Welcome back to the journal review. This is your walkthrough of Dermatologic Surgery for January 2026, and we've got four pieces to get through today — a large registry study on penile squamous cell carcinoma margins, a case report on an aggressive cutaneous squamous cell carcinoma arising in pregnancy, an ecological epidemiology study asking whether ultraviolet exposure drives cutaneous leiomyosarcoma, and a practical anatomy-heavy review on vulvar dermatofibrosarcoma protuberans. Let's get into it.

First up is an original study, and it's a good one for anyone who occasionally gets asked to weigh in on genital skin cancer: "Excision of Penile Squamous Cell Carcinoma Is Associated With High Rates of Positive Surgical Margins," out of NYU. The clinical problem here is familiar in shape even if the anatomic site is unusual for most of us. Penile squamous cell carcinoma is rare, organ-sparing surgery is first-line for early lesions because nobody wants to rush to penectomy, but unlike cutaneous squamous cell carcinoma, there's no standardized margin — National Comprehensive Cancer Network guidance allows anywhere from five to twenty millimeters, and Mohs micrographic surgery is listed almost as an afterthought, interchangeable with wide local excision or laser. The gap the authors identify is that nobody has actually characterized positive margin rates after excision of penile squamous cell carcinoma in a large surgical cohort.

Methodologically, this is a retrospective cohort pulled from the National Cancer Database, spanning diagnoses from 2004 to 2019, landing on just over eleven thousand patients. The registry approach here makes obvious sense — this is a disease so rare that you'd never accrue a meaningful prospective cohort at a single center, so a national database is really the only way to get the numbers needed for multivariable analysis. They looked at surgical margin status as the primary outcome and overall survival as secondary, using logistic regression for margin predictors and a Cox model for survival, with covariates chosen by standard information-criterion minimization rather than a hand-picked list — a nice touch that reduces some analyst bias in model building.

Now the results, and these are the numbers worth remembering. Across the whole cohort, thirteen percent of excisions came back with a positive margin. But when you split by surgical approach, organ-sparing surgery — which in this database means local excision or excisional biopsy — carried a positive margin rate of nearly nineteen percent, compared to under ten percent for partial penectomy. That's roughly double the risk, and it held up on multivariable analysis with more than twice the odds of a positive margin for organ-sparing surgery versus partial penectomy, and this was highly statistically significant. Broken down by stage, organ-sparing surgery produced positive margins in about eighteen to twenty percent of in-situ, T1, and T2 tumors — which the authors point out is among the highest positive-margin rate reported for any specialty-site cutaneous malignancy, higher than what's typically quoted for basal cell carcinoma, squamous cell carcinoma, or melanoma excised elsewhere on specialty sites. Preputial tumors were also more likely to come back positive, which the authors suspect reflects patients being treated with circumcision alone rather than a true wide excision. And critically, a positive margin wasn't just a pathology footnote — it was tied to meaningfully worse survival, roughly a fifty percent increase in hazard of death on multivariable analysis, and this held up even after controlling for age, comorbidity, insurance, facility volume, and stage.

On discussion and limitations — the manuscript text available to us cuts off before a full limitations section, but a few caveats are inherent to the design and worth naming even though the authors may address them further. This is registry data, so there's no information on actual millimeter margin width, no data on local recurrence itself, only margin status and survival as a surrogate. There's no central pathology review, no tumor grade in the models as presented, and no ability to assess surgeon specialty or experience — we don't know how many of these organ-sparing excisions were performed by genitourinary surgeons versus dermatologic surgeons, which matters enormously for interpretation. Facility-level clustering and unmeasured selection bias — sicker or larger tumors might have been selected for organ-sparing surgery for reasons not fully captured — also need to be kept in mind.

Practical takeaway: this is genuinely relevant, if not fully practice-changing on its own. It's strong epidemiologic support for what most of us intuited — that non-margin-controlled excision of penile squamous cell carcinoma leaves tumor behind at a rate that would be unacceptable anywhere else on the skin, and that this translates into a survival penalty, not just a cosmetic one. It builds the case for margin-controlled surgery, meaning Mohs, in penile squamous cell carcinoma, particularly for early-stage, organ-preserving candidates where the whole point is to spare tissue without sacrificing local control. What it doesn't do is give us a randomized comparison of Mohs specifically against wide local excision in this disease, so consider this a strong rationale-builder rather than a definitive practice mandate.

Next, a case report: "High-Stage Cutaneous Squamous Cell Carcinoma in a Pregnant Patient," from Washington University. This one's a teaching case about an underappreciated immunosuppressed state — pregnancy itself. A forty-one-year-old woman with no prior skin cancer history developed a rapidly growing erythematous nodule on the thigh at thirty-five weeks' gestation. Biopsy showed a well-differentiated squamous cell carcinoma. She reasonably deferred surgery until after delivery, but in the six and a half weeks between biopsy and her presurgical visit, the tumor grew about ten percent larger, and by the time Mohs surgery was performed eight weeks postpartum, the first stage already showed extensive perineural invasion involving nerves greater than a tenth of a millimeter in diameter. Clearance took four stages, and the tumor was ultimately staged Brigham and Women's Hospital T2b — meaning perineural invasion of a large-caliber nerve plus size at or above two centimeters.

The teaching point the authors emphasize is growth rate: rapid growth for cutaneous squamous cell carcinoma is defined as more than four millimeters per month, and this tumor went from under two centimeters to roughly four centimeters over about four months — vastly exceeding that threshold and signaling a genuinely aggressive biology. Genetic testing was pursued given the unusual behavior in an otherwise healthy young patient, and it turned up a heterozygous FANCM mutation — a Fanconi anemia complementation gene involved in DNA repair at stalled replication forks — present in her germline but interestingly not in the tumor itself. Given her age and this DNA-repair variant of uncertain significance, the radiation oncology team specifically chose electron therapy over photon-based radiation for her adjuvant treatment, to limit low-dose scatter and theoretically reduce the risk of a radiation-induced second malignancy down the road.

The broader message here, and it's a genuinely practical one: pregnancy is a physiologic immunosuppressed state and should be treated as a risk factor for aggressive cutaneous squamous cell carcinoma, not just an inconvenient scheduling problem. The authors cite survey data that roughly eighty percent of dermatologic surgeons alter management because of pregnancy or lactation status, typically by deferring treatment — yet current recommendations favor prompt management of skin cancer during pregnancy. This case is a vivid argument for not letting deferral drift too long, and for favoring Mohs over electrodesiccation and curettage in pregnant patients specifically because of the potential for unrecognized aggressive behavior. It's not a practice-changing statistic, since it's a single case, but it's a useful cautionary vignette for how you counsel pregnant patients and their obstetric teams about timing.

Third, an ecological epidemiology study: "No Association Between Ambient Ultraviolet Exposure and Cutaneous Leiomyosarcoma Incidence in the United States," using linked Surveillance, Epidemiology, and End Results — or SEER — and NASA satellite data. The setup: recent mutational profiling of cutaneous leiomyosarcoma has found classic ultraviolet-signature mutations, the C-to-T substitutions at dipyrimidine sites that we associate with sun-damage-driven carcinogenesis, raising the question of whether ultraviolet radiation is actually an etiologic driver of this rare pilar-smooth-muscle-derived sarcoma. Similar SEER-NASA linkage studies have already been done for cutaneous angiosarcoma and sebaceous carcinoma, so this fills an obvious gap for leiomyosarcoma.

Methodologically, this is an ecological study — meaning they're correlating population-level ultraviolet exposure with population-level cancer incidence, not looking at individual patients' actual sun exposure. That's a real design limitation baked into the method itself, and the authors are upfront about it: ecological findings, positive or negative, can't be assumed to hold at the individual level. Why do it this way anyway? Because you can't feasibly reconstruct individual lifetime ultraviolet dose for a cancer this rare, so linking county-level satellite ultraviolet index data to county-level SEER incidence, sorted into exposure quartiles, is really the only way to test the population-level hypothesis at scale. They used SEER-22 data from 2000 to 2020, identified about fifteen hundred and seventy patients with confirmed cutaneous leiomyosarcoma, and modeled incidence rate ratios across ultraviolet exposure quartiles using Poisson regression.

The result is a clean null. Overall incidence was about a quarter of a case per million person-years, mostly in men, with about half diagnosed before age sixty-five. The incidence rate ratio for ultraviolet exposure was essentially one — no meaningful difference across exposure quartiles, not statistically significant, and this held true when they stratified by age, sex, tumor site, grade, and stage. Nothing moved.

The discussion is actually the interesting part conceptually: there's a disconnect between the molecular signature — which looks sun-damage-driven — and the population-level epidemiology, which shows no geographic ultraviolet gradient at all. The authors' interpretation is that ultraviolet radiation may be one contributing mutagenic process but clearly isn't the dominant population-level driver, and they point to other commonly mutated genes in this tumor, like RB1, TP53, and KDM6B, which can also be altered through ionizing radiation, chemotherapy exposure, or epigenetic mechanisms unrelated to sun exposure. Limitations are the inherent ecological-study caveats — no individual-level causal inference, and static exposure assignment that doesn't account for people moving between high- and low-ultraviolet regions over their lifetime. The strength they lean on is that SEER-22 captures roughly half the US population, giving reasonable statistical power for a tumor this rare.

Practical takeaway: this is interesting, not actionable. It doesn't change how you counsel patients about sun protection in general, and it certainly doesn't change surveillance or treatment of cutaneous leiomyosarcoma. File it under useful biological nuance — a reminder that a positive mutational signature for ultraviolet damage doesn't automatically make ultraviolet exposure the epidemiologic driver of a given tumor.

Last is a review article, and this one is genuinely useful as a preoperative reference: "Vulvar Dermatofibrosarcoma Protuberans: Surgical Planning and Management Considerations for the Dermatologic Surgeon," from Mayo Clinic. Anogenital dermatofibrosarcoma protuberans makes up a small slice of all dermatofibrosarcoma protuberans cases — under four percent — but it carries roughly three times the metastatic risk of the disease elsewhere, and it arises in an anatomically unforgiving location, so the authors set out to build a practical planning guide rather than to answer a discrete research question, and the paper should be heard as exactly that — a synthesis and technique guide, not a study with its own results or limitations section.

They open with the rationale for Mohs over wide local excision here, citing existing literature showing reduced recurrence, lower disease-specific mortality, and improved overall survival with margin-controlled surgery compared to wide excision in this location — which matters because the tissue you're trying to spare includes the clitoris, urethra, and mucosal surfaces. On preoperative planning, they recommend routine MRI before surgery, since imaging outperforms palpation for detecting depth of subclinical extension, and they stress early multidisciplinary involvement — gynecologic surgery, urology, or plastic surgery — whenever imaging suggests deep invasion or proximity to critical structures. There's also a strong emphasis on goals-of-care conversations before the day of surgery, since patients vary in how they weigh complete tumor eradication against preservation of sexual function or urethral continence, and Mohs' real-time nature means that decision to stop or refer for completion excision can come up mid-case.

The anatomy section is the heart of the paper for a working surgeon — detailed cadaveric dissections mapping the pudendal nerve's perineal branch to the labia, the dorsal clitoral nerve supplying the clitoral body and glans, the cluneal nerve territory over the gluteal region, and deep dissections showing the suspensory ligament of the clitoris, the clitoral crura, and the bulbospongiosus and ischiocavernosus muscles — essentially a labeled map of what you risk running into once you go beyond superficial fascia.

On technique, several concrete pearls: tumescent anesthesia for both analgesia and hemostatic vasoconstriction, with liposomal bupivacaine injected after reconstruction to extend postoperative pain control for days; an initial debulking pass processed with vertical sectioning specifically to screen for fibrosarcomatous transformation, which carries worse prognosis and needs to be caught early; complete circumferential peripheral and deep margin assessment as the preferred technique given the tumor's infiltrative growth pattern, sometimes performed in a moat-like fashion with a double-bladed scalpel, which does require a separate horizontal en face assessment of the deep margin since the peripheral technique alone won't capture it. For mapping, they suggest working off a printed photograph of the surgical site rather than a generic diagram, using long-tailed silk sutures as orientation landmarks, and adhesive labels rather than ink for numbering systems that might smear. And they flag a genuinely practical pitfall — that prolonged multi-stage cases can generate a reactive neutrophilic inflammatory response that complicates margin interpretation, something worth remembering when a case is dragging into extra stages. The review also touches briefly on nonsurgical options, namely tyrosine kinase inhibitors, for metastatic or unresectable disease, though the excerpt available to us doesn't go deep into that arm.

Practical takeaway: this is a genuinely useful bedside and pre-op reference rather than a practice-changing trial, and that's fine — it's designed to be a checklist and atlas you'd actually pull up before booking one of these cases, particularly for anyone who doesn't treat vulvar dermatofibrosarcoma protuberans often enough to have the anatomy memorized cold.

That wraps this episode. To summarize the throughline across all four: a large registry study builds a strong case for margin-controlled surgery in penile squamous cell carcinoma without quite proving it in a randomized sense; a single case reinforces that pregnancy-related immunosuppression deserves real respect in aggressive squamous cell carcinoma; an elegant negative ecological study reminds us that a mutational signature doesn't equal a population-level cause; and a detailed anatomic review gives you an actual usable map for one of the more anxiety-inducing sites in our field. Thanks for listening, and I'll see you next month.