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basal cell carcinoma - Top 30 Publications

Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer predisposition syndromes: similar, but not the same.

Many cancer predisposition syndromes are preceded or accompanied by a range of typical skin signs. Gorlin syndrome is a rare multisystem inherited disorder which can predispose to basal cell carcinomas (BCCs), childhood medulloblastomas in addition to various developmental abnormalities; the majority of cases are due to mutations in the PTCH1 gene. Approximately 5% of cases have been attributed to a mutation in the SUFU gene. Certain phenotypic features have been identified as being more prevalent in individuals with a SUFU mutation such as childhood medulloblastoma, infundibulocystic BCCs and trichoepitheliomas. Recently hamartomatous skin lesions have also been noted in families with childhood medulloblastoma, a "Gorlin like" phenotype and a SUFU mutation. Here we describe a family previously diagnosed with Gorlin syndrome with a novel SUFU splice site deleterious genetic variant, who have several dermatological features including palmar sclerotic fibromas which has not been described in relation to a SUFU mutation before. We highlight the features more prominent in individuals with a SUFU mutation. It is important to note that emerging therapies for treatment of BCCs in patients with a PTCH1 mutation may not be effective in those with a SUFU mutation.

Radiotherapy regimens in patients with nonmelanoma head and neck skin cancers.

To assess the effectiveness and outcomes of adjuvant radiotherapy regimens for nonmelanoma skin cancers (NMSC) of the head and neck, particularly for elderly patients.

Quality of Life in Nonmelanoma Skin Cancer.

Unusual skin mass (primary cutaneous mucinous carcinoma).

Primary mucinous carcinoma of the skin is a rare malignant tumour of sweat gland origin. Diagnostic concerns include its deceptively benign appearance in some cases and the difficulty in differentiating it from secondary mucinous carcinoma of skin metastasising from a primary source elsewhere. A case of a 75-year-old man is reported who presented with a slowly growing painless mass near the lateral canthus of the right eye for about 2 years. Clinically, a diagnosis of basal cell carcinoma was made whereas histopathology revealed mucinous carcinoma of the skin. The primary source of the tumour could not be found on detailed physical examination and laboratory investigations. Immunohistochemistry, performed later, was consistent with primary cutaneous mucinous carcinoma.

Eyelid Reconstruction: Pediculated versus Non-Pediculated.

To compare the functional and cosmetic outcome of pediculated versus free anterior and posterior lamella reconstruction after large eyelid defects due to malignancy excision.

The PPARγ agonist efatutazone delays invasive progression and induces differentiation of ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast considered a precursor of invasive ductal carcinoma. This study aimed to determine whether activated PPARγ acts as a tumor suppressor in human DCIS progression.

Retrospective audit of patients referred for further treatment following Mohs surgery for non-melanoma skin cancer.

To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).

A Comparison of the Local Flap and Skin Graft by Location of Face in Reconstruction after Resection of Facial Skin Cancer.

Surgery for reconstruction of defects after surgery should be performed selectively and the many points must be considered. The authors conducted this study to compare the local flap and skin graft by facial location in the reconstruction after resection of facial skin cancer.

A synthetic combinatorial approach to disabling deviant Hedgehog signaling.

Mutations in components of the Hedgehog (HH) signal transduction pathway are found in the majority of basal cell carcinoma (BCC) and medulloblastoma incidents. Cancerous cells with intrinsic or acquired resistance to antagonists targeting the seven transmembrane effector Smoothened (SMO) frequently invoke alternative mechanisms for maintaining deviant activity of the GLI DNA binding proteins. Here we introduce a chemical agent that simultaneously achieves inhibition of SMO and GLI activity by direct targeting of the SMO heptahelical domain and the GLI-modifying enzymes belonging to the histone deacetylase (HDAC) family. We demonstrate a small molecule SMO-HDAC antagonist (IHR-SAHA) retains inhibitory activity for GLI transcription induced by SMO-dependent and -independent mechanisms frequently associated with cancer biogenesis. Synthetic combinatorial therapeutic agents such as IHR-SAHA that a priori disable cancer drivers and anticipated mechanisms of drug resistance could extend the duration of disease remission, and provide an alternative clinical development path for realizing combinatorial therapy modalities.

Angiosarcoma following treatment of basal cell carcinoma: a report of two cases.

Quadruple Neoplasms following Radiation Therapy for Congenital Bilateral Retinoblastoma.

The aim of this study was to describe a 34-year-old male with hereditary bilateral retinoblastoma treated with radiotherapy as a child who developed 4 distinct tumors within the radiation field.

Exploring Laser-Induced Breakdown Spectroscopy as a Potential Tool in Mohs Micrography: A Mini Review.

Mohs micrographic surgery is the technique of surgically removing skin tumors by gradually excising thin layers and visualizing under a microscope till a tumor-free zone is obtained. During the surgical procedure, visible tumors are surgically removed. During the second stage, if tumor margins are clear with the positive specimen at depth, only depth cavitations need to be done without altering the tumor diameter. Defining the depth during this procedure is a major challenge due to the nonexistence of proper guidelines. Using the laser-induced breakdown spectroscopy (LIBS) technique, depth profiling can be performed precisely, preventing excessive tissue removal and reducing time consumption during the microscopic examination.

Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline Cutaneous Squamous Cell Carcinoma.

Findings from polymerase chain reaction-based methods have suggested a role of Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is difficult to differentiate a coincidental FcaPV-2 infection and a causative association. Given that a key event in the pathogenesis of human papillomavirus-induced cancer is the expression of viral E6 and E7 oncogenes, localization of FcaPV-2 E6 and E7 transcription within neoplastic cells in feline SCCs would support a causative role for this papillomavirus. Therefore, RNAscope in situ hybridization was used to localize FcaPV-2 E6 and E7 transcripts in 18 formalin-fixed paraffin-embedded samples of cutaneous SCC. Positive signals were present within 5 of 9 samples (56%) from ultraviolet-protected sites and 0 of 9 samples from ultraviolet-exposed sites. In the 4 in situ hybridization-positive samples that contained adjacent hyperplastic skin, hybridization patterns in these regions were characterized by intense nuclear signals within the superficial epidermis and punctate signals within the basal epithelial layers. However, within the 5 SCCs, punctate signals were present within all layers of the epidermis, with progressive loss of intense nuclear signals within the superficial epidermis. This hybridization pattern is consistent with unregulated E6 and E7 transcription and decreased viral replication and is similar to the pattern observed in human papillomavirus-induced cancers as they progress from hyperplastic lesions containing productive infections to nonproductive neoplasms. These findings support a causative role for FcaPV-2 in the pathogenesis of feline SCC.

Dermoscopy of basal cell carcinoma.

Dermoscopy is widely used in dermatological practice. The method increases the accuracy of basal cell carcinoma (BCC) detection. Pigmented and nonpigmented variants of basal cell carcinoma present different dermoscopic features. Specific dermoscopy criteria have been recognized in different subtypes of BCC. Differentiation of superficial BCC from other subtypes is the most important issue, as it may determine further management decisions.

Subcutaneous basal cell carcinoma.

Dermatologic Lesions Submitted to an Oral and Maxillofacial Pathology Biopsy Service: An Analysis of 2487 Cases.

Skin lesions are often submitted to oral and maxillofacial pathology practices. The purpose of this study is to evaluate the frequency, distribution, variability, and composition of dermatologic lesions within a large oral and maxillofacial pathology biopsy service. An IRB-approved retrospective search of skin lesions diagnosed at University of Florida oral and maxillofacial pathology biopsy service between 1994 and 2015 was performed. 2487 cases were included in the study. Gender was reported in 2466 cases, of which 59% were male and 41% female. Age was provided in 2367 cases and ranged from 2 weeks to 96 years with an average of 55 years. Location was indicated in 2473 cases. Lips were the most common (41.7%), followed by face (25.3%), neck (7.4%), nose (6.5%), periorbital (5.3%), ear (4.1%), and scalp (3.8%). Of the 2487 cases, five diagnoses (actinic keratosis/cheilitis, intradermal nevus, epidermal inclusion cyst, seborrheic keratosis, and basal cell carcinoma) constituted 84.4% of the cases. 69 of 2487 cases (2.8%) resulted in dermatopathologic consultation prior to final reporting. Skin lesions accounted for ~ 1.0% of all lesions submitted to an oral and maxillofacial pathology biopsy service. This study found a large variation in the dermatologic lesions submitted to an oral pathology biopsy service. Although most were routine in complexity, dermatopathology consultation was an important tool in the diagnosis of the more challenging cases. This study may help pathologists gain a better understanding of the frequency and variability of dermatologic lesions submitted to an oral and maxillofacial pathology biopsy service and promote more interdisciplinary consultation within the field. This study evaluated the incidence and scope of dermatologic lesions submitted to a large oral and maxillofacial pathology biopsy service over a long time period. A wide scope of lesions was found, and dermatopathology consultation was important to quality assurance.

Role of Graft versus Host Disease in the Development of Secondary Skin Cancers in Hematopoietic Stem Cell Transplant Recipients: A Meta-analysis.

Microenvironment Stimuli HGF and Hypoxia Differently Affected miR-125b and Ets-1 Function with Opposite Effects on the Invasiveness of Bone Metastatic Cells: A Comparison with Breast Carcinoma Cells.

We examined the influence of microenvironment stimuli on molecular events relevant to the biological functions of 1833-bone metastatic clone and the parental MDA-MB231 cells. (i) In both the cell lines, hepatocyte growth factor (HGF) and the osteoblasts' biological products down regulated nuclear Ets-1-protein level in concomitance with endogenous miR-125b accumulation. In contrast, under hypoxia nuclear Ets-1 was unchanged, notwithstanding the miR-125b increase. (ii) Also, the 1833-cell invasiveness and the expression of Endothelin-1, the target gene of Ets-1/HIF-1, showed opposite patterns under HGF and hypoxia. We clarified the molecular mechanism(s) reproducing the high miR-125b levels with the mimic in 1833 cells. Under hypoxia, the miR-125b mimic maintained a basal level and functional Ets-1 protein, as testified by the elevated cell invasiveness. However, under HGF ectopic miR-125b downregulated Ets-1 protein and cell motility, likely involving an Ets-1-dominant negative form sensible to serum conditions; Ets-1-activity inhibition by HGF implicated HIF-1α accumulation, which drugged Ets-1 in the complex bound to the Endothelin-1 promoter. Altogether, 1833-cell exposure to HGF would decrease Endothelin-1 transactivation and protein expression, with the possible impairment of Endothelin-1-dependent induction of E-cadherin, and the reversion towards an invasive phenotype: this was favoured by Ets-1 overexpression, which inhibited HIF-1α expression and HIF-1 activity. (iii) In MDA-MB231 cells, HGF strongly and rapidly decreased Ets-1, hampering invasiveness and reducing Ets-1-binding to Endothelin-1 promoter; HIF-1α did not form a complex with Ets-1 and Endothelin-1-luciferase activity was unchanged. Overall, depending on the microenvironment conditions and endogenous miR-125b levels, bone-metastatic cells might switch from Ets-1-dependent motility towards colonization/growth, regulated by the balance between Ets-1 and HIF-1.

Guidelines of care for the management of basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed.

Noninvasive optical spectroscopy for identification of non-melanoma skin cancer: Pilot study.

Optical spectroscopy offers a noninvasive alternative to biopsy as a first-line screening tool for suspicious skin lesions. This study sought to define several optical parameters across malignant and benign tissue types.

Chemical imaging of aggressive basal cell carcinoma using time-of-flight secondary ion mass spectrometry.

A set of basal cell carcinoma samples, removed by Mohs micrographic surgery and pathologically identified as having an aggressive subtype, have been analyzed using time-of-flight secondary ion mass spectrometry (SIMS). The SIMS analysis employed a gas cluster ion beam (GCIB) to increase the sensitivity of the technique for the detection of intact lipid species. The GCIB also allowed these intact molecular signals to be maintained while surface contamination and delocalized chemicals were removed from the upper tissue surface. Distinct mass spectral signals were detected from different regions of the tissue (epidermis, dermis, hair follicles, sebaceous glands, scar tissue, and cancerous tissue) allowing mass spectral pathology to be performed. The cancerous regions of the tissue showed a particular increase in sphingomyelin signals that were detected in both positive and negative ion mode along with increased specific phosphatidylserine and phosphatidylinositol signals observed in negative ion mode. Samples containing mixed more and less aggressive tumor regions showed increased phosphatidylcholine lipid content in the less aggressive areas similar to a punch biopsy sample of a nonaggressive nodular lesion.

Overcoming the resistance mechanisms of Smoothened inhibitors.

Smoothened (Smo), the main transducer of the Hedgehog (Hh) signaling pathway, is a promising target for anticancer therapy. Although vismodegib and sonidegib have demonstrated effectiveness for the treatment of basal cell carcinoma (BCC), their clinical use has been associated with mutation-related drug resistance. In this review, we outline the resistance mechanisms of Smo inhibitors and point the way for future endeavors. We focus in particular on the development of second-generation Smo inhibitors based on co-crystal structures, inhibition of downstream components, and the regulation of other interacting pathways or mediators that could compensate for the inhibitory activity of upstream inhibitors.

Use of antihypertensive drugs and risk of keratinocyte carcinoma: A meta-analysis of observational studies.

Current epidemiologic evidence on the association between antihypertensive drugs and keratinocyte carcinoma (KC) risk is inconsistent. We sought to quantify this association by meta-analysis of observational studies.

Strategies to target the Hedgehog signaling pathway for cancer therapy.

Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first-in-class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma. The clinical success of vismodegib and sonidegib provided strong support for the development of Hh signaling pathway inhibitors via targeting the smoothened (Smo) receptor. Moreover, Hh signaling pathway inhibitors aimed to target proteins, which are downstream or upstream of Smo, have also been pursued based on the identification of additional therapeutic benefits. Recently, much progress has been made in Hh singling and inhibitors of this pathway. Herein, medicinal chemistry strategies, especially the structural optimization process of different classes of Hh inhibitors, are comprehensively summarized. Further therapeutic potentials and challenges are also discussed.

Nonmelanoma Skin Cancer Risk in Patients With Inflammatory Bowel Disease Undergoing Thiopurine Therapy: A Systematic Review of the Literature.

Azathioprine and 6-mercaptopurine (thiopurines) are common adjunct treatments for inflammatory bowel disease (IBD). Although thiopurine therapy in organ transplant recipients is known to increase nonmelanoma skin cancers (NMSCs), dermatologic literature yields less data regarding NMSC risk of thiopurine use in IBD.

The limitations of dermoscopy: false positive and false negative tumors.

Dermoscopy has been documented to increase the diagnostic accuracy of clinicians evaluating skin tumors, improving their ability to detect skin cancer and better recognize benign moles. However, dermoscopically "false positive" and "false negative" tumors do exist. False positive diagnosis usually leads to unnecessary excisions. False negative diagnosis is much more dangerous, since it might result in overlooking a cancer, with severe undesirable consequences for the patient and the physician. Therefore, management strategies should mainly focus on addressing the risk of dermoscopically false negative tumors. The most frequent benign tumors that might acquire dermatoscopic characteristics suggestive of malignancy are seborrheic keratosis (SK), including solar lentigo, melanoacathoma, irritated, clonal and regressive SK, angioma (mainly thrombosed angioma and angiokeratoma), dermatofibroma, benign adnexal tumors and nevi (Clark, Spitz, recurrent, combined, sclerosing). The most useful clues to recognize these tumors are the following: solar lentigo-broad network; melanoacanthoma-sharp border; irritated SK-regularly distributed white perivascular halos; clonal SK-classic SK criteria; regressive SK-remnants of SK; targetoid hemosiderotic angioma-dark center and reddish periphery; thrombosed angioma-sharp demarcation; angiokeratoma-dark lacunae; atypical dermatofibromas-palpation; follicular tumors-white color; sebaceous tumors-yellow color; Clark nevi-clinical context; Spitz/Reed nevi-age; combined nevi-blue central area; recurrent nevi-pigmentation within the scar; sclerosing nevi-age and location on the upper back; blue nevi-history Malignant tumors that might mimic benign ones and escape detection are melanoma (in-situ, nevoid, spitzoid, verroucous, regressive, amelanotic), squamous cell carcinoma (mainly well-differentiated variants) and rarely basal cell carcinoma (non-pigmented variants). The most useful clues to recognize the peculiar melanoma subtypes are: melanoma in situ-irregular hyperpigmented areas; nevoid melanoma-history of growth; spitzoid melanoma-age; verrucous melanoma: blue-black sign; regressive melanoma-peppering or scar-like depigmentation; amelanotic melanoma-pink color, linear irregular vessels, dotted vessels. In this paper we summarized the most frequent dermoscopic variations of common skin tumors that are often misinterpreted, aiming to assist clinicians to reduce the number of false diagnoses. This article is protected by copyright. All rights reserved.

Oncogenes and morphogens: intricacies of targeted therapy in cutaneous basal cell carcinoma.

Fisetin suppresses malignant proliferation in human oral squamous cell carcinoma through inhibition of Met/Src signaling pathways.

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonoid and has been indicated as a novel anti-cancer agent in several types of cancer cells. However, the mechanisms underlying the effect of fisetin in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that fisetin significantly inhibits tumor cell proliferation and induces apoptosis in OSCC (UM-SCC-23 and Tca-8113) cancer cell lines. Further analysis demonstrates that fisetin also inhibits Met/Src signaling pathways using the PathScan® receptor tyrosine kinases (RTK) Signaling Antibody Array Kit. Fisetin resulted in decreased basal expression of Met and Src protein in UM-SCC-23 cancer cell lines, which validated by western blot. A student's t-test (two-tailed) was used to compare differences between groups. Furthermore, fisetin significantly inhibited the expression of a disintegrin and metalloproteinase 9 (ADAM9) protein in OSCC cells. Taken together, these results provide novel insights into the mechanism of fisetin and suggest potential therapeutic strategies for human OSCC by blocking the Met/Src signaling pathways.

Never too old to regenerate? Wound induced hair follicle neogenesis after secondary intention healing in a geriatric patient?

Wound healing is a natural process to restore the structure and function of injured or diseased tissues. Repair of a skin wound usually leads to a scar while regeneration implies fully recovery of function and structure of the damaged tissue. Adult skin wound usually heals with scar while fetal skin heals scarless. Hair regeneration in elderly scalp wound has never been observed. We reported an 80-year-old patient with a large wound on the scalp after excision of a basal cell carcinoma healed by secondary intention wound healing. The patient's wound healed very well aesthetically. Interestingly, on approximate post wound day 180, a hair was observed to be growing towards the surface and eventually erupted in the center of the wound. The hair remained black at 42-month follow-up. This case demonstrated that neogenesis of hair is possible even in geriatric patient. To the best of our knowledge, this is the first report of hair regrow in human skin after wound healing.

Case report repairing orbital skin defects using composite flaps after giant eyelid-derived tumor excision and orbital exenteration.

Though giant malignant tumors arising in the eyelid are rare, they often require extensive surgery for removal along with orbital exenteration. Because of this, repairing orbital defects is an important factor in the surgical strategy.