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Year : 2013  |  Volume : 20  |  Issue : 3  |  Page : 193-197  

Anterior orbit and adnexal amyloidosis

1 King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
2 King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia; Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States of America

Date of Web Publication9-Jul-2013

Correspondence Address:
Deepak P Edward
King Khaled Eye Specialist Hospital, PO Box 7191, Riyadh - 11462, Kingdom of Saudi Arabia

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0974-9233.114789

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Purpose: To describe six cases of anterior orbital and adnexal amyloidosis and to report on proteomic analysis to characterize the nature of amyloid in archived biopsies in two cases.
Materials and Methods: The clinical features, radiological findings, pathology, and outcome of six patients with anterior orbit and adnexal amyloidosis were retrieved from the medical records. The biochemical nature of the amyloid was determined using liquid chromatography/mass spectroscopy archived paraffin-embedded tissue in two cases.
Results: Of the six cases, three had unilateral localized anterior orbit and lacrimal gland involvement. Four of the six patients were female with an average duration of 12.8 years from the time of onset to presentation eyelid infiltration by amyloid caused ptosis in five cases. CT scan in patients with lacrimal gland involvement (n = 3) demonstrated calcified deformable anterior orbital masses and on pathological exmaintionamyloid and calcific deposits replaced the lacrimal gland acini. Ptosis repair was performed in three patients with good outcomes. One patient required repeated debulking of the mass and one patient had recurrenct disease. Proteomic analysis revealed polyclonal IgG-associated amyloid deposition in one patient and AL kappa amyloid in the second patient.
Conclusion: Amyloidosis of the anterior orbit and lacrimal gland can present with a wide spectrum of findings with good outcomes after surgical excision. The nature of amyloid material can be precisely determined in archival pathology blocks using diagnostic proteomic analysis.

Keywords: Amyloidosis, Lacrimal Gland, Orbit, Pathology

How to cite this article:
Al Hussain H, Edward DP. Anterior orbit and adnexal amyloidosis. Middle East Afr J Ophthalmol 2013;20:193-7

How to cite this URL:
Al Hussain H, Edward DP. Anterior orbit and adnexal amyloidosis. Middle East Afr J Ophthalmol [serial online] 2013 [cited 2022 Nov 29];20:193-7. Available from: http://www.meajo.org/text.asp?2013/20/3/193/114789

   Introduction Top

Amyloidosis of the anterior and posterior orbit can be localized or associated with systemic disease. [1],[2],[3],[4] In the anterior orbit, amyloid infiltration affects the periocular tissue and lacrimal gland. The occurrence of amyloidosis in these anatomical sites is uncommon and is represented in the literature mainly as case reports, and a single large series that describes the the clinical features and course of periocular and orbital amyloidosis. [1],[5],[6],[7],[8],[9],[10]

This report of six cases highlight some of the clinical and histpathological features, course of disease, and treatment outcomes of anterior orbit and adnexal amyloidosis in Saudi Arabia. We also describe the determination of the biochemical nature of amyloid in archival paraffin-embedded orbital tissue using a recently described technique that utilizes protoemic analysis for detection of amyloid using chromatography-electrospray tandem mass spectrometry (LC-MS/MS). [11],[12]

   Materials and Methods Top

The patient demographics, duration of disease, clinical presentation, site of amyloid involvement, radiological, histopathological slides, and intraoperative findings as well as treatment outcomes were retrieved following IRB approval.

Tissue from paraffin blocks from two patients were used from diagnostic proteomic analysis. A tissue block from recurrence in case 2 and two separate biopsies from case 3 were segmented and submitted for mass spectroscopy. The areas of amyloid were segregated using laser capture microdissection and subjected to LC-MS/MS using a previously published method. [12] Briefly, trypsin generated digests of deparaffinized tissue fragments localized by laser capture were subjected to mass spectroscopy that determined the total proteome of the study specimens. However, to utilize the mass spectroscopy data as a diagnostic tool, the data was analyzed using known search algorithms to determine peptide fragments related to amyloid deposits. Tissue from other blocks were not tested as material was insufficient or blocks not available.

The study was approved by the Human Ethics Committee/Institutional Review Board of the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

   Results Top

In this series two cases were male and four were female with a mean age of presentation of 46.3 years (range, 25-75 years). The mean duration of symptoms based on history to the diagnosis of amyloidosis was 12.8 years (range, 3-30 years). The medical history for all patients was noncontributory. A medical examination was negative for systemic amyloidosis in all patients. Case 3 had a left anterior hemiblock but was not related to amyloid infiltration of the heart. Systemic investigations that included CBC, differential counts, and ESR were within normal limits in all patients. Case 2 in whom the amyloid recurred, had a workup for multiple myeloma, which was negative.

The clinical features are summarized in [Table 1]. The anterior orbit and lacrimal gland were involved in three cases with concurent conjuntival involvement. CT scan showed anterior orbital masses that extended to the lacrimal fossa with calcification [Figure 1] and [Figure 2].No bony erosion was noted.

Lid involvement with ptosis was seen in five patients with localized lid involvement in two cases. Three patients required ptosis surgery (Cases 4, 5, and 6) and in other cases the ptosis was mainly mechanical and resolved after excision of the mass. The outcome of ptosis surgery was good in the three patients. All patients had conjunctival cicatrization consistent with trachoma.
Figure 1: Case three: (a) Note amyloid infiltration into the anterior orbit, lacrimal gland, lower lid and conjunctiva (b) CT scan demonstrating diffuse mass and anterior orbit with calcification and without bony erosion

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Figure 2: Case four: (a) Note ptosis of right upper lid (b) CT scan showing diffuse mass involving right upper lid with areas of calcification (c) Intraoperative photograph showing amyloid in the pretarsal region

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Table 1: Clinical features of patients

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Intraoperatively, the amyloid deposits were firm and easily dissected from the surrounding tissues without excessive bleeding. In case 4, the mass was localized to the pretarsal region without infiltration into the surrounding periorbital tissue [Figure 2]. In case 2 (the case with a recurrence), the amyloid material appeared gelatinous and peeled easily without bleeding. Case 3 underwent mutiple debulking procedures for residual amyloid.

The pathological features are summarized in [Table 2]. In the eyelids, the amyloid material infiltrated the dermis, the tarsal plate focally in one patient and the conjunctival substantia propria in cases with conjunctival involvement. Variable degrees of chronic inflammatory infiltrate with foreign body giant cell reaction in the region of amyloid deposition was noted. Calcification of the amyloid material was seen in three out six biopsy specimens [Figure 3]a. The calfication was scattered within the amyloid material and did not involve the blood vessels. Perivascular deposition of amyloid was noted in all cases [Figure 3]b. The cases that radiologically appeared to involve the lacrimal gland did not show glandular tissue in the biopsy material except for a small fragment in case 4.

LC-MS/MS from paraffin embedded tissue from case 2 showed a polyclonal IgG type amyloidosis and in case 3, two separate biopsy specimens revealed AL kappa type amyloid. Immunhistochemistry with antibodies against kappa and lambda light chains were not performed.
Figure 3: (a) Microphotograph of biopsy specimen from Case 3 showing infiltration of amyloid from biopsy material in the region of the lacrimal gland. Note the absence of lacrimal gland acini and calcification (arrows) (Congo red; original magnification ×20) (b) Amyloid material showing typical birefringence and dichroism. Note perivascular infiltration with amyloid (arrow) (Congo red with polarization; original magnification ×20)

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Table 2: Pathological features of biopsy specimens

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   Discussion Top

This report highlights features of anterior orbital amyloidosis involving the eyelid and lacrimal gland. The age at presentation of patients in this case series was wide and comparable to a large series of patients with periorbital amyloid where the mean age of presentation was 57 years (median 59.5, range 27-85). [1] Gender predilection has not been described in amyloidosis; however, most patients in this series were female. Also of note was the long-standing nature of the disease in all patients with the mean interval between onset and diagnosis being over 12 years. In another series that reported on periorbital amyloid, this time interval averaged three years. [1] It is likely that the amyloid deposition occured at a slow rate causing patients to seek attention at a more advanced stage or this observation could be related to access to care resulting in patients presenting at a later stage.

Five of the six patients had eyelid involvement with ptosis. Others have reported ptosis as a presenting sign in 50% of patients with periorbital amyloid. [1] Eyelid amyloidosis can be part of a systemic disorder or localized to the eye and adnexa. [13],[14],[15],[16],[17],[18] In this series all patients had localized eyelid or adnexal amyloid infiltration without conjunctival involvement, eyelid amyloidosis is more frequently reported as an extension of conjunctival amyloid into the eyelid [19],[20],[21],[22] whereas, amyloid primarily localized to the eyelid as seen in three cases in this series is uncommon. Periocular amyloid involving the superficial dermis is described as having a waxy and papular appearance. [18],[21] This feature was not evident in our patients and may have been because of the deeper location of the amlyoid and possibly the darker color of the periocular skin in this population. Periocular ecchymoses, a finding reported in eyelid amyloid [23],[24] was also not observed in our patients despite perivascular infiltration by amyloid. All patients in this series had bilateral ocular signsconsisent with inactive trachoma of the eyelid. Although, corneal amyloidosis has been associated with trachomatous scarring. It is unlikely that trachoma played a role in the anterior orbital and lacrimal gland amyloidosis since cictracial changes were distal to the site of amyloid deposition. Also, trachomatous scarring is fairly common in this population whereas ocular amyloidosis is rare. Two patients had a history of lid trauma and it is possible that trauma in some way might have contributed to localized deposition of amyloid. Patients with ptosis required surgery when the amyloidosis was localized to the eyelid (as in cases 4, 5, and 6) and with good outcomes following repair. In others, the ptosis resolved following excision of the mass.

Lacrimal gland involvement with amyloid is unusual [1],[6],[7],[10],[25],[26] and was osberved in three of our patients. As noted in this series and reported by others, lacrimal gland amyloidosis should be suspected with CT scan findings of lacrimal gland enlargement that molds to the orbital rim and the presence of calcification. [7],[9] Calcification demonstration on CT scans is a fairly common finding in systemic amyloid. [27] The presence of calcification in our cases was confirmed by histology and was scattered in the amyloid deposits and not necessarily related to blood vessel involvement and phlebolith formation as previously hypothesized when the lacrimal gland was involved. [7] It was interesting to note that on pathology, lacrimal gland acinar structures were largely absent on pathological examination suggesting that the amyloid deposition resulted in extensive destruction of the lacrimal gland parenchyma.

The types of amyloid in tissue have typically been determined using immunohistochemistry and the results can often been difficult to interpret. [1],[10],[28],[29] In this study we used a recently described technique to determine the nature of amyloid in three biopsy specimens from two patients. This technique employs microdissection of the amyloid from formalin-fixed paraffin-embedded tissue sections and after specimen preparation is subjected to mass spectroscopy to determine the nature of proteins in the tissue. [12],[30] Amyloid in the tissue from case 2 showed AL kappa type amyloid [3],[29],[22],[31],[32] and in case 3, a polyclonal IgG type amyloid reported with local amyloidosis and multiple myeloma; [33],[34] however, none of our patients had systemic disease. This diagnostic approach using LC-MS/MS has not been previously used to characterize ocular amyloid. However, AL kappa was detected in orbital amyloid from deparaffinized tissue using extraction techniques, gel electrophoresis and Western blot for identification of the protein. [2] This LC-MS/MS technique facilitates specific identification of the type of amyloid protein which was variable using older techniques. Such testing is now available at selected university-based pathology laboratories in many Western countries.

Two patients experienced recurrence of amyloid whereas others remained recurrence free for many years. The rate of recurrence reported in the literature is derived from isolated case reports some of which suggest that recurrence does occur and others in which the patients have been symptom-free following debulking. [1],[3],[28]

In summary, this report describes the spectrum of clinical and histological findings in amyloidosis of the anterior orbit and adnexa. All patients progressed well after removal of the amyloid material and recurrence was rare. The utility of diagnostic proteomics as a useful adjunct in the pathological assessment of tissues infiltrated with amyloid needs to be validated in a larger sample of tissues.

   References Top

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]

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