Wendy Chen, MD, PhD: PGY-3Charleen T. Chu, MD, PhD:

Neuropathology

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

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

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

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

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

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

MedicationsTopical tacrolimus 0.1% prnLexaproAtivan

Va CC: 20/20 OUPupils: No APDIOP: 14 OUEOM: Full OUCVF: Full OU

OD OSExternal Acne rosacea Acne rosacea

Lids/Lashes LL with MGD, telangiectasia, diffuse erythema and thickening, no distortion of lash line or madarosis

Normal

Conj/Sclera White and quiet White and quiet

Cornea Clear Clear

AC Deep and quiet Deep and quiet

Iris Round and reactive Round and reactive

Lens Clear Clear

Vitreous Normal Normal

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.

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.

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

HyperkeratosisAcanthosisSquamous cell nests and strands infiltrating the dermis

Infiltrative border

Suggestion of early keratin pearl formation

Mitotic figures

Interface dermatitis with vacuolar degeneration

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.

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.

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.

Prior biopsy site Vertical extension of the lesion with minor distortion of lid architecture

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.

Dense interface dermatitis, architectural distortion.

Keratin pearl

Maturation & narrow strand-like extensions suggest pseudocarcinomatous hyperplasia

Thick basement membrane

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.

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

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

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

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.

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.

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