimated that double evaluation of melanocytic lesions by dermoscopy and reflectance confocal microscopy may allow up to 62% of unnecessary excisions to be avoided.
Project description:Utilization of dermoscopy and novel molecular triage technologies augments visual triage of pigmented skin lesions, promoting early detection of melanoma. One emerging in vivo genomic test, 3-GEP pigmented lesion assay (3-GEP PLA) aids in pigmented lesion triage by noninvasively detecting the presence of three genes associated with melanoma: LINC00518, PRAME, and TERT. The purpose of our retrospective case-control study was to identify dermoscopic features uniquely associated with the presence of LINC00518, PRAME, or TERT in the stratum corneum as determined by 3-GEP PLA testing. Images of suspicious pigmented lesions that had undergone 3-GEP PLA testing and received a definitive positive or negative result (n = 393) were evaluated for the presence of specific clinical and dermoscopic features associated with melanoma. We found that asymmetry of color was a significant predictor for PRAME expression (Odds Ratio (OR) 5.5, 95% Confidence Interval (CI) 1.6-34.5, p = 0.004), blue color and negative pigment network were significant predictors for LINC00518 expression (adjusted OR 2.7, 95% CI 1.2-5.5, p = 0.014 and adjusted OR 5.4, 95% CI 1.6-16.9, p = 0.010, respectively), and atypical polymorphous vessels present in a pigmented skin lesion were a significant predictor for TERT promoter mutations (OR 5.8, 95% CI 1.3-23.4, p = 0.022). The results presented suggest a hierarchy in the significance of these dermoscopic features and may help guide evaluation and management of pigmented skin lesions.
Project description:BackgroundInfiltrative basal cell carcinoma (BCC) has a higher risk for post-surgical recurrence as compared to the most common low-aggressive superficial and nodular BCC. Independent diagnostic criteria for infiltrative BCC diagnosis have not been still defined. Improving the pre-surgical recognition of infiltrative BCC might significantly reduce the risk of incomplete excision and recurrence.ObjectiveThe aim of this study is to define clinical and dermoscopic criteria that can differentiate infiltrative BCC from the most common low-aggressive superficial and nodular BCC.MethodsClinical and dermoscopic images of infiltrative, superficial, and nodular BCC were retrospectively retrieved from our database and jointly evaluated by two experienced dermoscopists, blinded for the histologic subtype. Pairwise comparisons between the three histologic subtypes were performed and multivariable logistic regression models were constructed in order to define clinical and dermoscopic factors independently associated with each subtype. To validate our findings, two experienced dermoscopists not previously involved in the study were asked to evaluate clinical and dermoscopic images from an external dataset, guessing the proper BCC subtype between infiltrative, nodular and superficial, before and after being provided with the study results.ResultA total of 481 histopathologically proven BCCs (51.4% nodular, 33.9% superficial, and 14.8% infiltrative) were included. We found that infiltrative BCC mostly appeared on the head and neck as an amelanotic hypopigmented plaque or papule, displaying ulceration on dermoscopic examination, along with arborizing and fine superficial telangiectasia. Shiny white structures were also frequently observed. Multivariate regression analysis allowed us to define a clinical-dermoscopic profile of infiltrative BCC.ConclusionsWe defined the clinical-dermoscopic profile of infiltrative BCC, allowing to differentiate this variant from superficial and nodular BCC. This will improve pre-surgical recognition of infiltrative forms, reducing the risk for post-surgical recurrence.
Project description:Pigmented viral plaque is most commonly seen in Pug dogs in association with canine papillomavirus (CPV). In the present study, nucleic acid sequence and localization of viral genes were examined in 4 cases of pigmented viral plaque in Pug dogs. The results of polymerase chain reaction and nucleic acid sequence analysis showed that the 3 cases with pigmented viral plaque were infected with CPV4, and 1 case with CPV18. In the case with CPV18-positive viral plaque, CPV18 gene was also detected in a lesion of cytokeratin-14- and P63-positive basal cell tumor that developed adjacent to a pigmented viral plaque. Moreover, CPV gene was detected in the squamous cells of pigmented viral plaques and the neoplastic cells of basal cell tumor by in situ hybridization. This is the first report of basal cell tumor associated with CPV18-infection in the dog. Infection of CPV18 may be associated with development of basal cell tumor.
Project description:Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.
Project description:Basal cell carcinoma (BCC) is the most frequently encountered neoplasm worldwide. While nodular BCC is the most frequent clinical subtype, other forms of BCC, such as superficial, cystic, morpheiform, infiltrative, and pigmented may also be encountered.We present the case of a 67-year-old male with a relatively well-defined infiltrative, pigmented plaque with multiple colours and peripheral growth situated in the right axillary region. The histopathologic examination performed after complete surgical excision of the tumour revealed a complex pigmented BCC with macronodular, fibroepithelioma-like, cystic, focally infiltrative and basosquamous features.Uncommon locations of BCCs in sun-protected areas such as the axillary region require a higher degree of suspicion for diagnosis. The complex histology of the presented case, including subtypes with differing biologic attributes, emphasises the importance of histopathological examination in the diagnosis and therapeutic management of BCC.
Project description:For most cutaneous basal cell and squamous cell carcinomas (nonmelanoma skin cancers (NMSCs)), data are insufficient to permit evidence-based choices among treatments. To compare tumor recurrence after treatments, we conducted a prospective cohort study of consecutive patients with primary NMSCs treated with the most common treatments, in two practices in 1999-2000. Recurrence was determined from medical records by observers blinded to treatment type. Follow-up was available for 1,174 patients with 1,488 tumors (93.8%) at median 7.4 years; of these tumors, 24.3% (N=361) were treated with destruction with electrodessication/curettage, 38.3% (N=571) with excision, and 37.4% (N=556) with histologically guided serial excision (Mohs surgery). The overall 5-year tumor recurrence rate (95% confidence interval) was 3.3% (2.3, 4.4). Unadjusted recurrence rates did not differ after treatments: 4.9% (2.3, 7.4) after destruction, 3.5% (1.8, 5.2) after excision, and 2.1% (0.6, 3.5) after Mohs surgery (P=0.26), and no difference was seen after adjustment for risk factors. In tumors treated only with excision or Mohs surgery, the hazard of recurrence was not significantly different, even after adjustment for propensity for treatment with Mohs surgery. These data indicate that common treatments for NMSCs were at least 95% effective, and further studies are needed to guide therapeutic choices for different clinical subgroups.
Project description:Dataset contains samples that are all fibroblast cells that have been cultured from fresh human tissue. Fibroblasts were derived either from tumor (basal cell carcinoma) or non-tumor (control) tissue. Samples were maintained in DMEM, 10% FBS, glutamine, pen/strep and passaged for 4 passages before RNA harvest was performed using Invitrogen FastTrack. Reference channel RNA is the same for each array in the dataset and is Stratagene Universal Reference RNA. Hybridizations were performed for 14-18 hours at 65 C. Scanning was performed using AxonScanner and data were analyzed using GenePix 3.0. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: Tumor-derived Computed
Project description:BACKGROUND:Basal cell carcinoma (BCC) is the most common type of skin cancer. The underlying mechanism leading to BCC formation is not fully uncovered. The aim of this study was to characterize miRNA-451a as a novel tumor suppressor in cutaneous BCC. METHODS:We first evaluated miRNA-451a level in human BCC clinical tissues and inducible BCC mouse model. Then we studied the impact of overexpressing or inhibiting miR-451a in cell proliferation, colony formation potential, and cell cycle pattern. Next, we employed luciferase reporter assay and western blotting to evaluate TBX1 as a downstream target of miRNA-451a. Lastly, we confirmed TBX1 expressional change in BCC tissues by qPCR. RESULTS:miRNA-451a was significantly reduced in human BCC tissues. The downregulation of miRNA-451a was also confirmed in BCC mouse model. Overexpressing miRNA-451a in tumor cells markedly suppressed cell growth through G1 cell cycle arrest. However, inhibiting miRNA-451a in primary cells promoted cell growth and colony formation capacity. TBX1 (602054) was predicted as a downstream target of miRNA-451a and this was confirmed by luciferase assay and protein expression. Finally, TBX1 level was shown upregulated in BCC tissues as inversely to miR451a. CONCLUSION:Our studies revealed that miRNA-451a/TBX1 axis played a pivotal role in BCC tumorigenesis.