Primary localized amyloidosis presenting as a tarsal mass: report of two cases.

Amyloidosis and its ophthalmic manifestations are rare. The unusual presentation can result in diagnostic delay and increase ocular morbidity. Additionally, there are various predisposing conditions and systemic involvement can affect various organs. Hence, localized disease warrants a thorough clinical evaluation and laboratory investigation. We report two cases of primary localized amyloidosis presenting as a tarsal mass and ptosis. The diagnosis was established on histopathology. There were no predisposing conditions and no systemic involvement. The disease was probably related to the local immunocyte disorder.

INTRODUCTION

Amyloidosis is a group of disorders caused by extracellular deposition of proteinaceous material with characteristic histopathologic properties.1 The disease presentation may vary from localized lesion to extensive systemic disease. Conjunctival, periocular, or orbital amyloidosis is not common.2 The most typical presentation of eyelid disease is waxy hemorrhagic papules usually seen with primary systemic amyloidosis.3 Localized forms of dermal amyloid affecting eyelid are generally secondary to other conditions such as basal cell carcinoma, Bowen's disease and seborrheic keratosis.3 We report two cases of localized amyloidosis presenting with thickening of the upper tarsus and ptosis without any predisposing conditions and systemic involvement.

CASE REPORTS

Case 1

A 46-year-old female presented with complaints of swelling and drooping of left upper lid with onset 2 years prior to presentation. This was associated with irritation and watering. There was no history of trauma and diurnal variation in ptosis. On examination, best corrected visual acuity (BCVA) was 20/30 OD and 20/80 OS. The left upper tarsus was thickened with normal overlying skin and conjunctiva [Figure 1a]. On palpation, the tarsal plate had an irregular surface and hard consistency. It was associated with severe ptosis. The levator muscle action was poor. Immature senile cataract was present bilaterally and the fundus was normal. Clinically, the differential diagnosis was chronic granulomatous disorder, trachoma and sebaceous gland neoplasm. Routine blood investigations and the chest X-ray were normal. To establish the cause, incision biopsy of tarsus, levator and lid skin was performed. On histopathological examination, the tarsus and levator showed densely collagenized fibroconnective tissue with hyalinised homogenous waxy material deposition around the subcutaneous tissue along the basement membrane of blood vessels and dermal appendage. The material was congophilic, showed metachromasia on methyl violet stain and polarization which were contributory to amyloid [Figures 1b and c]. The tissue was positive for lambda and kappa stains indicating presence of immunoglobulins. Also present was meibomian gland atrophy. Overall features were suggestive of amyloidosis with deposition of protein AL (light chain associated amyloid). To rule out systemic amyloidosis a complete medical, neurologic and dermatologic evaluation was performed along with complete blood count, antinuclear antibody (ANA) titres, kidney and liver function tests, serum and urine electrophoresis, electro-cardiogram and rectal biopsy. These investigations were negative for systemic amyloidosis.

Figure 1

(a) Clinical photograph of case 1 showing thickening of left upper tarsus. (b) Histology (×10) with congo red stain showing deposition of amyloid (arrow) around tarsal glands. (c) Shows (×20) metachromasia with methyl violet stain (arrow)

Case 2

A 35-year-old female presented with complaints of swelling of both upper eyelids with onset 1 year prior to presentation. On examination, BCVA was 20/20 OU. Both upper eyelids showed a well defined mass with irregular surface in the tarsal area. It was fixed to the tarsus and hard in consistency. On upper lid eversion, conjunctiva was involved on left side and overlying skin was normal [Figures 2a and b]. It was associated with severe ptosis bilaterally. The remainder of the anterior and posterior segment examination was normal. Strong clinical suspicion of chronic granulomatous disorder was considered. The chest X-ray, complete blood count, tuberculin test, serum ANA titres, angiotensin-converting enzyme (ACE) levels, perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) were normal. An incision biopsy of the swelling on the left side was initially performed. Peroperative, an irregular pinkish coloured mass was present involving the tarsus and levator muscle. On histopathology this mass showed the characteristic features of light chain associated amyloidosis [Figures 2c and d] with meibomian gland atrophy. Investigations for systemic amyloidosis as mentioned above were normal and similar histopathological features were seen on biopsy of the right side.

Figure 2

(a) Clinical photograph of case 2 showing bilateral upper tarsal mass. (b) Everted upper lid showing involvement of conjunctiva. (c) Histology (×10) with congo red stain showing deposition of amyloid (arrow). (d) Shows (×20) metachromasia with methyl violet stain (arrow)

DISCUSSION

Amyloidosis represents deposition of an abnormal protein. Glenner45 proposed a classification scheme, and histologically the three major types of amyloidosis included primary, secondary and heredofamilial. The frequency of newly diagnosed cases of periorbital and ocular amyloidosis vary from 1 in 1.5 years to 1 in 10 years (average, 1 in 3 years).2 The amyloid deposition usually occurs in eyelid skin, cornea, conjunctiva, orbital soft tissues, lacrimal gland and extraocular muscles, but may also be seen in iris, anterior chamber, vitreous or optic nerve.2

Due to variety of presentations diagnosis may be delayed. But the most typical clinical characteristic of adnexal disease is ptosis and ophthalmoplegia due to infiltration of extra-ocular muscles including the levator and Muller's muscle. Amyloidosis can cause necrosis of muscle in cases of levator involvement, compressive optic neuropathy, and lacrimal gland involvement can cause keratoconjunctivits sicca. This leads to either mechanical dysfunction and/or muscle necrosis. Meibomian gland atrophy observed in our cases could be explained similarly by deposition of amyloidosis in the tarsus. In such cases it will be useful to evaluate the patient for evaporative dry eye disease. Other features such as eyelid skin papules, proptosis, lacrimal gland enlargement, keratoconjuctivitis sicca and compressive optic neuropathy were absent in our cases.

The atypical feature in our cases was tarsal plate thickening (tylosis) which is seen rarely with amyloidosis.67 Previously only two cases of unilateral and one case of bilateral involvement have been reported.6–8 It can mimic a bone tumor with extensive calcification and ossification.8 Our cases were similar to these reports with evidence of only primary localized disease without any systemic involvement.

In localized primary amyloidosis, usually there are predisposing conditions that leads to deposition of amyloid.3 In previous case reports of tarsal thickening, the lesion was isolated and was not associated with any predisposing condition. Our cases also presented with no predisposing condition and it could be related to the local immunocyte disorder. Such a local B-cell or plasma cell disease could produce immunoglobulin light chains that can serve as a precursor to amyloid deposits.2 The deposition of local light chain amyloidosis has been previously reported in levator palpebrae muscle related to local monoclonal gammopathy.9 The localized form of amyloidosis in eyelids is mostly observed with concomitant basal cell carcinoma, Bowen's disease and seborrheic keratosis.3 An etiological relationship of amyloidosis with trachoma is disputed with one study findings indicating an association while another study did not supported this association.1011 In our cases, there was no associated localized cause.

Most commonly, amyloidosis causes mild ptosis but up to one-fourth cases may present with severe ptosis.2 Our cases presented with severe ptosis because of the levator involvement (in case one), and both levator involvement and mechanical ptosis caused by the significant size of lesion (in case two). The management of the localized form mainly relies on surgical debulking. Complete excision is not possible, and the aim of the treatment is relief of symptoms, restoration of function and prevention of ocular morbidity. Radiotherapy in such cases may also be useful. Unwarranted use of corticosteroids is to be avoided as it accelerates amyloid deposits.3 Fortunately most of the patients have no significant recurrence or obvious progression.2

In conclusion, amyloidosis is rare, slowly progressive disease associated with significant ocular morbidity. The presentation may be unusual and diagnosis may be delayed. The tarsal thickening caused by amyloidosis is rare and can be confused with trachoma, chronic granulomatous disorders and sebaceous gland neoplasms. The diagnosis is established by histo-pathology and thorough work up is necessary to rule out systemic amyloidosis.