Ally Khan Somani

Pten Loss Induces Autocrine FGF Signaling to Promote Skin Tumorigenesis

Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by Pten deletion is reversed by genetic disruption of the mTORC1 complex, which also prevents skin tumorigenesis in Pten mutants. We further show that ectopic expression of Fgf10 causes skin papillomas, whereas Pten deletion-induced skin tumors are inhibited by epidermal deletion of Fgfr2. Collectively, our data identify autocrine activation of FGF signaling as an essential mechanism in promoting Pten-deficient skin tumors.

Skin resurfacing procedures: new and emerging options

The demand for skin resurfacing and rejuvenating procedures has progressively increased in the last decade and has sparked several advances within the skin resurfacing field that promote faster healing while minimizing downtime and side effects for patients. Several technological and procedural skin resurfacing developments are being integrated into clinical practices today allowing clinicians to treat a broader range of patients’ skin types and pathologies than in years past, with noteworthy outcomes. This article will discuss some emerging and developing resurfacing therapies and treatments that are present today and soon to be available.

Fibroblast Senescence and Squamous Cell Carcinoma: How Wounding Therapies Could Be Protective

BACKGROUND Squamous cell carcinoma (SCC), which has one of the highest incidences of all cancers in the United States, is an age‐dependent disease, with the majority of these cancers diagnosed in people age 70 and older. Recent findings have led to a new hypothesis on the pathogenesis of SCC. OBJECTIVES To evaluate the potential of preventive therapies to reduce the incidence of SCC in at‐risk geriatric patients. MATERIALS AND METHODS Survey of current literature on wounding therapies to prevent SCCs. RESULTS This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in the dermis, resulting in a reduction in dermal insulin‐like growth factor‐1 (IGF‐1) expression. This lack of IGF‐1 expression sensitizes epidermal keratinocytes to fail to suppress ultraviolet light B (UVB)‐induced mutations, leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF‐1 expression, and correct the inappropriate UVB response found in geriatric skin, protecting geriatric keratinocytes from UVB‐induced SCC initiation. CONCLUSIONS In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC.

The microsecond 1064 nm Nd:YAG laser as an adjunct to improving surgical scars following Mohs micrographic surgery.

Background: Scarring following skin surgery is an unavoidable certainty. Scars resulting from Mohs Micrographic Surgery (MMS) can cause both cosmetic and functional problems. Various lasers have been used to treat scars, but the role of the microsecond pulsed 1064 nanometer neodymium-doped yttrium aluminum garnet (1064 nm Nd:YAG) in treating surgical scars is not well-defined. Objective: We aim to examine the clinical application of the 1064 nm Nd:YAG laser in improving surgical scars. Methods: Ten patients who were unhappy with cosmetic or functional outcomes of their surgical scars following MMS were treated with 1–3 sessions of the 1064 nm Nd:YAG laser to improve their scars. Therapy completion was determined by patient satisfaction with the appearance of their scars and/or resolution of any contractures that formed following surgery. Results: All ten patients were pleased with the improved appearance of their scars. Four patients saw complete resolution of an ectropion or eclabium that formed secondary to scar contractures from MMS. The side effects of laser treatments were limited to 1–2 hours of erythema, and there were no incidences of adverse effects or recurrence of contractures. Conclusion: Our clinical experience with the 1064 nm Nd:YAG laser provides promising data on improving appearance of and functionality from post-surgical scars.

Floaters in Mohs micrographic surgery.

Background Floaters are dislodged pieces of tumor tissue than can obscure Mohs micrographic surgery (MMS) frozen sections and confound their interpretation. Objective To understand the common causes of floaters and identify management strategies. Methods An initial virtual consensus conference of Mohs surgeons based on a 60‐item questionnaire. Data were validated in interviews with randomly selected Mohs surgeons. Results Based on retrospective reporting of 230 surgeon‐years and 170,404 cases of MMS by 26 surgeons, the mean rate of floaters per tumor treated was 1.8%, and the rate of floaters per tissue block was 0.70%. Not wiping blades between cuts when a stage is separated into subunits can predispose to floaters. There was also strong consensus that basal cell carcinomas, ulcerated tumors, and tissue from the first stage were more likely to yield floaters. There is little consensus on how to manage floaters, with possibilities including taking additional sections, taking an additional stage, or simply noting the floater. Conclusion Floaters are not rare and can complicate MMS margin assessment. There is significant expert consensus regarding the causes of floaters and the tissue features that may predispose to them. Floaters may be prevented by minimizing their likely causes. There is less consensus on what to do with a floater.

Scattering anisotropy-weighted mesoscopic imaging

Abstract. We report that when tissue images are formed via a small solid angle in the backward direction (i.e., back-directional gating), the image intensity is dominantly determined by tissue scattering anisotropy. Thus, this configuration allows for scattering anisotropy-weighted imaging that can provide an intrinsic contrast by capturing tissue structures and organizations. To demonstrate the immediate feasibility, we apply scattering anisotropy-weighted imaging to tissue blocks including basal-cell carcinomas as a pilot study. The main feature of our imaging approach is the high sensitivity to tumor locations and the simplicity for large-area visualization. We further envision that scattering anisotropy-weighted imaging could potentially be used to visualize tissue microenvironments in a mesoscopic (between microscopic and macroscopic) imaging setting.

Crescentic Alar Myocutaneous Island Pedicle Flap for Reconstructing Columellar Defects

A 64-year-old Caucasian man presented with an 8-mm exophytic squamous cell carcinoma extending from the surface of his right nasal sill onto his columella (Figure 1A). Mohs micrographic surgery was performed to remove the tumor in two stages, resulting in a 1.0by 1.4-cm defect involving the right columella extending down to cartilage, the right nasal sill, and the right upper cutaneous lip (Figure 1B). How would you reconstruct this defect?

Successful use of the microsecond 1,064-nm Nd: YAG laser as a novel treatment for surgical scar contractures on free margins.

Scar contractures are a common complication after cutaneous surgery. Contractures that occur at free margins on patients after Mohs micrographic surgery (MMS) can be especially troublesome and can lead to cosmetic issues anddeformities such as an ectropionor eclabium. These deformities can lead to functional problems and must be treated to prevent further complications. This 4-patient case series looks at a noninvasive and nondebilitating treatment for surgical contractures. The aim of this study was to evaluate the safety and efficacy of treatment of surgical scar contractures on free margins with the microsecond-pulsed 1,064-nm neodymium-doped yttrium aluminum garnet (1,064-nm Nd:YAG) laser.

Scattering anisotropy as an imaging contrast for tissue organization in mesoscopic imaging

We report the utilization of tissue scattering anisotropy as an intrinsic imaging contrast. This could potentially be used to probe tissue architecture and organization for mesoscopic (between microscopic and macroscopic) imaging settings.