Dermatology MCQ - Infiltrative and Neoplastic Disorders - Pseudoepitheliomatous hyperplasia

A biopsy is taken from the edge of a chronic, non-healing ulcer on the lower leg of a 65-year-old man. The pathology report describes irregular, downward projections of the epidermis into the dermis, composed of squamous cells with minimal cytologic atypia. The surrounding dermis shows a mixed inflammatory infiltrate and granulation tissue. Mitotic figures are present but are not atypical. Which of the following is the most accurate interpretation of these findings and the most important next step?

A. It is a well-differentiated squamous cell carcinoma; perform wide local excision.
B. It is pseudoepitheliomatous hyperplasia, a benign reactive process; treat the underlying cause of the ulcer.
C. It is a keratoacanthoma; treat with complete excision.
D. It is verrucous carcinoma; perform a deep excision to assess for invasion.
E. It is hypertrophic lichen planus; initiate treatment with high-potency topical corticosteroids.

Correct Answer: B. It is pseudoepitheliomatous hyperplasia, a benign reactive process; treat the underlying cause of the ulcer.

Answer and Explanation

The correct answer is B. This question describes the classic histopathology of pseudoepitheliomatous hyperplasia (PEH). The key findings are the irregular, infiltrative-looking epidermal projections but with a crucial lack of significant cytologic atypia. The presence of an inflammatory background and granulation tissue points to a reactive process secondary to chronic irritation or ulceration. PEH is a benign mimic of squamous cell carcinoma (SCC), and the most critical step is to address the stimulus causing it (e.g., infection, trauma, inflammation).

Why the Other Options are Incorrect:

• A. It is a well-differentiated squamous cell carcinoma: This is the primary diagnostic dilemma. The distinction hinges on cytologic atypia. In well-differentiated SCC, despite being well-differentiated, there is still significant nuclear atypia (enlargement, hyperchromasia, pleomorphism), abnormal mitoses, and often, individual cell keratinization deep within the dermis. PEH lacks these features.

• C. It is a keratoacanthoma: Keratoacanthoma is characterized by a central keratin crater and a distinctive "lipping" of the epidermis at the edges. While it can be considered a variant of SCC by many, its architecture is different from the irregular projections described in PEH, which lacks the large, central keratin core.

• D. It is verrucous carcinoma: Verrucous carcinoma is a very well-differentiated, low-grade SCC. It is characterized by a markedly exophytic (wart-like) growth with pushing, rather than infiltrative, borders. The clinical context of a chronic ulcer is less typical for verrucous carcinoma.

• E. It is hypertrophic lichen planus: While hypertrophic lichen planus can show epidermal hyperplasia, it is characterized by a very dense, band-like lymphocytic infiltrate immediately beneath the epidermis, which is not described here. The primary pathology is the lichenoid inflammation, not a secondary reactive hyperplasia to an ulcer.

Additional High-Yield Information for Exams:

• Histopathology: The hallmark is pseudo-invasion.

  • Architecture: Irregular, anastomosing strands and nests of squamous epithelium extending deep into the dermis. This is the "pseudo" aspect that mimics carcinoma.

  • Cytology: The keratinocytes are mature and well-differentiated with minimal to no atypia. Mitoses may be present but are normal in appearance.

  • Background: There is often an associated mixed inflammatory infiltrate, granulation tissue, fibrosis, or evidence of an underlying cause (e.g., fungi, mycobacteria).

• Underlying Causes (Differential Diagnosis): PEH is not a diagnosis but a reaction pattern. The key is to identify the trigger:

  • Inflammatory: Chronic ulcers (stasis, arterial), prurigo nodularis, granulomatous diseases (granuloma annulare, tuberculosis).

  • Infectious: Deep fungal infections (blastomycosis, chromoblastomycosis), atypical mycobacteria.

  • Neoplastic: Can occur at the edge of a true malignancy (e.g., melanoma, SCC). The pathologist must sample thoroughly to avoid missing the actual tumor.

  • Toxic/Miscellaneous: Reactions to drugs, bromoderma.

• Prognosis: The prognosis is that of the underlying condition. PEH itself is benign and will resolve if the causative stimulus is removed.

• Management & Rationale:

  • Rationale: The cornerstone of management is to identify and treat the underlying cause. Simply excising the PEH without addressing the trigger will lead to recurrence.

  • First-line: Thorough history and examination for the causes listed above. This may include:

    • Special Stains: Requesting fungal (PAS, GMS) and mycobacterial (Fite) stains on the biopsy tissue itself.

    • Tissue Culture: For bacteria, fungi, and mycobacteria.

    • Wound Care: Optimal management of the chronic ulcer.

  • Role of Excision: If the PEH is persistent and the underlying cause has been treated or ruled out, simple excision may be curative.