Welcome back to the journal review. This is the February twenty twenty-six issue of the Journal of the American Academy of Dermatology, and we've got three pieces worth your time this month — a two-part continuing medical education review on acral lentiginous melanoma, covering everything from epidemiology through systemic therapy, and then a shorter ethics case column dealing with a genuinely thorny clinical scenario: high-risk cutaneous squamous cell carcinoma in a pregnant patient. Let's get into it.

First up is part one of the acral lentiginous melanoma review, focused on epidemiology, etiology, clinical presentation, and diagnosis. This is a CME review article, not an original study, so there's no methods section to walk through — instead, think of this as the authors synthesizing the current state of evidence on a subtype you already encounter but that the literature has historically lumped in with cutaneous melanoma more broadly.

Acral lentiginous melanoma, or A-L-M, is the rarest subtype of cutaneous malignant melanoma, making up only two to three percent of cases overall, arising on palms, soles, and nail beds. The background problem the authors set up is straightforward but important: because it's rare, and because many datasets don't cleanly separate acral melanoma with lentiginous histology from other acral presentations, our collective understanding is muddier than it should be, and there are no dedicated treatment guidelines.

On epidemiology, the numbers are worth sitting with. Average US incidence is about two per million person-years, but that's notably higher in Germany and Japan, around seven per million, and in Mexico, around four to five per million — though the authors flag these as rough estimates given inconsistent registry reporting of histologic subtype. The more clinically important epidemiologic story is the racial disparity. Acral lentiginous melanoma is the least common melanoma subtype in white patients but among the most common in Black, Hispanic, and Asian patients — accounting for roughly a third of all melanomas in Black patients, compared to around one percent in white patients. And critically, this isn't just a story about later-stage detection. Even after controlling for tumor stage and thickness, Black patients had significantly lower five-year melanoma-specific survival than white patients, which points toward some combination of biological difference, delayed diagnosis, and disparities in access and socioeconomic status all operating together. Patients in the lowest socioeconomic quintiles had meaningfully higher risk of death, and Hispanic and Black patients each carried elevated mortality risk relative to white patients. The authors are candid that most of the underlying research comes from relatively homogeneous white and Asian cohorts, which limits how well any of this translates to Black and Hispanic populations specifically — an honest and important gap to flag rather than paper over.

The etiology and molecular section is where this tumor really distinguishes itself biologically, and this is genuinely useful for how you counsel patients and think about prognosis. Acral lentiginous melanoma has a low overall mutational burden, unlike sun-exposed melanomas, and BRAF V600E mutations — your usual targetable driver — show up in only a small minority, reported anywhere from roughly two to a third of cases depending on the cohort, meaningfully less common than in cutaneous melanoma generally. Instead, what dominates is chromosomal structural complexity — copy number variants and amplifications, recurrently hitting chromosomes five, eleven, twelve, and twenty-two, with genes like TERT, CCND1, and a relatively acral-specific driver called CRKL. There's a striking finding here about massively rearranged amplification clusters — the authors use the terms "tyfonas" or "hailstorms" — that appear unique to acral lentiginous melanoma and don't show up in conventional cutaneous melanoma, suggesting a genuinely distinct oncogenic mechanism rather than just a UV-poor version of the same disease. Consistent with the sun-protected anatomic sites, UV-signature mutations are found in only about ten to fifteen percent of these tumors, compared to the vast majority of cutaneous melanomas. Interestingly, when BRAF mutations do occur in acral lentiginous melanoma, evolutionary sequencing suggests they arise late, after the initiating structural rearrangement — the opposite sequence from conventional melanoma, where BRAF is typically an early, UV-associated driver event. Trauma and mechanical stress on weight-bearing plantar surfaces are raised as a plausible contributing factor, though this remains an association rather than an established causal mechanism.

The practical takeaway from part one is mostly about calibrating your index of suspicion and your counseling. This is not simply cutaneous melanoma that happens to occur acrally — it behaves differently, it's molecularly distinct, it disproportionately and more severely affects patients of color, and pigmented acral lesions in darker skin tones may be more easily overlooked because of blended coloration. None of this is practice-changing in a procedural sense yet, but it should sharpen your biopsy threshold and your discussion of prognosis with these patients.

That brings us to part two, the companion review covering staging, surgical management, systemic therapy, and the field's shortcomings — and this is where things get more directly relevant to your daily practice.

On staging, the authors use the standard AJCC eighth edition framework, but the key clinical point is that acral lentiginous melanoma tends to present thicker and more advanced than conventional melanoma — commonly at least T3, ulcerated in roughly forty percent of cases, and with nearly a third of patients already node-positive at diagnosis, the highest rate among melanoma subtypes. Given this, the authors advocate a lower threshold for radiologic staging than you'd typically apply in cutaneous melanoma — where usual guidelines reserve imaging for more advanced stage — recommending upfront CT or PET-CT for high-risk primaries, defined as depth beyond four millimeters, bulky or symptomatic tumors, palpable nodes, or clinical signs of spread, along with imaging the entire affected extremity given this tumor's propensity for in-transit metastases.

On surgery, the core message reinforces what you already practice: wide local excision with margins based on Breslow depth remains standard, and importantly, amputation does not improve overall or recurrence-free survival compared to more conservative, function-preserving approaches — so the authors explicitly recommend against amputation except for palliative indications like uncontrolled bleeding or infection. Mohs micrographic surgery has been studied here too, and while it hasn't shown an overall survival difference, it appears to offer improved local control and smaller defects, which matters enormously given how much of this disease occurs on weight-bearing plantar surfaces where reconstruction is a real consideration. One nuance worth remembering for your own practice: the study showing no survival difference used a staged paraffin technique rather than frozen sections, and the authors note that either fixation method provides adequate margin assessment through en face processing — so the technique choice is more about your workflow than about oncologic adequacy.

Sentinel lymph node biopsy is recommended more liberally here than you'd apply in conventional cutaneous melanoma — the authors suggest offering it even for thinner tumors given that roughly one in four acral lentiginous melanomas is sentinel-node positive, a notably higher rate than cutaneous melanoma overall. Consistent with the broader melanoma literature from the MSLT-two and DeCOG-SLT trials, though those weren't acral-specific, completion lymph node dissection isn't recommended for a positive sentinel node alone, since retrospective acral data similarly failed to show improved recurrence-free or distant metastasis-free survival.

For higher-stage disease, the authors lean toward more aggressive multimodality management than you might default to with conventional melanoma — adding systemic therapy or radiation to surgery for resectable stage IIB through IV disease, since stage III acral lentiginous melanoma patients treated with multimodality therapy have better survival than those treated with surgery alone. Adjuvant radiation is suggested for the same high-risk nodal features used in cutaneous melanoma — extranodal extension, multiple involved nodes, or large nodal masses.

On systemic therapy, the honest picture is one of borrowed evidence and modest results. Because dedicated trials are scarce, most data come from acral lentiginous melanoma patients folded into broader cutaneous melanoma trials. Adjuvant PD-1 checkpoint inhibition does appear beneficial compared to observation, and the authors recommend it consistent with FDA-approved indications for cutaneous melanoma, but they're explicit that the magnitude of benefit looks smaller than in conventional melanoma — consistent with the immune-excluded tumor microenvironment described in part one, which likely explains relatively blunted checkpoint inhibitor responsiveness. Even though BRAF mutations are uncommon, the authors still recommend testing for and treating eligible patients with BRAF and MEK targeted therapy when present. Tumor-infiltrating lymphocyte therapy is flagged as a promising but still early approach specifically worth watching in this population.

Putting the two parts together, here's the practical synthesis for your practice. Not practice-changing in the sense of new randomized data, but genuinely actionable: treat acral lentiginous melanoma as a biologically distinct, more aggressive disease that warrants a lower threshold for staging imaging, a more liberal approach to sentinel node biopsy even in thinner tumors, avoidance of amputation as a default, and multidisciplinary tumor board discussion for stage III and beyond given the multimodality survival benefit. What remains genuinely investigational rather than actionable is the systemic therapy landscape — checkpoint inhibitor and targeted therapy data here are extrapolated, not purpose-built, and the authors are appropriately cautious about tools like circulating tumor DNA or gene expression profiling, which have not been validated in this subtype and may misrepresent true risk if applied uncritically.

Our third piece this month is a different format entirely — an ethics case column, structured as a letter from a concerned dermatologist to "Dr Dermatoethicist," working through management of high-risk cutaneous squamous cell carcinoma in a pregnant patient. There's no methods or results section here; it's a case-based ethical discussion, and it's worth walking through because the scenario is one you will eventually face.

The case: first-trimester patient with a two-centimeter, four-millimeter-deep, poorly differentiated cutaneous squamous cell carcinoma of the lower vermillion lip, perineural invasion present, staged as T2N0M0 by AJCC and T2b by Brigham and Women's — high-risk by any measure, the kind of tumor where you'd normally be discussing surgery plus adjuvant radiation and possibly nodal staging. The patient wants to delay everything until after delivery, and the referring dermatologist is worried about progression given many months remaining in the pregnancy.

The ethicist's response threads together several principles. On beneficence and nonmaleficence, the reassuring practical point is that Mohs micrographic surgery — with cure rates in the high nineties — can be performed safely under local anesthesia during pregnancy, and both lidocaine and epinephrine have established safety records in this setting, with epinephrine actually reducing systemic lidocaine absorption. That's a concrete, shareable fact for counseling an anxious patient. Radiation, by contrast, is generally contraindicated in pregnancy, so adjuvant radiotherapy would need to wait. On staging imaging, the column makes an important point worth remembering for your own conversations: the actual radiation doses involved in typical staging CT or MRI protocols in this context fall well below thresholds associated with fetal harm, even though patients' intuitive fear of "radiation" during pregnancy is understandably high.

The autonomy discussion is the heart of the piece. The patient's preference to defer everything until after delivery is a legitimate expression of autonomy, but the ethicist argues the physician's obligation is to make sure that preference is genuinely informed — meaning a candid conversation about what deferral actually risks: local tissue destruction, a more extensive and morbid surgery later, and in the worst case, disease progression to a point where treatment options narrow and the conversation shifts toward far more difficult territory, including decisions around continuing the pregnancy if metastatic disease were to emerge.

The recommended path forward, and the piece's central practical takeaway, is a compromise rather than an all-or-nothing choice: proceed with surgical excision — Mohs being well suited here — during the pregnancy to address the primary tumor now, while deferring adjuvant radiation until after delivery. This is framed explicitly as shared decision-making, aligning evidence-based urgency around the primary tumor with the patient's fetal-safety concerns, rather than asking her to choose between treating the cancer and protecting the pregnancy. For your own practice, the actionable point is this: pregnancy is not, by itself, a reason to delay definitive surgical treatment of high-risk cutaneous squamous cell carcinoma, and you have genuine safety data on local anesthesia to bring into that conversation — the harder ethical work is in sequencing adjuvant treatment and communicating that sequencing plan transparently.

That wraps up this month's review. To summarize: acral lentiginous melanoma is biologically its own disease, deserving a more aggressive staging and multidisciplinary posture than conventional cutaneous melanoma, even though the surgical fundamentals you already practice remain sound; and pregnancy, while it changes your treatment sequencing, should not by default change your resolve to treat high-risk skin cancer promptly. Thanks for listening, and we'll see you next month.