Welcome back to the journal review. This is our June 2026 rundown from the Journal of the American Academy of Dermatology, and we've got four pieces worth your time today — a JAAD Reviews highlight on chemoprevention and photodynamic therapy, an original study on how we frame risk in decision aids for dysplastic nevi, a letter to the editor sparring over ultrasound diagnosis of subungual glomus tumors, and a brief report on combining surgical debulking with intralesional methotrexate for keratinocytic tumors. Let's get into it.

First up is a JAAD Reviews highlights piece by Shari Lipner, which functions as an editorial synthesis pulling together three separate publications — a review on nicotinamide safety and a two-part CME series on photodynamic therapy. Think of this as a framework piece rather than original data. The organizing idea is that cutaneous carcinogenesis is a continuum, from ultraviolet damage all the way to established keratinocyte carcinoma, and our interventions map onto different points along that continuum — some prevent, some treat.

On the chemoprevention side, the piece reviews nicotinamide, emphasizing mechanism first: it enhances DNA repair and blunts ultraviolet-induced immunosuppression, which is the proposed basis for its chemopreventive effect. The efficacy data get a nuanced treatment here, and this is worth sitting with, because you've probably had this conversation with patients a hundred times. The original ONTRAC trial showed a meaningful reduction in new nonmelanoma skin cancers, on the order of about one quarter, plus a more modest reduction in actinic keratoses, in immunocompetent high-risk patients. But the follow-up ONTRANS trial — a well-designed phase three randomized placebo-controlled trial specifically in solid organ transplant recipients, arguably the population that needs chemoprevention most — showed no significant benefit at all. That's a substantial gap in the evidence, and the review is appropriately blunt about it: nicotinamide should not be recommended as a blanket, routine intervention. Instead, think individualized use, and be cautious in patients with impaired renal or hepatic clearance, where long-term safety data are still thin even though short-term dosing up to a gram a day appears well tolerated.

The photodynamic therapy half of the piece, drawn from the two-part CME series, walks through mechanism in part one — photosensitizer activation generating reactive oxygen species, selective cytotoxicity, vascular injury, and immune activation, which together seem to explain why photodynamic therapy achieves durable field control rather than just spot treatment. Part two moves to clinical application, and the evidence grade is worth noting explicitly: level one-A evidence for actinic keratoses, with additional efficacy demonstrated for superficial basal cell carcinoma and Bowen's disease. The honest limitations flagged are the ones you already know from clinic — treatment-associated pain and logistical burden.

The takeaway here isn't practice-changing in the sense of new data — there's no new trial to act on. But it's a useful conceptual reset: nicotinamide and photodynamic therapy aren't competing options, they're addressing different biological time points, prevention versus field-directed treatment of existing disease, and patient selection should reflect that rather than defaulting to either one reflexively.

Next, an original study, and this one is squarely relevant to how we counsel patients with dysplastic nevi. This is a randomized A/B testing study out of Oregon Health and Science University, examining how the format of a patient decision aid — quantitative, meaning numeric risk statistics, versus qualitative, meaning verbal descriptors like "low" or "high" risk — affects patient understanding and treatment intent across three levels of dysplastic nevus severity: mild, moderate, and severe.

The gap they're addressing is a real one in our field. Management of dysplastic nevi, especially mild and moderate ones with positive margins, has increasingly moved toward observation, but clinical practice remains inconsistent, and severely atypical nevi remain genuinely controversial given sampling and histopathologic variability concerns. Shared decision-making guidelines say give patients numbers, but the actual risk data for dysplastic nevi come from small retrospective studies with wide confidence intervals — so there's real tension between being transparent and overstating precision you don't actually have.

Methodologically, this is a clean two-by-three factorial design: six hundred US adults recruited through an online platform, randomized to view either a quantitative or qualitative decision aid, and separately randomized to one of three hypothetical severity scenarios. Why crowdsourced hypothetical vignettes rather than actual patients facing an actual diagnosis? The paper doesn't spell this out explicitly, but my read is that this lets you isolate the framing variable cleanly, in a large enough sample to detect modest effects, without the ethical and practical complications of manipulating risk communication in patients with a real, anxiety-provoking diagnosis. The tradeoff, obviously, is generalizability, which we'll come back to. The numeric risk tiers themselves were developed with a multidisciplinary panel and rounded to clean whole-number bands — under one percent for mild or moderate, and two to five percent for severe — reflecting upper bounds of published ranges, which is a sensible compromise between honesty about uncertainty and clarity for a lay audience.

On results: quantitative framing modestly but significantly improved self-reported understanding, and also improved decision confidence and lowered perceived melanoma risk, both for monitoring and for excision. But — and this is the headline finding — none of that translated into a difference in actual treatment intent. Roughly half of participants in both arms said they'd choose excision, regardless of whether they'd seen numbers or words. What did move the needle on treatment intent, dramatically, was the severity label itself: intent to excise rose from about one third with a mild label, to four in ten with moderate, up to roughly seven in ten with a severe label. That's a large, clinically obvious gradient, and it was statistically robust. Satisfaction, interestingly, was uniformly high — around ninety out of one hundred — regardless of format or severity, suggesting patients don't necessarily know what they're missing when they get a less numerically precise aid.

The authors' honest limitation set here matters: this is a hypothetical vignette study in a general online population, not real patients with real biopsy results sitting in your office, so how this translates to actual clinical encounters is unproven. It's also worth noting that despite high comprehension scores, roughly a third of participants chose a management path diverging from expert consensus recommendations, which the authors frame as evidence that personal values, not just information delivery, are driving these choices.

So what do you actually do with this. I'd call the core message practice-relevant, though implemented carefully: better risk communication format alone will not necessarily change what patients choose to do, so if your goal is aligning patient choice with evidence-based management, framing tweaks to your decision aid are necessary but not sufficient. The severity label is doing enormous psychological work independent of the actual numeric risk behind it — which means how you name the pathology to the patient may matter more than the risk statistic you attach to it, and it's worth being deliberate about that language, especially for mild and moderate dysplastic nevi where the label "severe-sounding" terminology might be driving unnecessary excisions beyond what the biology supports.

Now to a letter to the editor, so no methods or results section here in the traditional sense — this is a critical response synthesizing evidence around a recently published retrospective study on high-frequency ultrasound for diagnosing subungual glomus tumors. The original study by Shan and colleagues had looked at sixty-five suspected cases and highlighted two ultrasound findings, the stem sign and cup-shaped bone remodeling, as diagnostic aids.

The letter writers, including Shari Lipner's group, raise a specificity concern: those ultrasound findings were reported at similar rates whether or not there was pathologic confirmation, and more than half the original cohort — thirty-six of sixty-five tumors — lacked histopathologic confirmation at all. They bring their own prior single-center data to bear here, a series of thirty patients where over a third of clinically suspected glomus tumors turned out, on excision, to be something else entirely, most often leiomyoma. That's the crux of their critique — sensitivity might be reasonable, but nobody has shown these ultrasound signs actually discriminate glomus tumors from other subungual lesions with similar imaging characteristics.

They also flag a discrepancy in the so-called stalk sign, the dominant connecting vessel — present in about a third of Shan's cohort versus nearly six in ten in another published series — and note that classic symptomatic triad of pain, cold sensitivity, and pinpoint tenderness is unreliable, present in only a minority of biopsy-proven cases in their own data, meaning symptom-based screening alone risks delayed diagnosis.

There's also a useful technical point buried in here for anyone doing nail unit imaging: magnetic resonance imaging has real limitations below three millimeters, while high-frequency ultrasound has been reported to detect tumors as small as two millimeters — though the letter is careful to say there's no established uniform approach yet for these very small lesions.

The practical takeaway is modest but real: high-frequency ultrasound is a useful, cost-effective adjunct for subungual tumor workup and surgical planning, but treat it as sensitivity-favoring rather than diagnostic in isolation, particularly for small lesions or atypical presentations, and don't let a reassuring ultrasound pattern substitute for histopathology when the clinical picture is ambiguous.

Last, a brief report — a retrospective cohort, single academic center, looking at a combination protocol of surgical debulking followed by intralesional methotrexate for keratinocytic tumors, specifically squamous cell carcinoma, squamous cell carcinoma in situ, and keratoacanthoma. The clinical rationale up front is one you'll recognize immediately: patients who aren't great surgical candidates, or lesions sitting in cosmetically sensitive locations, need an alternative to standard excision, and intralesional methotrexate has been proposed before but without a consistent protocol.

This cohort covers one hundred sixty-eight lesions in one hundred thirty-six patients over about six years. The protocol itself is refreshingly concrete, which is really the contribution here — debulk via shave, curettage, or cautery under local anesthesia, then inject methotrexate at the base weekly for three weeks, with dosing tied to lesion size: a lower dose for lesions under one and a half centimeters, double that above, and a ceiling total dose per visit when treating multiple lesions at once.

Results: an overall resolution rate of ninety-five percent without needing reinjection or surgical excision, which is a genuinely strong number for an office-based, surgery-sparing approach. Recurrence rates were highest for squamous cell carcinoma, in the range of one in seven, lower for squamous cell carcinoma in situ at under one in ten, and lowest for keratoacanthoma at one in twenty. The one signal worth flagging for anatomic planning is that head and neck squamous cell carcinomas recurred far more often than the rest of the cohort — roughly half — compared to single-digit recurrence for in-situ disease and keratoacanthoma in the same location. Tolerability was good: no systemic toxicity or hospitalizations, and the only complication was cellulitis in a small handful of lesions, resolved with oral antibiotics and a treatment pause.

The authors are upfront about the limitations, and they're the ones you'd expect from this design: retrospective, no control arm, and follow-up that's short relative to the natural history of squamous cell carcinoma, so durability of response beyond the study window is unknown.

Where does this land practically? I'd call it interesting and potentially useful rather than practice-changing in the sense of replacing surgery as a first-line approach — this is not a randomized comparison against standard excision or Mohs, and recurrence in head and neck squamous cell carcinoma specifically was substantial enough that I wouldn't reach for this protocol there without real reservations. But for genuinely poor surgical candidates, or in-situ and keratoacanthoma-type lesions where the biology is more forgiving, this gives you a standardized, reproducible dosing protocol where before there was mostly ad hoc practice — that standardization itself has real value, and it sets up the randomized trial the authors themselves say is needed next.

That wraps our four articles for this June issue — a conceptual bridge between chemoprevention and photodynamic therapy, a sobering look at how little framing changes actual patient choices in dysplastic nevi management, a specificity challenge to ultrasound diagnosis of glomus tumors, and a pragmatic debulking-plus-methotrexate protocol for patients who need an alternative to standard excision. Thanks for listening, and we'll see you next month.