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Ocular Pathology Clinical Case January 2010

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Wendy Chen, MD, PhD: PGY-3 Charleen T. Chu, MD, PhD: Neuropathology. Ocular Pathology Clinical Case January 2010. History of Present Illness. 50 yo Caucasian male presenting with right lower eyelid erythema and thickening. Itchy Erythema fluctuates, worse after sun exposure

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history of present illness
History of Present Illness
  • 50 yo Caucasian male presenting with right lower eyelid erythema and thickening.
    • Itchy
    • Erythema fluctuates, worse after sun exposure
    • No change in vision
    • Some AM eyelid matting/crusting
hpi cont d
HPI cont’d
  • Seen by dermatologist in 2006 -- bilateral periorbital rash, erythematous and itchy, scaling plaques, worsened by sun exposure.
  • ? Rosacea ---> treated with Akne-mycin (erythromycin 2%) without improvement.
  • Punch biopsy of LEFT lower eyelid
hpi cont d1
HPI cont’d
  • Dermatopathology report:

“lichenoid dermatitis with deep perivascular extension of the infiltrate . . . lupus erythematosis vs. lichenoid photodermatitis”

  • Subsequently,
    • PAS stain: thickened basement membrane
    • Colloidal iron: focal increase in dermal mucin
    • Favoring discoid lupus erythematosis
hpi cont d2
HPI cont’d
  • Treated with Protopic (tacrolimus 0.1%) – bilateral periorbital rash improved.
  • Serologic testing:
    • ANA, RF, Anti-DNA, Anti-histone, Anti-SS A/B negative.
    • C3, C4 WNL
    • CBC, LFTs, BMP WNL
    • RPR non-reactive
hpi cont d3
HPI cont’d
  • Over the next 3 years, pt continued to have intermittent flares of periorbital, facial, and scalp rashes ---> continued Protopic.
  • In 2009, presented to dermatology again with persistent RLL erythema and thickening accompanied by erythematous pustules of the face ---> acne rosacea
  • To ophthalmology for second opinion
medical history
Medical History
  • Past Medical/Surgical History
  • Acne rosacea
  • Lupus erythematosis, DISCOID, not systemic
  • Anxiety, Depression
  • S/P hernia repair
  • Past Ocular History
  • S/P left periorbital skin bx
  • Hyperopia
  • Astigmatism
  • Social History
  • Tob – none
  • EtOH – social use
  • Drugs – none
  • Excessive sun exposure and multiple severe sunburns prior to age 18
  • Medications
  • Topical tacrolimus 0.1% prn
  • Lexapro
  • Ativan
initial exam
Initial Exam

Va CC: 20/20 OU

Pupils: No APD

IOP: 14 OU

EOM: Full OU

CVF: Full OU

differential diagnosis
Differential Diagnosis
  • Ocular rosacea – typically bilateral, but can be asymmetric.
  • Discoid lupus without systemic involvement.
  • Infectious – viral, bacterial, fungal.
  • Malignancy – basal cell carcinoma, squamous cell carcinoma, sebaceous adenocarcinoma.
approach to management
Approach to management
  • Rosacea-associated blepharitis ---> Blephamide BID with resolution of symptoms.
  • Returned 5 months later with RLL recurrence (slow return of symptoms).
  • Referred to oculoplastics for biopsy.
work up
Work-up
  • Wedge resection of lateral portion of the RLL lesion in Oct 2009.
  • Conjunctival cultures taken:
    • Fungus culture negative
    • Virus culture negative
    • Bacterial culture with light coag neg Staph
    • Adenovirus PCR negative
    • HSV1/2 PCR negative
slide14
Hyperkeratosis

Acanthosis

Squamous cell nests and strands infiltrating the dermis

pathology report
Pathology report
  • EYELID RIGHT LOWER, WEDGE BIOPSY
    • A. SUPERFICIALLY INVASIVE SQUAMOUS CELL CARCINOMA (0.2 CM, 0.1 CMTHICK), WELL DIFFERENTIATED
    • NO ANGIOLYMPHATIC OR PERINEURAL INVASION PRESENT.
    • MARGINS FREE OF TUMOR.
clinical course cont d
Clinical course cont’d
  • Pt continued to have persistent RLL erythema and thickening.
  • Re-excision of adjacent area performed Nov. 2009, given prior diagnosis ---> suture with foreign body giant cell reaction, acute and chronic inflammation and fibrosis.
clinical course cont d1
Clinical course cont’d
  • Started po Doxycycline 100mg daily for further treatment of ocular rosacea.
  • Patient was followed q4 months for 1 yr with waxing and waning progression of RLL lesion.
  • Most recent visit revealed a change in appearance of RLL.
slide23
Prior biopsy site

Vertical extension of the lesion with minor distortion of lid architecture

management cont d
Management cont’d
  • Given the recent change in the appearance of the lesion and prior diagnosis of carcinoma, a repeat wedge resection was performed in January 2011 on the medial portion of the RLL lesion.
slide26
Maturation & narrow strand-like extensions suggest pseudocarcinomatous hyperplasia

Thick basement membrane

re review of prior excisions
Re-review of prior excisions
  • Review of initial wedge excision revealed that the diagnosis of carcinoma may have been incorrect.
    • Prolonged clinical history of rashes, chronic inflammation and suspicion of DLE were not known to the original pathologist.
  • Both excisions showed:
    • SQUAMOPROLIFERATIVE LESIONS WITH PSEUDOEPITHELIOMATOUS HYPERPLASIA.
squamous cell carcinoma
Squamous Cell Carcinoma
  • 10-40X less common than basal cell carcinoma.
  • Typically arise from actinic keratoses.
  • Lower eyelid most common ocular site.
  • Histologic characteristics:
    • Hyperkeratosis, acanthosis
    • Interface dermatitis, infiltrative nests and strands
    • Keratinocyte nuclear hyperchromasia and maturational ayptia, mitotic figures
    • Keratin pearls, dyskeratotic cells
pseudocarcinomatous hyperplasia also known as pseudoepitheliomatous hyperplasia
Pseudocarcinomatous Hyperplasia (also known as pseudoepitheliomatous hyperplasia)
  • Chronic inflammation can result in histologic changes that mimic invasive squamous carcinoma.
  • Features that can help differentiate PCH/PEH from SCC:
    • Narrow, strand-like infiltration of epithelium
      • Tangential section can result in isolation from surface
    • Lack of dysplastic hyperchromatic nuclei, lack of maturational atypia
      • Reactive atypia – pale nuclei with uniform nucleoli
eyelid involvement by chronic cutaneous lupus ccl
Eyelid involvement by chronic cutaneous lupus (CCL)
  • Systemic lupus more commonly causes corneal lesions, retinal vasculopathy
    • keratoconjunctivitis sicca, peripheral ulcerative keratitis, interstitial keratitis
  • Very rarely can give isolated lid lesions that mimic malignancy
  • CCL variants
    • Discoid lupus erythematosis – plaque lesions
    • Lupus erythematosis profundus (panniculitis)
    • Systemic disease - idiopathic orbital edema
eyelid involvement by chronic cutaneous lupus
Eyelid involvement by chronic cutaneous lupus
  • Unlike regular pseudoepitheliomatous hyperplasia, significant cytologic atypia (N/C ratio, hyperchromasia, mitoses) can occur.
  • Features that help differentiate DLE from SCC:
    • History of chronicity, rashes
      • SCC shows rapid onset/growth (< 6 mo), nodular or ulcerative changes.
    • Intradermal mucin (colloidal iron)
    • Thickened basement membrane (PAS)

Papalas et al. “Cutaneous Lupus Erythematosus of the Eyelid as a Mimic of Squamous Epithelial Malignancies” Ophthal Plast Reconstr Surg 2010.

distinguishing features cont d
Distinguishing features cont’d
  • Features that help differentiate CCL from SCC:
    • Perifollicular and acrosyringeal inflammation
    • Follicular plugging
    • Vacuolar interface change
    • Compact orthokeratosis
  • The “helpful” features may not be present or may not be recognized without a high index of suspicion
    • 37% of cutaneous LE cases incorrectly interpreted initially even by Board certified dermatopathologists

Zedek et al. “Cutaneous Lupus Erythematosis simulating squamous neoplasia: The clinicopathologic conundrum and histopathologic pitfalls” J Am Acad Dermatol 2007; 56: 1013-20.

summary
Summary
  • Persistent unilateral lower lid erythema/thickening despite treatment of discoid lupus and ocular rosacea warrants biopsy.
    • SCC can develop in lesions of discoid LE
  • The histologic DDx includes actinic keratosis/SCC, lichen planus-like keratosis & PCH/PEH
      • Combination of cytologic atypia from lupus and PCH/PEH (which normally lacks atypia) is a diagnostic pitfall
      • Chronic history and suspicion of lupus would raise the awareness threshold to prevent overcalling the lesion
  • Providing clinical history is key to avoiding misdiagnosis >> rare mimics of a common neoplasm
ad