Advertisement

Bilateral intratarsal dystrophic calcification and ossification in localized immunoglobulin light chain amyloid

Published:September 22, 2017DOI:https://doi.org/10.1016/j.jcjo.2017.07.016
      Amyloidosis is a heterogeneous group of rare disorders wherein insoluble fibrillar proteins are deposited in extracellular spaces within the body. The disorders may be localized, systemic, hereditary, and nonhereditary. Various subtypes of amyloid proteins are involved, and are most accurately characterized by mass spectrometry. We report herein a unique case of unsuspected bilateral localized intratarsal amyloid within specimens derived from blepharoptosis surgery. Bilateral focal dystrophic calcification and bone formation were present within the amyloid deposits, a unique finding in the eyelids.
      A healthy 75-year-old male presented with bilateral blepharoptosis (Fig. 1) and a mild “dry eye” condition. Visual acuity was 20/20 OU. Extraocular muscle function was normal. There was Meibomian gland dysfunction of the lower lids with mild corneal punctate staining. A well-healed bilateral LASIK flap from a several-year-old procedure was present. There was bilateral pseudophakia. Findings of each fundus examination, including optic nerves, were normal.
      The patient underwent a bilateral Fasanella-Servat tarsoconjunctival resection for correction of blepharoptosis. During surgery, a white, “spongy” material was noted near the upper border of each tarsus, presumably reflecting some sort of scarring. Each tarsus measured 16 mm in height, approximately double the average measurement. Pathologic examination of both tarsoconjunctival fragments showed intratarsal deposits of Congo-red–positive material that exhibited apple-green birefringence under polarized light. Some areas showed a foreign body granulomatous reaction to the amyloid (Fig. 2A). Each tarsus contained focal basophilic calcification of the amyloid deposits, some of which had undergone bone formation (Fig. 2C, D). Some nonossified amyloid also was present in Mueller’s muscle. Immunohistochemistry of a scant subconjunctival lymphoplasmacytic infiltrate disclosed polyclonality with respect to lymphocytes (an admixture of CD3-positive T cells and CD20-positive B cells) and plasma cells (an admixture of kappa and lambda light chains). These configurations denoted a garden-variety reactive pattern (chronic conjunctivitis) rather than a localized plasma cell proliferative disorder. Mass spectrometry performed at the Mayo Clinic disclosed the amyloid to be of the AL kappa type. Healing was unremarkable, and postoperative examination with lid-eversion showed no residual white deposits. Subsequent findings of an extensive systemic work-up, including complete blood count, basic metabolic panel, serum electrophoresis, serum calcium, and phosphorous, were all normal without evidence of systemic amyloidosis.
      Fig. 2
      Fig. 2(A) Tarsoconjunctival fragment shows conjunctivitis and contains amyloid deposition (a) with foreign body reaction (*) (hematoxylin–eosin, ×200). (B) Amyloid highlighted by Congo-red stain (×200). (C) Purplish calcification with granulomatous inflammation (arrowhead) (hematoxylin–eosin, ×200). (D) Bone formation (b) within amyloid (hematoxylin–eosin, ×100).
      Localized AL amyloidosis represents a rare occurrence within the spectrum of amyloid disorders and is most accurately diagnosed by mass spectrometry protein sequencing. A recent report of 2 cases of localized conjunctival AL light chain amyloid without systemic disease used mass spectrometry analysis at the Mayo Clinic.
      • Hamill E.B.
      • Thyparampil P.J.
      • Yen M.T.
      Localized immunoglobulin light chain amyloid of the conjunctiva confirmed by mass spectrometry without evidence of systemic disease.
      Our case illustrates the third such case. Because the disorder has been theorized to result from site-specific plasma cell clones producing fragmented monoclonal light chains,
      • Westermark P.
      Localized AL amyloidosis: a suicidal neoplasm?.
      we investigated the plasma cells and lymphocytes at the specimen borders and found no evidence of a monoclonal proliferation. A characteristic finding in the current case, unusual in systemic amyloidosis, was the presence of giant cells adjacent to both noncalcified and calcified amyloid deposits. This pattern may reflect a granulomatous foreign body reaction
      • Mukhopadhyay S.
      • Damron T.A.
      • Valenti A.L.
      Recurrent amyloidoma of soft tissue with exuberant giant cell reaction.
      or, in noncalcified amyloid, an immunohistochemical reaction to light chains.
      • Hamill E.B.
      • Thyparampil P.J.
      • Yen M.T.
      Localized immunoglobulin light chain amyloid of the conjunctiva confirmed by mass spectrometry without evidence of systemic disease.
      Amyloidal calcification, with and without ossification, has been described in various systemic sites, such as lung,
      • Xiang H.
      • Wu Z.
      • Wang Z.
      • Yao H.
      Nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary MALT lymphoma with extensive plasmacytic differentiation: report of a rare case and review of the literature.
      subcutaneous tissues,
      • Bandyopadhyay A.
      • Bhattacharya S.
      • Maiti B.
      • Bose K.
      Calcified amyloid tumor of neck with exuberant giant cell reaction.
      and orbit,
      • Gonçalves A.C.P.
      • Moritz R.B.
      • Monteiro M.L.
      Primary localized amyloidosis presenting as diffuse amorphous calcified mass in both orbits: case report.
      but this is—to our knowledge—the only case of such occurrence in the tarsus. The pathogenesis of the exceptional dystrophic calcification with bone formation in the current case and its absence in previously reported cases of conjunctival/eyelid amyloid is unclear.
      Intratarsal amyloid is much rarer than conjunctival or orbital amyloid and is nearly always unilateral.
      • Hubbard A.D.
      • Brown A.
      • Bonshek R.E.
      • et al.
      Surgical management of primary localised conjunctival amyloidosis causing ptosis.
      • Hill V.E.
      • Brownstein S.
      • Jordan D.R.
      Ptosis secondary to amyloidosis of the tarsal conjunctiva and tarsus.
      We could find only one report of bilateral tarsal involvement, and it did not show the calcification and ossification found in the current case.
      • Kamal S.
      • Goel R.
      • Bodh S.A.
      • Madhu S.
      Primary localized amyloidosis presenting as a tarsal mass: report of two cases.
      A single report of a unilateral, papillomatous, calcified nonamyloid tarsal mass was termed, oddly, “calcinosis cutis” by its authors
      • Jun I.
      • Kim S.E.
      • Lee S.Y.
      • et al.
      Calcinosis cutis at the tarsus of the upper eyelid.
      and may represent calcification of an underlying neoplasm. Calcification of ocular tissues may occur in hypercalcemic states such as hyperparathyroidism, but these conditions were excluded in our patient. It is probable that the intratarsal deposits of calcified and ossified amyloid—along with nonossified Mueller’s muscle deposits—contributed to the blepharoptosis.
      This case, like its recently reported analogues,
      • Hamill E.B.
      • Thyparampil P.J.
      • Yen M.T.
      Localized immunoglobulin light chain amyloid of the conjunctiva confirmed by mass spectrometry without evidence of systemic disease.
      illustrates that AL amyloidosis may be localized and characterized by a benign course. (Additional systemic follow-up is planned.) The case also underscores the importance of submitting tarsoconjunctival tissue for histologic examination rather than discarding the excised material.
      Although some institutions use immunohistochemistry for traditional amyloid typing, the results can be inaccurate. Contamination or formalin-induced epitope loss may produce high background staining. Furthermore, c-terminus light chain variability can result in lack of staining.
      • Vrana J.A.
      • Gamez J.D.
      • Madden B.J.
      • et al.
      Classification of amyloidosisby laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens.
      • Leung N.
      • Nasr S.H.
      • Sethi S.
      How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing.
      We strongly endorse interinstitutional referral for protein sequencing by liquid chromatography and mass spectrometry, which is nearly 100% accurate.

      Disclosure:

      The authors have no proprietary or commercial interest in any materials discussed in this article.

      References

        • Hamill E.B.
        • Thyparampil P.J.
        • Yen M.T.
        Localized immunoglobulin light chain amyloid of the conjunctiva confirmed by mass spectrometry without evidence of systemic disease.
        Ophthal Plast Reconstr Surg. 2016; ([Epub ahead of print])
        • Westermark P.
        Localized AL amyloidosis: a suicidal neoplasm?.
        Ups J Med Sci. 2012; 117: 244-250
        • Mukhopadhyay S.
        • Damron T.A.
        • Valenti A.L.
        Recurrent amyloidoma of soft tissue with exuberant giant cell reaction.
        Arch Pathol Lab Med. 2003; 127: 1609-1611
        • Xiang H.
        • Wu Z.
        • Wang Z.
        • Yao H.
        Nodular pulmonary amyloidosis and obvious ossification due to primary pulmonary MALT lymphoma with extensive plasmacytic differentiation: report of a rare case and review of the literature.
        Int J Clin Exp Pathol. 2015; 8: 7482-7487
        • Bandyopadhyay A.
        • Bhattacharya S.
        • Maiti B.
        • Bose K.
        Calcified amyloid tumor of neck with exuberant giant cell reaction.
        J Lab Physicians. 2015; 7: 61-63
        • Gonçalves A.C.P.
        • Moritz R.B.
        • Monteiro M.L.
        Primary localized amyloidosis presenting as diffuse amorphous calcified mass in both orbits: case report.
        Arq Bras Oftalmol. 2011; 74: 374-376
        • Hubbard A.D.
        • Brown A.
        • Bonshek R.E.
        • et al.
        Surgical management of primary localised conjunctival amyloidosis causing ptosis.
        Br J Ophthalmol. 1995; 79: 707
        • Hill V.E.
        • Brownstein S.
        • Jordan D.R.
        Ptosis secondary to amyloidosis of the tarsal conjunctiva and tarsus.
        Am J Ophthalmol. 1997; 123: 852-854
        • Kamal S.
        • Goel R.
        • Bodh S.A.
        • Madhu S.
        Primary localized amyloidosis presenting as a tarsal mass: report of two cases.
        Middle East Afr J Ophthalmol. 2012; 19: 426-428
        • Jun I.
        • Kim S.E.
        • Lee S.Y.
        • et al.
        Calcinosis cutis at the tarsus of the upper eyelid.
        Korean J Ophthalmol. 2011; 25: 440-442
        • Vrana J.A.
        • Gamez J.D.
        • Madden B.J.
        • et al.
        Classification of amyloidosisby laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens.
        Blood. 2009; 114: 4957-4959
        • Leung N.
        • Nasr S.H.
        • Sethi S.
        How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing.
        Blood. 2012; 120: 3206-3213