The failure of once promising target-specific therapeutic strategies often arises from redundancies in gene expression pathways. Even with new melanoma treatments, many patients are not responsive or develop resistance, leading to disease progression in terms of growth and metastasis. We previously discovered that the transcription factors ETS1 and PAX3 drive melanoma growth and metastasis by promoting the expression of the MET receptor. Here, we find that there are multiple ETS family members expressed in melanoma and that these factors have redundant functions. The small molecule YK-4-279, initially developed to target the ETS gene–containing translocation product EWS-FLI1, significantly inhibited cellular growth, invasion, and ETS factor function in melanoma cell lines and a clinically relevant transgenic mouse model, BrafCA;Tyr-CreERT2;Ptenf/f. One of the antitumor effects of YK-4-279 in melanoma is achieved via interference of multiple ETS family members with PAX3 and the expression of the PAX3-ETS downstream gene MET. Expression of exogenous MET provided partial rescue of the effects of YK-4-279, further supporting that MET loss is a significant contributor to the antitumor effects of the drug. This is the first study identifying multiple overlapping functions of the ETS family promoting melanoma. In addition, targeting all factors, rather than individual members, demonstrated impactful deleterious consequences in melanoma progression. Given that multiple ETS factors are known to have oncogenic functions in other malignancies, these findings have a high therapeutic impact. Significance: These findings identify YK-4-279 as a promising therapeutic agent against melanoma by targeting multiple ETS family members and blocking their ability to act as transcription factors.

This literature review introduces the integration of Large Language Models (LLMs) in the field of dermatopathology, outlining their potential benefits, challenges, and prospects. It discusses the changing landscape of dermatopathology with the emergence of LLMs. The potential advantages of LLMs include a streamlined generation of pathology reports, the ability to learn and provide up-to-date information, and simplified patient education. Existing instances of LLMs encompass diagnostic support, research acceleration, and trainee education. Challenges involve biases, data privacy and quality, and establishing a balance between AI and dermatopathological expertise. Prospects include the integration of LLMs with other AI technologies to improve diagnostics and the improvement of multimodal LLMs that can handle both text and image input. Our implementation guidelines highlight the importance of model transparency and interpretability, data quality, and continuous oversight. The transformative potential of LLMs in dermatopathology is underscored, with an emphasis on a dynamic collaboration between artificial intelligence (AI) experts (technical specialists) and dermatopathologists (clinicians) for improved patient outcomes.

Pityriasis lichenoides is an acute and/or chronic skin disease associated with recurrent erythematous papules that self-resolve. While its etiology is unknown, preceding viral infection may play a role. We present an atypical case of a 40-year-old woman with pityriasis lichenoides et varioliformis acuta as a complication of a COVID-19 infection.

A 50-year-old man, with a history of extensive sun exposure and multiple previous non-melanoma skin cancers, presented with an asymptomatic 8-× 10-millimeter scaly, skin-colored papule on his right shoulder. Subsequent biopsy and excision revealed epidermal hyperplasia containing large atypical basaloid cells with pagetoid spread. Immunoperoxidase staining for cytokeratin-20 demonstrated a focal perinuclear dot-like pattern, and after excluding other in situ entities, a diagnosis of Merkel cell carcinoma In Situ (MCCIS) was rendered. MCCIS is a very rare entity. Although approximately 18% of Merkel cell carcinomas have epidermal involvement, currently only 17 cases of MCCIS have been reported, of which only 7 had no associated neoplasm. Previously, MCCIS was considered a serendipitous or incidental finding, as most cases co-existed with squamous cell carcinoma in situ. This case is unique in that it was not associated with a squamous lesion, and in addition, the pagetoid spread was unusual and has only occasionally been described. As such, MCCIS should be added to list of in situ epidermal lesions with pagetoid spread.

Three hundred thousand new cases of Lyme disease are diagnosed annually in the United States. The earliest manifestation of the disease, erythema migrans, occurs earlier than serologic conversion, and skin biopsies can be very helpful in suggesting the diagnosis. Histopathologic findings vary depending on where in the lesion the specimen is taken, but typically consist of a superficial and deep perivascular and interstitial lymphocytic infiltrate with eosinophils centrally and with histiocytes and plasma cells at the periphery. Rare cases with interstitial histiocytes and rare-to-sparse plasma cells exist. We present a 67-year-old man whose skin biopsy, taken on day 2 of his eruption, demonstrated a subtle perivascular and interstitial infiltrate of histiocytes without plasma cells. Dermatopathologists need to be aware of this pattern and consider the diagnosis of erythema migrans, despite negative initial serologic testing.