Primary conjunctival amyloidosis.

A 19-year-old previously healthy male presented with a 4 year history of painless drooping of right upper eyelid. On eversion of the right upper eyelid, a yellowish pink mass was seen in the tarsal region. Rest of the ocular examination was normal in both the eyes. Initial biopsy showed chronic inflammation. Subsequently, the entire mass was excised and histopathological examination showed the presence of amyloid in the subconjunctival stroma. At 3 months follow-up, similar lesion was detected in the right lower, left upper, and lower lid, which were treated with cryotherapy, with partial resolution. Patient has been followed up for more than 2 years without any complaints. To our knowledge, this is the first case report of an isolated primary conjunctival amyloidosis with involvement of both the upper and lower palpebral conjunctiva of either eye. It was treated successfully by excision and cryotherapy.

Introduction

Amyloidosis is a disorder of protein metabolism characterized by the extracellular deposition of abnormal protein fibrils. It may be localized or distributed throughout the body, causing organ damage and serious morbidity. Major visceral involvement, especially of the kidneys and heart, is usually fatal.[1] Primary localized conjunctival amyloidosis is a chronic, slowly progressive disease, which is frequently bilateral.[2] It is rare, and usually diagnosed histopathologically. Systemic association is usually absent.[3]

The etiology of this lesion is believed to be an immunoglobulin light chain deposition in the conjunctiva. The exact reason for such protein collections is unknown, but they could be associated with a benign localized B-lymphocyte lineage disorder that produces free immunoglobulin light chains that serve as precursors to amyloid deposits.[3] Various treatment approaches such as conservative, surgical excision, cryotherapy, and superficial radiotherapy have been attempted with partial success.[4]

The extreme degree of rarity of this condition warrants the report of a single case.

Case Report

A 19-year-old male presented with the chief complaints of drooping and heaviness of right upper eyelid [Figure 1] for past 4 years. There was no history suggestive of eye infections (such as trachoma, blepharitis, etc.), trauma, chronic systemic illness, neuropathy, or familial involvement. Best corrected visual acuity (BCVA) in both the eyes was 20/20. He had 2 mm of right eyelid ptosis with thickened upper eyelid. On everting the right upper eyelid a pale dry yellowish pink growth was seen involving the whole of the tarsal conjunctiva [Figure 2]. The rest of the ocular examination was normal. The left eye was within normal limit.

Figure 1

Mild ptosis of right upper eyelid

Figure 2

Amyloid deposition in the palpebral conjunctiva of right upper eyelid

The patient was in normal health, with no previous history of any major illness. He was referred to a physician for systemic evaluation. There was no enlargement of liver or spleen, the kidneys were not palpable and cardiovascular system showed no abnormality. Routine blood investigations, random blood sugar, serum urea, and creatinine were all within normal limit. Contrast enhanced computed tomogram (CECT) of orbit and ultrasonography (USG) of whole abdomen was also normal.

Transconjunctival biopsy showed fibrocollagenous tissue and eosinophilic degenerated areas with chronic inflammatory cells. Subsequently the entire mass was excised and sent for histopathological examination (HPE). It revealed amyloid deposits in the subconjunctival stroma, confirmed by Congo red stain [Figures 3a and b].

Figure 3

Histopathology of right upper eyelid lesion (a) H and E stain (40 × 10) showing amorphous, eosinophilic amyloid like substance deposition in Conjunctival stroma (b) Congo Red stain (10 × 10) showing red color amyloid deposits

At 3 month follow-up similar lesions were found in right lower [Figure 4a], left upper [Figure 4b], and lower palpebral conjunctiva. These lesions were treated with two rounds of liquid nitrogen cryotherapy at an interval of 2 weeks. Cryotherapy was performed using a double freeze-thaw technique directly until the lesion appeared chalk white. A combination of moxifloxacin (0.5%) and prednisolone acetate (0.1%) eyedrops four times daily was given in both eyes for 1 week after each cycle of cryotherapy. Partial resolution was seen at 1 month follow-up [Figure 5]. There has been no ocular or systemic complaint till date.

Figure 4

Amyloid deposition in right lower (a) and left upper (b) Tarsal conjunctiva

Figure 5

Postoperative appearance at 4 months

Discussion

Amyloidosis has a variety of presentation in the periocular region and may be the sole presentation of the disease process.[5] Conjunctival amyloidosis as a manifestation of primary amyloidosis is rare, although systemic primary amyloidosis is not so uncommon. It was first described by Oettingen (1897) and brief mention was made by Fuchs (1919), de Schweinitz (1921), Collins and Mayou (1925), Wolff (1934), Castoviejo (1946), and Wahi, Wahi and Mathur (1954). Srinivasan (1949) showed its association with trachoma.[6]

The clinical signs and symptoms of the condition vary widely. A study by Leibovitch et al. in 24 patients showed visible or palpable periocular mass or tissue infiltration (95.8%), ptosis (54.2%), periocular discomfort or pain (25%), proptosis or globe displacement (21%), limitations in ocular motility (16.7%), recurrent periocular subcutaneous hemorrhages (12.5%), and diplopia (8.3%) with orbital involvement (7 cases), and periocular involvement (17 cases). Immunohistochemistry in seven patients showed B cells or plasma cells producing monoclonal immunoglobulin chains that were deposited as amyloid light chains. One patient was diagnosed with systemic amyloid light chain amyloidosis.[7] Epiphora[2] and an association with high intraocular pressure[8] has also been documented. It may simulate a lymphoproliferative disorder like lymphoma, plasmacytoma, or multiple myeloma with a characteristic “salmon-pink mass.”[5] In our case, ptosis and heaviness of the eyelid (RE) was the main presenting symptom without any systemic disease. The condition is known to recur locally with persistent ocular complaints that could perhaps be attributed to conservative local excision.[4]

Treatment modalities for localized conjunctival amyloidosis are limited. The mainstay of treatment is observation, surgical debulking with repeated debulking surgery should amyloidosis recur.[7] Superficial radiotherapy has been also tried in some cases with partial success.[4]

While there have been reports of complete resolution of the condition in some studies after cryotherapy; in our case, only partial resolution occurred. Cryotherapy mainly acts by disrupting the blood supply to the amyloid deposits by damaging the small caliber blood vessels and creating a haemostatic effect with cellular ischemia leading to regression of the mass. It may also act by killing local B-lymphocyte deposition, thereby preventing deposition of amyloid.[3] Liquid nitrogen is usually chosen as its low boiling point (-195.6°C) will have more profound effect on living cells due to rapid freeze than a slower freeze with alternative cryogens.[9]

Hence, as seen, primary conjunctival amyloidosis is a rare entity of poorly understood etiology, which may present with a wide spectrum of clinical findings and result in significant ocular morbidity. HPE may be confused with chronic inflammation at times. Amyloidosis should be carefully excluded in all cases with palpebral conjunctival masses. Although surgical debulking still constitutes the main mode of treatment, cryotherapy may also be considered as an adjunct in some cases.