What is the diagnostic approach for extramammary Paget's disease?

Diagnostic Approach for Extramammary Paget's Disease

Full-thickness skin biopsy with immunohistochemical staining is the gold standard for diagnosing extramammary Paget's disease (EMPD). 1

Clinical Presentation

• EMPD classically presents as a slowly growing, erythematous plaque that often mimics inflammatory conditions, leading to significant delays in diagnosis 1
• Common symptoms include pruritus, erythema, and scaling in the affected areas 2, 3
• Most commonly affects apocrine gland-bearing areas such as the perineal, scrotal, perianal, and genital regions 4, 3

Diagnostic Algorithm

Step 1: Clinical Evaluation

• Examine for erythematous, eczematous, or ulcerative lesions in apocrine-rich areas 2, 1
• Document any symptoms such as itching, bleeding, or pain 2
• Note that the clinical appearance often mimics dermatitis, leading to misdiagnosis and treatment delays 2, 1

Step 2: Skin Biopsy

• Perform full-thickness skin biopsy of the involved area 4, 1
• The biopsy should include adequate tissue for both histopathological examination and immunohistochemical staining 5
• For penile or scrotal lesions, a 2 cm margin outside the visible lesion is recommended for adequate sampling 3

Step 3: Histopathological Examination

• Look for characteristic Paget cells, which are large cells with abundant pale cytoplasm predominantly at the base of the epidermis 5
• In some cases (6%), well-defined nests of large Paget cells may mimic melanocytic nests 5

Step 4: Immunohistochemical Staining

• Essential for confirming diagnosis and differentiating from other conditions 5, 1
• Key stains include:
  • Carcinoembryonic antigen (CEA): positive in 93% of cases 5
  • Cam 5.2 (low molecular weight keratin): positive in 71% of cases 5
  • Mucin stains (Hale's colloidal iron): positive in 96% of cases 5
  • Additional stains may include CK7, CK20, GCDFP-15, and S-100 to differentiate from melanoma and other conditions 1

Step 5: Evaluation for Associated Malignancies

• Approximately 33% of EMPD cases are associated with underlying malignancies 5
• Common associated malignancies include:
  • Transitional cell carcinoma of the bladder 5
  • Adenocarcinoma underlying the skin 5
  • Anorectal adenocarcinoma 5
  • Vulvar adenocarcinoma 5
  • Prostate carcinoma 5
• Consider appropriate imaging studies based on the anatomical location of EMPD to rule out underlying malignancy 1

Important Diagnostic Considerations

• Negative staining for mucin and CEA occurs more frequently in patients with underlying malignancy (13% vs. 0% for mucin; 13% vs. 3% for CEA) 5
• Rapid frozen section pathology during surgical excision is recommended to ensure negative margins 3
• Long-term follow-up is mandatory to identify and treat any subsequent recurrence or concurrent malignancy 2

Common Pitfalls to Avoid

• Misdiagnosis as inflammatory dermatoses (eczema, psoriasis) or Bowen's disease is common 2, 1
• Inadequate biopsy sampling may miss the diagnosis 1
• Failure to perform immunohistochemical staining can lead to incorrect diagnosis 5
• Not evaluating for underlying malignancy can miss associated cancers 5