Artificial intelligence algorithms and 3D volumetric rendering for basal cell carcinoma detection and tumor depth assessment in RCM-OCT images: a pilot study.

The Reflectance Confocal Microscopy - Optical Coherence Tomography (RCM-OCT) device has shown utility in detecting and assessing depth of basal cell carcinoma (BCC) in vivo but is challenging for novices to interpret. Artificial intelligence (AI) applied to RCM-OCT could aid readers. We trained artificial intelligence (AI) models, using OCT rasters of biopsy-confirmed BCC, to detect and create 3D BCC rendering and automatically measure tumor depth. Trained AI models were applied to a separate test set containing rasters of BCC, benign lesions, and normal skin. Blinded reader analysis and tumor depth correlation with histopathology were conducted. BCC detection improved from viewing OCT rasters only (sensitivity 73.3%, specificity 45.5%) to viewing rasters with AI-generated BCC rendering (sensitivity 86.7%, specificity 48.5%). A Pearson Correlation r2 = 0.59 (p=0.02) was achieved for the tumor depth measurement between AI and histologic measured depths. Thus, addition of AI to the RCM-OCT device may expand its utility widely.

Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

BACKGROUND: Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. METHODS: For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. RESULTS: Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. CONCLUSIONS: Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.

A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer.

PURPOSE: We investigated reflectance confocal microscopy (RCM) as a possible noninvasive approach for the diagnosis of cancer and real-time assessment of surgical margins. EXPERIMENTAL DESIGN: In a phase I study on 20 patients, we established the RCM imaging morphologic features that distinguish oral squamous cell carcinoma (OSCC) from normal tissue with a newly developed intraoral RCM probe. Our subsequent phase II prospective double-blinded study in 60 patients tested the diagnostic accuracy of RCM against histopathology. Five RCM videos from the tumor and five from normal surrounding mucosa were collected on each patient, followed by a 3-mm punch biopsy of the imaged area. An experienced RCM reader, who was blinded to biopsy location and histologic diagnosis, examined the videos from both regions and classified each as "tumor" or "not tumor" based on RCM features established in phase I. Hematoxylin and eosin slides from the biopsies were read by a pathologist who was blinded to RCM results. Using histology as the gold standard, we calculated the sensitivity and specificity of RCM. RESULTS: We report a high agreement between the blinded readers (95% for normal tissue and 81.7% for tumors), high specificity (98.3%) and negative predictive values (96.6%) for normal tissue identification, and high sensitivity (90%) and positive predictive values (88.2%) for tumor detection. CONCLUSIONS: RCM imaging is a promising technology for noninvasive in vivo diagnosis of OSCC and for real-time intraoperative evaluation of mucosal surgical margins. Its inherent constraint, however, stems from the diminished capability to evaluate structures located at more substantial depths within the tissue.

Racial Disparities in Mycosis Fungoides/Sézary Syndrome-A Single-Center Observational Study of 292 Patients.

BACKGROUND: Clinical presentation of Mycosis fungoides/Sézary syndrome (MF/SS) in Black and African American (AA) patients can be heterogeneous with poor survival reported in AA/black patients. In this study, we aim to characterize differences between AA/black and white patients with MF/SS. PATIENTS AND METHODS: A retrospective single-center hospital-based case-control study including 292 MF/SS patients (146 AA/black matched with 146 white patients). We analyzed demographic, clinical and survival differences. RESULTS: AA/black patients were diagnosed at an earlier age (9 years younger), were predominantly females, had higher rates of Medicaid/Medicare insurance and lower income compared to matched white patients (P <.001). Adjusting for age, sex, insurance type, and income bracket, AA/black patients had significantly worse overall survival (hazard ratio [HR] 2.88, 95%CI 1.21-6.85, P = .017). Association of clinical MF phenotype with survival showed that hypopigmentation was associated with survival in AA/black patients but not in white patients. Erythroderma and ulceration were associated with worse survival risk in AA/black patients. CONCLUSIONS: AA/black patients with MF/SS have a significant worse survival outcome compared to white patients. The association between clinical phenotypes and survival differed between these groups. Further studies are required to investigate whether race-specific pathogenesis or genetic factors may explain these differences.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.

Pruritus related to trastuzumab and pertuzumab in HER2 + breast cancer patients.

PURPOSE: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2 + breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. METHODS: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2 + breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. RESULTS: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. CONCLUSIONS: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face.

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.

Family Planning Experiences and Challenges of Mohs Fellowship Trainees.

BACKGROUND: There is a paucity of literature describing family planning challenges faced by Mohs fellows. OBJECTIVE: To characterize perceptions about and experiences with family planning, fertility, lactation, and parental leave and identify ways to support parental health and family planning for Mohs fellows. MATERIALS AND METHODS: A voluntary, anonymous survey was distributed to Mohs surgeons who recently completed fellowship. RESULTS: In total, 116 Mohs surgeons completed the survey. Their mean age was 34.5 years old, and more were female ( n = 81, 69.8%) than male ( n = 35, 30.2%). Most had children before completion of their Mohs training ( n = 73, 62.9%). The most significant barrier to having children during fellowship was "loss of education or training time." Over 20% ( n = 23) of respondents or their partner had experienced infertility. Half of the 20 respondents ( n = 10) who breastfed or pumped did not have a convenient place to do so. CONCLUSION: This study elucidates trainee perceptions and gaps in parental support for Mohs fellowship trainees. In addition, barriers to implementing a universal family planning policy in Mohs surgery are discussed.

IL12/23 Blockade with Ustekinumab as a Treatment for Immune-Related Cutaneous Adverse Events.

Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Methods: Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. Results: Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. Conclusions: Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.

Acute febrile neutrophilic dermatosis (Sweet syndrome) in acute myeloid leukemia patients: a 28-year institutional experience.

INTRODUCTION: Sweet syndrome (SS) is well-known to be associated with underlying hematologic malignancies. The incidence and qualities of SS among novel targeted therapies for acute myeloid leukemia (AML) have not yet been described. METHODS: Through retrospective review of 19432 patients diagnosed with acute/chronic leukemia or myelodysplastic syndromes/ myeloproliferative neoplasms (MDS+/-MPN) over 28 years, we calculated the incidence of SS in the setting of select hematologic malignancies and described the clinicopathologic characteristics of SS in patients with onset of SS after initiation of novel AML-targeted therapies. RESULTS: Overall incidence of SS was 0.36% (95% CI: 0.27% - 0.45%), which was significantly higher among patients with AML (50/5248, 0.94%; 95% CI: 0.71% - 1.25%). Nine AML patients were on 4 classes of novel targeted treatments - IDH1/2 inhibitor alone, FLT3 inhibitor, IDH2 and DOT1L inhibitor, and anti-CD33 therapy. In therapies inducing myeloid blast differentiation, SS occurred at later onset following treatment. CONCLUSIONS: In AML patients with fever and unusual skin lesions, physicians may consider SS earlier which may shorten time to diagnosis. Future assessments of SS among patients treated with novel therapies for AML and molecular studies of biopsies may help further explain this dermatologic adverse event with earlier diagnosis and management of neutrophilic dermatoses in these patients.

Prospective validation of dermoscopy-based open-source artificial intelligence for melanoma diagnosis (PROVE-AI study).

The use of artificial intelligence (AI) has the potential to improve the assessment of lesions suspicious of melanoma, but few clinical studies have been conducted. We validated the accuracy of an open-source, non-commercial AI algorithm for melanoma diagnosis and assessed its potential impact on dermatologist decision-making. We conducted a prospective, observational clinical study to assess the diagnostic accuracy of the AI algorithm (ADAE) in predicting melanoma from dermoscopy skin lesion images. The primary aim was to assess the reliability of ADAE's sensitivity at a predefined threshold of 95%. Patients who had consented for a skin biopsy to exclude melanoma were eligible. Dermatologists also estimated the probability of melanoma and indicated management choices before and after real-time exposure to ADAE scores. All lesions underwent biopsy. Four hundred thirty-five participants were enrolled and contributed 603 lesions (95 melanomas). Participants had a mean age of 59 years, 54% were female, and 96% were White individuals. At the predetermined 95% sensitivity threshold, ADAE had a sensitivity of 96.8% (95% CI: 91.1-98.9%) and specificity of 37.4% (95% CI: 33.3-41.7%). The dermatologists' ability to assess melanoma risk significantly improved after ADAE exposure (AUC 0.7798 vs. 0.8161, p = 0.042). Post-ADAE dermatologist decisions also had equivalent or higher net benefit compared to biopsying all lesions. We validated the accuracy of an open-source melanoma AI algorithm and showed its theoretical potential for improving dermatology experts' ability to evaluate lesions suspicious of melanoma. Larger randomized trials are needed to fully evaluate the potential of adopting this AI algorithm into clinical workflows.

Management of immune-related cutaneous adverse events with dupilumab.

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70-90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.

PRO-CTCAE reveals under-recognition of dermatologic symptom burden in hospitalized cancer patients.

PURPOSE: Dermatologic adverse events (dAEs) occur frequently in hospitalized patients and can significantly reduce quality of life. Physicians grade dAEs using the Common Terminology Criteria of Adverse Events (CTCAE). However, they often underestimate symptom frequency and severity. The patient-reported outcomes (PRO) version of the CTCAE (PRO-CTCAE) was developed to assess symptoms from the patient's perspective. In this study, we assessed the patient-reported burden of dAEs via the PRO-CTCAE questionnaire and compared results with dAE assessment by treating oncologists and dermatologists. METHODS: Patients admitted to Memorial Sloan Kettering Cancer Center from 6/1/2018 to 4/30/2019 and received a dermatology consultation were eligible. Once enrolled, participants completed a PRO-CTCAE questionnaire on 14 dermatologic symptoms. CTCAE grades assigned by oncology and dermatology were obtained from clinical notes, and kappa statistics were calculated to evaluate the level of agreement between physician and patient evaluations. RESULTS: A total of 100 patients (mean age 59.4, 55% male) were prospectively enrolled. The most common patient-reported dAEs were rash (72%), swelling (67%), pruritus (64%), bruising (53%), and hives (37%). Oncologists and dermatologists underreported dAEs except for rash (median kappa values 0.3 [0.02-0.84] and 0.32 [0.02-0.87], respectively). Oncologists and dermatologists were concordant with each other's documented assessment of dAEs (median kappa value 0.985 [0.55-1]). CONCLUSION: Oncology patient-reported dAEs in a tertiary academic oncologic referral center were under-recognized by providers. PRO-CTCAE may be a useful tool to optimize inpatient dermatologic care for cancer patients by detecting and allowing management of patient-reported dAEs.

Pruritus Related to Trastuzumab and Pertuzumab in HER2+ Breast Cancer Patients.

Purpose: The combination of trastuzumab and pertuzumab (HP) as part of a taxane-based regimen has shown benefit in the adjuvant and metastatic HER2+ breast cancer setting. In the CLEOPATRA trial, pruritus was reported in 11-17.6% of patients. The clinical phenotype and potential treatment strategies for this event have not been reported. Methods: A retrospective review of 2583 patients receiving trastuzumab and pertuzumab for the treatment of HER2+ breast cancer from 11/23/2011 to 6/21/2021 was performed at Memorial Sloan Kettering Cancer Center (MSKCC). Patient demographics, pruritus characteristics, and treatments as documented in the electronic medical record (EMR) were included in this analysis. Results: Of 2583 pts treated with HP, 122 (4.72%) with pruritus were identified. On average, patients experienced pruritus 319.0 days (8-3171) after initiation of HP. The upper extremities (67.4%), back (29.3%), lower extremities (17.4%), and shoulders (14.1%) were the most commonly affected regions. Grade 1/2 pruritus (97.6%) occurred in most cases. Patients responded primarily to treatment with topical steroids (52.2%), antihistamines (29.9%), emollients (20.9%), and gabapentinoids (16.4%). Of those with pruritus, 4 patients (3.3%) required treatment interruption or discontinuation. Conclusions: Pruritus is uncommon in patients on trastuzumab and pertuzumab, generally a chronic condition, with gabapentinoids or antihistamines representing effective therapies.

Staging System Performance and Clinical Outcomes for Cutaneous Squamous Cell Carcinoma of the Ear: A Single-Center Retrospective Study.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) of the ear is associated with poor outcomes. No studies have evaluated current staging system performance in this specific location. OBJECTIVE: Describe clinicopathologic characteristics and outcomes of ear cSCC and evaluate the performance of current staging systems. METHODS: Retrospective study including cases diagnosed and treated at a cancer center from January 2000 to December 2014. Demographic, clinical, and pathologic data were collected from clinical records. Biopsy slides were rereviewed and patients were staged according to the American Joint Committee on Cancer (AJCC) seventh, eighth, and Brigham Women's Hospital (BWH) staging. RESULTS: Of 125 patients, the mean age at diagnosis was 71.9 years (SD 12.5), with most men (89.6%, n = 112). Median follow-up was 22.3 months. Local recurrence and survival risk factors were similar to cSCC outside the ear. The Akaike's Information Criterion (AIC) estimates showed that the BWH system better predicted outcomes than the AJCC seventh, and the AJCC eighth, with AIC values of 189.9, 270.5, and 274.1, respectively. Limitations of the study include retrospective design, single center study, and no control group. CONCLUSION: Current staging systems perform well at stratifying risk in ear cSCC.