Mechanical Properties of Growing Melanocytic Nevi and the Progression to Melanoma

Melanocytic nevi are benign proliferations that sometimes turn into malignant melanoma in a way that is still unclear from the biochemical and genetic point of view. Diagnostic and prognostic tools are then mostly based on dermoscopic examination and morphological analysis of histological tissues. To investigate the role of mechanics and geometry in the morpholgical dynamics of melanocytic nevi, we study a computation model for cell proliferation in a layered non-linear elastic tissue. Numerical simulations suggest that the morphology of the nevus is correlated to the initial location of the proliferating cell starting the growth process and to the mechanical properties of the tissue. Our results also support that melanocytes are subject to compressive stresses that fluctuate widely in the nevus and depend on the growth stage. Numerical simulations of cells in the epidermis releasing matrix metalloproteinases display an accelerated invasion of the dermis by destroying the basal membrane. Moreover, we suggest experimentally that osmotic stress and collagen inhibit growth in primary melanoma cells while the effect is much weaker in metastatic cells. Knowing that morphological features of nevi might also reflect geometry and mechanics rather than malignancy could be relevant for diagnostic purpose

The use of reflectance confocal microscopy for examination of benign and malignant skin tumors

Reflectance confocal microscopy (RCM) is a modern, non-invasive diagnostic method that enables real-time imaging of epidermis and upper layers of the dermis with a nearly histological precision and high contrast. The application of this technology in skin imaging in the last few years has resulted in the progress of dermatological diagnosis, providing virtual access to the living skin erasing the need for conventional histopathology. The RCM has a potential of wide application in the dermatological diagnostic process with a particular reference to benign and malignant skin tumors. This article provides a summary of the latest reports and previous achievements in the field of RCM application in the diagnostic process of skin neoplasms. A range of dermatological indications and general characteristics of confocal images in various types of tumors are presented

Towards an Effective Imaging-Based Decision Support System for Skin Cancer

The usage of expert systems to aid in medical decisions has been employed since 1980s in distinct ap plications. With the high demands of medical care and limited human resources, these technologies are required more than ever. Skin cancer has been one of the pathologies with higher growth, which suf fers from lack of dermatology experts in most of the affected geographical areas. A permanent record of examination that can be further analyzed are medical imaging modalities. Most of these modalities were also assessed along with machine learning classification methods. It is the aim of this research to provide background information about skin cancer types, medical imaging modalities, data mining and machine learning methods, and their application on skin cancer imaging, as well as the disclosure of a proposal of a multi-imaging modality decision support system for skin cancer diagnosis and treatment assessment based in the most recent available technology. This is expected to be a reference for further implementation of imaging-based clinical support systems.info:eu-repo/semantics/publishedVersio

The Advanced Applications For Optical Coherence Tomography In Skin Imaging

Optical coherence tomography (OCT), based on the principle of interferometry, is a fast and non-invasive imaging modality, which has been approved by FDA for dermatologic applications. OCT has high spatial resolution up to micrometer scale compared to traditional ultrasound imaging. In addition, OCT can provide real-time cross-sectional images with 1 to 2 mm penetration depth, which makes it an ideal imaging technique to assess the skin micro-morphology and pathology without any tissue removal. Many studies have investigated the possibilities of using OCT to evaluate dermatologic conditions, such as skin cancer, dermatitis, psoriasis, and skin damages. Hence, OCT has tremendous potential to provide skin histological and pathological information and assist differential diagnosis of various skin diseases. In this study, we used a swept-source OCT with 1305 nm central wavelength to explore its advanced applications in dermatology. This dissertation consists of four major research projects. First, we explored the feasibility of OCT imaging for assisting real-time visualization in skin biopsy. We showed that OCT could be used to guide and track a needle insertion in mouse skin in real-time. The structure of skin and the movement of needle can be clearly seen on the OCT images without any time delay during the procedures. Next, we tested the concept of performing the punch biopsy using OCT hand-held probe attached to a piercing tip in a phantom. We proved that using the OCT is a reliable technique to delineate the margin of lesion in phantom. And it is possible to perform the punch biopsy with the OCT probe. Second, we tested the performance of contrast-enhanced OCT in melanoma detection in an in vitro study. Melanoma is the most lethal type of skin cancer. Early detection could significantly improve the long-term survival rate of patients. In this initial study, a contrast agent (Gal3-USGNPs) is developed by conjugating melanoma biomarker (Gal3) to ultra-small gold nanoparticles (USGNPs). We showed that the contrast agent can differentiate B16 melanoma cells from normal skin keratinocytes in vitro. To avoid systemic administration of USGNPs, the third project continues to explore the enhanced topical delivery of USGNPs. In this study, we used OCT to monitor the topical delivery of nanoparticles on pig skin over time. And the diffusion and penetration of USGNPs in skin can be improved by applying chemical and physical enhancers such as DMSO and sonophoresis. Finally, in addition to image the cross-sectional structure of skin, we also aim to extract quantitative information from OCT images. The skin optical properties such as attenuation coefficient can be measured from OCT images. We measured and compared the skin attenuation coefficient in the skin of forehead and lateral hip, the skin of three different age groups, and the skin of three different Fitzpatrick types. The statistical analysis showed that epidermis has much higher attenuation coefficient than dermis. And the skin type V & VI have a relatively lower attenuation coefficient than the other skin types. These studies could aid the detection of skin cancer using imaging techniques and provide some new insights into the future applications of OCT in dermatology

Histopathological correlates of the biological variation in primary melanomas

Primary cutaneous melanoma is a highly heterogeneous tumour. My hypothesis is that the histopathological heterogeneity reflects biological variation, which is likely to have prognostic and predictive significance. A histopathological review of 798 primary melanomas from the Leeds Melanoma Cohort Study was recorded using virtual pathology. The tumour blocks had previously been sampled using a tissue microarray needle, yielding a core from which RNA was extracted and assayed using Illumina® WG-DASL. This provided the opportunity to compare histopathological characteristics with gene expression data derived from consistently sampled regions. RandomSpot© was used to estimate the percentage of stroma (POS) within cored regions. Statistical analyses were performed using STATA v14.2. Inter- and intraobserver agreement were analysed and robust measures were retained. Histopathological characteristics were analysed with respect to germline BAP1 mutation status to assess whether they could predict germline BAP1 mutation status. BAP-like histopathology was not significantly associated with germline BAP1 mutation status (deleterious versus none, Fisher’s exact test, p=0.1). A personal history of mesothelioma (Fisher’s exact test, p=0.005), or a family history of meningioma (Fisher’s exact test, p=0.005) or BCC (Fisher’s exact test, p=0.02) was associated with deleterious, germline BAP1 mutations. Cancer history appeared to be a better indicator of germline BAP1 mutation status than BAP-like histopathology. Several histopathological factors were predictive of melanoma-specific survival, including the POS. The area under the curve increased by 3% when the POS and AJCC stage were combined in ROC curve analysis. The POS was an independent predictor of melanoma-specific survival (HR 0.99, 95% CI 0.98-0.99, Cox proportional hazards model, p=0.005), even adjusting for known prognostic factors. SDF1 gene expression was significantly associated with the POS and was independently protective for melanoma-specific death (HR 0.8, 95% CI 0.68-0.94, Cox proportional hazards model, p=0.005) in adjusted analyses. The POS and SDF1 could represent novel predictive and prognostic biomarkers

Histopathological correlates of the biological variation in primary melanomas

Primary cutaneous melanoma is a highly heterogeneous tumour. My hypothesis is that the histopathological heterogeneity reflects biological variation, which is likely to have prognostic and predictive significance. A histopathological review of 798 primary melanomas from the Leeds Melanoma Cohort Study was recorded using virtual pathology. The tumour blocks had previously been sampled using a tissue microarray needle, yielding a core from which RNA was extracted and assayed using Illumina® WG-DASL. This provided the opportunity to compare histopathological characteristics with gene expression data derived from consistently sampled regions. RandomSpot© was used to estimate the percentage of stroma (POS) within cored regions. Statistical analyses were performed using STATA v14.2. Inter- and intraobserver agreement were analysed and robust measures were retained. Histopathological characteristics were analysed with respect to germline BAP1 mutation status to assess whether they could predict germline BAP1 mutation status. BAP-like histopathology was not significantly associated with germline BAP1 mutation status (deleterious versus none, Fisher’s exact test, p=0.1). A personal history of mesothelioma (Fisher’s exact test, p=0.005), or a family history of meningioma (Fisher’s exact test, p=0.005) or BCC (Fisher’s exact test, p=0.02) was associated with deleterious, germline BAP1 mutations. Cancer history appeared to be a better indicator of germline BAP1 mutation status than BAP-like histopathology. Several histopathological factors were predictive of melanoma-specific survival, including the POS. The area under the curve increased by 3% when the POS and AJCC stage were combined in ROC curve analysis. The POS was an independent predictor of melanoma-specific survival (HR 0.99, 95% CI 0.98-0.99, Cox proportional hazards model, p=0.005), even adjusting for known prognostic factors. SDF1 gene expression was significantly associated with the POS and was independently protective for melanoma-specific death (HR 0.8, 95% CI 0.68-0.94, Cox proportional hazards model, p=0.005) in adjusted analyses. The POS and SDF1 could represent novel predictive and prognostic biomarkers

In Vivo Melanoma Cell Morphology Reflects Molecular Signature and Tumor Aggressiveness

Melanoma is the deadliest type of skin cancer, characterized by high cellular heterogeneity which contributes to therapy resistance and unpredictable disease outcome. Recently, by correlating Reflectance-Confocal-Microscopy (RCM) morphology with histopathological type, we identified four distinct melanoma-subtypes: dendritic-cell (DC), round-cell (RC), dermal-nest (DN), and combined-type (CT) melanomas. In the present study, each RCM-melanoma subtype expressed a specific biomolecular profile and biological behavior in vitro. Markers of tumor aggressiveness, including Ki67, MERTK, nestin and stemness markers, were highest in the most invasive CT and DN melanomas, as compared to DC and RC. This was also confirmed in multicellular tumor spheroids. Transcriptomic analysis showed a modulation of cancer progression-associated genes from DC to CT melanomas. The switch from E- to N-cadherin expression proved the epithelial-to-mesenchymal transition from DC to CT subtypes. The DN melanoma was predominantly located in the dermis, as also shown in skin reconstructs. It displayed a unique behavior and a molecular profile associated with a high degree of aggressiveness. Altogether, our results demonstrate that each RCM-melanoma subtype has a distinct biological and gene expression profile, related to tumor aggressiveness, confirming that RCM can be a dependable tool for in vivo detecting different types of melanoma and for early diagnostic screening

Dermatoscopy

This book is a collection of chapters on dermatoscopy, which is a fast, easy-to-learn, low-cost, and non-invasive diagnostic method utilizing the Rayleigh scattering phenomenon to visualize epidermal and subepidermal structures. Dermatoscopy has become increasingly popular for allowing visualization of structures that are impossible to see with the naked eye. Its use provides insight into the biological potential of skin lesions, enabling efficient management and follow-up. The book focuses on the features of some of the most common skin neoplasms, such as combined nevi, as well as those that are more challenging to assess, such as pigmented lesions of the eyelid margins. It also provides novel insights into the role of dermatoscopy in palmoplantar dermatoses and discusses precautions in dermatoscopy during the SARS-CoV2 pandemic