What are the differential diagnoses for a skin lesion whose biopsy shows psoriasiform epidermal hyperplasia with retained granular layer, moderate spongiosis, hyperkeratosis, parakeratosis, dermal edema and a perivascular lymphocytic infiltrate with occasional plasma cells and eosinophils?

Differential Diagnosis of Psoriasiform Epidermal Hyperplasia with Retained Granular Layer and Spongiosis

The most likely differential diagnoses are psoriasis (particularly early, resolving, or palmoplantar variants), spongiotic dermatitis/eczema, or a hybrid/overlap pattern, with psoriasis being favored if you identify vertically-oriented alternating parakeratosis and orthokeratosis. 1, 2

Primary Diagnostic Considerations

Psoriasis (Most Likely)

The combination of psoriasiform hyperplasia with an intact granular layer is a critical non-classic feature that appears in 65% of clinically confirmed psoriasis cases 1. Your biopsy shows several features supporting psoriasis:

• Psoriasiform epidermal hyperplasia is the defining architectural pattern of psoriasis and related disorders 3
• Parakeratosis with hyperkeratosis occurs in 96% of confirmed psoriasis cases 1
• Dermal edema (papillary dermal edema) is present in 29.4% of psoriasis cases 2
• Perivascular lymphocytic infiltrate is the expected inflammatory pattern 3
• Rare eosinophils appear in 49% of confirmed psoriasis biopsies 1
• Rare plasma cells are documented in 16% of psoriasis cases 1

Key diagnostic clue: Look specifically for multiple vertically-oriented foci of parakeratosis alternating with orthokeratosis—this is the only statistically significant histologic feature (p=0.005) that differentiates palmoplantar psoriasis from eczema, present in 76.5% of psoriasis cases 2.

Spongiotic Dermatitis/Eczema (Second Most Likely)

The moderate spongiosis is the feature that creates diagnostic uncertainty, as this is more characteristic of eczematous processes:

• Spongiosis appears in 76% of clinically confirmed psoriasis cases, challenging the traditional teaching that spongiosis excludes psoriasis 1
• Neutrophilic spongiosis (spongiform pustules) occurs in 61% of psoriasis cases 1
• Eosinophilic spongiosis is documented in 8% of psoriasis cases 1
• In eczema, spongiosis is typically more prominent and diffuse throughout the epidermis, whereas in psoriasis it tends to be restricted to lower epidermal layers (47.1% of cases) 2

Palmoplantar Psoriasis vs. Palmoplantar Eczema

If this biopsy is from palmoplantar skin, the diagnostic challenge intensifies because these two entities share extensive histologic overlap 2:

• Spongiotic vesicles appear in 76.5% of palmoplantar psoriasis cases 2
• Multiple parakeratotic foci occur in 70.6% of palmoplantar psoriasis 2
• The presence of plasma cells and eosinophils in the infiltrate does not exclude psoriasis 1, 2

Critical Histologic Features to Re-examine

Features Favoring Psoriasis:

• Vertically-oriented alternating parakeratosis/orthokeratosis (most specific, p=0.005) 2
• Neutrophils within parakeratotic foci (94.1% of psoriasis cases) 2
• Psoriasiform (regular) epidermal hyperplasia (88.2% of cases) 2
• Dilated and tortuous papillary dermal capillaries (76.5% of cases) 2
• Dyskeratotic cells (82.4% of cases) 2
• Thinning of suprapapillary plates (58.8% of cases) 2

Features Favoring Eczema:

• Diffuse spongiosis extending throughout all epidermal layers 2
• Absence of the vertically-oriented parakeratosis pattern 2
• More prominent dermal edema without vascular ectasia 2

Features That Do NOT Exclude Psoriasis:

• Intact/preserved granular layer (hypergranulosis in 65% of confirmed psoriasis) 1
• Irregular acanthosis (84% of confirmed psoriasis) 1
• Spongiosis (76% of confirmed psoriasis) 1
• Eosinophils in dermis (49% of confirmed psoriasis) 1
• Plasma cells (16% of confirmed psoriasis) 1

Algorithmic Approach to Final Diagnosis

1. Examine the parakeratosis pattern carefully: If you see multiple vertically-oriented foci of parakeratosis alternating with orthokeratosis, diagnose psoriasis 2

2. Assess spongiosis distribution: If spongiosis is restricted to lower epidermis with upper epidermal psoriasiform changes, favor psoriasis; if diffuse throughout, favor eczema 2

3. Look for neutrophils: Neutrophils within parakeratotic foci (94.1%) or in the epidermis strongly support psoriasis 2, 3

4. Evaluate vascular changes: Dilated, tortuous papillary dermal capillaries favor psoriasis (76.5%) 2

5. Correlate with clinical presentation: Obtain information about lesion morphology, distribution, chronicity, and family history—psoriasis requires classic morphology and/or distribution as mandatory clinical criteria 1

Common Pitfalls to Avoid

• Do not exclude psoriasis based on intact granular layer alone—this appears in 65% of confirmed cases 1
• Do not exclude psoriasis based on spongiosis—this appears in 76% of confirmed cases and can even form spongiotic vesicles in palmoplantar psoriasis 1, 2
• Do not over-rely on eosinophils or plasma cells—these appear in approximately half and one-sixth of psoriasis cases respectively 1
• Do not diagnose based on H&E alone—only 31% of erythrodermic cases can be correctly diagnosed on morphology alone without clinical correlation 4

Additional Differential Considerations (Less Likely)

Given the perivascular lymphocytic infiltrate with eosinophils and plasma cells, also consider:

• Drug eruption (psoriasiform drug reaction)—would require medication history 1
• Early mycosis fungoides—but would expect more epidermotropism and atypical lymphocytes 4
• Seborrheic dermatitis—but typically shows follicular involvement and different scale pattern 5

Recommend clinical correlation focusing on: lesion morphology, distribution pattern, chronicity, nail changes, family history, and medication history to finalize the diagnosis between psoriasis and spongiotic dermatitis 1, 2.