Clinicopathologic features, demographics, disease burden, and therapeutics in alopecic sarcoidosis: a case series and systematic review.

Background: Alopecic sarcoidosis is an uncommon cutaneous manifestation of sarcoidosis. Scarring and nonscarring alopecic sarcoidosis have been reported; however, information on the epidemiology, systemic disease associations, and treatment efficacy is limited. Objective: To address these gaps, we conducted a retrospective chart review and systematic literature review of alopecic sarcoidosis cases. Methods: Full-text English publications from PubMed, Scopus, and Google Scholar from inception to August 2023 were analyzed. Treatment evidence quality was assessed using the modified Oxford Centre for Evidence-Based Medicine rating scale. Three patients with biopsy-proven alopecic sarcoidosis were included as a case series, all demonstrating systemic sarcoidosis and 2 requiring multiple therapies. Among 1778 search results, 60 articles representing 77 cases of alopecic and scalp sarcoidosis were included. Patients were categorized into 4 distinct alopecic subgroups. Black patients constituted the majority of all subgroups. Results: Extracutaneous sarcoidosis burden was high across all alopecic subgroups, with ocular disease appearing overrepresented. Topical and oral corticosteroids were the main treatments. Though scarring alopecia patients had poor outcomes despite receiving immunomodulators/cx, limited data suggest potential efficacy of tumor necrosis factor-alpha inhibitors. Limitations: This study has a small sample size. Conclusion: Our findings underscore the importance of evidence-based strategies for improving alopecic sarcoidosis management. Prompt diagnosis and systemic evaluation, especially for scarring alopecia, are essential for timely intervention to optimize patient outcomes.

Treatment of Bullous Pemphigoid With Dupilumab: A Case Series of 30 Patients.

Bullous pemphigoid is often difficult to treat with the limited therapies available. Here, we describe clinical outcomes among 30 adults with bullous pemphigoid patients treated with dupilumab. We performed a multicenter, retrospective case series between March 2020 to August 2022. Patients received a loading dose of dupilumab 600 mg, followed by 300 mg maintenance dose with varying administration frequency tailored to individual patient response. All patients experienced at least some improvement in blister formation and pruritus, with 23 (76.7%) of patients demonstrating either complete clearance of blistering or marked response. Complete clearance of pruritus or marked response was noted in 25 (83.3%) of patients. Eight patients were effectively maintained solely on dupilumab. One (3.3%) patient reported an injection site reaction. Thirty patients represent a small sample, however, to our knowledge, this is the second largest group of BP treated with dupilumab. Furthermore, we provide an understandable framework for clinicians outside of academics to follow and assess treatment responses in their BP patients treated with dupilumab. Dupilumab should be considered as a therapeutic option in patients with bullous pemphigoid given its ability to induce sustained blistering and pruritus response in both typical and refractory cases while maintaining a favorable safety profile. J Drugs Dermatol. 2024;23(6):e144-e148. doi:10.36849/JDD.8258e.

Papule Protruding Into the Nasal Cavity.

An 18-year-old male with no significant medical history presented for evaluation of a nasal papule that was asymptomatic without any associated pain, pruritus, or bleeding with no changes for a year. What is your diagnosis?

Quantitative multiplex immunohistochemistry reveals inter-patient lymphovascular and immune heterogeneity in primary cutaneous melanoma.

Introduction: Quantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms and tissue structures that determine leukocyte distribution within and around tumor nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates that blood and lymphatic vessels (lymphovasculature) also dictate leukocyte trafficking within tumor microenvironments and thereby impact anti-tumor immunity. Here we interrogate these relationships in primary human cutaneous melanoma. Methods: We established a quantitative, multiplexed imaging platform to simultaneously detect immune infiltrates and tumor-associated vessels in formalin-fixed paraffin embedded patient samples. We performed a discovery, retrospective analysis of 28 treatment-naïve, primary cutaneous melanomas. Results: Here we find that the lymphvasculature and immune infiltrate is heterogenous across patients in treatment naïve, primary melanoma. We categorized five lymphovascular subtypes that differ by functionality and morphology and mapped their localization in and around primary tumors. Interestingly, the localization of specific vessel subtypes, but not overall vessel density, significantly associated with the presence of lymphoid aggregates, regional progression, and intratumoral T cell infiltrates. Discussion: We describe a quantitative platform to enable simultaneous lymphovascular and immune infiltrate analysis and map their spatial relationships in primary melanoma. Our data indicate that tumor-associated vessels exist in different states and that their localization may determine potential for metastasis or immune infiltration. This platform will support future efforts to map tumor-associated lymphovascular evolution across stage, assess its prognostic value, and stratify patients for adjuvant therapy.

Characterization of Immunosuppressive Myeloid Cells in Merkel Cell Carcinoma: Correlation with Resistance to PD-1 Pathway Blockade.

PURPOSE: Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Although essentially all MCCs are antigenic through viral antigens or high tumor mutation burden, MCC has a response rate of only approximately 50% to PD-(L)1 blockade suggesting barriers to T-cell responses. Prior studies of MCC immunobiology have focused on CD8 T-cell infiltration and their exhaustion status, while the role of innate immunity, particularly myeloid cells, in MCC remains underexplored. EXPERIMENTAL DESIGN: We utilized single-cell transcriptomics from 9 patients with MCC and multiplex IHC staining of 54 patients' preimmunotherapy tumors, to identify myeloid cells and evaluate association with immunotherapy response. RESULTS: Single-cell transcriptomics identified tumor-associated macrophages (TAM) as the dominant myeloid component within MCC tumors. These TAMs express an immunosuppressive gene signature characteristic of monocytic myeloid-derived suppressor cells and importantly express several targetable immune checkpoint molecules, including PD-L1 and LILRB receptors, that are not present on tumor cells. Analysis of 54 preimmunotherapy tumor samples showed that a subset of TAMs (CD163+, CD14+, S100A8+) selectively infiltrated tumors that had significant CD8 T cells. Indeed, higher TAM prevalence was associated with resistance to PD-1 blockade. While spatial interactions between TAMs and CD8 T cells were not associated with response, myeloid transcriptomic data showed evidence for cytokine signaling and expression of LILRB receptors, suggesting potential immunosuppressive mechanisms. CONCLUSIONS: This study further characterizes TAMs in MCC tumors and provides insights into their possible immunosuppressive mechanism. TAMs may reduce the likelihood of treatment response in MCC by counteracting the benefit of CD8 T-cell infiltration. See related commentary by Silk and Davar, p. 1076.

Acute regression of a melanocytic neoplasm.

Immune-mediated regression of melanocytic neoplasms is predominantly lymphocytic, driven by CD8+ anti-tumoral T-cells and, rarely, natural killer cells. Histopathologic features of regression include effacement of the epidermis, replacement of tumor cells by a fibrotic stroma, varying degrees of chronic inflammation (usually lymphocytes) and melanophages, as well as vascular ectasia and angioplasia. The understanding of regression and the complex immune response in melanoma has led to the development of targeted immunotherapy in melanoma. Here, we report a case of near-complete regression of a melanocytic neoplasm associated with neutrophilic and eosinophilic inflammation, suggesting a non-traditional pathway of regression that has yet to be explored.

Differences in nomenclature usage and preference among dermatopathologists for "dysplastic" nevi: A national survey.

BACKGROUND: Ongoing controversy exists regarding terminology used to describe atypical melanocytic nevi. Efforts to standardize nomenclature, including the 1992 NIH consensus conference, have been largely unsuccessful. Significant advances have revealed an increasingly detailed genetic picture of melanocytic neoplasms, including strong evidence for the existence of those with "intermediate" behavior. METHODS: We sent an electronic survey to dermatopathologists (n = 846) to assess trends in nomenclature usage and attitudes toward developing new consensus nomenclature for atypical melanocytic nevi. RESULTS: There were 229 complete responses (27.1% response rate). The most used/preferred nomenclature was "dysplastic nevus" (43%/39%, respectively), followed by the NIH-recommended terminology (28%/26%). Three-tier grading systems were most heavily used/preferred (79%/63%). Dermatopathologists based in New England were most likely to use the NIH terminology; on the other hand, "dysplastic nevus" or "other" were most used elsewhere (p = 0.029). Most (76%) expressed at least "moderate" enthusiasm for developing consensus nomenclature, with 47% "very" or "extremely" enthusiastic. CONCLUSION: Little has changed with the wide variation in terminology for atypical melanocytic nevi. There continues to be no one dominant terminology in use. However, there is enthusiasm for standardization. A new attempt at updated consensus nomenclature may be fruitful.

Tumoral melanosis mimicking residual melanoma in the setting of talimogene laherparepvec treatment.

Talimogene laherparepvec (T-VEC) has become an increasingly popular treatment option for surgically non-resectable, recurrent melanoma, usually of cutaneous metastases. The complete response (CR) rate has been reported to be ~20% with a median of ~9 months to achieve it. In real-world practice, decrease of tumor size often occurs rapidly within the first 2-3 months, while improvement of the pigmentation takes several more months. Such clinical observation of lasting pigmentation could be explained by tumorous melanosis-a histopathological term referring to the presence of a melanophage-rich inflammatory infiltrate without remaining viable tumor cells. Herein, we report six patients with metastatic cutaneous melanoma who were treated with T-VEC. Biopsies were performed after observing clinical responses in the injected tumors. Pathological evaluation demonstrated non-viable or absent tumor tissue with tumorous melanosis in all cases. To accurately assess response to therapy and potentially decrease unnecessary additional T-VEC treatments, serial biopsy of 'stable' lesions should be considered to assess the presence or absence of viable tumor.

Cutaneous Ganglioneuromas With Overlying Epidermal Hyperplasia: A Case Series Presentation and Proposal of Potential Etiopathogenesis.

ABSTRACT: Cutaneous ganglioneuromas (GNs) are exceptionally uncommon tumors, and many reported cases describe association with overlying epidermal hyperplasia that may be interpreted as seborrheic keratosis (SK) or SK-like proliferation. We report 5 cases of cutaneous GN in adult patients; all of which were discovered incidentally in the immediate vicinity of epidermal hyperplasia. A review of the literature demonstrates the current-although likely imperfect-understanding of the etiopathogenesis of both SK and GN in the skin. We explore the putative pathophysiologies of other common, well-characterized skin lesions and, taking them into account, provide rationale for the coexistence of cutaneous GN with overlying SK and SK-like epidermal changes. However, we ultimately acknowledge a dilemma of causality and, given the rarity of their co-occurrence, objectively question whether occasional cameo appearances by GN lying subjacent to SK and SK-like hyperplasia may be due merely to chance.

Skin Tone Representation in Dermatology Textbooks: Approximating the Gap.

Dermatology heavily relies on photographs in its literature to depict diseases and demonstrate treatment modalities. Previous studies have established that general medical and dermatology textbooks have limited photographic representation of individuals with skin of color (SOC), even those diseases highly prevalent in these populations. As the US population continues to grow and diversify, there is an increase in individuals with SOC seeking cosmetic and procedural services. We set out to investigate the current trends of SOC representation in the surgical and cosmetic sections of current dermatology textbooks.