2023-04/January 30


Ayat Ghazy; Georgia State University, Georgia, USA; Lara Harik, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia

A male in his 60s presents with a complaint of a skin rash in the right inguinal region and scrotum.



1- What is the provisional diagnosis?
a- Extramammary paget’s disease
b- Melanoma
c- Squamous cell carcinoma in situ(SCCIS) with pagetoid pattern
d- Herpetic lesions
e- Eczema

2- Which of the following immunohistochemical markers is expected to be positive in this case?
a- CD34
b- CK7
c- MART1
d- S100
e- CDX2

1. A
2. B

Extramammary paget’s disease

Extramammary Paget’s disease (EMPD) is a rare neoplasm that arises from apocrine glands rich areas (such as vulva, scrotum, perianal, axillary regions). EMPD can be classified into primary (arising from the epithelium at the site of presentation) and secondary (extracutaneous origin). As the treatment and prognosis differ, accurate diagnosis with a detailed histopathological evaluation of immunohistochemical markers is required.

Histopathological examination shows Paget cells, which are atypical large cells with abundant, clear, sometimes eosinophilic cytoplasm. The cells can present singly or form clusters. The epidermis often shows acanthosis with ulceration, hyperkeratosis or parakeratosis. Non-invasive EMPD originates from the epidermis/squamous epithelium and frequently extend to involve the epithelium of eccrine glands and/or hair follicles, whereas invasive EMPD extends to involve the dermis/lamina propria.

Paget cells (whether primary or secondary EMPD) are usually positive for the diastase-periodic acid-Schiff (PAS), Her 2 and CEA. However, comprehensive evaluation using multiple markers, including CK7/20, gross cystic-disease fluid protein-15(GCDFP-15), CDX-2, and uroplakin II and III, is required for accurate discrimination of primary and secondary EMPD. The microscopic morphology and distribution of tumor cells in melanoma and Bowen disease also sometimes resemble EMPD. Whereas melanoma cells are typically positive for S-100, HMB-45, and Melan-A, and atypical keratinocytes of Bowen disease are typically positive for p63, on the other hand, Paget cells in EMPD are usually negative for all of these molecules. Additionally, negative staining of PAS and CEA in melanoma and Bowen disease tumor cells also aid in distinguishing these diseases from EMPD.
In our case, the tumor (Paget’s cells) showed positivity for CK7, GATA3 and Her2 neu (2-3+), whereas CK20, CDX2, NKX3.1 and SOX10 were negative.

The outcome and the prognosis of EMPD varies according to whether it is primary or secondary, invasive or non-invasive, where non-invasive primary EMPD has a good prognosis when completely resected. On the other hand, invasive EMPD carries a worse prognosis. However, long-term follow-up is required because of the multi-focal nature of the disease and the high recurrence rate

– Hegarty, Paul K., Jane Suh, Mark B. Fisher, Jennifer Taylor, Tri H. Nguyen, Doina Ivan, Victor G. Prieto, Lance C. Pagliaro, and Curtis A. Pettaway. “Penoscrotal extramammary Paget’s disease: the University of Texas MD Anderson Cancer Center contemporary experience.” The Journal of urology 186, no. 1 (2011): 97-102.
– Ishizuki S, Nakamura Y. Extramammary Paget’s Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments. Current Oncology. 2021; 28(4):2969-2986.
– Shabihkhani, Maryam, Pallavi Patil, Belkiss Murati-Amador, Jose A. Plaza, Adeboye O. Osunkoya, Kara Lombardo, Jonathan I. Epstein, and Andres Matoso. “Extramammary Paget disease of the scrotum: a contemporary clinicopathologic analysis of 20 cases in the United States.” Applied immunohistochemistry & molecular morphology: AIMM 28, no. 7 (2020): 524.

Ayat Ghazy; Georgia State University, Georgia, USA; Lara Harik, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia


Paget’s disease, scrotum