Faculty Bibliography

It is well established that immunosuppressed patients are at increased risk for poor outcomes (PO) from cutaneous squamous cell carcinoma (cSCC), including local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). Defining PO risk is challenging but may be beneficial in guiding management. We aimed to define PO risk factors and evaluated their importance in immunosuppressed versus immunocompetent patients. We conducted a 4-year single-center retrospective review of patients with cSCC. Patient and tumor characteristics were evaluated in those that experienced PO. Immunosuppressed patients were ~ 11-fold more likely than immunocompetent patients to develop PO (10/85 vs. 15/1332, p < 0.0001). Among those with PO, immunosuppressed patients had diminished relapse free (p = 0.026) and progression free (p < 0.001) survival compared to immunocompetent. Immunosuppression was significantly associated with LR (p < 0.00001). Immunosuppressed patients were also more likely to develop NM, DM and experience DSD (p = 0.027). Mohs Appropriate Use Criteria was associated with NM, DM and DSD (p = 0.029), with area H tumors more likely to result in metastasis and death. In conclusion, immunosuppressed patients are more likely to develop LR, metastasis, and DSD from cSCC compared to immunocompetent patients. Immunosuppressed status was an independent risk factor for PO in this cohort and further considered for its inclusion in prognostication schema is warranted.

Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.

BACKGROUND:Vulvar melanoma is a rare malignancy with frequent recurrence and poor prognosis. National guidelines recommend wide local excision of these tumors with allowances for narrower margins for anatomic and functional limitations, which are common on specialty sites. There is presently a lack of data of margin positivity after standard excision of vulvar melanomas. OBJECTIVE:We aim to evaluate the rate of positive margins after standard excision of vulvar melanomas. MATERIALS AND METHODS/METHODS:Retrospective cohort study of surgically excised vulvar melanomas from the NCDB diagnosed from 2004 to 2019. RESULTS:We identified a total of 2,226 cases. Across surgical approaches and tumor stages, 17.2% (Standard Error [SE]: 0.8%) of cases had positive surgical margins. Among tumor stages, T4 tumors were most commonly excised with positive margins (22.9%, SE: 1.5%). On multivariable survival analysis, excision with positive margins was associated with significantly poorer survival (Hazard Ratio 1.299, p = .015). CONCLUSION/CONCLUSIONS:We find that positive margin rates after standard excision of vulvar malignancies are higher than for other specialty site melanomas. Our data suggest that use of surgical approaches with complete margin assessment may improve local control and functional outcomes for patients with vulvar melanoma as they have for patients with other specialty site melanomas.

There is controversy regarding the optimal surgical modality and ideal recommended margins for treating melanoma in situ (MIS) and invasive melanoma (IM). Although wide local excision is recommended, staged excision offers excellent margin control and low recurrence rates. In this manuscript, we reviewed a 10-year experience of staged excisions for the treatment of MIS and IM. A retrospective review was performed of 130 MIS and 32 IM cases treated with staged excision from April 2012 to April 2022. Staged excision was performed on the head and neck in 102 (79%) MIS and 23 (72%) IM cases. Approximately 10% of cases required surgical margins above the current recommendations (11 (9%) MIS and 6 (19%) IM). Twenty-three (19%) MIS and 7 (22%) IM cases required more than one excision to obtain clearance. Recurrence rates among MIS and IM were 0.0% and 0.6%, respectively. Upstaging occurred in 5 (4%) MIS and 7 (22%) IM cases. Complex repairs were performed on 82 (63%) MIS and 17 (53%) IM cases. Our findings revealed that staged excision provides effective margin control and low recurrence rates. Approximately 10% of patients required margins greater than the current recommendations, leading to larger defects and more complex repairs.

INTRODUCTION/BACKGROUND:Nasal reconstruction has important functional and cosmetic considerations, as proper repair of nasal defects is necessary to maintain function of the nasal airway and to recreate the normal appearance of this central facial structure. Cheek advancement flaps provide matched, mobile and highly vascularized tissue for the reconstruction of nasal defects, allowing for the concealment of incisions within natural creases in a one-stage approach. However, cheek advancement flaps are often underutilized for nasal reconstruction because of their difficulty restoring nasal contour. METHODS:We describe reconstruction of 19 nasal dorsal and sidewall defects 0.8 to 3.0 centimeters (cm) in size. We incorporated a periosteal anchoring suture to maintain/restore nasal contour and additionally removed a half standing cone inferior to the defect to prevent encroachment of the nasal ala or alar crease. All patients were evaluated at least 3 months post-operatively. RESULTS:In all patients, we were able to restore concavity of the nasofacial sulcus, preserve the biconvex nasal tips, prevent alar flaring and retraction and conserve the alar groove. All patients had excellent functional and cosmetic outcomes. CONCLUSION/CONCLUSIONS:We believe this modified cheek advancement flap provides functionally and aesthetically superior results and can be considered as a first-line approach for repair of nasal dorsal and sidewall defects in sub selected patients.

LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies implicate LINE-1 in a range of diseases, especially in the context of aging, but without an accurate understanding of where and when LINE-1 is expressed, a full accounting of its role in health and disease is not possible. We therefore developed a method-5' scL1seq-that makes use of a widely available library preparation method (10x Genomics 5' single cell RNA-seq) to measure LINE-1 expression in tens of thousands of single cells. We recapitulated the known pattern of LINE-1 expression in tumors-present in cancer cells, absent from immune cells-and identified hitherto undescribed LINE-1 expression in human epithelial cells and mouse hippocampal neurons. In both cases, we saw a modest increase with age, supporting recent research connecting LINE-1 to age related diseases.

IMPORTANCE/UNASSIGNED:Primary cutaneous squamous cell carcinoma is usually curable; however, a subset of patients develops poor outcomes, including local recurrence, nodal metastasis, distant metastasis, and disease-specific death. OBJECTIVES/UNASSIGNED:To evaluate all evidence-based reports of patient risk factors and tumor characteristics associated with poor outcomes in primary cutaneous squamous cell carcinoma and to identify treatment modalities that minimize poor outcomes. DATA SOURCES/UNASSIGNED:PubMed, Embase, and SCOPUS databases were searched for studies of the topic in humans, published in the English language, from database inception through February 8, 2022. STUDY SELECTION/UNASSIGNED:Two authors independently screened the identified articles and included those that were original research with a sample size of 10 patients or more and that assessed risk factors and/or treatment modalities associated with poor outcomes among patients with primary cutaneous squamous cell carcinoma. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Data extraction was performed by a single author, per international guidelines. The search terms, study objectives, and protocol methods were defined before study initiation. A total of 310 studies were included for full-text assessment. Owing to heterogeneity of the included studies, a random-effects model was used. Data analyses were performed from May 25 to September 15, 2022. MAIN OUTCOMES AND MEASURES/UNASSIGNED:For studies of risk factors, risk ratios and incidence proportions; and for treatment studies, incidence proportions. RESULTS/UNASSIGNED:In all, 129 studies and a total of 137 449 patients with primary cutaneous squamous cell carcinoma and 126 553 tumors were included in the meta-analysis. Several patient risk factors and tumor characteristics were associated with local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death were identified. Among all factors reported by more than 1 study, the highest risks for local recurrence and disease-specific death were associated with tumor invasion beyond subcutaneous fat (risk ratio, 9.1 [95% CI, 2.8-29.2] and 10.4 [95% CI, 3.0- 36.3], respectively), and the highest risk of any metastasis was associated with perineural invasion (risk ratio, 5.0; 95% CI, 2.3-11.1). Patients who received Mohs micrographic surgery had the lowest incidence of nearly all poor outcomes; however, in some results, the 95% CIs overlapped with those of other treatment modalities. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This meta-analysis identified the prognostic value of several risk factors and the effectiveness of the available treatment modalities. These findings carry important implications for the prognostication, workup, treatment, and follow-up of patients with primary cutaneous squamous cell carcinoma. TRIAL REGISTRATION/UNASSIGNED:PROSPERO Identifier: CRD42022311250.