Ocular Pathology Clinical Case January 2010

1. Wendy Chen, MD, PhD: PGY-3 Charleen T. Chu, MD, PhD: Neuropathology Ocular PathologyClinical CaseJanuary 2010

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. Initial Exam Va CC: 20/20 OU Pupils: No APD IOP: 14 OU EOM: Full OU CVF: Full OU

10. Slit Lamp Exam

11. 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.

12. 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.

13. 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

14. Hyperkeratosis Acanthosis Squamous cell nests and strands infiltrating the dermis

15. Infiltrative border

16. Suggestion of early keratin pearl formation

17. Mitotic figures

18. Interface dermatitis with vacuolar degeneration

19. 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.

20. 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.

21. 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.

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

24. 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.

25. Dense interface dermatitis, architectural distortion. Keratin pearl

26. Maturation & narrow strand-like extensions suggest pseudocarcinomatous hyperplasia Thick basement membrane

27. 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.

28. 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

29. 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

30. 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

31. 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.

32. 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.

33. 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