Faculty Bibliography

Standard histopathology is currently the gold standard for assessment of margin status in Mohs surgical removal of skin cancer. Ex vivo confocal microscopy (XVM) is potentially faster, less costly and inherently 3D/digital compared to standard histopathology. Despite these advantages, XVM use is not widespread due, in part, to the need for pathologists to retrain to interpret XVM images. We developed artificial intelligence (AI)-driven XVM pathology by implementing algorithms that render intuitive XVM pathology images identical to standard histopathology and produce automated tumor positivity maps. XVM images have fluorescence labeling of cellular and nuclear biology on the background of endogenous (unstained) reflectance contrast as a grounding counter-contrast. XVM images of 26 surgical excision specimens discarded after Mohs micrographic surgery were used to develop an XVM data pipeline with 4 stages: flattening, colorizing, enhancement and automated diagnosis. The first two stages were novel, deterministic image processing algorithms, and the second two were AI algorithms. Diagnostic sensitivity and specificity were calculated for basal cell carcinoma detection as proof of principal for the XVM image processing pipeline. The resulting diagnostic readouts mimicked the appearance of histopathology and found tumor positivity that required first collapsing the confocal stack to a 2D image optimized for cellular fluorescence contrast, then a dark field-to-bright field colorizing transformation, then either an AI image transformation for visual inspection or an AI diagnostic binary image segmentation of tumor obtaining a diagnostic sensitivity and specificity of 88% and 91% respectively. These results show that video-assisted micrographic XVM pathology could feasibly aid margin status determination in micrographic surgery of skin cancer.

It is well known that solid-organ transplant recipients (SOTRs) have a 65- to 100-fold increase in the risk of developing skin cancer, namely, nonmelanoma skin cancers (NMSCs) such as cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). In addition, these patients are also at increased risk for development of melanoma as well as other less common cutaneous malignancies (Merkel's cell carcinoma, Kaposi's sarcoma). SOTRs with NMSC (namely cSCC) are also at significantly increased risk of poor clinical outcomes including local recurrence, nodal and distant metastasis, and disease-specific death relative to patients who are not immunosuppressed. Increased surveillance and monitoring in patients at risk of aggressive disease and poor outcomes who are on immunosuppression is essential in patients with lung transplants given the high degree of immunosuppression. Increased awareness of risks, treatments, and management allows for improved outcomes in these patients. This article will provide an overview of the risk factors for the development of cutaneous malignancies in organ transplant recipients as well as a detailed discussion of various immunosuppressant and prophylactic medications used in this patient population that contribute to the risk of developing cutaneous malignancies, with an emphasis on NMSC (cSCC and BCC) in lung transplant recipients. Finally, this article includes a discussion on the clinical and dermatologic management of this high-risk immunosuppressed population including a review of topical and systemic agents for field therapy of actinic damage and chemoprevention of keratinocyte carcinomas. In addition, indications for additional treatment and preventive measures such as adjuvant radiation treatment after surgical management of cutaneous malignancies and potential modification of immunosuppressive medication regimens are discussed.

Merkel cell carcinoma (MCC) is an aggressive and rare cutaneous cancer of the mechanoreceptor unit of the skin with a neuroendocrine origin. MCC incidence has been on the rise over the past two decades. Risk factors include old age, chronic UV exposure, and immunosuppression. Although MCC is a cutaneous malignancy that is often misdiagnosed as a benign nodule at the time of diagnosis, it has an aggressive disease course due to its high recurrence and metastatic potential. The PD-1/PD-L1 checkpoint blockade has recently shown promising results in the management of advanced MCC. Avelumab and pembrolizumab are considered the new standard of care for metastatic MCC. Despite advances in the field, studies are needed to elucidate the role of immunotherapy for patients who are resistant to treatment. Most ongoing clinical trials aim to assess the efficacy of checkpoint inhibitor combination therapies. This article reviews the most current literature on the surgical and medical management of MCC.

There have been several significant advances in cancer treatment in the last decade that are applicable to the treatment of melanoma and advanced nonmelanoma skin cancers. Among these are the development of immune checkpoint inhibitors targeting the programmed death protein-1 (PD-1)/programmed death legand-1 (PDL-1) axis, as well as targeted inhibitors of the BRAF/MEK signaling cascade in melanoma, and the hedgehog signaling pathway in basal cell carcinoma (BCC). These immune-based and targeted therapies have dramatically changed the treatment options for locally advanced and metastatic melanoma, Merkel's cell carcinoma, cutaneous squamous cell carcinoma (cSCC), and BCC. In this article, we will briefly review the currently approved targeted and immunotherapy-based treatments for locally advanced and metastatic melanoma, Merkel's cell carcinoma, and cSCC and discuss various combinations of approved therapies, as well as emerging therapeutic candidates that are currently in clinical trials, including novel checkpoint inhibitors in development, intratumoral oncolytic agents (viral and nonviral), and various immune-based therapies such as toll-like receptor (TLR) agonists, adoptive T-cell therapy, T-cell costimulation, and innate immune cell therapy. For advanced BCC, we will discuss trials investigating the currently approved smoothened (SMO) inhibitors for neoadjuvant use, emerging SMO inhibitors in development, topical SMO inhibitors, alternative targets in the hedgehog signaling pathway, and the use of anti-PD-1 agents for advanced BCC both alone and in combination with SMO inhibitors.

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) is an organization of more than 500 physicians and scientists focused on the treatment of cutaneous malignancies following solid organ transplantation and in other forms of immunosuppression. It is well known that solid organ transplant recipients (SOTRs) have an approximate 100-fold increase in the risk of developing skin cancer with consensus guidelines recommending these patients be managed as high risk for local recurrence and metastasis associated with poor outcomes. In September 2018, ITSCC and its European counterpart, the Skin Care in Organ Transplant Patients-Europe (SCOPE), held their biennial scientific retreat in Essex, MA to discuss novel findings in the pathogenesis of cutaneous malignancy including new treatment and prevention strategies in this at risk population for significant morbidity and mortality from their cutaneous disease. This meeting report is a summary of the novel findings discussed.