Faculty Bibliography

BACKGROUND:Merkel cell carcinoma (MCC) is a highly aggressive cutaneous malignancy. Guidelines recommend surgical excision with histologically negative margins for clinically node-negative disease. Adjuvant radiation therapy (aRT) is recommended for positive margins; however, its ability to offset the adverse impact of residual microscopic disease remains uncertain. OBJECTIVE:Evaluate the association between surgical margin status and oncologic outcomes among patients treated with excision and aRT. METHODS:Using the National Cancer Database (2004-2022), the authors identified patients with cN0 MCC who underwent excision followed by aRT with documented margin status. Multivariable logistic regression assessed predictors of regional lymph node metastasis, and Cox modeling evaluated all-cause mortality. RESULTS:Among 7,510 patients, 11.7% had positive surgical margins. Margin positivity was more common in older patients, head and neck tumors, and higher T-stage disease. Positive margins were independently associated with increased odds of regional lymph node metastasis (aOR 1.57, 95% confidence interval CI 1.24-1.99; p < .001) and higher all-cause mortality (HR 1.60, 95% CI 1.43-1.78; p < .001). CONCLUSION/CONCLUSIONS:Their findings suggest that positive surgical margins are an adverse prognostic factor despite aRT. Achieving histologically negative margins remains an important prognostic consideration in the management of MCC.

BACKGROUND:Cutaneous squamous cell carcinoma exhibits a significant disease burden due to local relapses and metastasis. Despite advances in prognosis, little evidence exists on prognostic factors of early and late relapse, which could provide more personalized management and follow-up schedules. METHODS:We conducted a multicenter retrospective cohort study including 23,166 cases of cutaneous squamous cell carcinoma. Patients were categorized into those with early recurrence (≤4 months), late recurrence (>24 months), and no recurrence. Risk factors and tumor characteristics were analyzed to identify patterns associated with early and late relapses. RESULTS:Some risk factors show a different impact depending on the type of recurrence and its timing. Lymphovascular invasion (subdistribution hazard ratios [SHR] = 3.01) and large caliber and deep perineural invasion (SHR = 2.55) show a statistically significant association with early locorregional metastasis, losing impact with time. Poor differentiation shows impact early (SHR = 3.26) and late (SHR = 4.63), with less relevance from 4 to 24 months (SHR = 1.68). Other features keep a similar impact along the whole period. LIMITATIONS/CONCLUSIONS:Retrospective cohort study. CONCLUSIONS:Lymphovascular invasion and large caliber and deep perineural invasion are risk factors associated with early locorregional metastasis and should encourage nodal staging at diagnosis. Poor differentiation keeps importance beyond 24 months, and longer follow-up might be recommended in patients with this feature.

BACKGROUND:Current staging systems for head and neck cutaneous squamous cell carcinoma (HNCSCC), such as AJCC8 and BWH, often fail to adequately stratify high-risk patients, particularly due to the exclusion of important biological and host factors. This study aimed to identify independent prognostic factors for HNCSCC outcomes in the largest multi-institutional retrospective series to date. METHODS:De-identified data from 8,610 primary HNCSCC tumors, treated with curative intent surgery across multiple international centers, were analyzed. Outcomes included local recurrence (LR), locoregional metastasis (LM), distant metastasis (DM), and disease-specific death (DSD). Multivariable Fine-Gray subdistribution hazard regression models with robust standard errors clustered at the patient level were fitted to generate exploratory hypotheses regarding independent hazard determinants. RESULTS:During a median follow-up of 31.4 months (IQR 14.2-52.8), the cumulative incidence was 3.3% for LR, 2.7% for LM, 0.5% for DM, and 1.2% for DSD. Multivariable analysis confirmed that tumor diameter, poor differentiation, deep invasion, and large-caliber perineural invasion (LCPNI) were the strongest predictors, being significantly associated with at least three of the four outcomes. Notably, factors currently excluded from or weighted differently in staging systems also proved critical: Immunosuppression was significantly associated with LR (SHR 2.03) and DSD (SHR 1.70); and lymphovascular invasion (LVI) was independently associated with LM (SHR 3.00). Poor differentiation demonstrated high prognostic impact, being a significant predictor for all four endpoints. CONCLUSION/CONCLUSIONS:Tumor diameter, poor differentiation, deep invasion, LCPNI, immunosuppression status, and LVI are the most critical independent factors for HNCSCC prognosis. Our multi-institutional data provide a robust framework for hypothesis generation, highlighting that incorporating host biological features and non-anatomic variables could significantly refine future staging system discussions.

IMPORTANCE/UNASSIGNED:There is no consensus on staging and surveillance imaging for cutaneous squamous cell carcinoma (CSCC). Although imaging has been shown to affect management, broad recommendations from the National Comprehensive Cancer Network have led to variability in clinical practice. OBJECTIVE/UNASSIGNED:To develop multidisciplinary consensus recommendations on the use of staging and surveillance imaging of localized CSCC. EVIDENCE REVIEW/UNASSIGNED:A multidisciplinary expert panel across academic and clinical practice settings convened a Delphi consensus, with 3 iterative survey rounds from January to June 2025. Data were analyzed from February 2025 to January 2026. Eligibility defined by at least 1 to 2 CSCC publications during the previous 5 years, involvement in a relevant clinical trial, experience treating at least 3 patients monthly with CSCC, and/or 5 years or longer of clinical practice. Fifty-four experts were invited and 45 (83%) completed all 3 rounds and were included in the final analysis. Structured Delphi surveys evaluated clinical scenarios, imaging modalities, and surveillance strategies for CSCC. Consensus and near-consensus recommendations were generated, defined as 80% or greater and 70% to 79% agreement, respectively. FINDINGS/UNASSIGNED:The 45 participants (21 female individuals [47%] and 24 male individuals [53%]; 14 Asian individuals [31%], 1 multiracial individual [2%], and 30 White individuals [67%]) consisted of dermatology (15 [33%]), medical oncology (7 [16%]), radiation oncology (9 [20%]), radiology (9 [20%]), surgery (3 [7%]), and otolaryngology specialists (2 [4%]). The Delphi panel recommended staging and surveillance for CSCCs with at least a 15% risk of metastasis. Consensus or near consensus was reached to recommend staging and surveillance imaging for tumors with a concern for metastasis, bone invasion, invasion beyond subcutaneous fat, large-caliber nerve invasion, or a diameter of 4 cm or larger or the combination of tumors with poorly differentiated histology and any of the following: diameter of 2 cm or larger, lymphovascular invasion and subcutaneous fat invasion, or lymphovascular invasion and small-caliber perineural invasion. Computed tomography imaging was the preferred modality for nodal staging (38 [84%]) and surveillance (35 [78%]). For surveillance duration, consensus was reached to provide imaging for at least 2 years, and near consensus was reached for at least 3 years. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study provides an expert consensus-based framework to standardize imaging in localized CSCC that may inform future guidelines.

Onychopapilloma (OP) is a benign nail unit tumor of the distal nail matrix and nail bed that typically presents as solitary longitudinal erythronychia with distal subungual hyperkeratosis and focal onycholysis. Atypical OP is a newly recognized and evolving concept in dermatopathology. Herein, we present a histopathologically-proven atypical OP with a classic clinical appearance that developed during pregnancy. A 37-year-old Gravida two Para one woman presented with a red longitudinal band on the left thumbnail that appeared during the first trimester of an uncomplicated pregnancy. The lesion was asymptomatic; however, it was gradually increasing in size, prompting a longitudinal excisional biopsy of the lesion post-partum. Histopathologic evaluation of the nail unit revealed common features of an OP, including acanthosis and papillomatosis of the nail bed with focal matrix metaplasia. There were focal areas of cytologic atypia and mitotic figures with corresponding increased suprabasilar Ki-67 expression. The tumor was excised with Mohs micrographic surgery in one stage, and the resulting defect healed with secondary intention. No recurrence was observed at 6-month follow-up. This case expands the current literature on histopathologically-proven atypical OP and describes the novel occurrence during pregnancy.

BACKGROUND:Solid organ transplant recipients (SOTRs) face frequent advanced cutaneous malignancies, yet data guiding systemic therapy are limited. MATERIALS AND METHODS/METHODS:We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review of immune checkpoint inhibitors (ICIs), talimogene laherparepvec (T-VEC), and Sonic Hedgehog Pathway Inhibitors (HPIs) for locally advanced or metastatic cutaneous squamous cell carcinoma, melanoma, Merkel cell carcinoma, and basal cell carcinoma in SOTRs, including a novel case from our institution. Outcomes included tumor response, graft rejection, and graft failure. RESULTS:Among 196 SOTRs treated with ICIs (101 cutaneous squamous cell carcinoma, 83 melanoma, 12 Merkel cell carcinoma), the overall response rate (ORR) was 39.3%, and lack of progression occurred in 58.0%. Graft rejection occurred in 36.9% and graft failure in 22.3%. A higher number of baseline immunosuppressive agents decreased odds of rejection (OR 0.55) and failure (OR 0.38). Tacrolimus was associated with reduced tumor response (OR 0.41), whereas mTOR-based regimens and cemiplimab were associated with fewer transplant rejection. T-VEC was reported in 10 SOTRs with an ORR of 90% and no graft rejection or failure. HPIs in six SOTRs with basal cell carcinoma demonstrated ORR of 83% without graft loss. CONCLUSION/CONCLUSIONS:ICIs provide antitumor activity but substantial graft-related risk, while T-VEC and HPIs show high response rates with no reported rejection.