Question

Difficulty: HardPathology and Biopsy Interpretation

A 72-year-old woman presents to the gynecology clinic complaining of severe, persistent vulvar pruritus and a burning sensation for the past 8 months. She notes that the symptoms have not improved despite applying an over-the-counter topical hydrocortisone cream. On physical examination, there is a well-demarcated, erythematous, crusted, and slightly weeping plaque measuring 3.5 cm on the right labium majus. A punch biopsy of the lesion is performed. Light microscopy of the hematoxylin and eosin (H&E) stained section reveals an intact basement membrane with a proliferation of large, atypical cells containing abundant pale-staining cytoplasm and prominent nucleoli. These cells are scattered singly and in small clusters throughout the epidermis, predominantly in the basal and suprabasal layers. Immunohistochemical staining demonstrates that the atypical cells are strongly reactive for cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA), but are completely negative for S100 protein, Melan-A, and p63. Which of the following is the most definitive diagnosis established by these histopathologic and immunohistochemical findings?

  1. Extramammary Paget diseaseAnswer
  2. B
    Amelanotic melanoma in situ
  3. C
    Squamous cell carcinoma in situ
  4. D
    Lichen sclerosus
  5. E
    Langerhans cell histiocytosis

Answer

The correct answer is Extramammary Paget disease, diagnosed by the presence of large, atypical, CK7-positive and CEA-positive intraepidermal cells.
The correct answer describes a neoplasm consisting of large, pale-staining atypical cells spreading through the epidermis (Paget cells). Because Extramammary Paget disease is an intraepithelial adenocarcinoma, these cells express epithelial and glandular markers such as cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA). They do not express markers of melanocytes (S100, Melan-A) or squamous cells (p63), which makes this immunohistochemical profile pathognomonic for the disease.

Step-by-Step Solution

1
Analyze the clinical presentation.
A 72-year-old woman with an erythematous, crusted, pruritic vulvar plaque refractory to topical steroids.
This presentation is highly suspicious for a vulvar malignancy or pre-malignant condition, necessitating a biopsy.
2
Interpret the morphologic histopathology findings.
The biopsy shows an intact basement membrane (in situ disease) with large, atypical cells featuring pale cytoplasm scattered in the epidermis (Pagetoid spread).
The morphologic differential diagnosis for Pagetoid intraepidermal spread includes Extramammary Paget disease, melanoma in situ, and squamous cell carcinoma in situ.
3
Synthesize the immunohistochemical (IHC) staining profile.
The atypical cells are CK7(+) and CEA(+), indicating glandular epithelial differentiation. They are S100(-) and Melan-A(-), ruling out melanocytic origin. They are p63(-), ruling out squamous origin.
IHC is required to definitively determine the cellular lineage of the intraepidermal neoplasm.
4
Formulate the definitive diagnosis.
The combination of Pagetoid morphology with a glandular IHC profile establishes the diagnosis of Extramammary Paget disease.
This exactly matches the specific pathologic diagnostic criteria for this disease entity.

Key Concept

The diagnosis of Extramammary Paget disease requires differentiating Pagetoid intraepidermal cells from melanoma and squamous cell carcinoma in situ by relying on immunohistochemical markers; Paget cells are positive for low-molecular-weight cytokeratins (CK7) and CEA, but negative for S100 and p63.
Estimated Time:1m 30s
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