Welcome to this July 2026 review from the Journal of the American Academy of Dermatology, where we cover four items relevant to Mohs and dermatologic oncology practice: a surgical pearl on liquid nitrogen handling, a Game Changer commentary on hydrochlorothiazide and skin cancer risk, a single-institution study on racial disparities in acral lentiginous melanoma treated with Mohs surgery, and a modified Delphi consensus statement on topical five-fluorouracil combined with calcipotriene for actinic keratosis and superficial keratinocyte carcinoma. Let's get into it.

First, a surgical pearl titled "A Novel Container for Liquid Nitrogen for Mohs Tissue Processing," by Debra Keith and Shari Ochoa from Mayo Clinic Arizona. This is a technical note rather than a data-driven study, so there's no clinical question being tested statistically, but the practical problem is well recognized: liquid nitrogen is used in the Mohs lab for flash freezing to minimize ice crystal artifact, and for pretreating adipose-rich specimens to improve section quality. The issue is that liquid nitrogen evaporates quickly at ambient temperature when stored in the standard expanded polystyrene cup used in the cryostat, requiring histotechnicians to repeatedly don and doff protective gear and make multiple refill trips during a Mohs day, which cuts into processing efficiency. The authors propose substituting a vacuum-insulated stainless steel container, specifically a commercial Thermos-brand jar, placed in the cryostat with the lid left off to prevent pressure buildup as the nitrogen slowly evaporates. Because of the vacuum insulation, a single fill at the start of the day reportedly lasts the entire Mohs day without needing to be replenished. The stated advantages are fewer interruptions for technicians, reduced liquid nitrogen waste and associated cost, and improved physical stability in the cryostat compared with polystyrene, lowering the risk of an inadvertent spill. There is no comparative data presented, no measured cost savings, and no formalized time-efficiency analysis, so this should be understood as an anecdotal, experience-based pearl rather than a validated protocol change. The practical takeaway for Mohs labs is straightforward: if your lab wrestles with frequent liquid nitrogen refills and cup instability, this is a low-cost, easily reproducible swap worth trialing internally.

Next is a Game Changer piece by Robert Brodell, summarizing the earlier CNODES study, "Hydrochlorothiazide Use and Risk of Keratinocyte Carcinoma and Melanoma: A Multisite Population-Based Cohort Study," originally published in JAAD in 2023. The clinical question addressed by the original study was whether hydrochlorothiazide, a first-line antihypertensive, is associated with increased risk of keratinocyte carcinoma and melanoma. Brodell's commentary distills the practice-changing message: patients treated with hydrochlorothiazide for longer duration or with higher cumulative doses have keratinocyte carcinoma risk roughly one and a half times expected. No confidence intervals or granular subgroup data are provided in this commentary itself, since it's a narrative reflection rather than a re-analysis, so for precise effect estimates and dose-response detail, the original 2023 CNODES paper should be consulted directly. The takeaway for surgical practice is straightforward and immediately actionable: obtaining a thorough medication history, specifically identifying hydrochlorothiazide use and its duration, should prompt more explicit counseling on sun protection and sun avoidance, and may reasonably heighten your index of suspicion for keratinocyte carcinoma in long-term users presenting for skin checks or biopsy.

Third, "Perioperative Racial Disparities in Patients with Acral Lentiginous Melanoma Undergoing Mohs Micrographic Surgery: A Single-Institution Retrospective Cohort Study." This addresses whether perioperative disparities in treatment timeliness and outcomes persist for people of color undergoing Mohs surgery for acral lentiginous melanoma, a melanoma subtype that disproportionately affects people of color and is associated with delayed diagnosis and more advanced disease at presentation. The design was a retrospective matched cohort study at a single academic center spanning 2006 to 2023, comprising 86 patients total, with 43 people of color and 43 non-Hispanic white patients matched one-to-one by sex and by age within five years. Within the people-of-color group, 60.5% identified as Black or African American, 9.3% Asian, 2.32% Native American or Alaskan Native, 6.98% some other race, and 20.9% Hispanic or Latinx ethnicity. The primary endpoint was time from biopsy to first Mohs surgery, with insurance type included as a covariate; secondary outcomes included pre- and post-operative defect size, Breslow depth, melanoma in situ versus invasive status, number of Mohs stages, digital amputation rate, and graft utilization.

The key finding: people of color experienced significantly longer time to surgery, with a median of 48 days, interquartile range 30 to 72 days, compared with 34 days, interquartile range 20 to 45 days, in non-Hispanic white patients, a difference reaching statistical significance at P equals .016. In adjusted multivariable linear regression, classification as a person of color remained independently associated with increased time to surgery, with a beta coefficient of 20.9 days, standard error 10.45, ninety-five percent confidence interval 0.4 to 41.4, P equals .049; note that value is right at the threshold of significance. Insurance type, by contrast, was not independently associated with delay, beta coefficient 12.42 days, standard error 10.56, ninety-five percent confidence interval negative 8.3 to 23.1, P equals .82.

Markers of disease severity were also greater among people of color. Pre-operative defect size averaged 9.12 square centimeters versus 3.48 square centimeters in non-Hispanic white patients, P equals .004. Post-operative defect size averaged 28.7 square centimeters versus 10.6 square centimeters, P equals .008. Graft use for reconstruction was required in 44.2% of people-of-color patients versus 18.6% of non-Hispanic white patients, P equals .038. Breslow depth averaged 1.12 millimeters versus 0.63 millimeters, P equals .022. Despite these differences, the number of Mohs stages was essentially identical between groups, median 1, interquartile range 1 to 2 in both, P equals .945; digital amputation rates were similar, 20.9% versus 18.6%, P equals 1.00 by Fisher's exact test; and the proportion of melanoma in situ versus invasive disease did not differ significantly, 62.8% versus 67.4% in situ, P equals .651.

The authors interpret the larger defects, higher graft utilization, and greater Breslow depth as most likely reflecting more advanced disease at the time of treatment rather than any difference in surgical technique or Mohs efficiency, since staging and amputation rates were comparable between groups. Limitations explicitly noted include the retrospective single-center design, limited statistical power for subgroup analyses within the heterogeneous "people of color" category, lack of baseline tumor measurements at the time of biopsy, which precludes distinguishing progression during delay from more advanced disease at initial presentation, and the fact that the cohort only captures patients who successfully reached Mohs surgery, potentially underestimating the true disparity if people of color face greater barriers to specialty referral in the first place. For surgical practice, the takeaway is that even within a population that successfully accessed Mohs surgery, meaningful delays in time to surgery and greater tumor burden persist for patients of color, reinforcing the need for expedited referral pathways and heightened clinical suspicion for acral lentiginous melanoma across skin tones, independent of insurance status.

Fourth, "Topical Combined 5-Fluorouracil and Calcipotriene for Actinic Keratosis and Superficial Keratinocyte Carcinoma: Modified Delphi Expert Panel Recommendations from the International Immunosuppression and Transplant Skin Cancer Collaborative," or ITSCC. The clinical question here is how to standardize use of combined topical five-fluorouracil and calcipotriene, abbreviated 5-FU/C, for actinic keratosis, squamous cell carcinoma in situ, and superficial basal cell carcinoma, given that formal treatment guidelines have been lacking despite growing use. This was not a clinical trial but a structured expert consensus process. The background literature review, summarized in the article's table, includes the foundational Cunningham et al 2017 randomized trial in which four days of twice-daily 5-FU/C produced an 87.87% reduction in actinic keratoses in the treatment arm of 64 patients versus 26.3% in the vaseline-plus-5-FU control arm of 65 patients at 8 weeks post-treatment, with site-specific reductions of 87.8% on the face, 76.4% on the scalp, 68.8% on the right upper extremity, and 79% on the left upper extremity, all significantly greater than controls. A post-hoc analysis by Azin et al in 2022 showed even greater regional reductions on the face, 93.4% on the forehead and 94.8% on the temples, compared with 83.4% on the scalp and 69.7% on the forearm. The Oka et al 2025 trial, using six days of twice-daily 5-FU/C, reported 8-week reductions of 95% on the face, 82% on the scalp, 65% on the right upper extremity, and 68% on the left upper extremity. For keratinocyte carcinoma specifically, a prospective trial comparing 7 versus 14 days of twice-daily 5-FU/C in squamous cell carcinoma in situ found 83% and 88% of lesions negative for residual tumor on pathology at over 201 days post-treatment, respectively. A retrospective study of 209 superficial keratinocyte carcinomas across 163 patients reported a 91% overall clinical complete response rate after 5 to 10 days of twice-daily treatment, with comparable response rates in lesions with adnexal extension, 90% in 19 lesions, and in immunosuppressed patients, 89% in 42 lesions, over a mean follow-up of 15 months. Chemopreventive data cited include a post-hoc analysis showing significantly fewer squamous cell carcinomas developing in treated fields versus controls at 3 years, and a small case series of two xeroderma pigmentosum patients showing decreased skin cancer development with repeated 5-FU/C application over multiyear follow-up.

Building on this literature, the ITSCC surveyed 34 clinician members electronically; respondents were predominantly surgical dermatologists, 77%, with more than 5 years of experience in 70%, working in academic settings in 82%, and managing high-risk skin cancer populations in 82%. While 94% of respondents prescribe 5-FU/C for moderate to severe actinic keratosis, only 53% prescribe it for squamous cell carcinoma in situ and only 20% for superficial basal cell carcinoma, and 74% do not prescribe it to immunosuppressed patients at all, reflecting substantial practice variation and caution around off-label use.

The subsequent expert panel comprised 9 dermatologists and dermatologic surgeons with over 5 years of post-training experience or extensive 5-FU/C prescribing experience, using a modified Delphi method with a 70% agreement threshold for consensus. Of 18 preliminary statements across 11 topics, 11, or 61%, reached consensus in the first voting round; 6 required revision and a second round; and one statement was excluded entirely due to insufficient evidence. Final recommendations: for actinic keratosis, twice-daily 5-FU/C for 4 to 5 days on the face and neck, extending to 7 to 10 days for scalp, trunk, and extremities, or for face and neck if an initial shorter course fails; for extensive or rapidly recurring actinic keratosis, repeat treatment courses every 3 to 6 months may be considered based on clinical exam. For squamous cell carcinoma in situ, the panel recommends 7 to 10 days twice daily for face and neck and 10 to 14 days twice daily for scalp, trunk, and extremities. For superficial basal cell carcinoma, the panel endorsed 5-FU/C as an option but explicitly declined to recommend a specific treatment duration given limited data, instead emphasizing close clinical follow-up. Actinic cheilitis recommendations mirror the shorter actinic keratosis regimen, 4 to 5 days twice daily, with counseling on potentially severe local reaction. Notably, the panel recommended no treatment modification based on immunosuppression status, though they advise closer clinical follow-up in immunosuppressed patients to assess whether more prolonged or frequent treatment is warranted. The panel also agreed that choice between separate prescriptions versus a compounded single product should be guided by patient preference and cost considerations.

Limitations acknowledged by the authors are significant: the panel itself was small, only 9 experts, and the underlying evidence base remains largely single-institution, retrospective, and small in sample size, meaning these recommendations should be viewed as pragmatic, experience-informed guidance rather than guideline-level evidence. For surgical oncology practice, the actionable takeaway is that 5-FU/C now has a reasonably defined, expert-vetted dosing framework for actinic keratosis and squamous cell carcinoma in situ that can inform patient counseling and treatment planning, particularly for patients who are poor surgical candidates or have extensive field disease, while use for superficial basal cell carcinoma and in immunosuppressed populations still warrants individualized judgment and close follow-up pending stronger prospective data.

That concludes this July 2026 review. In summary: a simple, low-cost thermos-based modification may improve liquid nitrogen handling efficiency in the Mohs lab; hydrochlorothiazide's roughly one-and-a-half-fold association with keratinocyte carcinoma reinforces the value of medication history and sun-protection counseling; meaningful racial disparities in time to surgery and disease burden persist among acral lentiginous melanoma patients even after they reach Mohs surgery, independent of insurance status; and a new expert consensus offers structured, if still evidence-limited, dosing guidance for topical 5-fluorouracil plus calcipotriene across actinic keratosis and superficial keratinocyte carcinoma. Thanks for listening.