Differential Molecular Expression Patterns Associated with Metastasis in Cutaneous Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

The majority of cutaneous squamous cell carcinomas are treated by surgical removal; however, approximately 4% of tumors will metastasize. Molecular expression testing may improve accuracy in estimating the prognosis and defining the mechanisms important in the disease progression, which may impact response to therapy. Using PubMed (MEDLINE) and EMBASE, a systematic review was performed to evaluate studies published from January 2005 to August 2019 reporting tumor protein or RNA expression along with either outcomes (metastasis or death) or a comparison of primary with metastatic tumor samples. Inclusion criteria were met by 45 studies containing 81 comparisons of 44 distinct proteins and 25 microRNAs. On meta-analysis of studies analyzing primary tumor samples in terms of later outcomes, high primary tumor expression of PD-L1 (OR = 2.34, 95% confidence interval = 1.09-5.02, P = 0.030), EGFR (OR = 2.57, 95% confidence interval = 1.24-5.33, P = 0.011), and podoplanin (OR = 2.33, 95% confidence interval = 1.00-5.41, P = 0.049) conferred increased odds for metastasis. In comparison, metastatic tissue was more likely to have a high expression of PD-L1 than primary tissue (OR = 3.13, 95% confidence interval = 1.00-9.75, P = 0.049). Further studies are needed to confirm whether testing for PD-L1, EGFR, and podoplanin expression aids in cutaneous squamous cell carcinomas prognostic estimation of metastasis or death or predicts response to therapy.

Diagnostic Biopsy via In-Office Frozen Sections for Clinical Nonmelanoma Skin Cancer.

BACKGROUND: Treatment of nonmelanoma skin cancer (NMSC) by Mohs surgery has traditionally relied on previous pathologic evaluation of paraffin-embedded tissue. Tissue processing by frozen sections allows for expedited diagnosis and treatment; however, data on its accuracy are limited. OBJECTIVE: To measure the accuracy and outcomes of biopsy via frozen sections for clinical NMSC. METHODS: Biopsies of clinical NMSCs processed via frozen sections with in-office diagnosis rendered by one Mohs surgeon were retrospectively reviewed by one board-certified dermatopathologist. Discordant diagnoses were re-read in blinded fashion by both physicians. If still discordant, final diagnosis was determined by consensus discussion. Inter-rater reliability was calculated using Cohen's kappa statistic. RESULTS: Two hundred ninety-seven lesions from 208 patients were included. Correlation between in-office and final diagnosis was 0.876 indicating "almost perfect" concordance. Sensitivity and specificity of in-office diagnosis for detecting malignancy were 98.1% and 94.4%. Seven cases (2.0%) had a clinically relevant change in final diagnosis, but appropriate treatment had been rendered. Two benign lesions (0.7%) initially diagnosed as malignant underwent excision. CONCLUSION: In-office biopsy via frozen sections is highly accurate in confirming NMSC. This practice may speed diagnosis and treatment thus improving outcomes and patient satisfaction.

Molecular prediction of metastasis in cutaneous squamous cell carcinoma.

PURPOSE OF REVIEW: Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent malignancy frequently occurring on body surfaces chronically exposed to ultraviolet radiation. While a large majority of tumors remain localized to the skin and immediate subcutaneous tissue and are cured with surgical excision, a small subset of patients with cSCC will develop metastatic disease. Risk stratification for cSCC is performed using clinical staging systems, but given a high mutational burden and advances in targeted and immunotherapy, there is growing interest in molecular predictors of high-risk disease. RECENT FINDINGS: Recent literature on the risk for metastasis in cSCC includes notable findings in genes involved in cell-cycle regulation, tumor suppression, tissue invasion and microenvironment, interactions with the host-immune system, and epigenetic regulation. SUMMARY: cSCC is a highly mutated tumor with complex carcinogenesis. Regulators of tumor growth and local invasion are numerous and increasingly well-understood but drivers of metastasis are less established. Areas of importance include central system regulators (NOTCH, miRNAs), proteins involved in tissue invasion (podoplanin, E-cadherin), and targets of existing and emerging therapeutics (PD-1, epidermal growth factor receptor). Given the complexity of cSCC carcinogenesis, the use of machine learning algorithms and computational genomics may provide ultimate insight and prospective studies are needed to verify clinical relevance.

A 63-Year-Old Male with AIDS and Diffuse Violaceous Plaques.

Hyperkeratotic Kaposi's sarcoma (KS) is a rare clinicopathologic variant of AIDS-related KS that typically presents with chronic lymphedema and diffuse hyperkeratotic plaques of the lower extremities. Histopathologically, this variant is defined by epidermal hyperplasia, thickened lymphatic walls, and increased numbers of dermal fibroblasts and vascular spaces. Herein, we report the case of a 63-year-old HIV-positive male who presented with this rare hyperkeratotic variant of AIDS-related KS.

A 71-Year-Old Female with Myocardial Infarction and Long-Standing Ulcers on the Thigh.

Calciphylaxis is most commonly encountered in patients with end-stage renal disease; however, it is increasingly observed in nonuremic patients as well. It is important to consider and diagnose nonuremic calciphylaxis early, as prompt treatment and mitigation of associated risk factors is essential to improve long-term outcomes for these patients. Here, we present the case of a 71-year-old woman with atrial fibrillation on warfarin, but without renal disease, who presented with two long-standing ulcers on her thigh and was diagnosed with the aid of biopsy with calciphylaxis. We review the existing literature on the subject and offer this case as a representative report of a clinicopathologic correlation for this disorder.

Trichophytum rubrum endonyx onychomycosis resistant to standard oral and topical therapies.

We present a 45 year-old man with an eight-year history of discoloration of the nail plate on his left hallux. He had been treated with two courses of oral terbinafine and topical 8% ciclopirox for presumed onychomycosis. On exam, his left great toenail contained a wide yellow-white longitudinal band involving a majority of the nail plate. No subungual debris, hyperkeratosis, or paronychial inflammation was present in the affected nail. Histopathology of the nail plate revealed numerous fungal elements arranged transversely and longitudinally, solely within the keratin layers of the nail plate; these were highlighted with periodic acid-Schiff (PAS) stain confirming endonyx onychomycosis. Cultures grew Trichophyton rubrum. All types of onychomycosis under the new classification system proposed by Hay et al. have now been associated with T. rubrum. Endonyx related to T. rubrum may be a particularly difficult infection to treat with oral or topical agents owing to the absence of robust local immune response and limited drug penetration to the interior nail plate. Physicians should be aware that this type of infection may require treatment with dual-agent therapy or alternative modalities including chemical or surgical plate avulsion or photodynamic therapy.

Basal cell carcinomas of the ear are more aggressive than on other head and neck locations.

BACKGROUND: On pathology review, basal cell carcinomas (BCCs) on the ear more commonly present as aggressive subtypes. It is unclear if this histologic observation translates into more clinically aggressive tumors. OBJECTIVE: We sought to determine the clinical aggressiveness of ear BCCs compared with BCCs elsewhere on the head and neck. METHODS: We conducted a retrospective chart review of all BCCs treated at an academic center from 2005 through 2012. Subjects were divided into ear and non-ear groups. Subtypes classified as "aggressive" included morpheaform, infiltrative, micronodular, adenoid, metatypical, and mixed histology. RESULTS: Of the 7732 head and neck BCCs, 758 (9.8%) were on the ear. Ear BCCs presented as larger lesions (1.28 vs 0.98 cm(2)), required more Mohs layers (16.5% vs 10.7%), and produced a larger final defect (4.29 vs 3.49 cm(2)) than non-ear lesions. When comparing only aggressive subtypes, ear BCCs also presented as larger lesions (1.42 vs 1.23 cm(2)), more frequently required 3 or more layers for clearance (22.3% vs 14.2%), and produced a larger final defect (4.92 vs 4.21 cm(2)) than non-ear lesions. LIMITATIONS: Limitations include single-center design and lack of long-term follow-up. CONCLUSION: Ear BCCs appear to exhibit greater subclinical extension compared with non-ear head and neck BCCs. Therefore, the ear should be considered a high-risk location for BCCs.

A mentorship-based preclinical elective increases exposure, confidence, and interest in surgery.

BACKGROUND: The predicted shortage of surgeons is of growing concern with declining medical student interest in surgical careers. We hypothesized that earlier exposure to operative experiences and the establishment of resident mentors through a preclinical elective would enhance student confidence and interest in surgery. METHODS: We developed a preclinical elective in surgery, which served as an organized curriculum for junior medical students to experience surgery through a paired resident-mentorship model. We assessed student exposure and confidence with clinical activities before and after the elective (N = 24, 100% response rate). We compared these students with a cohort of peers not enrolled in the elective (N = 147, 67% response rate). RESULTS: We found significantly improved confidence (2.8 vs 4.4) and clinical exposure (2.4 vs 4.3) before versus after the elective, with precourse scores equal to matched peers. CONCLUSIONS: This elective incorporates elements that have been shown to positively influence student decision making in surgical career choice. The mentorship model promotes residents as educators, whereas the elective provides a means for early identification of students interested in surgery.