Enfortumab vedotin-induced cutaneous eruption: Ring mitotic figures as a distinctive histopathologic feature.

Enfortumab vedotin (EV), a nectin-4-binding agent that affects microtubules, has become standard therapy for advanced urothelial carcinoma. The agent, now given in combination with pembrolizumab, frequently induces cutaneous reactions. Here, we report a severe EV-induced cutaneous eruption. A 58-year-old woman with metastatic urothelial carcinoma developed a rash after receiving simultaneous first doses of EV and pembrolizumab. The eruption began on the flank and spread to involve her trunk and extremities with prominent involvement of folds, including the axillae and medial thighs. Skin biopsy revealed extensive vacuolar alteration of the basal epidermis and numerous epidermal keratinocytic mitotic figures, often suprabasilar, including ring and "starburst" forms. The findings supported a diagnosis of EV-induced eruption. With EV cessation and systemic corticosteroids, the rash resolved over a few weeks. Pembrolizumab was restarted as monotherapy, and the patient's cancer showed a significant radiographic treatment response at 3 months. An emerging literature of small series and case reports, largely from oncologic literature, presents the histopathology of EV-induced cutaneous eruption as a vacuolar interface dermatitis with the inconsistently reported feature of arrested mitotic figures. This case study demonstrates distinctive clinical and histopathologic features of EV-induced eruption, which may inform dermatologic and oncologic management.

Cutaneous Rosai-Dorfman disease with MAP2K1 mutation, initially mimicking an infection with parasitized histiocytes.

Rarely, Rosai-Dorfman disease (RDD) manifests exclusively in the skin, typically as nodules on the trunk and extremities. Recognition of characteristic histopathologic features enables diagnosis of RDD. A 55-year-old female presented with a 7-year history of cutaneous nodules involving the trunk and extremities. A prior skin biopsy specimen at a different institution had demonstrated a dense dermal lymphohistiocytic infiltrate with histiocytes containing GMS+ forms, favored to represent cryptococcal organisms, with a differential diagnosis including other infections with parasitized histiocytes. Despite antibiotic therapy, lesions persisted. After a presentation to our institution, a biopsy specimen showed a diffuse infiltrate, including histiocytes with voluminous pale cytoplasm with focal emperipolesis of inflammatory cells and S100 immunohistochemical positivity. Clinical and radiologic examinations did not identify significant extracutaneous involvement. A genetic study performed on the biopsy specimen identified a K57Q mutation of MAP2K1. The presence of this mutation correlated with prior reports of MAP2K1 mutation in classic RDD, thereby supporting our histopathologic diagnosis of RDD over an infectious process and further illuminating options for targeted therapies. At 3-year follow-up, the patient has been managed with a course of systemic corticosteroids and excision of bothersome lesions. Consideration of systemic therapy is ongoing.