Welcome to this July twenty twenty-six review from the Journal of the American Academy of Dermatology. In this episode we're covering four articles: a feasibility study of peer mentorship for facial Mohs surgery patients, a clinical review on cutaneous adverse effects of immunosuppressive agents in solid organ transplant recipients, a published response letter clarifying methodology in a study of radiologic imaging for high-risk cutaneous squamous cell carcinoma, and a retrospective cohort study examining sex and tumor location outcomes in Merkel cell carcinoma. Let's get into it.

Our first article is titled "Buddy Relationships in Dermatologic Excisions for Skin Cancer: A Feasibility Study of One-to-One Peer Mentorship in Patients with Facial Skin Cancers Treated with Mohs Micrographic Surgery," by Alomary, Baker, Taylor, and Mollanazar. The clinical question here was whether a one-to-one peer support program is feasible and whether it improves satisfaction and quality of life in patients undergoing Mohs micrographic surgery for facial skin cancer, a population known to experience quality of life fluctuations around the time of surgery. This was a prospective feasibility study conducted at an academic center between November twenty eighteen and July twenty nineteen. Eleven mentors, previous Mohs patients recruited more than one year after their own surgery, were paired with two mentee cohorts: thirteen presurgical mentees who received peer support before their procedure plus standard counseling, and eleven same-day mentees who received peer support on the day of surgery plus standard counseling. A control group of twenty-five patients received standard counseling alone. Quality of life was tracked using the Skin Cancer Index, administered before surgery, one to two weeks after surgery, and three months after surgery, across three subscales: emotional, social, and appearance-related impact, each scored zero to one hundred.

On key findings: across all three cohorts, total Skin Cancer Index scores were highest at the three-month mark compared with the presurgical and immediate postsurgical time points. Same-day mentees numerically outperformed the other two groups at every time point, reaching a mean total score of eighty-five point one, standard deviation thirteen point four, at three months, compared with sixty-seven point eight for presurgical mentees and seventy-one point eight for controls. However, none of these between-group differences reached statistical significance, with the three-month total score comparison landing at a P value of point one one. Program feedback was favorable, with a mean satisfaction score of five point two out of seven, standard deviation one point one. Notably, there was a significant baseline demographic imbalance, with female representation ranging from thirty-six percent in the same-day mentee group to seventy-six percent in controls, a difference reaching a P value of point zero four.

The clear limitation, acknowledged by the authors, is sample size. With only forty-nine mentees and controls combined, the study was underpowered to detect meaningful between-group differences in quality of life, and the demographic imbalance introduces potential confounding. For surgical practice, the takeaway is that a peer mentorship program integrated around Mohs surgery is logistically feasible and well received, with a signal toward improved quality of life in same-day mentees, but this remains hypothesis-generating. Larger, adequately powered trials are needed before peer mentorship can be considered an evidence-based adjunct to standard perioperative counseling, and future work should aim to identify which patient subsets are most likely to benefit.

Our second article is a clinical review titled "Immunosuppressive Agents in Solid Organ Transplantation: Cutaneous Adverse Effects and Dermatologic Considerations," by Burke, Cabeza, Jaller, and Tang. This is not a primary data study but a practical, agent-specific synthesis aimed at equipping dermatologists to recognize and manage the cutaneous toxicities of induction and maintenance immunosuppression in solid organ transplant recipients. Given that these patients are living longer post-transplant, the cumulative dermatologic burden of chronic immunosuppression is increasingly relevant to Mohs practices managing transplant-related skin cancer.

Working through the induction agents: antithymocyte globulin, a polyclonal antibody causing profound T-cell depletion, is associated with serum sickness in approximately seven to twenty-seven percent of renal transplant recipients, typically presenting seven to fourteen days after first exposure, though it can appear within twelve to thirty-six hours in previously sensitized patients receiving repeat dosing. The authors emphasize that dermatologists should maintain a high index of suspicion for new symmetric urticarial or morbilliform eruptions on the trunk and proximal extremities during this window, since cutaneous findings are often the earliest manifestation. Management is prompt discontinuation and systemic corticosteroids, typically prednisone at zero point five to one milligram per kilogram per day, with plasma exchange reserved for refractory cases. Alemtuzumab, targeting CD52, is more associated with immune reconstitution phenomena such as vitiligo, alopecia areata, or chronic urticaria, generally mild and self-limited. Basiliximab, an interleukin-2 receptor antagonist, carries a three to ten percent incidence of nonspecific pruritic rashes, cysts, herpes reactivation, hypertrichosis, and ulceration.

Among maintenance agents, calcineurin inhibitors are central to long-term dermatologic surveillance planning. Cyclosporine causes hypertrichosis and gingival hyperplasia early in treatment, while chronic use of calcineurin inhibitors increases cutaneous squamous cell carcinoma risk through PI3K-AKT pathway activation, impaired DNA repair, and VEGF-mediated angiogenesis. The authors recommend dermatologic surveillance every six to twelve months, with closer intervals for patients with prior skin cancer or significant actinic damage, and they note that in patients developing multiple or aggressive cutaneous squamous cell carcinomas, transition to mammalian target of rapamycin inhibitors should be discussed with the transplant team. Tacrolimus is linked to diffuse nonscarring alopecia resembling telogen effluvium.

For antimetabolites, mycophenolate mofetil causes a maculopapular rash in up to twenty-six percent of clinical trial participants, generally manageable with topical corticosteroids without drug interruption, and can cause aphthous ulcers managed with dexamethasone rinse and supportive measures. Azathioprine carries a distinct profile: photosensitive dermatitis resembling chronic actinic damage from impaired UVA-mediated DNA repair, and importantly, a dose-independent systemic hypersensitivity syndrome in the first four weeks of therapy that mandates immediate discontinuation and contraindicates rechallenge given its potentially life-threatening course. Long-term azathioprine use markedly increases cutaneous squamous cell carcinoma risk, warranting the same six to twelve month surveillance interval.

Mammalian target of rapamycin inhibitors, sirolimus and everolimus, show a different toxicity signature. Aphthous stomatitis occurs in approximately ten to twenty percent of patients, typically within the first month, and is dose-dependent, requiring serum level monitoring. Acneiform eruptions develop in fifteen to forty-five percent of patients on sirolimus. Most clinically significant for surgical practice, wound-healing complications occur in five to forty-seven percent of patients on sirolimus and six to forty percent of those on everolimus, a critical consideration when planning Mohs reconstruction timing in transplant patients on these agents. The review also highlights the skin and ultraviolet neoplasia transplant risk assessment calculator, referred to as SUNTRAC, as a tool to guide referral timing and surveillance intensity. As this is a review article without its own original cohort or statistical testing, the main limitation is that recommendations are drawn from a heterogeneous evidence base of varying study designs cited throughout, rather than from a single controlled dataset. The practical takeaway for Mohs surgeons is to maintain agent-specific awareness, particularly regarding calcineurin inhibitor and azathioprine-associated squamous cell carcinoma risk, mammalian target of rapamycin inhibitor-associated wound healing impairment relevant to reconstruction planning, and to coordinate closely with transplant teams when adjusting immunosuppression around skin cancer treatment.

Our third piece is a response letter titled "Response to Xie et al, 'Radiologic Imaging in High-Risk Cutaneous Squamous Cell Carcinoma: Clarifying the Role Beyond Selection Bias,'" authored by Wei, Cassard, Fan, Seck, Rodriguez Vazquez, Bena, Stultz, Koyfman, and Vidimos. This is a published exchange responding to critiques of the authors' earlier retrospective cohort study on radiologic imaging in high-risk cutaneous squamous cell carcinoma. The original critique raised concerns about selection bias driving the high rate of positive imaging findings, given that imaged tumors had significantly higher-risk features, including greater diameter, greater depth, and poorer differentiation, compared with the non-imaged cohort.

In their response, the authors concede that the decision to image did reflect real-world clinical suspicion and acknowledge that propensity score matching or multivariable regression would have been the ideal statistical approach, but state that the imaged cohort's sample size presented power constraints that limited feasibility of such adjustment. They clarify that their study's primary objective was to evaluate diagnostic yield and immediate impact on staging and management decisions, not to serve as a survival analysis, and they emphasize that only management changes occurring after and as a direct result of imaging findings were counted, supporting a plausible causal attribution. On the survival data specifically, the authors note that overall survival was comparable between imaged and non-imaged groups despite the imaged cohort having more aggressive baseline tumor characteristics, and they interpret this as a signal that upstaging and resulting management changes may have offset the poorer expected prognosis, while explicitly stating this observation requires cautious interpretation absent multivariable adjustment. They also address the critique regarding underutilization of ultrasonography, noting their study period of two thousand ten to two thousand twelve predated broader adoption of nodal ultrasound for cutaneous squamous cell carcinoma surveillance in the United States, and they support further investigation into modality-specific sensitivity and specificity in contemporary cohorts.

The methodological limitation here is one the authors themselves acknowledge directly: retrospective design without adjustment for confounding by indication, and a likely underpowered imaged cohort for advanced statistical modeling. The practical takeaway for surgical oncology practice is that this exchange reinforces imaging's role in detecting actionable occult disease and prompting real management changes in high-risk cutaneous squamous cell carcinoma, while underscoring that current evidence cannot yet isolate an independent survival benefit from imaging, pending prospective, multi-institutional studies with larger cohorts.

Our fourth article is titled "Sex and Tumor Location Outcomes in Merkel Cell Carcinoma: A Retrospective Cohort Study Utilizing Mayo Clinic Platform," by Amjad, Koblinski, Starghill, Shao, Breinholt, Arpey, Baum, Pirgousis, Dronca, Mangold, Jakub, and Costello. The clinical question was whether sex-based differences in Merkel cell carcinoma prognosis are truly attributable to sex, or whether they instead reflect tumor location distribution and associated biology. This was a retrospective, multicenter cohort study using propensity-matched subgroups, drawing on deidentified electronic health record data through the Mayo Clinic Platform Discover, and it included one thousand ninety-two patients diagnosed with Merkel cell carcinoma in total, with the primary matched analysis performed on one thousand twenty-nine patients.

Key findings: in propensity-matched cohorts of two hundred sixty-six males versus two hundred sixty-six females, males showed significantly worse survival at sixty months, fifty-five point four percent versus sixty-nine point eight percent, P equals point zero zero five, and at one hundred twenty months, forty-one point four percent versus fifty-five percent, P equals point zero zero seven. Critically, there were no significant differences at twelve, eighteen, or twenty-four months between sexes, indicating the previously reported female survival advantage does not hold in the short term. Males were significantly more likely to have Merkel cell carcinoma of the scalp, sixteen point nine percent versus ten point two percent, P equals point zero two three, and to have immunodeficiency, seven point five percent versus two point six percent, P equals point zero one. However, when the analysis was restricted to matched head and neck Merkel cell carcinoma specifically, comparing fifty-five males to fifty-five females, sex-based differences in survival, tumor location, and immunodeficiency all disappeared, suggesting that anatomic location, not sex per se, drives much of the previously observed disparity.

Separately, the combined-sex head and neck cohort, two hundred twenty-eight patients, showed significantly worse short-term survival than the non-head-and-neck cohort, also two hundred twenty-eight patients: eighteen-month survival of seventy-one point two percent versus eighty percent, P equals point zero two four, and twenty-four-month survival of sixty-five percent versus seventy-four percent, P equals point zero three six, though long-term survival differences between these two location-based cohorts were not significant. The head and neck cohort also had significantly higher rates of squamous cell carcinoma overall, twenty point six percent versus thirteen point two percent, P equals point zero three four, and site-specific squamous cell carcinoma of the face, ear, scalp, and lower extremity, each reaching statistical significance.

Limitations include the retrospective design and reliance on propensity matching rather than randomization, and the relatively small subgroup sizes in some matched comparisons, such as the fifty-five versus fifty-five head and neck sex comparison, which may limit power to detect true differences. For surgical practice, the key evidence-based takeaway is that anatomic tumor location, particularly head and neck involvement, appears to be a more important driver of both short-term mortality and squamous cell carcinoma co-occurrence than sex alone in Merkel cell carcinoma, and that any perceived female survival advantage is not present in the first two years after diagnosis, the window during which most recurrences occur. This has direct implications for surveillance intensity and prognostic counseling based on tumor site rather than sex.

That concludes this July twenty twenty-six roundup. Across these four articles, the throughlines for practice are clear: psychosocial interventions around Mohs surgery show promise but need larger trials before adoption; transplant immunosuppression carries agent-specific, time-dependent cutaneous risks that demand tailored surveillance intervals and close coordination with transplant teams; imaging in high-risk cutaneous squamous cell carcinoma provides real, actionable diagnostic and management yield even as survival benefit remains statistically unproven; and in Merkel cell carcinoma, anatomic location rather than sex appears to be the stronger prognostic driver, particularly in the critical first two years. Thank you for listening, and we'll see you next month.