Ocular pemphigus vulgaris presenting as a persistent conjunctival mass — A diagnostic mimicker of ocular surface squamous neoplasia

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A 47-year-old woman presented with bilateral chronic ocular symptoms for nearly 11 years, including recurrent pricking pain, photophobia, tearing, redness, itching and burning sensation. There was progressive worsening of the above symptoms in the right eye. Seven years after symptom onset, she observed a slowly enlarging, fleshy lesion over the temporal bulbar conjunctiva of the right eye which grew gradually and exacerbated discomfort over the preceding three months. No history of oral, nasal, genital or cutaneous erosions/blisters and no antecedent features suggestive of cicatrising conjunctivitis, were present. On examination, uncorrected visual acuity was 6/9 (right eye) and 6/18 (left eye), with normal intraocular pressure bilaterally. Slit lamp revealed eyelid oedema with rounded lid margins, bilateral conjunctival hyperaemia with marked conjunctival hyperplasia (prominent over upper tarsal/palpebral conjunctiva) in right eye. Lateral conjunctivalisation of the cornea was present in the right eye with round/reactive pupils, quiet anterior chamber and normal iris in bilateral eyes. A lobulated fleshy 10 × 5 mm mass occupied the temporal bulbar conjunctiva of the right eye, extending onto the cornea [Figures 1a and b]. Reduced corneal sensation (right eye) and bilateral meibomian gland dysfunction were noted. No forniceal shortening, symblepharon or conjunctival scarring occurred in bilateral eyes. Differentials included mucous membrane pemphigoid (MMP), ocular surface squamous neoplasia (OSSN), paraneoplastic pemphigus (PNP) and ocular pemphigus vulgaris (PV). An excisional biopsy of the conjunctival mass with partial-thickness scleral biopsy demonstrated intraepithelial clefting, with focal areas of suprabasal clefting and basal keratinocytes giving ‘row of tombstone’ appearance, prominent acantholytic cells and mixed inflammatory infiltrate in dermis, consistent with pemphigus vulgaris [Figures 2a and b]. Direct immunofluorescence (DIF) revealed focal intercellular IgG in a ‘fish-net’ pattern in conjunctival epidermis, while enzyme-linked immunosorbent assay (ELISA) detected increased titer of anti-desmoglein-3 antibodies, confirming ocular PV (extended testing for other desmogleins/desmocollins was limited by finances). She was initially managed with topical dexamethasone 0.1% eye drops twice daily and one dexamethasone–cyclophosphamide pulse (IV dexamethasone over three days, IV cyclophosphamide on day two, followed by oral cyclophosphamide). Inadequate response led to initiation of rituximab (two 1 g IV doses, 15 days apart), yielding complete mass resolution and symptom improvement. At six-month follow-up, sustained remission persisted with ophthalmic examination showing smooth conjunctival surface, reduced hyperaemia/watering and symptomatic relief. Residual nebulomacular corneal opacity marked prior limbal biopsy site [Figure 3].

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Figure 1a: Oedematous eyelid, conjunctivalisation of cornea laterally, a lobulated, fleshy, 10 x 5 mm mass on the temporal bulbar conjunctiva of the right eye extending into the cornea, palpebral conjunctiva shows hyperplasia and pigmentation.

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Figure 1b: Conjunctival hyperaemia and papillary hyperplasia.

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Figure 2a: Conjunctival biopsy showing a deroofed intraepidermal blister with villous appearance, with keratinocytes along the basement membrane focally showing ‘row of tombstones’ appearance (black arrows), characteristic of pemphigus vulgaris (Haematoxylin & eosin, 400x).

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Figure 2b: Conjunctival biopsy showing acantholytic keratinocytes within the blister cavity (black arrow) along with mixed inflammatory infiltrate in the underlying stroma (Haematoxylin & eosin,100x).

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Figure 3: Post-treatment palpebral and bulbar conjunctiva shows decreased hyperplasia and smooth conjunctival surface, nebulomacular corneal opacity is observed due to growth over limbus which had been excised for biopsy.

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Pemphigus vulgaris (PV) is an autoimmune blistering disorder due to anti-desmoglein antibodies causing intraepithelial acantholysis. It classically involves skin/oral mucosa; isolated ocular involvement is uncommon, reported in 7% to 16.5% of cases, often misdiagnosed or diagnosed late, causing visual morbidity.¹ Most presentations of ocular PV are mild/non-specific, manifesting as chronic non-cicatricial conjunctivitis, irritation and hyperaemia. Severe manifestations (symblepharon, ulceration, perforation) and mass-forming lesions are exceedingly rare.² Chronic conjunctival masses evoke suspicion of OSSN, requiring histopathological confirmation.³ MMP differs in causing subepithelial blistering/progressive conjunctival scarring.⁴ PNP was considered due to severe/chronic mucosal (ocular) involvement, but lack of constitutional symptoms, lymphadenopathy, painful stomatitis, polymorphous eruptions or bronchiolitis obliterans argued against it. Histopathology showing focal suprabasal clefting with acantholytic cells, DIF showing intercellular IgG deposits in conjunctival epidermis without linear deposition at basement membrane zone and ELISA showing raised anti-desmoglein-3 antibody titer supported the diagnosis of mucosal-dominant PV. Systemic corticosteroids and immunomodulatory agents are the mainstay of treatment of PV; rituximab helps via targeted B-cell depletion.^5,6 Hodak et al. ² documented conjunctival hyperaemia/irritation as early manifestations, sometimes preceding characteristic PV lesions by months/years, but ocular changes are subtle without masses. Avisar et al.³ described eyelid papillomatous lesions, though not a bulbar conjunctival mass, as in our case. Namba et al.⁶ have reported a similar pseudo-neoplastic hyperplasia (giant cobblestone-like papillae) in the eye in PV. Our case is unique in view of an isolated ocular involvement for 11+ years, discrete lobulated mass with unilateral dominance, significant diagnostic delay sans cicatrisation/systemic/erosive disease; poor response to conventional immunosuppression but resolution with rituximab, stressing the importance of early initiation of biologics in refractory isolated ocular disease.

Ocular PV should be considered in the differential diagnosis of chronic conjunctival masses, particularly when clinical features are atypical for neoplasia or cicatrising disorders. Early biopsy with immunopathological evaluation is pivotal for accurate diagnosis, and timely initiation of systemic therapy can prevent visual morbidity and avoid unnecessary surgical or oncologic interventions.