The Facial Artery Perforator Flap.

BACKGROUND: Reconstruction of facial melanoma defects can be challenging. Large defects of the midface, cheek, and nasolabial fold are often reconstructed using a cervicofacial flap which requires significant flap elevation and undermining. Surgeons are often hesitant to commit to such a large reconstruction without definitive pathologic evidence of negative margins. However, local perforator flaps may be used as an alternative to large flaps with less dissection and donor site morbidity and may also allow for more facile re-advancement in the event of a positive margin on final pathology. The goal of this study is to evaluate a perforator flap based on the facial artery to determine if it is a safe and cosmetically favorable option to immediately repair oncologic-related defects on the cheek and midface. METHODS: A retrospective review of all melanoma cases performed by the senior author between January 2016 and December 2021 was conducted. Patients who underwent reconstruction using a facial artery perforator flap were included. RESULTS: Sixteen patients were included in our cohort. The average age was 67.3 years and 53% (n=8) were female. Fourteen patients had the primary defect located on the cheek, 1 from the nasolabial fold, and 1 from the distal nasal sidewall. All patients received immediate reconstruction. Excisional margins ranged from 0.5 to 2 cm. Two patients had positive margins following pathology results with one undergoing treatment with imiquimod and the other opting for re-excision. No complications involving the defect or donor site were reported after an average follow-up time of 113.8 days. CONCLUSION: The facial artery perforator flap is a safe and cosmetically favorable option to immediately repair oncologic-related defects on the cheek and midface.

Merkel Cell Carcinoma: Changing Practice Patterns and Impact on Recurrence-Free and Overall Survival at a Single Institution and Nationally.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Our report describes the evolution of management and characteristics associated with recurrence, disease-specific survival (DSS) and overall survival (OS) in the treatment of MCC. METHODS: A single institution retrospective review of MCC and SEER data to determine factors associated with RFS, DSS, and OS using a multivariable Cox regression on inverse-probability weighted cohorts. RESULTS: One hundred fifty-nine patients were identified with a median age of 75. Of these, 96% were Caucasian and 60% male. Fifty-eight out of 159 (36%) of all patients were deceased with 21/58 (36%) dead from MCC with a median follow-up of 3.1 years. Institutionally, trends over time demonstrated an increased use of immunotherapy with a concomitant decrease in chemotherapy and decreased use of radiotherapy alone. Institutionally and nationally, there has been increased surgical nodal staging. Institutionally, factors associated with shorter DSS included advanced age, active cigarette smoker (p = 0.002), cT2 disease (p = 0.007), and MCC with unknown primary (p < 0.001). Institutionally, factors associated with shorter OS included ages ≥ 75 years (p < 0.001), an immunocompromised state (p < 0.001), truncal primary site (p = 0.002), and cT2 disease (HR 9.59, p < 0.001). CONCLUSION: Changing practice patterns in MCC management have been driven by the adoption of immunotherapy. Our study highlights that competing risks of mortality in MCC patients likely prevents OS from being an accurate surrogate outcome measure to understand factors associated with DSS.

External Tissue Expansion in Complex Extremity Reconstruction.

Skin grafting and flap-based reconstruction have been the conventional treatments for complex extremity wounds. However, these methods can be associated with relatively high complication rates and involve increasing levels of complexity. External tissue expansion has recently emerged as an attractive alternative to its conventional counterparts. It is a technically simple and low-morbidity technique for complex wound reconstruction. This article provides a review of internal and external tissue expansion with a focus on the evolution, indications, and recent successes of external expansion for soft tissue coverage.

Examination of the human motor endplate after brachial plexus injury with two-photon microscopy.

INTRODUCTION: After traumatic nerve injury, neuromuscular junction remodeling plays a key role in determining functional outcomes. Immunohistochemical analyses of denervated muscle biopsies may provide valuable prognostic data regarding clinical outcomes to supplement electrodiagnostic studies. METHODS: We performed biopsies on nonfunctioning deltoid muscles in two patients after gunshot wounds and visualized the neuromuscular junctions using two-photon microscopy with immunohistochemistry. RESULTS: Although the nerves in both patients showed evidence of acute Wallerian degeneration, some of the motor endplates were intact but exhibited significantly decreased surface area and volume. Both patients exhibited substantial recovery of motor function over several weeks postinjury. DISCUSSION: Two-photon microscopic assessment of neuromuscular junction integrity and motor endplate morphometry in muscle biopsies provided evidence of partial sparing of muscle innervation. This finding supported the clinical judgment that eventual recovery would occur. With further study, this technique may help to guide operative decisionmaking after traumatic nerve injuries.

Thumb Amputations in Children: Classification and Reconstruction by Microsurgical Toe Transfers.

PURPOSE: Traumatic amputations of the thumb are rare in children compared with adults, but hand surgeons remain reticent to consider microsurgical reconstruction with toe-to-thumb transfers. This study reports the functional outcomes and complications of children with traumatic thumb amputations who underwent toe-to-thumb reconstruction. METHODS: A retrospective review of children who sustained thumb amputations and whose parents elected for their child to undergo reconstruction by toe-to-thumb transfer was performed. Details of the level of thumb amputation, whether other fingers were also amputated, which toe was transferred on which vascular pedicle, survival of the transfer, and complications, were collected. Opposition, sensation, and growth of the toe-to-thumb transfers was measured. Functional and psychosocial outcomes were evaluated by both the parents and the older children using the Pediatric Outcomes Data Collection Instrument questionnaire. RESULTS: Twenty-one thumb amputations in 19 children between the ages of 2 and 17 years were referred for secondary reconstruction. Ten were isolated thumb amputations and 11 were combined thumb and multiple finger amputations. Two children had bilateral thumb amputations. Twenty-one toe-to-thumb transfers were performed: 14 second toe transfers and 7 great toe transfers (3 great toe and 2 trimmed and 2 Morrison wraparound variations). There were no immediate postoperative reexplorations of the microsurgical anastomoses and all toe transfers survived completely. All children regained pinch and grasp function and sensation. There were no gait problems in the donor feet. CONCLUSIONS: Microsurgical toe-to-thumb transfers should be offered as an alternative option to the traditional techniques of distraction lengthening and pollicization, for posttraumatic thumb reconstruction in children for any level of amputation from just distal to the carpometacarpal joint to the interphalangeal joint. Toe-to-thumb transfer provides length, opposition, and sensation without disturbing ambulation and is associated with excellent psychosocial outcomes as evaluated by both parents and older children. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The Repair of International Clefts in the Current Surgical Landscape.

Cleft lip and palate (CLP) constitute a significant global disease burden. There are two general models that exist to deliver cleft care: surgical missions and comprehensive cleft centers (CCC). While surgical missions offer high quality surgical care to patients who would be unlikely to ever receive treatment, they may fail to provide sustainable solutions. The development of CCC is growing in popularity worldwide. CCC are permanent centers that offer a multidisciplinary team approach to the treatment of cleft lip and palate. Operation Smile has adopted the concept of specialized surgical care centers. These centers are shown to be safe, cost-effective, and provide sustainable solutions for cleft care. The authors discuss some of the benefits and drawbacks of the classic mission-based model and highlight why there may be a paradigm shift towards CCC.

Evaluation of cranial bone transport distraction with and without adipose grafting.

Transport distraction osteogenesis (DO) can be used to autologously reconstitute calvarial defects. The purpose of this study is to histomorphologically interrogate osteogenic formation during cranial transport distraction using a novel device. We also evaluate the effect of fat grafting on the regenerate and soft-tissue stability during distraction. This study was approved by Yale IACUC. Ten male New Zealand white rabbits (3 mo; 3.5 kg) were used (8 treatment, 2 control). A 16 × 16 mm defect was created abutted by a 10 × 16 mm transport disc. The device was fixated anterioposteriorly. Four animals were fat-grafted using 2 mL of subdermal intrascapular fat deposited along the distraction site. Latency (1 d), active distraction (12-14 d) (1.5 mm/d), and consolidation (4 wk) followed. Calcein and xylene orange fluorochromes were injected subcutaneously during and post-distraction to mark sites of bone formation. Following sacrifice, osteogenesis was assessed using microCT, histology, and fluorescence. Treatment animals demonstrated regenerate bone between distracted segments on microCT. MicroCT analysis of non-fat-grafted and fat-grafted animals revealed a mean density of 2271.95 mgHA/ccm and 2254.27 mgHA/ccm (P = 0.967), respectively, and defect bone versus total volume (BV/TV) of 0.0999 and 0.0766 (P = 0.5979), respectively. Controls had minimal reossification. Histologically, mean densities measured 43.63% and 8.19%, respectively. Fluorescence revealed ossification from the callus as well as from dura and periosteum in the cranial defect. Transport distraction is effective to reconstruct critically sized rabbit calvarial defects. Regenerate bone arises predominantly from the callus with contribution from surrounding dura and periosteum. Adipose grafting is well tolerated but does not enhance osseous regeneration.

Skipped sentinel lymph node basin in a patient with forearm cutaneous melanoma: A case report.

Sentinel lymph node biopsy is an important tool in the management of malignant melanoma, particularly in predicting micrometastasis to regional lymph nodes. Cases of secondary drainage to lymph nodes outside of conventional nodal basins and overall unusual lymph node localization have been reported. The present study reports a unique case of a 'skipped sentinel lymph node basin' pattern in a patient with a right forearm malignant melanoma. Lymphatic mapping using cutaneous lymphoscintigraphy revealed localization at the right supraclavicular lymph node, bypassing right axilla localization despite no prior axillary dissection or previous surgery or radiation. This unique pattern outlined in the present report adds to our understanding of disease localization and unique presentations.

Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies. METHODS: We assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018. Using a panel of 62 validated immune-oncology markers, we performed digital spatial profiling using the NanoString GeoMx platform and quantified expression in three tissue compartments defined by fluorescence colocalization (tumor (S100+/PMEL+/SYTO+), leukocytes (CD45+/SYTO+), and non-immune stroma (S100-/PMEL-/CD45-/SYTO+)). RESULTS: We observed higher expression of immune checkpoints (lymphocyte-activation gene 3 [LAG-3] and cytotoxic T-lymphocyte associated protein-4 [CTLA-4]) and cancer-associated fibroblast (CAF) markers (smooth muscle actin (SMA)) in the tumor compartments of pure DMs than mixed DMs. When comparing lymphoid aggregates (LA) to non-LA tumor cores, LAs were more enriched with CD20+B cells, but non-LA intratumoral leukocytes were more enriched with macrophage/monocytic markers (CD163, CD68, CD14) and had higher LAG-3 and CTLA-4 expression levels. Higher intratumoral PD-1 and LA-based LAG-3 expression appear to be associated with worse survival. CONCLUSIONS: Our proteomic analysis reveals an intra-tumoral population of SMA+CAFs enriched in pure DM. Additionally, increased expressions of immune checkpoints (LAG-3 and PD-1) in LA and within tumor were associated with poorer prognosis. These findings might have therapeutic implications and help guide treatment selection in addition to informing potential prognostic significance.

Characteristics and Experiences Associated with Interest in Global Surgery: What Brings US Medical Students to the Field?

INTRODUCTION: An estimated 5 billion people lack access to safe surgical care. Development and nurturing of medical student interest in global surgery can play a part in addressing this need. This study examines characteristics and experiences of medical students in the United States (US) associated with interest in global surgery. METHODS: A cross-sectional survey study of US-based medical students was performed. Student leaders from the Global Surgery Student Alliance were recruited via email and distributed the online survey to peers at their institutions. Responses from students currently training outside of the US were excluded, as were surveys with <80% completion. Descriptive statistics and multivariate analysis were performed with p < 0.05 indicating significance in R (Vienna, Austria). RESULTS: About 708 responses from students at 38 US medical schools were analyzed. 251 students (34.6%) identified as being interested in global surgery. After adjusting for covariates on multivariable regression, demographic factors significantly associated with interest in global surgery were Hispanic/Latino ethnicity (in comparison to Non-Hispanic White/Caucasian, OR = 1.30) and being born outside of the United States (OR = 1.21). Increased interest was also associated with previous clinical experiences in low or middle-income countries (OR = 1.19), public or global health experiences (OR = 1.18), and international service experiences (OR = 1.13). CONCLUSIONS: While many factors may influence student interest in global surgery, previous global health experience and nonclinical global service work are important predictors regardless of background. Our results suggest that medical educators should look to both international clinical and nonclinical collaborations as a means to cultivate and nourish global surgery interest in medical students.

Immunotherapy utilization in stage IIIA melanoma: less may be more.

Background: Immunotherapy agents are approved for adjuvant treatment of stage III melanoma; however, evidence for survival benefit in early stage III disease is lacking. Current guidelines for adjuvant immunotherapy utilization in stage IIIA rely on clinician judgment, creating an opportunity for significant variation in prescribing patterns. This study aimed to characterize current immunotherapy practice variations and to compare patient outcomes for different prescribing practices in stage IIIA melanoma. Study design: Patients with melanoma diagnosed from 2015-2019 that met American Joint Committee on Cancer 8th edition criteria for stage IIIA and underwent resection were identified in the National Cancer Database. Multiple imputation by chained equations replaced missing values. Factors associated with receipt of adjuvant immunotherapy were identified. Multivariable Cox proportional hazards regression compared overall survival across groups. Results: Of 4,432 patients included in the study, 34% received adjuvant immunotherapy. Patients had lower risk-adjusted odds of receiving immunotherapy if they were treated at an academic center (OR=0.48, 95%CI=0.33-0.72, p<0.001 vs. community facility) or at a high-volume center (OR=0.69, 0.56-0.84, p<0.001 vs. low-volume). Immunotherapy receipt was not associated with risk-adjusted survival (p=0.095). Moreover, patients treated at high-volume centers experienced longer overall risk-adjusted survival than those treated at low-volume centers (HR=0.52, 0.29-0.93, p=0.030). Risk-adjusted survival trended toward being longer at academic centers than at community centers, but the difference was not statistically significant. Conclusion: Academic and high-volume centers utilize significantly less adjuvant immunotherapy in stage IIIA melanoma than community and low-volume centers without compromise in overall survival. These findings suggest that this population may benefit from more judicious immunotherapy utilization.

Immunotherapy Initiation at the End of Life in Patients With Metastatic Cancer in the US.

Importance: While immunotherapy is being used in an expanding range of clinical scenarios, the incidence of immunotherapy initiation at the end of life (EOL) is unknown. Objective: To describe patient characteristics, practice patterns, and risk factors concerning EOL-initiated (EOL-I) immunotherapy over time. Design, Setting, and Participants: Retrospective cohort study using a US national clinical database of patients with metastatic melanoma, non-small cell lung cancer (NSCLC), or kidney cell carcinoma (KCC) diagnosed after US Food and Drug Administration approval of immune checkpoint inhibitors for the treatment of each disease through December 2019. Mean follow-up was 13.7 months. Data analysis was performed from December 2022 to May 2023. Exposures: Age, sex, race and ethnicity, insurance, location, facility type, hospital volume, Charlson-Deyo Comorbidity Index, and location of metastases. Main Outcomes and Measures: Main outcomes were EOL-I immunotherapy, defined as immunotherapy initiated within 1 month of death, and characteristics of the cohort receiving EOL-I immunotherapy and factors associated with its use. Results: Overall, data for 242 371 patients were analyzed. The study included 20 415 patients with stage IV melanoma, 197 331 patients with stage IV NSCLC, and 24 625 patients with stage IV KCC. Mean (SD) age was 67.9 (11.4) years, 42.5% were older than 70 years, 56.0% were male, and 29.3% received immunotherapy. The percentage of patients who received EOL-I immunotherapy increased over time for all cancers. More than 1 in 14 immunotherapy treatments in 2019 were initiated within 1 month of death. Risk-adjusted patients with 3 or more organs involved in metastatic disease were 3.8-fold more likely (95% CI, 3.1-4.7; P < .001) to die within 1 month of immunotherapy initiation than those with lymph node involvement only. Treatment at an academic or high-volume center rather than a nonacademic or very low-volume center was associated with a 31% (odds ratio, 0.69; 95% CI, 0.65-0.74; P < .001) and 30% (odds ratio, 0.70; 95% CI, 0.65-0.76; P < .001) decrease in odds of death within a month of initiating immunotherapy, respectively. Conclusions and Relevance: Findings of this cohort study show that the initiation of immunotherapy at the EOL is increasing over time. Patients with higher metastatic burden and who were treated at nonacademic or low-volume facilities had higher odds of receiving EOL-I immunotherapy. Tracking EOL-I immunotherapy can offer insights into national prescribing patterns and serve as a harbinger for shifts in the clinical approach to patients with advanced cancer.

Circulating Tumor Reactive KIR+CD8+ T cells Suppress Anti-Tumor Immunity in Patients with Melanoma.

Effective anti-tumor immunity is largely driven by cytotoxic CD8+ T cells that can specifically recognize tumor antigens. However, the factors which ultimately dictate successful tumor rejection remain poorly understood. Here we identify a subpopulation of CD8+ T cells which are tumor antigen-specific in patients with melanoma but resemble KIR+CD8+ T cells with a regulatory function (Tregs). These tumor antigen-specific KIR+CD8+ T cells are detectable in both the tumor and the blood, and higher levels of this population are associated with worse overall survival. Our findings therefore suggest that KIR+CD8+ Tregs are tumor antigen-specific but uniquely suppress anti-tumor immunity in patients with melanoma.

Disseminating surgery effectively and efficiently in Haiti.

The need for surgical care in Haiti remains vast despite the enormous relief efforts after the earthquake in 2010. As the poorest country in the Western hemisphere, Haiti lacks the necessary infrastructure to provide surgical care to its inhabitants. In light of this, a multidisciplinary approach led by Partners In Health and Dartmouth-Hitchcock Medical Center is improving the access to surgical care and offering treatment of a broad spectrum of pathology. This article discusses how postearthquake Haiti partnerships involving academic institutions can alleviate the surgical burden of disease and, in the process, serve as a profound educational experience for the academic community. The lessons learned from Haiti prove applicable in other resource-constrained settings and invaluable for the next generation of surgeons.

The Aesthetics of Digit Amputation.

Background: The goal of surgery, when treating a patient with a traumatized hand, is to restore function. The importance of the aesthetics on a patient's psychological well-being should also be considered. The biomechanical ideals for creating a useful hand after digit amputation have been defined; however, ideal aesthetic levels for finger amputation have not been elucidated. The purpose of this study was to determine the general population's visual preferences for different levels of digit amputation in the hand. Methods: In all, 310 participants were surveyed to identify preferences of different levels of single digit amputations in dorsal and volar views. A normal hand was digitally manipulated to simulate various levels of digit amputation. The aesthetics of amputation at the distal interphalangeal (DIP) joint, proximal interphalangeal (PIP) joint, metacarpophalangeal (MCP) joint, and ray amputation were compared to one another via rank order. Average rank for each level of amputation for a digit was determined. Results: Amputation at the DIP was favored over all other levels; however, ray amputation was the second most aesthetic, particularly in the middle and ring fingers even when compared to amputation at the PIP level. Conclusion: When presented a choice at which level to perform a completion amputation or a primary amputation of a digit, and functionality at multiple levels of amputation is equivocal, aesthetic outcomes should be considered. Amputation at the DIP joint is preferable, but ray amputation is aesthetically more pleasing than amputation at the PIP or MCP joints in the index, middle, ring, and small fingers.

Combined Tripier and V-Y Advancement Flaps for Reconstruction of Large Lid-cheek Junction Defects.

Reconstruction of lid-cheek junction defects has a known risk of ectropion. Cervicofacial flaps require significant dissection and can still be prone to ectropion. V-Y advancement flaps have been described as less morbid, but their use is limited to moderate-size defects that do not involve the lid margin. The authors present a technique of combined Tripier and V-Y advancement flaps for reconstruction of large defects of the lid-cheek junction involving the lower eyelid. A retrospective review of patients undergoing the authors' technique was performed. A facial artery perforator flap was designed in a V-Y fashion and advanced into the cheek. An orbicularis oculi myocutaneous flap (Tripier flap) was elevated from the upper eyelid and rotated into the lower eyelid/upper cheek to meet the superior edge of the V-Y flap. A separate review of patients undergoing cervicofacial flap reconstruction was also performed. Demographics, operative details, and complications were recorded and compared. This technique was applied to five patients with large-size (19.9 ± 5.6 cm2) defects of the lid-cheek. In all cases, healing was achieved without ectropion, hematoma, infection, dehiscence, flap necrosis, or facial nerve injury. Twenty-four patients separately underwent cervicofacial flap reconstruction for defects of comparable size (15.8 ± 10.7 cm2). Two patients developed ectropion, one patient developed a hematoma, and two patients developed an infection. Combined Tripier and V-Y advancement flaps is a useful technique to reconstruct lid-cheek junction defects. This method allows for the reconstruction of large lid-cheek junction defects that involve the lid margin.

The Treatment of Complex Extremity Wounds Using External Tissue Expansion: A Case Series.

SUMMARY: The goal of wound reconstruction is the approximation of soft tissue and re-establishment of an acceptable appearance with minimal risk of complications. For large wound closure in the extremities, skin graft and flap reconstruction are common treatments but are associated with a variety of complications. Comparatively, tissue expansion can provide the opportunity to reconstruct large wounds with native, durable, and sensate tissue without significant donor site morbidity. External tissue expansion is less invasive and avoids complications associated with internal expansion. The authors treated 11 patients with varying extremity wound types and sizes with an external tissue expansion device. Patient age ranged from 18 to 68 years with an average age of 43.7 years (SD, ± 13.1 years). Average wound surface area was approximately 235 cm 2 (SD, ± 135.3 cm 2 ). Devices were affixed and left for 7 to 11 days before closure of the wounds. Outcomes were assessed at 2 to 36 weeks postoperative follow-up. All wounds were fully closed after treatment without need for secondary reconstructive procedures. No patient experienced major complications. All patients demonstrated intact sensation within the area of reconstruction equivalent to surrounding tissues. External tissue expansion, an excellent treatment option in extremity reconstruction, is efficacious and associated with lower complication rates compared with internal tissue expansion, skin grafts, and flap reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Case report: Metastatic Merkel cell carcinoma presenting seven years after loco-regional disease resection of primary tumor with interval in-transit and nodal metastases.

Merkel cell carcinoma (MCC) is a rare tumor with a high risk of recurrence after definitive therapy; however, the optimal duration of surveillance is unclear. First recurrences typically occur within 3 years. National guidelines recommend that patients undergo physical examination and imaging for surveillance during this time period. However, the duration of surveillance beyond this is not defined. Here, we describe a case of a patient developing a recurrence of MCC 7 years after the primary diagnosis with interval in-transit and regional lymph node metastases 15 months following the treatment of the primary MCC. Such late recurrences are rare, largely not reported, and the risk factors contributing to late recurrences are not well described. This case highlights the possibility of late recurrences of MCC after an initial in-transit and nodal recurrence and underscores the importance of identifying predictors of recurrence that may better guide the duration of surveillance.

Malignant Melanoma in Older Adults: Different Patient or Different Disease?

Objective In this study, we aimed to compare the clinical outcomes between older and younger patients with melanoma and to evaluate for differences in tumor genetic makeup that might explain differences in clinical behavior between older and younger cohorts. Materials and methods A consecutive sample of patients diagnosed with melanoma at a single institution from 1984 to 2019 was categorized by age into younger, middle, and older cohorts. Tumor characteristics, melanoma-specific survival, and recurrence-free survival were assessed while accounting for differential follow-up and death from other causes using Kaplan-Meier analysis with log-rank testing. Results A total of 4378 patients were included in the study. Older patients presented with a higher incidence of T3 and T4 tumors, and a lower incidence of T1 tumors (p<0.001). The same group of patients had a lower nodal positivity at any given Breslow thickness (p<0.01). Melanoma-specific survival was lower for older patients with T2 tumors (p=0.046). There was no difference in recurrence-free survival among all age groups and tumor thicknesses (p>0.05). For patients with a given genetic profile, the melanoma-specific survival and recurrence-free survival were equivalent across ages. BRAF was the most common driver in the younger group, while NRAS and other mutations increased in prevalence as age rose. Conclusions Older adults have decreased melanoma-specific survival for T2 tumors and lower nodal positivity, suggesting a different pattern of metastatic progression. The mutational drivers of cutaneous melanoma change with age and may play a role in the different metastatic progression as well as the differential melanoma-specific survival across all age cohorts.