Paget’s Disease
Paget’s disease of the skin is a rare intraepithelial (in situ) adenocarcinoma, defined by malignant Paget cells scattered singly or in clusters throughout the epidermis. It occurs as two biologically distinct entities: mammary Paget’s disease (MPD) and extramammary Paget’s disease (EMPD). Its biggest challenge is that it looks very much like common benign skin conditions such as eczema, atopic dermatitis or fungal infection, so diagnosis is frequently delayed. A prolonged misdiagnosis can give an underlying invasive adenocarcinoma time to grow, invade and spread.
At Haute-Derma, we combine detailed histopathologic diagnosis with comprehensive imaging to screen for internal malignancy. Our integrated treatment strategy—margin-controlled excision, photodynamic therapy (PDT) and targeted therapies—aims to clear the disease effectively, lower the risk of recurrence and preserve as much function and appearance as possible.
Clinical Features and Pathology
Clinical Types and Pathogenesis
- Mammary Paget’s disease (MPD):
- Pathogenesis: More than 90–95% of MPD cases are associated with an underlying breast carcinoma (invasive ductal carcinoma or DCIS). Tumor cells from the milk ducts migrate upward (epidermotropic migration) into the epidermis of the nipple and areola.
- Presentation: A solitary red, scaly, weeping, eroded or fissured patch on the nipple/areola (usually on one side), sometimes with nipple retraction or a palpable breast lump.
- Extramammary Paget’s disease (EMPD):
- Pathogenesis: It arises either from apocrine/eccrine gland progenitor cells within the skin itself (primary EMPD) or from tumor cells spreading from a nearby internal cancer, such as colorectal, bladder, or cervical/vaginal cancer (secondary EMPD).
- Presentation: A well-demarcated red plaque with a thin, spongy surface, white scale or eczema-like oozing (eczematous plaque) and persistent itch, found in apocrine-rich areas (perineum, vulva, groin, scrotum, perianal skin, armpits).
Histopathology
- Paget cells: Large glandular tumor cells with abundant pale or vacuolated, mucin-containing cytoplasm and large, hyperchromatic, eccentric nuclei with prominent nucleoli.
- Distribution in the epidermis: Paget cells lie singly along the basal layer or gather in nests and clusters within the epidermis, compressing the surrounding keratinocytes while the basement membrane stays intact (unless the tumor has invaded the dermis).
- Special stains: Paget cells stain positive with mucin stains such as mucicarmine, diastase-resistant PAS (periodic acid–Schiff) and Alcian blue.
Differential Diagnosis and Immunohistochemistry (IHC)
An immunohistochemistry (IHC) panel is essential for separating Paget’s disease from melanoma in situ and squamous cell carcinoma in situ (Bowen’s disease), and for determining whether it is primary or secondary:
| Condition | Histology and IHC Markers |
|---|---|
| Mammary Paget’s disease (MPD) | CK7 (+); CEA (+); CAM 5.2 (+); HER2 (+) (very high, 80–90%); GATA3 (+); S100 (−); p63 (−). |
| Primary EMPD | CK7 (+); GCDFP-15 (+); CK20 (−); CDX2 (−); CEA (+). |
| Secondary EMPD | • Colorectal origin: CK20 (+), CDX2 (+), CK7 (−), GCDFP-15 (−). • Urogenital origin: CK20 (+), uroplakin III (+), GATA3 (+). |
| Melanoma in situ | Atypical melanocytes; S100 (+); SOX10 (+); Melan-A (+); HMB-45 (+); cytokeratin (−); CEA (−). |
| Bowen’s disease (cSCC in situ) | Full-thickness atypical keratinocytes with intercellular bridges; p63/p40 (+); CK5/6 (+); CK7 (−); CEA (−). |
Our Approach to Paget’s Disease of the Skin
Haute-Derma manages Paget’s disease with a thorough, cautious approach:
- Never treated as chronic eczema: Any red, scaly, eczema-like patch on the nipple or in the anogenital region that has not responded to topical corticosteroids within 2–4 weeks is biopsied straight away.
- Mandatory screening for internal cancer:
- MPD: mammography and breast MRI are required.
- EMPD: screening of the gastrointestinal tract (colonoscopy), urinary tract (abdominal ultrasound/CT, cystoscopy) and gynecologic or male genital organs is required to rule out secondary EMPD.
- Definitive surgery with microscopic margin control: Margin-controlled wide excision or Mohs micrographic surgery to remove tumor cells that have spread beneath clinically normal-looking skin.
- Combined treatment and function preservation: Photodynamic therapy (PDT), topical immunomodulators and treatment of any underlying primary cancer within a multidisciplinary plan.
How We Diagnose Paget’s Disease at Haute-Derma
To confirm the diagnosis under the microscope and rule out an associated internal cancer, Haute-Derma follows a four-step process:
- Clinical examination and high-magnification dermoscopy: We look for a well-defined red plaque, milky-red areas, gray-white structureless zones and abnormal (polymorphous or dotted) vessels.
- Punch or incisional biopsy: The sample includes both the lesion and its edge with surrounding normal skin, so the pathologist can look for Paget cells and check that the basement membrane is intact.
- Histopathology and IHC panel: Staining for CK7, CK20, CDX2, GCDFP-15, HER2, S100 and p40 confirms the diagnosis and distinguishes primary from secondary disease.
- Imaging and systemic screening: Mammography/breast MRI for MPD; for EMPD, colonoscopy, abdominopelvic CT and tumor markers (CEA, CA 19-9, PSA).
How Paget’s Disease Is Treated at Haute-Derma
Treatment at Haute-Derma is tailored to the site of the disease and to whether an internal cancer is also present:
- Mammary Paget’s disease (MPD):
- Working closely with breast surgeons and oncologists, we arrange breast-conserving surgery (lumpectomy) with removal of the nipple–areola complex and sentinel lymph node biopsy, or mastectomy, depending on the underlying breast cancer.
- Adjuvant chemotherapy, radiotherapy or HER2-targeted therapy (trastuzumab) when the underlying tumor calls for it.
- Extramammary Paget’s disease (EMPD):
- Mohs micrographic surgery (MMS) / margin-controlled wide local excision (WLE): Because EMPD extends microscopically far beyond its visible border, excision with 2–3 cm margins or Mohs surgery, which examines 100% of the surgical margin, is the gold standard for preventing recurrence.
- Photodynamic therapy (PDT): ALA-PDT for extensive superficial anogenital EMPD that cannot be excised, or as an adjuvant after surgery.
- Topical therapy (imiquimod 5%): For primary in situ EMPD or recurrences that are no longer suitable for surgery.
- Genital and perineal reconstruction: Local skin flaps restore function and appearance after wide excision.
