Ninety-eighth issue
November 12th, 2025
Stage alone can’t handle the heat, but TCR sequencing cools things down with clonotype insight.
Cutaneous T-cell lymphomas, like mycosis fungoides (MF) and Sézary syndrome (SS), don’t all behave the same, and stage alone can miss who will progress. This single-center retrospective cohort (125 patients, stages IA-IVB) used lesional-skin T-cell receptor (TCR) next-generation sequencing to see whether certain TCR β (TCRB) or γ (TCRG) clonotypes line up with aggressive histology, immune checkpoint expression, and overall survival (OS).
What did they find?
Cutaneous T-cell lymphomas, like mycosis fungoides (MF) and Sézary syndrome (SS), don’t all behave the same, and stage alone can miss who will progress. This single-center retrospective cohort (125 patients, stages IA-IVB) used lesional-skin T-cell receptor (TCR) next-generation sequencing to see whether certain TCR β (TCRB) or γ (TCRG) clonotypes line up with aggressive histology, immune checkpoint expression, and overall survival (OS).
What did they find?
- Clonality was common: ≥1 clonal TCRB and/or TCRG in 78% of samples; TCRG was detected more often than TCRB (74% vs 58%).
- Vβ20 = high risk: Present only in advanced-stage MF/SS, often with folliculotropism (FT) and large-cell transformation (LCT) (41% vs 0%; P < 0.001) and tied to worse 2–3 year OS.
- Vγ8 = advanced disease: More frequent in advanced MF/SS than early MF (47% vs 21%; P = 0.01) and linked to poorer OS.
- High clonal burden matters: Higher % TCRG reads (≥40–50%) correlated with FT/LCT and higher PD-1 and ICOS expression, suggesting an exhausted but targetable microenvironment.
- Stacked risk: Patients with Vβ20, Db1, and Vγ8 together almost always had aggressive CTCL.
Yellow nails, big signs: look closer, it’s more than a polish problem!
Yellow nail syndrome (YNS) is a rare multisystem disorder defined by the triad of xanthonychia, respiratory disease, and lymphedema. Existing literature on YNS is limited to isolated case reports and small case series, and standardized guidelines for diagnosis and management are lacking. To address this gap, an international, multi-institutional retrospective cohort study of 111 patients was undertaken to comprehensively propose recommendations for the management of YNS.
What did they find?
Yellow nail syndrome (YNS) is a rare multisystem disorder defined by the triad of xanthonychia, respiratory disease, and lymphedema. Existing literature on YNS is limited to isolated case reports and small case series, and standardized guidelines for diagnosis and management are lacking. To address this gap, an international, multi-institutional retrospective cohort study of 111 patients was undertaken to comprehensively propose recommendations for the management of YNS.
What did they find?
- Diagnosis was frequently delayed, with an average interval of 3.2 years from nail symptom onset to recognition, and only 21% of patients presented for consultation with the complete triad.
- Xanthonychia was present in nearly all patients (99.1%), with frequent nail findings including growth arrest (91.6%), increased transverse curvature (68.7%), thickening (38.4%), and onycholysis (37.4%). Respiratory tract involvement occurred in 78.4% of patients (most commonly sinusitis (27.6%), bronchiectasis (21.8%), and chronic obstructive pulmonary disease (20.7%)) and lymphedema was observed in 30.7% of patients (most commonly involving the lower extremities (74.2%)).
- Nail clipping or fungal culture was performed in 47.5% of patients, with onychomycosis confirmed in 22.9%; bacterial culture was obtained in 3.8%, identifying Pseudomonas aeruginosa in two cases and Citrobacter koseri in one case.
- Notable comorbidities of YNS included autoimmune diseases (14%) and malignancies (9%), most commonly of the breast or lung, while active or former smoking was reported in 23.3% of patients and exposures to respiratory irritants and titanium in 6.7% and 20.8% of patients, respectively.
- Combination therapy with oral vitamin E and an oral azole antifungal (fluconazole or itraconazole) elicited the most effective response rates (33.3–35.3%), compared with 7.5% for vitamin E monotherapy, while spontaneous resolution occurred in only 2.7% of cases.
Metabolism-based scoring of cutaneous squamous cell carcinoma: Predicting tumor behavior and response to DHODH inhibition
British Journal of Dermatology
British Journal of Dermatology
When metabolism varies, treatment response does too.
Cutaneous squamous cell carcinoma (cSCC) often looks similar under the microscope, yet tumors with the same stage can behave in dramatically different ways. Current staging can’t fully explain why some cSCCs metastasize, resist treatment, or remain indolent. To uncover the biology driving this variability, researchers performed large-scale proteomic and bioenergetic profiling across 60 patient samples, from actinic keratosis to metastatic disease, and tested whether metabolic signatures predict response to the dihydroorotate dehydrogenase (DHODH) inhibitor, leflunomide.
What did they find?
Cutaneous squamous cell carcinoma (cSCC) often looks similar under the microscope, yet tumors with the same stage can behave in dramatically different ways. Current staging can’t fully explain why some cSCCs metastasize, resist treatment, or remain indolent. To uncover the biology driving this variability, researchers performed large-scale proteomic and bioenergetic profiling across 60 patient samples, from actinic keratosis to metastatic disease, and tested whether metabolic signatures predict response to the dihydroorotate dehydrogenase (DHODH) inhibitor, leflunomide.
What did they find?
- Three metabolic subgroups were identified across all stages of cSCC: low, medium, and high.
- Metabolic scores reflected functional activity, where low-score tumors had suppressed bioenergetics and high-score tumors were metabolically active.
- Response to leflunomide varied by score; low-score tumors responded best, while high-score tumors were resistant.
- DHODH expression corresponded with sensitivity, as high DHODH expression was identified in low-score tumors and low DHODH expression in high-score tumors.
- Overexpressing DHODH made resistant cells sensitive to leflunomide, showing that modifying DHODH altered drug response.
In Stain Sight
Skin biopsies play a central role in diagnosing primary cutaneous or disseminated infections, particularly in immunocompromised patients. While tissue culture remains the gold standard for identifying infectious agents, results can take days to weeks. In this retrospective study, researchers evaluated the diagnostic utility of histochemical special stains compared with culture results in 319 skin biopsy specimens from immunocompromised hosts.
What did they find?
Skin biopsies play a central role in diagnosing primary cutaneous or disseminated infections, particularly in immunocompromised patients. While tissue culture remains the gold standard for identifying infectious agents, results can take days to weeks. In this retrospective study, researchers evaluated the diagnostic utility of histochemical special stains compared with culture results in 319 skin biopsy specimens from immunocompromised hosts.
What did they find?
- Gram stain for bacteria showed low sensitivity (0.34) but high specificity (0.95).
- Fungal stains, methenamine silver and periodic acid-Schiff diastase, had moderate sensitivity (0.62 and 0.5, respectively) and high specificity (0.92 and 0.93, respectively).
- Mycobacterial stains, Ziehl-Neelsen and Fite, showed moderate to high sensitivity (0.5 and 0.83, respectively) and high specificity (0.99 and 1.0, respectively)
- All special stains demonstrated relatively high negative predictive values (NPV), with Gram stain yielding the lowest NPV.
Just another relaxing day under local anesthesia.
Mohs micrographic surgery (MMS) provides the highest cure rates for nonmelanoma skin cancer while minimizing tissue loss, but its success also depends on patient satisfaction. This systematic review analyzed 10 prospective cohort studies (n = 2,140 patients, 2009-2024) assessing patient satisfaction, anxiety, pain, and communication using standardized scales such as the Patient Satisfaction Questionnaire-18 (PSQ-18) and FACE-Q.
What did they find?
Mohs micrographic surgery (MMS) provides the highest cure rates for nonmelanoma skin cancer while minimizing tissue loss, but its success also depends on patient satisfaction. This systematic review analyzed 10 prospective cohort studies (n = 2,140 patients, 2009-2024) assessing patient satisfaction, anxiety, pain, and communication using standardized scales such as the Patient Satisfaction Questionnaire-18 (PSQ-18) and FACE-Q.
What did they find?
- Patient satisfaction averaged 4.29-4.34/5, with 76-93% rating ≥4/5 in the first month and up to 95% by 12 months post-surgery.
- Top satisfaction drivers: surgeon’s technical skill, empathy, and communication quality, each rated >4.4/5.
- Pain and anxiety management using music, benzodiazepines, or smoke evacuators significantly improved patient experience (P<0.05).
- Lower satisfaction was linked to cost, convenience, and multiple procedural stages.
Novel cyclized hexapeptide-9 outperforms retinol against skin aging: A randomized double-blinded, active- and vehicle-controlled clinical trial
Journal of Cosmetic Dermatology
Journal of Cosmetic Dermatology
Peptides vs. retinol for wrinkles: a head-to-head, split-regimen showdown.
Retinoids are the clinical standard for treating photoaging, but can be unstable and irritating. Peptides are appealing for their safety profile, yet classic linear peptides struggle with stability and penetration. This randomized, double-blinded, three-arm clinical trial of 96 adults tested whether a cyclized hexapeptide-9 (CHP-9, 0.002%), engineered for greater rigidity, stability, and skin permeability, can outperform 0.002% retinol and vehicle, both used twice-daily, for 56 days.
What did they find?
Main Takeaway: Cyclized hexapeptide-9 (0.002%) delivered broader and stronger anti-aging benefits than 0.002% retinol, with excellent tolerability. Cyclization appears to meaningfully enhance peptide performance in vivo, supporting CHP-9 as a promising retinol alternative, especially with longer-term use.
Retinoids are the clinical standard for treating photoaging, but can be unstable and irritating. Peptides are appealing for their safety profile, yet classic linear peptides struggle with stability and penetration. This randomized, double-blinded, three-arm clinical trial of 96 adults tested whether a cyclized hexapeptide-9 (CHP-9, 0.002%), engineered for greater rigidity, stability, and skin permeability, can outperform 0.002% retinol and vehicle, both used twice-daily, for 56 days.
What did they find?
- CHP-9 significantly reduced crow’s feet and forehead wrinkle number, area, and roughness (P < 0.01); retinol improved fewer parameters.
- CHP-9 increased skin elasticity (R2, R5) and firmness (F4) more than retinol.
- CHP-9 use showed greater improvement in brightness, even tone, and glossiness, with a larger drop in melanin index.
- No irritation or adverse events in any group were reported.
Main Takeaway: Cyclized hexapeptide-9 (0.002%) delivered broader and stronger anti-aging benefits than 0.002% retinol, with excellent tolerability. Cyclization appears to meaningfully enhance peptide performance in vivo, supporting CHP-9 as a promising retinol alternative, especially with longer-term use.
Derm: We need histology
Cross-modal imaging: I am histology
Skin biopsies are considered the gold standard for histologic diagnosis, but what if you could visualize cellular features noninvasively and in real time? This multicenter observational study evaluated a cross-modal imaging device that combines reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) to generate histology-like images.
What did they find?
Cross-modal imaging: I am histology
Skin biopsies are considered the gold standard for histologic diagnosis, but what if you could visualize cellular features noninvasively and in real time? This multicenter observational study evaluated a cross-modal imaging device that combines reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) to generate histology-like images.
What did they find?
- 65 participants underwent cross-modal imaging and matched lesion biopsies.
- Blinded physicians identified primary histologic features with 96.4% accuracy (95% CI, 94.2%–98.7%).
- Secondary features were identified with 98.5% accuracy (95% CI, 98.1%–98.9%).
- Interrater agreement exceeded 90%, with Fleiss κ scores of 0.94 for region and 0.93 for feature.
- The procedure was well-tolerated, with no adverse events and a mean pain score of 0.15 (on a 0–10 scale).
Hidradenitis suppurativa unroofing procedure costs in the context of medical inflation
Student Spotlight
Student Spotlight
Are costs for hidradenitis suppurativa unroofing procedures outpacing medical inflation?
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting ~1–2% of people in the United States and disproportionately impacting low-SES and disadvantaged populations. This retrospective claims analysis used 15 years of IBM MarketScan® Commercial Claims data to evaluate cost trends for HS unroofing procedures.
What did they find?
Main Takeaway: Unroofing costs for HS have risen substantially, and patient out-of-pocket spending increases alongside total costs. This likely worsens access disparities in already underserved populations and underscores the need for policy and reimbursement advocacy.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting ~1–2% of people in the United States and disproportionately impacting low-SES and disadvantaged populations. This retrospective claims analysis used 15 years of IBM MarketScan® Commercial Claims data to evaluate cost trends for HS unroofing procedures.
What did they find?
- 2005–2020 cost growth per claim: Inguinal +116%, perianal/umbilical +80.6%, axillary +56%.
- Positive correlation between patient out-of-pocket expenses and total cost per claim for CPT (Current Procedural Terminology) codes:
- CPT 55620 (vulva, perineum, introitus): r = 0.91 (95% CI 0.75–0.97)
- CPT 11462 (inguinal, simple or intermediate): r = 0.92 (95% CI 0.79–0.97)
- CPT 11450 (axillary, simple or intermediate): r = 0.89 (95% CI 0.70–0.96)
- Included CPT codes are not HS-specific and may capture procedures performed for other conditions.
Main Takeaway: Unroofing costs for HS have risen substantially, and patient out-of-pocket spending increases alongside total costs. This likely worsens access disparities in already underserved populations and underscores the need for policy and reimbursement advocacy.
DERMLITE Dermoscopy QUESTION OF THE WEEK
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Copyright © 2025 - All Rights Reserved.
Copyright © 2025 - All Rights Reserved.