Mice with a Targeted Mutation of Patched2 Are Viable but Develop Alopecia and Epidermal Hyperplasia

ABSTRACT Hedgehog (Hh) signaling plays pivotal roles in tissue patterning and development in Drosophila melanogaster and vertebrates. The Patched1 (Ptc1) gene, encoding the Hh receptor, is mutated in nevoid basal cell carcinoma syndrome, a human genetic disorder associated with developmental abnormalities and increased incidences of basal cell carcinoma (BCC) and medulloblastoma (MB). Ptc1 mutations also occur in sporadic forms of BCC and MB. Mutational studies with mice have verified that Ptc1 is a tumor suppressor. We previously identified a second mammalian Patched gene, Ptc2, and demonstrated its distinct expression pattern during embryogenesis, suggesting a unique role in development. Most notably, Ptc2 is expressed in an overlapping pattern with Shh in the epidermal compartment of developing hair follicles and is highly expressed in the developing limb bud, cerebellum, and testis. Here, we describe the generation and phenotypic analysis of Ptc2 tm1/tm1 mice. Our molecular analysis suggests that Ptc2 tm1 likely represents a hypomorphic allele. Despite the dynamic expression of Ptc2 during embryogenesis, Ptc2 tm1/tm1 mice are viable, fertile, and apparently normal. Interestingly, adult Ptc2 tm1/tm1 male animals develop skin lesions consisting of alopecia, ulceration, and epidermal hyperplasia. While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis.

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Optical Coherence Tomography of Peri-Ocular Skin Cancers: An Optical Biopsy

Ocular Oncology and Pathology ◽

10.1159/000511188 ◽

2020 ◽

pp. 1-9

Author(s):

Sabrina Bergeron ◽

Bryan Arthurs ◽

Debra-Meghan Sanft ◽

Christina Mastromonaco ◽

Miguel N. Burnier Jr.

Keyword(s):

Squamous Cell Carcinoma ◽

Optical Coherence Tomography ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Basal Cell ◽

Skin Lesions ◽

Sebaceous Carcinoma ◽

Optical Coherence ◽

Oct Imaging

Introduction: Optical coherence tomography (OCT) imaging has been used as a diagnostic tool for retinal disease for several years, and OCT apparatuses are becoming increasingly powerful. However, OCT has yet to reach its full potential in ophthalmology clinics. Alike retinal layers, it has been shown that OCT is able to generate cross-sectional images of the skin and allows visualization of skin lesions in a histopathology-like manner. Objective: We aim to validate OCT as an imaging modality for peri-ocular skin cancer. Through a series of cases, we highlight findings for 3 common eyelid malignancies: basal cell carcinoma, squamous cell carcinoma and sebaceous carcinoma. We propose an OCT image-based signature for basal cell carcinoma. Methods: This is a prospective study. Fifty-eight lesions suspicious of malignancy from 57 patients were subjected to OCT imaging prior to the surgical excision of the lesion. OCT images were analysed and scored according to previously identified OCT features. Eight representative examples are presented, highlighting the OCT patterns for each malignancy side by side to its corresponding histopathological sections. Results: Out of the 58 lesions analysed, 53 were malignant. A loss of the dermal-epidermal junction is observed in all malignant lesions. A strong link is observed between the presence of subepithelial hyporeflective nests on OCT and the diagnosis of basal cell carcinoma (present in 83% of cases). Conversely, lesions of epithelial origin such as squamous cell carcinoma are most often represented on OCT by acanthosis. Two supplementary cases, one basal cell carcinoma and one sebaceous carcinoma, are provided to illustrate how OCT imaging is a valuable tool in cases where clinical observations may be unusual. Conclusions: We provide evidence supporting the use of OCT for the evaluation of peri-ocular cancers. OCT enables visualization of the skin layers in vivo, before biopsy. Our results show that certain OCT features can contribute to include or exclude a diagnosis of basal cell carcinoma. By integrating this non-invasive imaging methodology into the routine assessment of peri-ocular skin lesions, especially in health care centres where access to specialists is limited, OCT imaging can increase clinical precision, reduce delays in patient referral and enhance patient care.

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A Rare Case of a Symptomatic Tumor Found in the Groin Area: An Atypical Location Unexposed to the Known Causes

Case Reports in Oncology ◽

10.1159/000442148 ◽

2015 ◽

Vol 8 (3) ◽

pp. 536-539

Author(s):

Ellen Toyonaga ◽

Hiroo Hata ◽

Chihiro Nakayama ◽

Erina Homma ◽

Toshiyuki Miyashita ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Early Onset ◽

Rare Case ◽

Gorlin Syndrome ◽

Developmental Abnormalities ◽

Wide Range ◽

First Onset ◽

Hereditary Condition

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The syndrome consists of early-onset and/or multiple BCC. Herein we report a rare NBCCS case in which the first BCC onset occurred in the groin area. To the best of our knowledge, there have been no reports of first-onset BCC in the groin area in an NBCCS patient of any race.

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Automated Detection and Segmentation of Vascular Structures of Skin Lesions Seen in Dermoscopy, With an Application to Basal Cell Carcinoma Classification

IEEE Journal of Biomedical and Health Informatics ◽

10.1109/jbhi.2016.2637342 ◽

2017 ◽

Vol 21 (6) ◽

pp. 1675-1684 ◽

Cited By ~ 14

Author(s):

Pegah Kharazmi ◽

Mohammed I. AlJasser ◽

Harvey Lui ◽

Z. Jane Wang ◽

Tim K. Lee

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Skin Lesions ◽

Automated Detection ◽

Vascular Structures

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The Role of Dermal Fibroblasts in Nevoid Basal Cell Carcinoma Syndrome Patients: An Overview

International Journal of Molecular Sciences ◽

10.3390/ijms21030720 ◽

2020 ◽

Vol 21 (3) ◽

pp. 720 ◽

Cited By ~ 1

Author(s):

Barbara Bellei ◽

Silvia Caputo ◽

Anna Carbone ◽

Vitaliano Silipo ◽

Federica Papaccio ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Genetic Disorder ◽

Dermal Fibroblasts ◽

Phenotypic Traits ◽

Skin Area ◽

Gorlin Syndrome ◽

Activated State ◽

The Impact

Nevoid basal cell carcinoma syndrome (NBCCS), also named Gorlin syndrome, is a rare multisystem genetic disorder characterized by marked predisposition to basal cell carcinomas (BCCs), childhood medulloblastomas, maxillary keratocysts, celebral calcifications, in addition to various skeletal and soft tissue developmental abnormalities. Mutations in the tumor suppressor gene PATCHED1 (PTCH1) have been found to be associated in the majority of NBCCS cases. PATCH1 somatic mutations and loss of heterozygosity are also very frequent in sporadic BCCs. Unlike non-syndromic patients, NBCCS patients develop multiple BCCs in sun-protected skin area starting from early adulthood. Recent studies suggest that dermo/epidermal interaction could be implicated in BCC predisposition. According to this idea, NBCCS fibroblasts, sharing with keratinocytes the same PTCH1 germline mutation and consequent constitutive activation of the Hh pathway, display features of carcinoma-associated fibroblasts (CAF). This phenotypic traits include the overexpression of growth factors, specific microRNAs profile, modification of extracellular matrix and basement membrane composition, increased cytokines and pro-angiogenic factors secretion, and a complex alteration of the Wnt/β-catenin pathway. Here, we review studies about the involvement of dermal fibroblasts in BCC predisposition of Gorlin syndrome patients. Further, we matched the emerged NBCCS fibroblast profile to those of CAF to compare the impact of cell autonomous “pre-activated state” due to PTCH1 mutations to those of skin tumor stroma.

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Diagnosing Basal Cell Carcinoma by Dermatoscopy

Journal of Cutaneous Medicine and Surgery ◽

10.1177/120347549800300202 ◽

1998 ◽

Vol 3 (2) ◽

pp. 62-67 ◽

Cited By ~ 7

Author(s):

David M. Carroll ◽

Elizabeth M. Billingsley ◽

Klaus F. Helm

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Blood Vessels ◽

Basal Cell ◽

Skin Surface ◽

Skin Lesions ◽

Noninvasive Technique ◽

Cutaneous Malignancy ◽

Basal Cell Carcinomas ◽

Pigmented Skin Lesions

Background: Dermatoscopy (DS) has been used primarily to evaluate pigmented skin lesions. Little information is available on DS findings of basal cell carcinoma (BCC). Dermatoscopy is a noninvasive technique that allows visualization of cutaneous features from the skin surface to the papillary dermis. Basal cell carcinoma, the most common cutaneous malignancy, is traditionally diagnosed clinically and confirmed with biopsy. Objective: To determine the dermatoscopic features of non-pigmented basal cell carcinomas. Methods: The dermatoscopic findings of 27 lesions that clinically were suspicious for BCC were analyzed. Results: Of these 27 clinically suspect lesions, the biopsies revealed BCC in 20 specimens and squamous cell carcinoma (SCC) in two specimens. Twenty of these 22 specimens had dermatoscopic findings of BCC: diffusely distributed, branching blood vessels, asymmetric, and narrow blood vessels distributed deeper in the dermis, or a milky-red corona with superficial wide blood vessels. One nodular BCC in our study showed no distinct findings. Conclusions: Many BCCs have characteristic DS findings; however, dermatoscopic examination of some tumours will not demonstrate any known characteristic findings. As such, the DS criteria we propose for BCC are best utilized as an adjunctive study of clinical impressions. Biopsy remains the definitive diagnostic tool.

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A Review of Topical Imiquimod in the Management of Basal Cell Carcinoma, Actinic Keratoses, and Other Skin Lesions

Clinical Medicine Therapeutics ◽

10.4137/cmt.s1969 ◽

2009 ◽

Vol 1 ◽

pp. CMT.S1969

Author(s):

Jubin Ryu ◽

F. Clarissa Yang

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Antiviral Agents ◽

Nucleoside Analogs ◽

Skin Lesions ◽

Off Label ◽

Trade Name ◽

Superficial Basal Cell Carcinoma ◽

External Genital Warts

Imiquimod (trade name Aldara™) is a small molecule of the imidazoquinoline family, a group of nucleoside analogs that were first synthesized as potential antiviral agents. It has since been discovered to activate both innate and adaptive immunity, as well as apoptosis. Clinically, it has been approved for three indications thus far: external genital warts, actinic keratosis, and superficial basal cell carcinoma. In addition to these applications, a number of off-label uses have been reported in the literature. In this review, we summarize and discuss the literature describing imiquimod's mechanism of action, its approved and off-label clinical uses, and its safety and tolerability.

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A Monoclonal Antibody Established from the Immunization of Basal Cell Carcinoma (BCC) Tissues Reacts to the Intercellular Space of BCC and Hair Follicles

The Journal of Dermatology ◽

10.1111/j.1346-8138.2002.tb00209.x ◽

2002 ◽

Vol 29 (11) ◽

pp. 718-725 ◽

Cited By ~ 1

Author(s):

Satoshi Kore-eda ◽

Norihisa Matsuyoshi ◽

Masamichi Ueda ◽

Yuji Horiguchi ◽

Yoshiki Miyachi ◽

...

Keyword(s):

Monoclonal Antibody ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Intercellular Space ◽

Hair Follicles

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The Safety and Effectiveness of Elastic Scattering Spectroscopy and Machine Learning in the Evaluation of Skin Lesions for Cancer

Iproceedings ◽

10.2196/35441 ◽

2021 ◽

Vol 6 (1) ◽

pp. e35441

Author(s):

Cristiane Benvenuto-Andrade ◽

A Cognetta ◽

D Manolakos

Keyword(s):

Squamous Cell Carcinoma ◽

Elastic Scattering ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Basal Cell ◽

Predictive Value ◽

Prevalence Rate ◽

Skin Lesions ◽

Elastic Scattering Spectroscopy

Background Elastic scattering spectroscopy (ESS) is an optical biopsy technique that can distinguish between a normal and abnormal tissue in vivo without the need to remove it. The handheld device measures ESS spectra of skin lesions and classifies lesions as either malignant or benign with an output of “Investigate Further” or “Monitor,” respectively, with positive results accompanied by a spectral score output from 1 to 10, indicating how similar the lesion is to the malignant lesions the device was trained on. The algorithm was trained and validated with over 11,000 spectral scans from over 3500 skin lesions. Objective The purpose of this study was to evaluate the safety and effectiveness of the handheld ESS device in detecting the most common types of skin cancer. Methods A prospective, single-arm, investigator-blinded, multicenter study conducted at 4 investigational sites in the United States was performed. Patients who presented with skin lesions suggestive of melanoma, basal cell carcinoma, squamous cell carcinoma, and other highly atypical lesions were evaluated with the handheld ESS device. A validation performance analysis was performed with 553 lesions from 350 subjects with algorithm version 2.0. An independent test set of 281 lesions was selected and used to evaluate device performance in the detection of melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Statistical analyses included overall effectiveness analyses for sensitivity and specificity as well as subgroup analyses for lesion diagnoses. Results The overall sensitivity of the device was 92.3% (95% CI: 87.1 to 95.5%). The sensitivity for subgroups of lesions was 95% (95% CI 75.1% to 99.9%) for melanomas, 94.4% (95% CI 86.3% to 98.4%) for BCCs, and 92.5% (95% CI 83.4% to 97.5%) for SCCs. The overall device specificity was 36.6% (95% CI 29.3% to 44.6%). There was no statistically significant difference between the dermatologist performance and the ESS device (P=.2520). The specificity of the device was highest for benign melanocytic nevi (62.5%) and seborrheic keratoses (78.2%). The overall positive predictive value (PPV) was 59.8%, and the negative predictive value (NPV) was 81.9% with the study’s malignancy prevalence rate of 51%. For a prevalence rate of 5%, the PPV was estimated to be 7.1%, and the NPV was estimated to be 98.9%. For a prevalence rate of 7%, the PPV was estimated to be 9.8%, and the NPV was estimated to be 98.4%. For a prevalence rate of 15%, the PPV was estimated to be 20.3%, and the NPV was 96.4%. Conclusions The handheld ESS device has a high sensitivity for the detection of melanoma, BCC, and SCC. Coupled with clinical exam findings, this device can aid physicians in detecting a variety of skin malignancies. The device output can aid teledermatology evaluations by helping frontline providers determine which lesions to share for teledermatologist evaluation as well as potentially benefitting teledermatologists’ virtual evaluation, especially in instances of suboptimal photo quality. Acknowledgments This study was sponsored by Dermasensor Inc. Conflicts of Interest None declared.

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