To characterize the clinical and histopathologic features of actinic granuloma of the conjunctiva.
Retrospective observational case series
Institutional pathology records between 2014 and 2020 were searched for all cases of conjunctival actinic granuloma. Information collected included age, sex, ocular and medical history, clinical findings, laboratory workup, treatment, follow-up, pathologic diagnosis, and histopathologic inflammation pattern.
Eight eyes of 8 patients, 5 men and 3 women, with a median age of 43 years (mean 49, range 24-83) were identified. Clinical diagnosis was pterygium (n = 4, 50%), inflamed pterygium (n = 1, 13%), pterygium vs conjunctival squamous cell carcinoma (n = 1, 13%), episcleritis vs inflamed pinguecula (n = 1, 13%), and scleritis vs keratoacanthoma (n = 1, 13%). Of 5 lesions with follow-up information, none recurred following excision with a median follow-up of 9 weeks (mean 19 weeks, range 1-61 weeks). Allergy/atopy was documented in 4 of 7 (57%) patients with available medical information. There were no other systemic associations. Histopathologically, actinic granuloma was associated with pterygium (n = 6, 75%) and pinguecula (n = 2, 25%). All lesions were composed predominantly of histiocytes and a variable number of foreign body–type giant cells associated with a focus of severe actinic elastosis. The inflammatory pattern was giant cell (n = 4, 50%), sarcoidal (n = 2, 25%), histiocytic (n = 1, 13%), and combined histiocytic and sarcoidal (n = 1, 13%).
Conjunctival actinic granuloma has diverse clinical and histopathologic manifestations, which need to be distinguished from other autoimmune, neoplastic, and infectious etiologies. This lesion frequently occurs in pre-existing pterygium and pinguecula and may be associated with allergy and atopy.
T he term actinic granuloma was originally coined in 1975 by John O’Brien, who described an unusual lesion in sun-damaged skin, characterized by the presence of a foreign body giant cell inflammatory infiltrate in close association with abnormal elastotic fibers. , Cutaneous actinic granuloma, also known as annular elastolytic giant cell granuloma, has a female predilection (female-to-male ratio of 1.2:1 to 2:1) with a mean age of onset in the fourth and fifth decades, clinically presenting as an annular plaque with elevated erythematous borders. In addition to its association with exposure to sun, radiation, intense light, and/or heat, cutaneous actinic granuloma has been associated with diabetes mellitus and giant cell arteritis.
Actinic granuloma of the conjunctiva is histopathologically similar to cutaneous actinic granuloma. Thus far, conjunctival actinic granuloma has been reported nearly exclusively in young females, presenting characteristically over the course of several weeks as an isolated, solitary, raised, yellow-to-pink nodule in the sun-exposed bulbar conjunctiva. Conjunctival actinic granuloma is a clinically and histopathologically underrecognized entity with only 9 well-characterized cases documented, to our knowledge, in the literature. We report herein 8 patients with actinic granuloma of the conjunctiva, with attention to the clinical presentation, histopathologic features, and systemic associations, and review the previously reported cases of this unusual conjunctival lesion.
Patients and Methods
The Wills Eye Hospital Institutional Review Board approved this retrospective observational case series and deemed that informed consent was not required for this study. The study was performed in compliance with HIPAA guidelines and with the tenets of Declaration of Helsinki.
Wills Eye Hospital pathology records were searched for all cases of actinic granuloma between December 1, 2014, and December 1, 2020. Medical records of identified patients were reviewed. Data collected included patient’s age, sex, past ocular and medical history, review of systems, presenting symptoms and their duration, clinical findings at presentation, clinical diagnosis, ancillary studies when performed (imaging, laboratory, and microbiology), management, and follow-up information. Histopathology was reviewed and the following parameters were recorded: gross lesion size, presence and severity of actinic elastosis, inflammatory cell type associated with the lesion, histopathologic pattern as defined by O’Brien ( Table 1 ), and pathologic diagnosis.
|Original or giant-cell pattern||No obvious vascular component. The lesion commences as a small focus of granulomatous inflammation with prominent giant cells, which becomes annular by advancing into surrounding elastotic tissue.|
|Histiocytic pattern||Histocytes are scattered near elastotic fibers. Giant cells, if present, are small.|
|Sarcoid pattern||Typical sarcoid (tuberculoid) granulomas; sarcoid-like granulomas with a central aggregate of elastotic fibers; asteroid-like elastolytic bodies in giant cells. The stroma shows atrophy, fibrosis, and varying degrees of persistent inflammatory reaction.|
|Necrobiotic (vascular pattern)||Vascular occlusion due to actinic arteriopathy (basophilic degeneration, fragmentation, and variable loss of internal elastic lamina of arterioles, associated with variable degree of lymphohistiocytic inflammatory reaction). Single or multiple foci of ischemic necrosis occur in the advancing granulomatous edge.|
PubMed and Google Scholar database search was conducted for all articles published between 1988 and 2020 using a combination of the following terms: “actinic granuloma AND conjunctiva,” “actinic granuloma AND eye,” “annular elastolytic granuloma AND conjunctiva,” and “annular elastolytic granuloma AND eye.” Additional articles were found by reference searching.
Review of pathology and medical records identified 8 patients with conjunctival actinic granuloma, 5 males and 3 females, with a median age of 43 years (mean 49, range 24-83). Patient clinical characteristics are summarized in Table 2 and documented in Figure 1 . Three patients (3/8, 38%) presented with 2-4 weeks of pain and redness corresponding to an inflammatory lesion clinically suggestive of scleritis vs keratoacanthoma (n = 1, 13%) ( Figure 1 ), episcleritis vs inflamed pinguecula (n = 1, 13%), and an inflamed pterygium (n = 1, 13%). The remaining patients presented with long-standing blurred vision (n = 4, 50%), foreign body sensation (n = 2, 25%), and epiphora (n = 1, 13%) in a setting of pterygia. Conjunctival squamous cell carcinoma was a diagnostic consideration in 1 patient (13%) ( Figure 1 ). All 6 lesions with known location were situated in the sun-exposed nasal bulbar conjunctiva. Two of 8 (25%) patients had additional pinguecula and pterygium. Of 6 patients with known information, preoperative therapies included topical antibiotics (n = 1, 25%), topical steroids (n = 1, 25%), combination of topical antibiotics and steroids (n = 1, 25%), and artificial tears (n = 1, 25%), administered over the course of 2-4 weeks, with no appreciable response. Of 5 lesions with follow-up information, none recurred following excision with a median follow-up of 9 weeks (mean 19, range 1-61 weeks). History of atopy/allergy was documented in 4 of 7 patients (57%) with available medical information. Diabetes was documented in 1 patient (14%). Review of systems was negative for skin lesions and symptoms of temporal arteritis (headaches, scalp tenderness, myalgias, jaw claudication, fatigue, and weight loss). None of the patients had evidence of ischemic optic neuropathy. Autoimmune and infectious workup in 2 patients (1 and 8; Table 2 ) with clinical concern for scleritis/episcleritis was negative. This included CBC, rheumatoid factor, CRP, RPR, interferon-gamma release assay, serologic studies (ANA, antiCCP, cANCA, xANCA, Lyme, HIV, FTA), and chest radiograph.
|Pt No.||Age (y)Sex||Presenting Symptoms, Duration||Preoperative Diagnosis||Location, Laterality||Prior Treatment||Surgical Procedure||Relevant Ocular History||Relevant Medical History||Follow-up Duration, Outcome|
|1||34 F||Pain, redness x3 wk||Keratoacanthoma, nodular scleritis||Nasal bulbar, OS||Topical antibiotics||Excision with cryotherapy||None||None||1 wk, no recurrence|
|2||37 F||Pain, redness, photophobia × 2 wk||Pterygium, inflamed||Nasal bulbar, OD||Topical steroids||Excision with autograft||Dry eyes||Asthma, hypothyroid||NA|
|3||71 M||Blurred vision, long-standing||Recurrent pterygium||Nasal bulbar, OD||None||Excision with graft||None||Diabetes mellitus, allergies||5 mo, no recurrence|
|4||68 M||Blurred vision, foreign body sensation, long-standing||Pterygium, squamous cell carcinoma||Nasal bulbar, OS||Unknown||Excision with amniotic graft||Pterygium temporal bulbar, OS||Asthma||NA|
|5||27 M||Foreign body sensation, unknown duration||Pterygium||NA, OS||Unknown||Excision with amniotic graft||None||NA||2 mo, no recurrence|
|6||83 M||Blurry vision||Pterygium||Nasal bulbar, OS||Artificial tears||Excision with autograft||Pinguecula, OD||None||1 wk, no recurrence|
|7||48 M||Blurred vision, epiphora, long-standing||Pterygium||Nasal bulbar, OD||None||Excision with graft||None||None||NA|
|8||24 F||Pain, redness × 4 wk||Inflamed pinguecula, episcleritis||Bulbar, OD||Topical steroids and antibiotics||Excision with autograft||None||Rhinitis, urticaria hypothyroid||14 mo, no recurrence|