Using Initial Biopsies and Vertical Sections to Improve Trainees' Confidence in Performing Mohs Surgery.

BACKGROUND: Tissue preservation and tumor clearance are hallmarks of Mohs micrographic surgery, but no standardized method currently exists to guide trainees on how to balance the two. OBJECTIVE: The authors provided residents and fellows with additional histologic information to enhance their surgical decision-making without changing the standard methodology of Mohs surgery. METHODS AND MATERIALS: Trainees were provided initial biopsy slides (IS) and frozen vertical sections (VS) of the first Mohs layer. All Mohs layers were excised in standard fashion, and vertically oriented sections were taken from the layer without disturbing the surgical margins to obtain VS. Surveys were used to assess trainees' confidence in performing Mohs surgery with and without these tools. RESULTS: Trainees reported increased confidence in performing Mohs surgery when they reviewed IS before surgery and viewed VS of the first layer. CONCLUSION: Reviewing IS and VS improved trainees' confidence in performing Mohs surgery. This additional histological information was obtained while maintaining the usual steps of Mohs surgery. Objective information obtained from IS and VS may explain why trainees' confidence increased using this technique. Both IS and VS can be valuable teaching tools that may enhance trainees' ability to perform Mohs surgery.

Cardiac Arrest Associated With Psilocybin Use and Hereditary Hemochromatosis.

Recreational drug use is a significant public health concern in various countries. It is well understood that usage of psychedelics/hallucinogens, such as lysergic acid diethylamide (LSD), ecstasy, phencyclidine (PCP), and psilocybin-containing mushrooms, has increased significantly over the last few decades, particularly in adolescents and young adults, yet the effects of these recreational drugs are poorly understood. Psilocybin has recently been studied as an alternative to traditional antidepressant therapies with potentially benign side effects. Here, we present the case of a 48-year-old male with a past medical history of attention-deficit/hyperactivity disorder on lisdexamfetamine who presented after a syncopal episode witnessed by his wife at home. He was found to be in ventricular fibrillation and subsequently had an extensive workup with cardiac magnetic resonance imaging (MRI), ischemic evaluation, and electrophysiology, which were unrevealing. He then received an automatic implantable cardiac defibrillator and was incidentally found to have hereditary hemochromatosis on outpatient follow-up. His polypharmacy may have potentially led to catecholamine release, leading to ventricular arrhythmia.

Development of High-Grade Sarcoma After Second Dose of Moderna Vaccine.

Coronavirus disease 2019 (COVID-19) is a disease characterized by predominantly respiratory symptoms, which can progress to respiratory failure. Due to the novelty of the vaccines, it is difficult to assess if there are any associated long-term side effects. Here, we present a case of an elderly female who received the Moderna COVID-19 vaccine and developed a high-grade sarcoma at the site of the injection. A 73-year-old female with a past medical history of hypertension, hyperlipidemia, and renal angiomyolipoma status post resection in 2019 presented with worsening right upper arm swelling for the past two weeks. She noticed the swelling two to four days after receiving her second dose of the Moderna vaccine within 1 cm from the prior injection site. Physical examination was remarkable for a 6 cm, circular, mobile, soft mass present in the right upper arm. MRI with and without contrast revealed a 5.2 cm soft tissue mass overlying the triceps region with irregular features concerning for malignancy. Fine needle aspiration revealed pathologic characteristics indicative of high-grade sarcoma. The patient ultimately had resection of the mass four months after the initial visit and was diagnosed as having grade 3, stage IIIA undifferentiated, pleomorphic high-grade sarcoma. Herein, we present a case demonstrating the development of high-grade sarcoma at the injection site in an elderly female patient within days of receiving the second dose of the Moderna COVID-19 vaccine. Currently, it is unclear whether there is a true association between the vaccines and malignancy or inflammatory response exacerbating underlying malignancy. This case highlights the necessity to investigate and be aware of such rare, adverse complications that may be associated with the novel COVID-19 vaccinations to guide physicians in their differential diagnosis.

Significance of Basal Cell Carcinomas Exhibiting Intravascular Invasion.

ABSTRACT: Intravascular invasion of tumor cells can be associated with metastasis in many cancers. Basal cell carcinomas (BCCs), however, rarely metastasize; therefore, the clinical impact of intravascularly invasive BCC (IVBCC) is currently unclear. Because of these facts and the rarity of IVBCC, questions have arisen on whether IVBCC truly exists. We present 4 cases of IVBCC: one case with obvious tumor islands within immunolabeled blood vessels in the context of advanced disease and 3 cases found incidentally during Mohs micrographic surgery. We discuss the difficulty in studying IVBCC, the idea that it could be due to artifact, and the lack of direct clinical-pathological correlation. Given these challenges, we propose diagnostic criteria for IVBCC to decrease ambiguity for pathological diagnosis. Such criteria may facilitate further studies on the clinical significance of IVBCC.

IgA Vasculitis With Concurrent ANCA-Positivity in the Setting of Bacterial Endocarditis.

Cutaneous small vessel vasculitis (CSVV) or leukocytoclastic vasculitis (LCV) is a group of immune complex mediated vasculitides that affect dermal capillaries or post-capillary venules and classically presents as lower extremity palpable purpura. CSVV can be subdivided by antibody type and clinical features. In patients presenting with signs of LCV and ANCA positivity, clinicopathologic correlation is important in characterizing the type of vasculitis. We report an uncommon case of IgA vasculitis with concurrent ANCA-positivity attributed to bacterial endocarditis.

MOC-31 Antibody Immunolabeling During Mohs Surgery.

BACKGROUND: Ber-EP4 is an antibody that labels basal cell carcinoma (BCC) by targeting epithelial cell adhesion molecule (Ep-CAM). MOC-31, a monoclonal mouse antibody, also targets Ep-CAM and is currently used to differentiate several extracutaneous epithelial tumors. However, the utility of MOC-31 has not been fully described in cutaneous tumors and in Mohs micrographic surgery (MMS). OBJECTIVE: To evaluate MOC-31 labeling in BCC and other cutaneous tumors and to compare immunolabeling intensity of MOC-31 and Ber-EP4 in BCCs. MATERIALS AND METHODS: Nineteen permanently fixed and 29 frozen BCC specimens and 23 other cutaneous tumors were labeled with MOC-31; labeling intensity of tumors, epidermis, and adnexal structures were recorded. In a separate study, a blinded dermatopathologist compared labeling intensities of 8 BCC specimens, each labeled with MOC-31 and Ber-EP4.4. RESULTS: MOC-31 labeled all BCCs. Eccrine coils and follicular bulbs did label variably, although this did not detract utility of MOC-31. Five of thirteen cutaneous squamous cell carcinomas and one of two Merkel cell carcinomas demonstrated MOC-31 positivity. MOC-31 and Ber-EP4 labeled BCCs similarly. CONCLUSION: MOC-31, an antibody directed against Ep-CAM, is sensitive for BCCs in frozen specimens encountered in MMS and permanently fixed specimen. In addition, MOC-31 demonstrated comparable immunolabeling characteristics with Ber-EP4 for BCCs.

The Gut Microbiome: Human Health and Inflammatory Skin Diseases.

The human microbiome is a rich environment consisting of bacteria, fungi and other commensal microorganisms of the gut, mucosa and skin. The functional role of the gut microbiome includes facilitation in metabolism of macronutrients, maturation of the immune system, and production of pro- or anti-inflammatory signaling molecules and peptides. The identification of these resident organisms has brought about a new understanding of disease processes. Nevertheless, more questions remain regarding the interactions within the microbiome, its interactions with the host, and its contributions to the pathophysiology of disease. The purpose of this review is to examine the existing medical literature to highlight the role of the gut microbiome in human health, also paying attention to its role in several inflammatory skin diseases, namely atopic dermatitis, psoriasis, and rosacea.

Erratum: The Gut Microbiome: Human Health and Inflammatory Skin Diseases.

[This corrects the article on p. 265 in vol. 32.].

Demographics, Risk Factors, and Incidence of Melanoma in Patients in the New England VA Healthcare system.

INTRODUCTION: A recent study found that the incidence of melanoma and melanoma-related mortality was decreasing in residents of the New England region. However, it is unknown whether this trend is conserved in Veterans of New England who constitute more than 14% of the national Veteran population. Given this, our goal was to analyze the incidence of melanoma in patients of Veteran Integrated Service Network-1 (VISN-1) (geographically consisting of VA health care facilities in Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) and to calculate an incidence rate ratio (IRR) of melanoma in VISN-1 compared to the general population. Additional goals were to ascertain the risk/susceptibility of this patient population with a view to improve quality of care and outcomes. MATERIALS AND METHODS: Data for 523 cases of melanoma [2000-2011] were obtained from the regional branch of the Veterans Affairs Central Cancer Registry (VACCR) within the geographic area comprising VISN-1. A detailed retrospective chart review was conducted on these cases to gather demographic, risk factor, and clinical practice data. Demographic and incidence data from VISN-1 were compared to the general population via data from Surveillance, Epidemiology and End Results Program (SEER) from the same time period. Person-years (PY) were calculated for both populations to measure IRRs which was further standardized for age and gender. RESULTS: VISN-1 patients were predominantly older (94.26% >50 years), Caucasian (99.43%) males (96.75%). Compared to the general population, VISN-1 patients experienced more invasive lesions defined as stage T1 or greater (4.33% vs. 57.12%, p < 0.001), but reduced melanoma-associated mortality (40.96% vs. 19.05%, p < 0.001) although all-cause mortality was approximately doubled (52.20% vs. 26.14%, p < 0.001). Metastatic disease-rates were similar in both [approximately 4% in both]. IRR of melanoma in VISN-1 patients was 0.36 (95% CI: 0.20-0.67; p = 0.0063) which persisted in all age groups/genders. 60.92% of VISN-1 patients had recreational sun-exposure history and 72.41% of tobacco use. 95.02% of melanomas were located in continuously/intermittently sun-exposed areas, 93.28% were surgically-treated with a median treatment delay of 31 days [range 18-48]. Median lost to follow-up was 0 day [range 0-681 days]. CONCLUSIONS: Compared to the general population, melanoma incidence was lower in the VISN-1 cohort, possibly due to decreased UV index in the New England region, protective effects of past tobacco use, improved access to care through the VA and regional public health educational efforts. Yet melanomas were more often invasive in the VISN-1 cohort due to advanced age and male sex both of which are associated with more advanced disease at diagnosis. A strength of this study is the calculation of IRR using PY as this method enhances accuracy of incidence calculations. The data were limited by the fact that the population was from one geographic region and consisted mainly of elderly Caucasian males. Descriptive variable data such as sun-protective habits and risk factors from military service are limited by potential recall bias given the retrospective study design. Further study is necessary to replicate these results and to compare our data to Veteran populations from different geographic regions within the USA.

Cutaneous Rosai-Dorfman Disease With Linear Lesions and Monoclonal Gammopathy.

Cutaneous Rosai-Dorfman disease (CRDD), a benign histiocytosis of unknown etiology, typically presents as a solitary or clusters of lesions. Although the histopathology is fairly distinctive, the laboratory abnormalities are not; past reports note elevated erythrocyte sedimentation rate, anemia, and polyclonal hyperglobulinemia. We describe a 61-year-old African American diabetic gentleman who presented with nodules in a linear distribution on the flank. Histopathologic examination of a biopsied nodule revealed a pandermal sheet-like infiltrate of plasma cells and histiocytes, some demonstrating elastophagocytosis and emperipolesis. The lesional histiocytes were S100 and CD68 positive and CD1a negative-findings consistent with a diagnosis of CRDD. Additional laboratory work-up performed 12 weeks after the biopsy was taken revealed an elevated serum κ light chain concentration of 37.26 mg/L (reference range: 3.30-19.40 mg/L), which correlated with an M-protein spike identified as IgG κ proteins per serum protein electrophoresis. Given the difficulty in excising a large area and preexisting diabetes, a course of low-dose methotrexate was selected for therapy with a recommendation of close follow-up for the monoclonal gammopathy. To the best of our knowledge, this is the first report of CRDD associated with a linear distribution of lesions and serum protein electrophoresis-confirmed monoclonal gammopathy.

Changes in Self-Perceptions of Photoaging Severity and Skin Cancer Risk After Objective Facial Skin Quality Analysis.

Background: Despite public education efforts, many people at risk for skin cancer do not practice safe sun behaviors.

Objective: To determine whether machine-based evaluation of UV-induced alterations (VISIA scan) changes self-assessment of facial photoaging, skin cancer risk, and willingness to improve sun protective habits. In addition, to determine whether VISIA scan analysis reveals differences between those with versus without a history of skin cancer, men versus women, those older than 50 versus less than 50 years of age, and Fitzpatrick skin types I-III versus IV-VI.

Methods: Volunteers attending a health expo were recruited and queried about their perceived risk of skin cancer and degree of skin photoaging. All participants underwent facial skin quality analysis of both sides of the face, and then completed a follow-up survey.

Results: Participants' scored self-perceptions of overall skin aging were all statistically significantly worse after VISIA scan analysis. There was no change in perceived skin cancer risk, but most participants expressed intent to improve their sun protection habits.

Limitations: Limitations to this study include selection bias, recall-misclassification bias, and social desirability bias.

Conclusion: Intervention with facial skin analysis can positively affect subjects' stated intent to use sun protection, indicating the importance of appearance in these health decisions.

J Drugs Dermatol. 2017;16(5):453-459.

The Impact of Obesity on Patient Reported Outcomes Following Stereotactic Body Radiation Therapy for Prostate Cancer.

OBJECTIVES: The relationship between obesity (Body Mass Index ->30 kg/m(2)) and quality of life (QoL) following prostate cancer (PCa) radiation therapy (RT) is unknown. Excess abdominal fat may compromise the precise delivery of radiation, putting surrounding organs at risk for greater radiation exposure. Stereotactic body radiation therapy (SBRT) utilizes a real-time tracking system that provides updated prostate position information and allows for correction of the therapeutic beam during treatment with high accuracy. In this study, we evaluate the impact of obesity on patient reported outcomes following SBRT for prostate cancer. MATERIALS AND METHODS: Between February 2008 and April 2012, 88 obese and 178 non-obese patients with PCa were treated with SBRT at Georgetown University Hospital, Washington, DC. Health-related quality of life (HRQol) was assessed via the expanded prostate cancer index composite (EPIC)-26 at baseline, 6, 12, 18, and 24 months after 5-fraction delivery of 35-36.25 Gy with the CyberKnife. Patients who received androgen deprivation therapy (ADT) were excluded from this analysis due to its known negative impact on HRQoL. RESULTS: Pretreatment characteristics of obese and non-obese patient groups were similar except that obese patients had lower total testosterone levels. Urinary and bowel function and bother scores between the two patient cohorts were comparable at baseline and subsequent follow-ups. Sexual function and bother were also similar at baseline between both groups. Bother was defined by displeasure patients may experience from functional decline. At 24 months post-SBRT, obese men experienced borderline clinically significant decrease in sexual function and greater sexual bother compared to non-obese patients. Fatigue was significantly higher in obese patients compared to non-obese patients at 18 months post-SBRT. CONCLUSIONS: Prostate SBRT affects obese and non-obese patients similarly in total HRQoL scores and majority of its domains. Obesity has been associated with cancer recurrence; therefore longer follow-up is required to determine the impact of obesity on cancer control.

Dual inhibition of EGFR and MET induces synthetic lethality in triple-negative breast cancer cells through downregulation of ribosomal protein S6.

Triple-negative breast cancer (TNBC) exhibits innate resistance to the EGFR inhibition despite high level expression of EGFR. Recently, we found that the proliferation of basal-like (BL) subtype TNBC cells is synergistically inhibited by combination of EGFR and PI3K/AKT inhibitors. On the contrary, TNBC cells of mesenchymal stem-like (MSL) subtype are resistant to these combinations. To identify potential synthetic lethal interaction of compounds for treatment of MSL subtype TNBC cells, we performed MTT screening of MDA-MB­231 cells with a small library of receptor tyrosine kinase inhibitors (RTKIs) in the presence of gefitinib, an EGFR inhibitor. We identified MET inhibitors as potent RTKIs that caused synthetic lethality in combination with gefitinib in MDA-MB­231 cells. We demonstrated that combination of a MET inhibitor SU11274 with various EGFR inhibitors resulted in synergistic suppression of cell viability (in MTT assay) and cell survival (in colony formation assay) of MSL subtype TNBC cells. We further demonstrated that SU11274 alone induced G2 arrest and gefitinib/SU11274 combination sustained the SU11274-induced G2 arrest in these cells. In addition, SU11274/gefitinib combination synergistically reduced the level of ribosomal protein S6 (RPS6) in MSL subtype TNBC cells. In addition, knockdown of RPS6 itself, in both HS578T and MDA-MB­231, markedly reduced the proliferation of these cells. Taken together, our data suggest that dual targeting of EGFR and MET inhibits the proliferation of MSL subtype TNBC cells through downregulation of RPS6.

Extracellular matrix, gap junctions, and retinal vascular homeostasis in diabetic retinopathy.

The vascular basement membrane (BM) contains extracellular matrix (ECM) proteins that assemble in a highly organized manner to form a supportive substratum for cell attachment facilitating myriad functions that are vital to cell survival and overall retinal homeostasis. The BM provides a microenvironment in which bidirectional signaling through integrins regulates cell attachment, turnover, and functionality. In diabetic retinopathy, the BM undergoes profound structural and functional changes, and recent studies have brought to light the implications of such changes. Thickened vascular BM in the retinal capillaries actively participate in the development and progression of characteristic changes associated with diabetic retinopathy. High glucose (HG)-induced compromised cell-cell communication via gap junctions (GJ) in retinal vascular cells may disrupt homeostasis in the retinal microenvironment. In this review, the role of altered ECM synthesis, compromised GJ activity, and disturbed retinal homeostasis in the development of retinal vascular lesions in diabetic retinopathy are discussed.

ß-TrCP1 degradation is a novel action mechanism of PI3K/mTOR inhibitors in triple-negative breast cancer cells.

An F-box protein, ß-TrCP recognizes substrate proteins and destabilizes them through ubiquitin-dependent proteolysis. It regulates the stability of diverse proteins and functions as either a tumor suppressor or an oncogene. Although the regulation by ß-TrCP has been widely studied, the regulation of ß-TrCP itself is not well understood yet. In this study, we found that the level of ß-TrCP1 is downregulated by various protein kinase inhibitors in triple-negative breast cancer (TNBC) cells. A PI3K/mTOR inhibitor PI-103 reduced the level of ß-TrCP1 in a wide range of TNBC cells in a proteasome-dependent manner. Concomitantly, the levels of c-Myc and cyclin E were also downregulated by PI-103. PI-103 reduced the phosphorylation of ß-TrCP1 prior to its degradation. In addition, knockdown of ß-TrCP1 inhibited the proliferation of TNBC cells. We further identified that pharmacological inhibition of mTORC2 was sufficient to reduce the ß-TrCP1 and c-Myc levels. These results suggest that mTORC2 regulates the stability of ß-TrCP1 in TNBC cells and targeting ß-TrCP1 is a potential approach to treat human TNBC.