A Diagnostic Challenge: Vegetative Pyoderma Gangrenosum versus Giant Squamous Cell Carcinoma Keratoacanthoma Type

Summary: Background: Pyoderma gangrenosum (PG) is an uncommon inflammatory neutrophilic dermatosis characterized by painful ulcers with undermined violaceous borders. It is often associated with systemic diseases, with the most common being inflammatory bowel disease. PG can be difficult to diagnose, due to a lack of pathognomonic clinical, laboratory, and histopathologic features. The diagnosis is typically obtained by exclusion of other conditions, especially infections. Distinguishing pseudoepitheliomatous hyperplasia (PEH) from squamous cell carcinoma (SCC) can also be challenging histopathologically. The association of PEH with PG is poorly recognized, and cases of PG mimicking SCC keratoacanthoma type or well-differentiated SCC with infiltrative pattern have been very rarely reported in the literature. Methods: We report a case of vegetative PG accompanied by PEH, originally mistaken for squamous cell carcinoma. A 78-year-old woman with a past medical history of acute myeloid leukemia and chronic neutropenia presented with an exophytic, ulcerated, and painful mass on her right lower leg, which first appeared in December 2022. The lesion was a 15 cm exophytic friable mass which gradually progressed in size. She was hospitalized in April and Dermatology was consulted in May 2023. A telescoping punch biopsy was performed to rule out ​​PG vs infection vs leukemia cutis and was non-diagnostic. Tissue cultures grew candida parapsilosis, which was suspected to be a contaminant. Tissue PCR was negative for fungi, bacteria, and mycobacteria. A larger incisional biopsy, though not full thickness, showed PEH and neutrophilic microabscesses. Initially, these histopathologic features raised concern for SCC keratoacanthoma type with PEH or well-differentiated SCC infiltrative pattern. However, following additional review by dermatopathologists and discussion at the cutaneous oncology tumor board, the diagnosis of vegetative PG with associated PEH was favored. The patient was treated with oral prednisone taper, sulfamethoxazole and trimethoprim, broad-spectrum antibiotics, vitamin D3, topical metronidazole, and local wound care. Results: The treatment regimen resulted in healing of the exophytic, ulcerating lesion with residual hyperpigmentation at approximately 5 months after initial presentation. Conclusions: This case raises awareness of the presence of PEH as a histopathology feature that can be seen in PG, with the potential diagnostic confusion of PG with SCC. We emphasize the importance of promptly establishing a diagnosis of PG by integrating clinical and histopathologic findings in order to avoid diagnostic delays and unnecessary surgeries or treatments that could result in severe pathergy.