Welcome to this October twenty twenty-six review of the Journal of the American Academy of Dermatology. We've got four pieces this time — three of them are JAAD Game Changer columns, which are short narrative reflections written by an invited commentator about an article that previously ran in the journal, so I'll treat those for what they are: concise clinical takeaways rather than full methods walkthroughs. The fourth is a proper brief report with its own data, so we'll spend more time there. Let's get into it.

First up, a Game Changer piece on five-fluorouracil five percent cream for squamous cell carcinoma in situ, reflecting on factors that affect treatment response. The clinical problem here is a familiar one — you've got a patient with biopsy-proven squamous cell carcinoma in situ who either can't or doesn't want surgery, and you're trying to decide whether topical five-fluorouracil is a reasonable alternative, and if so, for whom. The commentary highlights two practical variables from the original study: duration of treatment and tumor size. Response was meaningfully better when five-fluorouracil was used for at least four weeks, and when the lesion was under two centimeters. Below that duration or above that size, you're less likely to get a durable response with cream alone. The other notable finding, and arguably the more interesting one for our population, is that immunosuppression did not appear to blunt the clinical response. That matters because a lot of the patients we're selecting for field therapy or topical therapy over surgery are exactly the organ transplant recipients or chronically immunosuppressed patients where you might assume impaired response — and this suggests you don't need to write off topical five-fluorouracil in that group. The practical takeaway is straightforward and genuinely useful for informed consent: if you're going to try five-fluorouracil for squamous cell carcinoma in situ, commit to at least a month of treatment, reserve it for smaller lesions under two centimeters, and don't let immunosuppression alone push you away from offering it. This is a nice case of a paper giving you concrete numbers to quote a patient rather than a vague sense that "topical treatment sometimes works."

Second is a Game Changer on factors associated with residual tumor at the time of Mohs micrographic surgery for basal cell and squamous cell carcinomas. This one speaks directly to a conversation we all have constantly — the patient who asks why they need Mohs surgery when the biopsy site looks completely clear. The original study quantifies exactly what's still there despite a reassuring clinical exam. Sixty-eight percent of basal cell carcinomas had residual tumor identified at the time of Mohs surgery, and forty-one percent of squamous cell carcinomas did as well, even though there was no visible clinical evidence of residual cancer going into the case. The factors that increased this likelihood were male sex, high-risk anatomic locations, smaller biopsy size, and larger original tumor size — which lines up with biological intuition: a small superficial biopsy sampling a large tumor is more likely to leave disease behind than a generous biopsy of a small lesion. The practical value here is almost entirely in the informed consent conversation. When a patient pushes back on the necessity of surgical clearance because "the spot's not there anymore," you now have two clean numbers to cite — roughly two in three basal cell carcinomas and two in five squamous cell carcinomas still harbor tumor despite an unremarkable clinical exam — and you can tailor your confidence in that statement based on their sex, tumor location, biopsy size, and original lesion size. This isn't practice-changing in the sense of altering what you do, since most of us are already doing Mohs regardless of clinical appearance, but it meaningfully strengthens the evidence base behind that recommendation when a patient questions it.

Third is a Game Changer on ribonucleic acid analysis of tape strips to rule out melanoma in lesions that are clinically concerning for cutaneous malignant melanoma — this one's explicitly framed as a diagnostic study, so it's worth pausing on the test characteristics themselves rather than just the bottom line. The test uses a noninvasive adhesive tape strip to pull ribonucleic acid from the stratum corneum and look for a molecular signature associated with melanoma, applied to lesions that already look clinically worrisome enough that a biopsy is being considered. The commentary reports a sensitivity of one hundred percent and a specificity of thirty-two percent. It's worth teaching the logic here because this pairing of numbers is not a flaw, it's the point. A test with sensitivity at or near one hundred percent, when negative, effectively rules a diagnosis out — the mnemonic some of you will remember is "SnNout," a highly sensitive test, when negative, rules out disease — because a true melanoma is essentially never going to slip through as a false negative. The tradeoff is specificity, which here is low at thirty-two percent, meaning a lot of lesions that are ultimately benign will still test positive and need to go on to biopsy anyway. So this is not a test that tells you who has melanoma — it's a test that tells you, with a high degree of confidence, who does not. The commentary's framing is that this lets you confidently avoid biopsy in roughly one in three pigmented lesions that would otherwise have gone under the blade, while accepting that a positive result doesn't resolve anything and still routes the patient to biopsy. The author's take, and I'd agree, is that this is mature enough evidence to begin using selectively now — not as a replacement for biopsy on anything concerning, but as a triage tool to spare a meaningful subset of patients an unnecessary surgical procedure, particularly useful in lower-suspicion lesions, cosmetically sensitive sites, or patients who are poor surgical candidates.

Now the main course — a retrospective cohort study on the management of post-procedure eruptive keratoacanthomas, and this is a brief report with genuine original data worth spending real time on. The clinical problem: keratoacanthomas that erupt at or near a procedure site within a year of surgery are a recognized but poorly standardized entity. The open question the authors are circling is biological and practical at once — are these lesions actually early invasive squamous cell carcinomas that need aggressive management, or are they more of an exuberant wound-healing or immunologic reaction to trauma that might regress on its own and tolerate a lighter touch?

On methods — and I want to flag this clearly — despite being labeled a retrospective cohort study, this is really a practice-pattern survey of seventy representative members of the American College of Mohs Surgery, asking them to report on their own experience identifying and managing these lesions. That's an important distinction from a chart-level retrospective cohort, and it shapes how much weight you should put on the numbers. The authors used a validated, previously published method for assembling a "representative" cohort of Mohs surgeons for exactly this kind of survey work, which is a reasonable way to get a broad practice snapshot without the logistical burden of pooling charts across dozens of institutions. The one methodological detail worth teaching here is how they aggregated the responses — they used weighted averages, weighting each surgeon's answers by their self-reported volume of keratoacanthoma cases. The logic is simple but important: if you just averaged every respondent's percentage equally, a surgeon who's only seen two of these lesions in their career would count exactly as much as a surgeon who's managed two hundred, which would let low-experience, potentially idiosyncratic answers dilute the signal from your most experienced observers. Weighting by volume is essentially a crude proxy for giving more statistical trust to the respondents with the most information, the same instinct behind weighting any pooled estimate by sample size. It's a reasonable fix, but it's still built on self-report and recall rather than verified chart data, so keep that caveat running underneath everything that follows.

On to results. Respondents reported eruptive keratoacanthomas following about two and a half percent of squamous cell carcinomas treated with Mohs surgery or excision, compared with about one percent of those treated with destruction — so there's a real signal that more aggressive surgical modalities carry a higher rate of this reactive eruption than lighter destructive techniques, which fits a trauma- or wound-healing-driven mechanism. Anatomically, these lesions were heavily concentrated on the lower extremities, accounting for roughly three in four cases, with the upper extremity a distant second and the trunk and head and neck accounting for only a small fraction — consistent with what we already know about delayed or complicated wound healing being more of a problem on the legs. Diagnostically, about two-thirds of the time these were identified on clinical exam alone, while just over a third underwent biopsy — and when biopsy was done, the pathology came back as squamous cell carcinoma in a slim majority, about fifty-four percent, versus keratoacanthoma in the remainder. That near coin-flip split is really the crux of the clinical dilemma this paper is circling: even pathology doesn't cleanly separate these into a reassuring "benign reactive" bucket, which argues for a reasonably low threshold to biopsy and a cautious default toward treating these as potential squamous cell carcinoma until proven otherwise.

On treatment, intralesional five-fluorouracil was the most commonly used approach at about six in ten cases, followed by Mohs surgery at roughly one in four, with intralesional corticosteroids, intralesional methotrexate, electrodesiccation and curettage, shave removal, and full-thickness re-excision each used in small minorities. In terms of effectiveness, intralesional five-fluorouracil and Mohs surgery were essentially comparable, with complete clinical resolution by three months in about seven in ten cases for five-fluorouracil and just under seven in ten for Mohs. Everything else — corticosteroids, methotrexate, electrodesiccation and curettage, shave removal, re-excision — clustered down in the single digits for three-month resolution, which is a pretty stark gap and worth sitting with.

On discussion and limitations, the authors are appropriately cautious about over-interpreting that gap. This is not a randomized comparison — surgeons are presumably reaching for intralesional five-fluorouracil or Mohs surgery preferentially for lesions they already judge to be more classically keratoacanthoma-like or more amenable to resolution, while reserving corticosteroids or methotrexate for more refractory or atypical presentations, which would make those lower resolution numbers reflect patient selection as much as treatment efficacy. The whole dataset also rests on surgeon recall and perception of "resolution" confirmed only by clinical exam, not by any standardized or blinded outcome assessment, and there's no real denominator cohort of actual patients being tracked prospectively. The authors also note that observation alone was rarely used, and when it was, continued growth often prompted a switch to active treatment — which they reasonably attribute to post-procedure eruptive keratoacanthomas being perceived as more likely to represent invasive disease than the garden-variety sporadic keratoacanthoma, reinforcing that higher use of Mohs surgery in this specific population.

For practical takeaways, I'd frame this as useful and actionable, with one caveat. The practice-changing piece is the practical algorithm: when you see multiple nodules erupting at or near a recent surgical site, particularly on the lower extremity, with that classic crateriform rapid-growth appearance, keep squamous cell carcinoma on the differential seriously — pathology came back as carcinoma better than half the time in this series — and lean toward biopsy rather than assuming a benign reactive process. For management, this data supports intralesional five-fluorouracil as a legitimate first-line option, particularly for multiple or clustered lesions where re-excising each one individually is impractical, with resolution rates that look comparable to Mohs surgery itself in this survey. What's interesting but not yet fully actionable is the precise comparative efficacy ranking of the less common modalities — intralesional steroids, methotrexate, electrodesiccation and curettage — since those numbers are almost certainly confounded by which lesions got selected for those approaches in the first place, and this survey design can't sort that out.

That wraps our four pieces for this month — three Game Changer commentaries giving you quotable numbers for patient conversations around topical therapy for squamous cell carcinoma in situ, residual tumor rates before Mohs surgery, and a tape-strip ribonucleic acid test for triaging pigmented lesions, plus a practice-pattern survey giving some real structure to how the field is currently managing post-procedure eruptive keratoacanthomas. Thanks for listening, and I'll see you next issue.