Mohs Micrographic Surgery in the Surgical Treatment Paradigm of Melanoma In Situ and Invasive Melanoma: A Clinical Review of Treatment Efficacy and Ongoing Controversies.

Mohs Micrographic Surgery (MMS) for treatment of melanoma offers several advantages over wide local excision (WLE), including complete histologic margin evaluation, same-day resection and closure, and sparing of healthy tissue in critical anatomic sites. Recently, a large volume of clinical data demonstrating efficacy in MMS treatment of melanoma was published, leading to emerging patient safety considerations of incurred treatment costs, risk of tumor upstaging, and failure of care coordination for sentinel lymph node biopsy (SLNB). MMS offers a safe, effective, and value-based treatment for both melanoma in situ (MIS) and invasive melanoma (IM), particularly with immunohistochemistry use on frozen sections. Compared to WLE, MMS treatment demonstrates similar or improved outcomes for local tumor recurrence, melanoma-specific survival, and overall survival at long-term follow-up. Tumor upstaging risk is low, and if present, alteration to clinical management is minimal. Discussion of SLNB for eligible head and neck IM cases should be done prior to MMS. Though challenging, successful multidisciplinary coordination of SLNB with MMS has been demonstrated. Herein, we provide a detailed clinical review of evidence for MMS treatment of cutaneous melanoma and offer recommendations to address current controversies surrounding the evolving paradigm of surgical management for both MIS and IM.

Multicenter prospective blinded melanoma detection study with a handheld elastic scattering spectroscopy device.

Background: The elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a noninvasive, painless, adjunctive tool for skin cancer detection. Objectives: To investigate the performance of the ESS device in the detection of melanoma. Methods: A prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists' standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. Results: The observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5% to 98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2% to 38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. Limitations: The device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. Conclusion: The ESS device's high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

Nodular lymphangitis related to methicillin-resistant staphylococcus aureus infection.

Nodular lymphangitis, also known as lymphocutaneous syndrome or sporotrichoid lymphangitis, presents with inflammatory nodules along the lymphatic vessels, typically involving the upper or lower extremities. Although the most common cause of nodular lymphangitis is infection due to Sporothrix schenckii, Nocardia brasiliensis, Mycobacterium marinum, or Leishmania braziliensis, it is important for clinicians to be aware of methicillin-resistant Staphylococcus aureus as a rare cause of nodular lymphangitis and perform gram stain, bacterial culture, and antibiotic sensitivity profiles when appropriate. History of recent travel or exposures, incubation time, presence of systemic symptoms, and presence of ulceration, suppuration, or drainage can serve as diagnostic clues, but microbiological tissue cultures and histopathologic studies confirm the diagnosis. Herein, we present a case of nodular lymphangitis caused by methicillin-resistant Staphylococcus aureus (MRSA); tissue culture and antibiotic sensitivities were used to guide treatment.

Cannabis arteritis presenting with Raynaud's and digital ulcerations: a case-based review of a controversial thromboangiitis obliterans-like condition.

Thromboangiitis obliterans (TAO), or Buerger's disease, is a non-atherosclerotic inflammatory disease of the small and medium-sized arteries, veins, and nerves of the legs and arms, strongly associated with the use of tobacco products in young adults. Cannabis arteritis (CA), an entity with similar clinical and pathological features, has been described in marijuana users as a subtype of TAO. Distinction between TAO and CA is challenging, given that most patients use tobacco and marijuana products concomitantly. Herein, we report the case of a male in his late forties who was referred to rheumatology with a 2-month history of hand swelling and bilateral painful digital ulcers with blue discoloration on his fingers and toes. The patient reported daily use of marijuana in blunt wraps and denied tobacco use. His laboratory work-up was negative for scleroderma and other connective tissue diseases. His angiogram confirmed the diagnosis of thromboangiitis obliterans, which was attributed to cannabis arteritis. The patient was started on aspirin and nifedipine daily and discontinued marijuana use. His symptoms resolved within 6 months and have not recurred for more than a year with continued avoidance of marijuana. Our case is one of the few that features primarily marijuana-driven CA and highlights the importance of not only considering marijuana use but also blunt wrap use in patients presenting with Raynaud's phenomenon and ulcerations as cannabis use rises globally.

Transcriptional Profiling Supports the Notochordal Origin of Chordoma and Its Dependence on a TGFB1-TBXT Network.

Chordoma is a rare malignant tumor demonstrating notochordal differentiation. It is dependent on brachyury (TBXT), a hallmark notochordal gene and transcription factor, and shares histologic features and the same anatomic location as the notochord. This study involved a molecular comparison of chordoma and notochord to identify dysregulated cellular pathways. The lack of a molecular reference from appropriate control tissue limits our understanding of chordoma and its relationship to notochord. Therefore, an unbiased comparison of chordoma, human notochord, and an atlas of normal and cancerous tissue was conducted using gene expression profiling to clarify the chordoma/notochord relationship and potentially identify novel drug targets. The study found striking consistency in gene expression profiles between chordoma and notochord, supporting the hypothesis that chordoma develops from notochordal remnants. A 12-gene diagnostic chordoma signature was identified and the TBXT/transforming growth factor beta (TGF-ß)/SOX6/SOX9 pathway was hyperactivated in the tumor, suggesting that pathways associated with chondrogenesis were a central driver of chordoma development. Experimental validation in chordoma cells confirmed these findings and emphasized the dependence of chordoma proliferation and survival on TGF-ß. The computational and experimental evidence provided the first molecular connection between notochord and chordoma and identified core members of a chordoma regulatory pathway involving TBXT. This pathway provides new therapeutic targets for this unique malignant neoplasm and highlights TGF-ß as a prime druggable candidate.

Sun protective behaviors in sun-sensitive individuals: a cross-sectional study examining for ethnic and racial differences.

The rates of non-melanoma skin cancer continue to rise in the United States. We investigated if differences exist in skin cancer preventive behaviors among sun-sensitive non-Hispanic whites and other racial and ethnic groups. The National Health Information Survey was used to perform the cross-sectional study. Outcomes of interest included multiple sun-protective methods. Individuals were determined to be sun-sensitive if Fitzpatrick skin phototype (SPT) I/II. Multivariable logistic regression was used to examine the associations between the use of sun-protective practices and race and ethnicity, SPT, and survey year. The study included 67,471 individuals. Adjusted prevalences of skin cancer preventive behaviors revealed that across all SPTs, non-Hispanic whites were more likely to use sunscreen, undergo physician-administered FBSE, and have multiple sunburns or tan indoors in the past year compared to corresponding SPT other racial and ethnic groups. In contrast, other racial and ethnic groups with any SPT were more likely to practice sun avoidance than corresponding SPT non-Hispanic whites. Additionally, other racial and ethnic groups with SPT III+ were more likely to wear sun-protective clothing than non-Hispanic white individuals with similar SPTs. For all SPT and racial and ethnic groups, there were significant increases in sunscreen use and decreases in past-year indoor tanning. Full body skin examination prevalence, regardless of sun sensitivity, increased for all non-Hispanic whites, but remained unchanged for sun-sensitive other racial and ethnic groups. Adjusted prevalence of multiple sunburns and use of protective clothing remained unchanged for all racial and ethnic groups across all SPT categories. There are differences in sun-protective behaviors among sun-sensitive individuals by race and ethnicity with the magnitude of some of these differences increasing. Future research and public health campaigns are needed on photosensitive individuals and the relationship between skin protective behaviors and race/ethnicity. When discussing sun protection, care providers should not only consider the influence of sun-sensitivity, but also race and ethnicity, and its impact on sun prevention behaviors.

Cumulative Erythemal Ultraviolet Radiation and Risk of Cancer in 3 Large US Prospective Cohorts.

Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and noncutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined 3 US prospective cohorts, the Health Professionals Follow-up Study (HPFS) (1986) and Nurses' Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding nonmelanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 men; 212,449 women) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as referent, for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared with the lowest quintile, risk of any cancer was slightly increased across all other quintiles (highest quintile hazard ratio (HR) = 1.04, 95% confidence interval (CI): 1.01, 1.07; P for heterogeneity = 0.41). All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR = 1.17, 95% CI: 1.04, 1.31; P for heterogeneity = 0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and noncutaneous cancers.