Case report: Regression of in-transit metastases of cutaneous squamous cell carcinoma with combination pembrolizumab and topical diphencyprone.

While typically low-risk, cutaneous squamous cell carcinoma (cSCC) can infrequently progress to metastatic disease with in-transit lesions, localized to the dermis or subcutaneous tissue between the primary tumor and draining regional lymph nodes. These lesions are associated with poor prognostic values, including decreased survival rates and increased risk of recurrence. We present the case of a 75-year-old male with cSCC and in-transit metastases on his scalp treated with the immune checkpoint inhibitor (ICI) pembrolizumab in conjunction with diphencyprone (DPCP), a topical hapten that induces a delayed-type hypersensitivity reaction in the skin. The patient was enrolled in a clinical trial (NCT05481658) that involved the twice-weekly application of DPCP 0.04% ointment to four of the in-transit metastases on his frontal scalp, concurrent with pembrolizumab 300 mg administered every three weeks. Following effective sensitization and a twelve-week treatment course, complete clearance of all lesions, DPCP-treated and non-DPCP treated, was achieved, with no adverse events. The immunologic profiles of the post-treatment biopsies were analyzed by TaqMan Low Density Array quantitative real-time polymerase chain reaction to measure immune marker gene expression. Relative to the non-DPCP-treated lesion, the DPCP-treated lesion demonstrated increased pro-inflammatory genetic markers and T-cell activation. This case represents the first reported instance of in-transit metastases of cSCC successfully treated with DPCP and an ICI. It highlights the potential safety and efficacy of DPCP with systemic immunotherapy for the management of in-transit metastases of cSCC in patients for whom surgery and radiation may be contraindicated.

A Survey of Demographics and Treatments in Melanoma Case Reports: Retrospective Bibliometric Analysis.

Melanoma case reports show variations in treatment by age and sex.

Use of a topical Janus kinase inhibitor in immune checkpoint inhibitor-induced eczematous reaction: a case report.

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. Our case report highlights a novel therapeutic option for an eczematous cirAE: the topical JAK 1/2 inhibitor, ruxolitinib. CirAEs can occur in up to 55% of patients on ICIs, a class of medications seeing rapidly increasing use in cancer therapy, and prior research has demonstrated that ICI-induced dermatitis may involve different pathways than traditionally observed in their spontaneous counterparts. Specifically, marked Th1 skewing is noted in ICI-induced dermatitis, as opposed to a predominant Th2 response which typically characterizes spontaneous atopic dermatitis. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

Risk for second primary cancers among pediatric and young adult melanoma survivors.

BACKGROUND/OBJECTIVES: Second primary cancers (SPCs) are a leading cause of morbidity and mortality among cancer survivors. In this study, we aimed to characterize the incidence of SPCs among pediatric and young adult survivors of CM. METHODS: Using the Surveillance, Epidemiology, and End Results Program data spanning 2000-2018, we calculated standardized incidence ratios (SIR) to assess SPC risk in all pediatric (0-18 years) and young adult (19-29 years) patients with a first primary cancer diagnosis of CM. RESULTS: Of 7,169 total CM survivors, 632 (8.82%) developed a SPC, corresponding to a 5-fold increased risk (standardized incidence ratio [SIR] 4.98; 95% confidence interval [CI] 4.60-5.38) compared to the general population. There was a highly elevated risk for second primary melanoma across all age groups (SIR 32.5; 95% CI 29.7-35.6), constituting the majority of SPC diagnoses (N = 485). Infants diagnosed with CM before 1 year of age had the highest risk for any SPC (SIR 164; 95% CI 19.8-592) and young adults diagnosed at 25-29 years had the lowest risk (SIR 4.64; 95% CI 4.19-5.13). SPC incidence was highest within the first year of CM diagnosis (SIR 27.5; 95% CI 23.7-31.6) and progressively decreased with time. CONCLUSIONS: Variation exists in the incidence and type of SPC according to age among pediatric and young adult survivors of CM.

Laser capture microdissection provides a novel molecular profile of human primary cutaneous melanoma.

Melanoma accounts for the majority of skin cancer-related mortality, highlighting the need to better understand melanoma initiation and progression. In-depth molecular analysis of neoplastic melanocytes in whole tissue biopsies may be diluted by inflammatory infiltration, which may obscure gene signatures specific to neoplastic cells. Thus, a method is needed to precisely uncover molecular changes specific to tumor cells from a limited sample of primary melanomas. Here, we performed laser capture microdissection (LCM) and gene expression profiling of patient-derived frozen sections of pigmented lesions and primary cutaneous melanoma. Compared to bulk tissue analysis, analysis of LCM-derived samples identified 9528 additional differentially expressed genes (DEGs) including melanocyte-specific genes like PMEL and TYR, with enriched of pathways related to cell proliferation. LCM methodology also identified potentially targetable kinases specific to melanoma cells that were not detected by bulk tissue analysis. Taken together, our data demonstrate that there are marked differences in gene expression profiles depending on the method of sample isolation. We found that LCM captured higher expression of melanoma-related genes while whole tissue biopsy identified a wider range of inflammatory markers. Taken together, our data demonstrate that LCM is a valid approach to identify melanoma-specific changes using a relatively small amount of primary patient-derived melanoma sample.

Melanoma clinicopathological groups characterized and compared with dermoscopy and reflectance confocal microscopy.

BACKGROUND: Dermoscopic and reflectance confocal microscopy (RCM) correlations between morphologic groups of melanoma have not yet been described. OBJECTIVE: Describe and compare dermoscopic and RCM features of cutaneous melanomas with histopathological confirmation. METHODS: Single center, retrospective analysis of consecutive melanomas evaluated with RCM (2015-2019). Lesions were clinically classified as typical, nevus-like, amelanotic/nonmelanoma skin cancer (NMSC)-like, seborrheic keratosis (SK)-like and lentigo/lentigo maligna (LM)-like. Presence or absence of common facial and nonfacial melanoma dermoscopic and RCM patterns were recorded. Clusters were compared with typical lesions by multivariate logistic regression. RESULTS: Among 583 melanoma lesions, significant differences between clusters were evident (compared to typical lesions). Observation of dermoscopic features (>50% of lesions) in amelanotic/NMSC-like lesions consistently displayed 3 patterns (atypical network, atypical vascular pattern + regression structures), and nevus-like and SK-like lesions and lentigo/LM-like lesions consistently displayed 2 patterns (atypical network + regression structures, and nonevident follicles + heavy pigmentation intensity). Differences were less evident with RCM, as almost all lesions were consistent with melanoma diagnosis. LIMITATIONS: Small SK-like lesions sample, single RCM analyses (no reproduction of outcome). CONCLUSION: RCM has the potential to augment our ability to consistently and accurately diagnose melanoma independently of clinical and dermoscopic features.