What Is Extramammary Paget’s Disease?

Extramammary Paget’s disease (EMPD) is a rare skin cancer that develops in areas outside the breast, most often in the genital, groin, and perianal regions. It is classified as an adenocarcinoma that originates in the outer layer of the skin or from nearby skin glands, specifically in zones rich in apocrine sweat glands.¹ The disease tends to grow slowly and can look remarkably like eczema or a fungal infection, which means it often goes undiagnosed for months or even years. Despite its slow pace, EMPD carries the potential for deeper invasion, lymph node spread, and association with internal cancers, making accurate diagnosis and thorough screening essential.

How EMPD Relates to Mammary Paget’s Disease

The term “Paget’s disease” in dermatology traces back to Sir James Paget, who in 1874 described a chronic, eczema-like change on the nipple that preceded breast cancer. The extramammary form was first established as a separate entity by Crocker in 1889.² Although mammary and extramammary Paget’s disease share many features under a microscope, they differ in one critical respect: mammary Paget’s disease is almost always associated with an underlying breast cancer, while EMPD is linked to an internal malignancy far less often.³ That distinction matters because it shapes the urgency and type of screening patients receive after diagnosis.

Where It Appears and Who Gets It

EMPD develops in skin that contains apocrine glands. In practice, this means the vulva, the penis and scrotum, the perianal area, the groin folds, and occasionally the armpits. Among women, the vulva is by far the most common site, accounting for more than 80% of female cases. In men, cases are more evenly split between the penis and scrotum and non-genital skin sites.⁴⁵

EMPD is predominantly a disease of older adults. A large analysis of U.S. registry data found the mean age at diagnosis is around 70 to 72 years, with roughly 46% of patients aged 75 or older. The disease affects more women than men, partly because vulvar EMPD is the most prevalent subtype. The vast majority of diagnosed patients in U.S. databases have been white, though a disproportionately high share of Asian and Pacific Islander patients also appears in the data, suggesting either a true higher risk or different patterns of diagnosis.⁵

Symptoms and the Problem of Delayed Diagnosis

EMPD typically begins as a red, scaly, or weeping patch on the skin that looks deceptively benign. The most common symptom across all anatomic sites is itching. In one meta-analysis, itching was reported in over 90% of penoscrotal cases and about half of perianal cases.⁶ Patients may also notice burning, tenderness, or a moist surface that does not heal. Some lesions develop small bumps or areas of darker or lighter pigmentation, which can further confuse the picture.

Because EMPD so closely resembles common conditions like eczema, fungal infections, or contact dermatitis, misdiagnosis is a persistent problem. The average delay between the first symptom and a correct diagnosis is nearly two years for vulvar and perianal cases, and about a year for penoscrotal cases.⁶ Dermoscopy, a technique that magnifies skin structures under polarized light, is now being studied as a tool to help distinguish EMPD from chronic eczema earlier. EMPD lesions tend to show a milky-red background with evenly distributed dot-like blood vessels and gray-brown structures, while eczema typically shows clustered dot-like vessels and more prominent scaling.⁷

A biopsy is the only way to confirm the diagnosis. Under a microscope, the hallmark finding is large, pale “Paget cells” scattered through the outer layer of the skin, often with obvious cellular abnormalities and sometimes forming glandular patterns.⁸

Primary Versus Secondary EMPD

One of the most important distinctions after an EMPD diagnosis is whether the disease is primary or secondary, because the treatment strategy differs substantially. Primary EMPD starts in the skin itself as a standalone cancer. This is the far more common type, accounting for roughly 70% or more of all cases. Secondary EMPD, by contrast, is caused by cancer cells from an internal organ spreading upward into the skin. The underlying cancer is usually from a nearby organ: colorectal cancer for perianal EMPD, bladder or urethral cancer for genital EMPD.⁹¹⁰

Telling the two types apart under a microscope alone is difficult. Pathologists use a panel of protein markers on the tissue to help. Both types stain positive for a protein called CK7, but secondary EMPD is more likely to also stain positive for CK20 and a marker called CDX2, which point toward a colorectal origin.¹¹ A newer marker, TRPS1, may further sharpen the distinction: in one study, 88% of primary EMPD cases expressed TRPS1, while none of the secondary cases did.¹⁰ Even with these tools, imaging studies like CT scans and endoscopy are often needed to rule out an internal cancer with certainty.

Screening for Associated Internal Cancers

Whether or not the EMPD turns out to be primary, screening for associated cancers is recommended for all patients at the time of diagnosis. The risk of a hidden internal malignancy varies sharply by where the EMPD is located. Perianal EMPD carries the highest risk, with about 25% of cases associated with an underlying cancer, most commonly colorectal. Vulvar and penoscrotal EMPD have lower rates, roughly 6% each, and the associated cancers tend to be of urinary tract or reproductive organ origin.¹²

The specific screening approach depends on the anatomic site and how high-risk the case appears:

Perianal EMPD: Colonoscopy, urine testing, and CT imaging of the chest, abdomen, and pelvis are recommended given the high association with colorectal cancer.
Penoscrotal EMPD: Lower-risk screening typically includes urine cytology, a stool blood test, and a PSA test for men under 70.
Vulvar EMPD: Urine cytology and mammography are recommended as a baseline for lower-risk cases.

Cases with high-risk features, such as invasive disease or certain protein-marker patterns, may warrant more extensive organ-specific testing.¹² A separate study at a single institution found that urine cytology, mammography, and PSA testing were the most productive tests for uncovering hidden cancers in EMPD patients.¹³

Surgical Treatment and the Challenge of Margins

Surgery is the primary treatment for EMPD that has not spread beyond the skin. The central challenge is that Paget cells frequently extend well beyond the visible borders of the lesion, making it difficult to remove the entire cancer in one pass. Two main surgical approaches are used: wide local excision (removing the visible lesion plus a broad margin of surrounding tissue) and Mohs micrographic surgery (removing tissue in thin layers and checking each layer under a microscope before cutting further).

A systematic review and meta-analysis found that Mohs surgery results in substantially lower recurrence rates than wide excision. The local recurrence rate after Mohs surgery was about 7%, compared with roughly 26% after standard wide excision. Patients treated with wide excision were nearly three times more likely to have the cancer return at the same site.¹⁴ Despite these numbers, recurrence remains a frustrating hallmark of EMPD regardless of the surgical method. Published recurrence rates across all surgical approaches range from 15% to 70%, and repeat operations carry significant physical and emotional costs.¹⁵

When surgery removes large areas of genital skin, particularly for vulvar EMPD, reconstructive procedures using local skin flaps help close the wound and restore anatomy. One series of 47 patients (nearly half of whom had EMPD) used different flap techniques based on the location and size of the defect, with wound complications occurring in about 21% of patients overall and oncologic recurrence at 15% over two years.¹⁶

Radiation Therapy

Radiation is used in several roles for EMPD: after surgery to reduce the chance of recurrence, as a standalone treatment when surgery is not feasible, and for advanced disease. One retrospective study with a median follow-up of about three and a half years found that radiation alone achieved local disease control in 88% of patients at three years, with overall survival of 93% at three years and 68% at five years. No severe radiation-related side effects were observed.¹⁷

When given after surgery, radiation appears to provide excellent local control. In a study of patients who received postoperative radiation, all had local disease control at a median follow-up of 38 months, though six patients still developed distant metastases. Having cancer in the groin lymph nodes at the time of treatment was a significant risk factor for later distant spread.¹⁸ A more recent analysis of over 100 patients reinforced these findings, concluding that radiation following Mohs surgery provides excellent local control, and that radiation alone can effectively manage tumors that include metastases.¹⁹

Topical Treatment for Non-Invasive Disease

For patients with EMPD confined to the skin surface who cannot undergo or prefer to avoid surgery, a topical immune-stimulating cream called imiquimod has shown promise. In a small study of nine patients with non-invasive disease, imiquimod applied three times per week for 16 weeks produced a response in every patient, including complete clearance of the cancer in five of the nine. The most common side effect was local skin irritation, which resolved when the cream was temporarily stopped.²⁰ These results are encouraging, but the evidence base is limited to small case series. Imiquimod is generally considered an alternative rather than a first-line treatment, and long-term recurrence data in EMPD remains sparse.

Systemic Therapy and Targeted Drugs for Advanced Disease

When EMPD invades deeply or spreads to lymph nodes or distant organs, the disease becomes much harder to treat. Standard chemotherapy has been used, but response rates vary by regimen. In a Korean study of 31 patients with advanced EMPD, platinum-based chemotherapy achieved tumor shrinkage in about 46% of patients, while taxane-based chemotherapy achieved it in about 63%, though neither approach produced long-lasting remissions for most patients.²¹

A more exciting development involves drugs that target a protein called HER2, which is overexpressed in a significant fraction of EMPD tumors. In the same Korean study, patients who received chemotherapy combined with the HER2-targeting antibody trastuzumab had a 100% response rate and a median time before the disease worsened of over 13 months, notably better than chemotherapy alone.²¹ A separate molecular analysis found HER2 overexpressed in about 30% of metastatic EMPD cases, and HER2-directed therapies were durably effective in those patients.²²

Newer antibody-drug conjugates, which attach a chemotherapy payload directly to an antibody that homes in on HER2, may widen the pool of patients who benefit. One study found that as many as 95% of EMPD tumors express some level of HER2, even if the level is low by traditional scoring, suggesting that these conjugate drugs could work even when the cancer would not qualify for standard HER2-targeted antibodies.²³ This is still early-stage research, but for a cancer with so few systemic treatment options, it represents one of the most promising avenues in a generation.

Prognosis and What Drives It

For the majority of patients whose EMPD is caught while still confined to the outer skin layer, the outlook is generally favorable. The disease is slow-growing, and properly treated in-situ EMPD rarely threatens life. The picture changes when the cancer invades more deeply. Deep dermal invasion was identified as a strong predictor of poor outcomes in a Taiwanese analysis, with those patients having a significantly higher risk of disease-related death.²⁴ A multicenter study of 249 patients confirmed that both deep invasion (1 mm or more) and the presence of metastatic disease at diagnosis were associated with significantly worse disease-specific survival.²⁵

The anatomic location also matters. Perianal EMPD tends to be diagnosed at a more advanced stage: about half of perianal cases are already invasive at diagnosis, compared with roughly 30% to 37% of vulvar and penoscrotal cases.⁶ That higher rate of invasion, combined with the strong association with colorectal cancer, makes perianal EMPD the subtype with the most guarded prognosis.

Living with EMPD and Finding Support

Beyond the medical facts, EMPD takes a toll that clinical studies only partially capture. The disease sits in intimate areas of the body, and both the disease itself and its treatments can affect sexual function, urination, and basic comfort. The high recurrence rate means patients often face repeated biopsies and surgeries over many years, each one adding physical scarring and emotional weight.¹⁵ Because the disease is rare, many patients find that their general practitioners and even dermatologists have limited experience with it, which can compound the frustration of the diagnostic delay they have often already endured.

Online support communities have emerged to fill part of this gap. A pilot survey of one international EMPD patient support group highlighted the heterogeneous care these patients receive, with wide variation in treatments, follow-up schedules, and screening protocols from one provider to the next.²⁶ Clinical practice guidelines published in recent years are beginning to standardize care, recommending age- and site-appropriate malignancy screening and outlining treatment options by disease stage.²⁷ For anyone diagnosed with EMPD, seeking out a dermatologic surgeon or oncology team that has treated the disease before is one of the most impactful steps toward getting consistent, evidence-based care.

1
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