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Department of Ophthalmology & Visual Sciences, University of Adelaide, Adelaide, AustraliaSouth Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia
Department of Ophthalmology & Visual Sciences, University of Adelaide, Adelaide, AustraliaSouth Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia
Department of Ophthalmology & Visual Sciences, University of Adelaide, Adelaide, AustraliaSouth Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia
Amyloidosis is a heterogeneous collection of conditions that presents with variable organ dysfunction due to extracellular aggregation of abnormally folded proteins. Systemic light chain amyloidosis is an uncommon disease, and involvement of orbital structures is particularly rare. We present a case of chronic dacryoadenitis in which λ light chain amyloid deposition was detected in the lacrimal gland 6 months after a nonspecific biopsy.
Case report
A 44-year-old white male presented with a 6-week history of bilateral upper eyelid swelling associated with discomfort that was worse on the left. His medical history was significant for multiple autoimmune conditions including membranous nephropathy, chronic inflammatory demyelinating polyneuropathy, pustular psoriasis, immune thrombocytopenic purpura, and myasthenia gravis. Current medications included immunosuppressant therapy (prednisolone 5 mg twice daily), antihypertensives (amlodipine 320 mg, valsartan 10 mg, and hydrochlorothiazide 25 mg daily), a retinoid (acitretin 25 mg nocte), and treatment for thrombocytopenia (eltrombopag 50 mg daily).
At presentation, best corrected visual acuity was 6/12 bilaterally with no evidence of optic neuropathy. Both lacrimal glands were enlarged and were firm and nontender to palpation. There was no proptosis or limitation of extraocular movements. Intraocular pressures were within normal limits, and the remainder of the examination was unremarkable.
Serum autoimmune, endocrine, and infectious screens were negative. Magnetic resonance imaging of the orbits demonstrated diffusely enlarged lacrimal glands that were hyperintense on fat-suppressed T1-weighted sequence and displayed homogeneous enhancement with contrast (Fig. 1).
Fig. 1T1-weighted fat-suppressed magnetic resonance imaging showing bilateral enlargement of the lacrimal glands with diffuse enhancement postcontrast in the coronal plane (A) and axial plane (B).
Idiopathic autoimmune dacryoadenitis was suspected, and a biopsy was taken of the left lacrimal gland. There was intraoperative evidence of fibrosis. Histopathological evaluation revealed dense fibrous connective tissue consistent with scarring (Fig. 2A). A trial of increased oral steroids with dose tapering and intralesional injection of triamcinolone had no benefit.
Fig. 2Histological images of left-sided lacrimal gland biopsies. A, Hematoxylin and eosin stain of initial lacrimal gland biopsy showing dense fibrous connective tissue consistent with scarring. B, Hematoxylin and eosin staining of tissue sample taken from lacrimal gland debulking demonstrating amorphous eosinophilic material. C, Positive staining with Congo red dye. D, Strong staining of amyloid with antibody directed immunohistochemistry evaluation for λ light chain showing strong staining of amyloid.
After 6 months of progressive swelling, the patient reported impairment of peripheral vision particularly on the left side. A decision to debulk the left lacrimal gland was made and performed via an extended skin crease incision. Tissue sampling at the time found extensive deposition of amyloid within connective and perivascular tissues (Fig. 2B–D). Congo red staining demonstrates apple green dichroism and birefringence with polarized light, and immunohistochemistry illustrates the λ light chain protein antigenicity of the amyloid protein in this case. Significant postoperative swelling developed, and a hematoma was suspected. Surgical exploration found accumulation of solid material that again revealed amyloid on histological evaluation.
Screening for systemic amyloidosis found elevated serum κ and λ light chains of 165 mg/L and 935 mg/L, respectively (reference range, κ 3–19 mg/L and λ 6–26 mg/L) and decreased κ/λ ratio of 0.18 (reference range, 0.25–1.65). Bone marrow biopsy was normocellular with no identifiable plasma cell dyscrasia or amyloid deposition. A biopsy of the left submandibular gland demonstrated amyloid deposition. A small pericardial effusion was identified on echocardiography. Twenty-four hour total urine protein was elevated (1562 mg/24 hours) containing elevated λ light chain Bence Jones protein (240 mg/L). A diagnosis of systemic light chain amyloidosis was made. Cervical lymphadenopathy and swelling at the base of the tongue developed. The bilateral submandibular glands received a course of 8 Grays palliative radiotherapy to minimal effect. The patient was treated with a chemotherapy regimen of Velcade, cyclophorsphomide, and dexamethasone. At 3-month review the lacrimal gland swelling had not increased further.
Discussion
Amyloidosis encompasses a spectrum of organ dysfunction disorders caused by the extracellular deposition of abnormally folded proteins.
Over 30 precursor proteins have been identified, all displaying pathognomonic Congo red staining, which demonstrates apple green dichroism and birefringence with polarized light.
Immunohistochemical subtyping of amyloid deposits is essential to guide management. A protein amyloid (AA) typically accumulates in patients with chronic inflammatory diseases, while λ and κ light chain proteins deposit as a consequence of B-cell dyscrasia or plasma cell clonal expansion.
In the current case, A protein amyloid may have been expected in the context of chronic lacrimal gland inflammation; however, λ light chains were identified 6 months after a nonspecific biopsy.
There are only a small number of similar reports in which the initial biopsy of chronically inflamed tissue demonstrated nonspecific or normal tissue with subsequent identification of AL amyloid at repeat biopsy.
It is unclear whether histopathological findings in these cases were due to sampling error or if there was an insufficient amount of amyloid at the time of tissue sampling to elucidate characteristic features.
In this case, demonstration of λ AL amyloid was unexpected and highlights the utility of repeat tissue sampling when nonspecific histopathological features are found.
Systemic AL amyloidosis presents variably, frequently producing nonspecific features that may manifest in any organ system.
Evidence of peripheral neuropathy and cardiovascular disease were observed in our patient, and it is possible that amyloid had deposited in these organs. Peripheral neuropathy is present in approximately one-fifth of patients with systemic AL disease and is commonly confused with other polyneuropathies.
Involvement of oral soft tissues is well-recognized in systemic AL disease; submandibular swelling occurs commonly, and macroglossia is considered a pathognomonic sign but is present in fewer than one-third of patients.
Tissue biopsy of the submandibular glands may provide a suitable diagnostic investigation for systemic AL amyloidosis where biopsy results from other locations has failed to demonstrate amyloid.
Recognizing extraorbital manifestations of systemic amyloidosis may aid in diagnosing orbital involvement and prevent treatment delays.
In summary, we present a case of systemic light chain amyloidosis producing chronic lacrimal gland enlargement. Despite chronic dacryoadenitis and a previously normal biopsy, light chain disease was detected in the lacrimal gland rather than the expected A protein amyloidosis.
Disclosure
The authors have no proprietary or commercial interest in any materials discussed in this article.
References
Nielsen N.S.
Poulsen E.T.
Klintworth G.K.
Enghild J.J.
Insight into the protein composition of immunoglobulin light chain deposits of eyelid, orbital and conjunctival amyloidosis.
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