Pathology of Extramammary Paget's Disease

Dr Sampurna Roy MD    

Fifteen years later Crocker described the first case of extramammary Paget's disease affecting the scrotum and penis.

Dubreuilh described the first case of vulvar extramammary Paget's disease in 1901.

Extramammary Paget's disease is an uncommon neoplastic condition observed mostly in areas with numerous apocrine and or eccrine glands.

The most common site is the anogenital region followed by axilla, eyelid and external ear.

This condition can be classified into primary (of cutaneous origin) and secondary (of extracutaneous origin).

The secondary extramammary Paget disease results from spread of an internal malignancy, most commonly of an anorectal origin or of urothelial origin (bladder, urethra).

A small number of intraepithelial Paget's disease is associated with adnexal adenocarcinoma.

This is referred to as 'pagetoid spread' from the adnexal adenocarcinoma.

Clinically, extramammary Paget's disease begins insidiously with pruritis and burning sensation.

The macroscopic appearance ranges from flaking, oozing and maceration to crusted plaque and tumour formation.

Differential Diagnosis:

The differential diagnosis includes superficial spreading malignant melanoma, Bowen's disease, the epidermal phase of neuroendocrine carcinoma , mycosis fungoides, Toker cells, clear cell papulosis and pagetoid spread of visceral carcinoma.

In superficial spreading melanoma, the tumour cells show prominent nesting along the dermoepidermal junction.

Immunohistochemically, these cells  are negative for CAM 5.2, EMA, CEA (these are positive in Paget's disease) and are positive for S100 and HMB45.

No intracellular mucin is seen and there is no  acinar formation in melanoma. In 25% cases S100 expression has been noted in mammary Paget's disease. In extramammary Paget's disease only occasional cells show S100 positivity.

In pagetoid Bowen's disease no signet ring cells, intracellular mucin or acinar structures are identified.

Immunohistochemical staining will confirm the diagnosis (CAM 5.2, EMA,  CEA negativity).

In mycosis fungoides the 'cerebriform cells' with pale cytoplasm may resemble Paget's cells.

However T cell markers will help in establishing the diagnosis. (CD3, UCHL-1 positive in mycosis fungoides).

In rectal carcinoma with pagetoid spread the cells show immunopositivity with CK7 and CK20 together with  CAM 5.2, EMA and CEA and negativity with GCDFP-15 . 

In extramammary paget's disease  CK20 is negative  and GCDFP-15 is positive.

In pagetoid spread of prostatic carcinoma the cells show immunopositivity with PSA and CAM5.2 .

The others stains are negative.

In pagetoid spread of neuroendocrine carcinoma paranuclear dot positivity is noted with  CAM 5.2, CK20, EMA and Synaptophysin are also positive.

Toker cells are normally found in the nipple epithelium and is characterised by clear cytoplasm and small eccentric nuclei.

In clear cell papulosis the histological  features are similar to toker cell hyperplasia.

Unlike Paget's cells, these cells have a bland appearance.

The treatment for noninvasive extramammary Paget's disease is wide surgical excision  (ideally with 1cm margin of normal skin). 

In cases of locally invasive extramammary Paget's disease  radical surgery with or without adjuvant radiotherapy is advocated.

Primary extramammary Paget's disease, confined to epidermis has a good  prognosis. 

The diagnosis of extramammary Paget's disease warrants a thorough search for associated adnexal or visceral malignancy.

In conclusion, extramammary Paget's disease is a rare entity which may take a progressive course, if not treated early.

Histologically, the most common differential diagnosis includes superficial spreading melanoma and Bowen's disease.

A careful clinicopathological correlation and histological assessment with appropriate histochemical and immunohistochemical staining should allow a confident histological diagnosis of extramammary Paget's disease to be  made in most cases.