“Dark Paget” Cells in Extramammary Paget Disease of the Vulva—Diagnostic Features and Interpretative Pitfalls

Extramammary Paget disease (EMPD) is characterized by intraepithelial neoplastic glandular cells with hyperchromatic nuclei and abundant pale, mucin-rich cytoplasm. One of our authors previously reported 3 cases of primary EMPD exhibiting an unusual morphology characterized by darker pagetoid cells ("Dark Paget"). Our study aims to identify additional cases to further describe this unique presentation. Our database was queried for vulvar EMPD (2018-2025). We defined "Dark Paget" cells as smaller in size with an increased nuclear to cytoplasmic ratio, a striking absence of abundant pale cytoplasm, and hyperchromatic nuclei with irregular contours. Support was provided by staining with CK7 (and additional stains as applicable) for all patients. Patient age, clinical presentation and treatment were recorded. A total of 96 vulvar EMPD specimens were identified, of which 10 cases from 3 patients (age range: 34-84 yr, mean: 72) fit the morphologic criteria for "Dark Paget." EMPD was clinically suspected in all (10/10, 100%) cases; all 10 (100%) represented a recurrence and shared similar prior treatment modalities. On low-power magnification, "Dark Paget" mimicked an HPV-associated squamous intraepithelial lesion in 6 (60%) and differentiated vulvar intraepithelial neoplasia in 4 (40%) cases. This unusual presentation of vulvar EMPD, termed "Dark Paget," represents a diagnostic pitfall, potentially leading to delay in proper diagnosis and management. Awareness of this subtle presentation and careful histopathologic evaluation, combined with a low threshold for ancillary staining, is essential to avoid misdiagnosis. A potential association between patients with recurrent disease, "Dark Paget" morphology and prior treatment modalities requires further investigation.