What is the differential diagnosis for a skin lesion with histopathological features of psoriasiform hyperplasia, orthokeratosis, neutrophil collection in stratum corneum, and mild superficial perivascular and peradnexal lymphocytic infiltrate, with a retained granular layer?

Differential Diagnosis of Psoriasiform Hyperplasia with Retained Granular Layer

Your initial impression of psoriasis is correct, but the retained granular layer is atypical and significantly narrows the differential—this histopathological pattern most strongly suggests pityriasis rubra pilaris (PRP), psoriasiform keratosis, or an early/resolving psoriatic lesion rather than classic psoriasis. 1, 2

Key Histopathological Analysis

The combination of features you describe creates a specific diagnostic pattern:

• Psoriasiform hyperplasia with orthokeratosis and retained granular layer is inconsistent with fully developed psoriasis, which characteristically shows hypogranulosis or absent granular layer 2, 3
• Neutrophil collections in stratum corneum support a psoriasiform process but can occur in multiple conditions 4, 2
• Mild superficial perivascular and peradnexal lymphocytic infiltrate is relatively nonspecific but the sparse nature argues against robust psoriasis 1, 2

Primary Differential Diagnoses

1. Pityriasis Rubra Pilaris (Most Likely Alternative)

• Alternating orthokeratosis and parakeratosis in both vertical and horizontal directions is the hallmark feature that distinguishes PRP from psoriasis 1
• Focal or confluent hypergranulosis (retained granular layer) is characteristic of PRP, not psoriasis 1
• Thick suprapapillary plates, broad rete ridges, and sparse superficial perivascular lymphocytic infiltrate all support PRP 1
• Look clinically for "islands of sparing," significant palmoplantar keratoderma, and follicular papules 5

2. Psoriasiform Keratosis

• Presents with irregular verrucous epidermal acanthosis, hyperkeratosis, parakeratosis, hypergranulosis, and intracorneal collections of neutrophils 6
• Typically solitary lesions (mean <1 cm diameter), dome-shaped, scaly, yellow to gray-tan, most common on extremities 6
• Mean age 66.8 years, no clinical evidence of disseminated psoriasis on follow-up 6
• This represents either a rudimentary manifestation of psoriasis or a distinct entity 6

3. Early or Resolving Psoriasis

• Early psoriatic lesions may show subtle psoriasiform changes with less prominent hypogranulosis 2
• Resolving lesions can show restoration of the granular layer 2
• However, the presence of neutrophils suggests active disease, making this less likely 2

4. Secondary Syphilis (Critical to Exclude)

• Can present with psoriasiform histology, particularly with palmoplantar involvement 7
• The American Academy of Dermatology recommends serologic testing (RPR/VDRL and treponemal-specific tests) for symmetric palmoplantar lesions with red-brown macules 7
• Acute onset over weeks (rather than chronic course) favors syphilis over psoriasis 7
• Always obtain HIV screening as syphilis and HIV frequently coexist 7

Diagnostic Algorithm

Step 1: Clinical Correlation

• Examine for distribution pattern: Solitary lesion favors psoriasiform keratosis; "islands of sparing" with palmoplantar keratoderma favor PRP; symmetric palmoplantar involvement requires syphilis exclusion 1, 6, 7
• Assess chronicity: Acute onset (weeks) suggests secondary syphilis; chronic stable course suggests psoriasis or PRP 7
• Look for classic psoriasis features: Silvery white scale, Auspitz sign, and Koebner phenomenon have high diagnostic accuracy for psoriasis 3

Step 2: Review Histopathology Details

• Granular layer assessment: Absent/thin granular layer strongly supports psoriasis; focal or confluent hypergranulosis supports PRP 1, 3
• Parakeratosis pattern: Alternating orthokeratosis and parakeratosis in both vertical and horizontal directions is pathognomonic for PRP 1
• Suprapapillary plates: Thick plates favor PRP; thin plates favor psoriasis 1
• Dermal papillae: Narrow papillae favor PRP; broad papillae favor psoriasis 1

Step 3: Additional Testing When Indicated

• For palmoplantar lesions: Obtain RPR/VDRL, treponemal-specific testing, and HIV screening 7
• PAS stain: Negative for yeasts/dermatophytes helps exclude fungal infection 6
• Multiple biopsies: Consider if diagnosis remains uncertain, as this enhances diagnostic accuracy 5

Critical Pitfalls to Avoid

• Do not diagnose classic psoriasis vulgaris with a retained granular layer—this feature is inconsistent with fully developed psoriasis and should prompt consideration of PRP or psoriasiform keratosis 1, 2, 3
• Never miss secondary syphilis—always consider serologic testing for palmoplantar psoriasiform lesions, especially with acute onset 7
• Avoid relying solely on neutrophils in stratum corneum—while characteristic of psoriasis, this finding occurs in all forms of psoriasis including pustular variants and does not distinguish between entities 4, 2
• Do not overlook clinical context—solitary lesions in elderly patients favor psoriasiform keratosis over disseminated psoriasis 6