—  SPECIALTY CONFERENCE  —

Ophthalmic Pathology

Case 3 - Keratopathy of Monoclonal Gammopathy

Gordon K. Klintworth, Duke Univ Medical Center, Durham, NC





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Introduction:
A 55 year-old myopic white female presented to an ophthalmologist with progressive clouding of vision in both eyes for eight years. Her vision could not be corrected with refraction. Her past medical history was notable for hypertension, hypercholesterolemia, and seasonal allergies. She did not have any significant previous ocular history other than spectacle corrected myopia and a chronic complaint of dry eyes for which she took artificial tears. None of her family members were known to have any eye disorders. The patient was a longtime smoker, but did not abuse alcohol or other substances. On examination the patient's best corrected visual acuity was 20/50 -2 OD and 20/70 -1 OS. Bilateral diffuse, geographic shaped stromal opacities were noted in her corneas. They involved the visual axis and impeded good visualization of the rest of the anterior chamber and posterior eye structures. A penetrating keratoplasty (PK) was performed in the left eye in 2004. The patient was followed post-operatively at regular intervals and her visual acuity worsened to 200 E at 3 feet OD and 20/50 OS. Six months after the PK subepithelial deposits were noted in the corneal graft. They appeared to be similar to those previously seen in the pre-PK left cornea and to those currently seen in the right corneal stroma. One year later a PK was performed on the right eye.

Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Corneal tissue removed at penetrating keratoplasty from each cornea was processed for light microscopy. Microscopic examination of the excised corneal button from both disclosed large confluent deposits of eosinophilic material within the corneal stroma. The Masson trichrome stain manifested strong fuchsinophilia of the stromal deposits, but a Congo red stain was negative for amyloid. An immunohistochemical stains for both kappa and lambda light chains within the stromal deposits was positive.


Case 3 - Figure 1
Acellular abnormal material in posterior corneal stroma. Masson trichrome stain
Case 3 - Figure 2
Acellular abnormal material in posterior corneal stroma. Hematoxylin and eosin stain.
Case 3 - Figure 3
Multifocal markedly eosinophilic spindle shaped acellular regions in superficial corneal stroma. Hematoxylin and eosin stain.

Case 3 - Figure 4
Higher magnification of Fig 2. Hematoxylin and eosin stain.
Case 3 - Figure 5
Extensive acellular eosinophilic accumulation adherent to the corneal stroma. Descemet membrane is not evident. Hematoxylin and eosin stain.
Case 3 - Figure 6
Multifocal acellular spindle shaped foci in the superficial corneal stroma. Note similarity to Case 3-Fig 3. Masson trichrome stain.

Differential Diagnoses:
The presence of eosinophilic deposits in the cornea have a differential diagnosis that includes amyloid (lattice corneal dystrophy type 1 and 2) and the granular corneal dystrophies (granular corneal dystrophy types 1, 2, and 3).

Final Diagnosis:
Keratopathy of monoclonal gammopathy.

Case Discussion:
After the diagnosis was established the patient was referred back to her primary care physician for an evaluation of systemic disease. Her complete blood count, albumin, and electrolyte panel were normal, but her total protein was slightly elevated (8.3 g/dl (compared to the control levels of 6.0-8.0 g/dl)) and the serum protein electrophoresis showed a monoclonal component in the gamma region (1.78 g/dl compared to control values of 0.53-1.37 g/dl). Other than her corneal findings, she continued to be asymptomatic and no other systemic abnormalities were noted by her primary care team.

Review of the Literature/Treatment Options:
Monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 1% in individuals 50 years and older and 10% in those 75 years and older [5]. MGUS is often asymptomatic and sometimes it presents clinically with crystals in the cornea. Identical crystals occur in patients having hypergammaglobilinemia due to multiple myeloma and other disorders [1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13]. In many cases the systemic disease is diagnosed only after bilateral delicate scintillating corneal crystals initiate a systemic work-up. Aside from the cornea, crystals may occur in the bulbar conjunctiva or lens. Klintworth et al. [4] established that the crystalline corneal deposits in multiple myeloma were composed of immunoglobulin and that these deposits were similar to those previously seen in the cytoplasm of neoplastic or reactive plasma cells, in crystallized plasma gammaglobulins, and in the renal tubular epithelium in multiple myeloma. The location of the corneal immunoglobulin deposits varies considerably from case to case. They may involve different sites in the cornea and are sometimes dispersed throughout the cornea. Later it was appreciated that the IgG deposits within the cornea in MGUS are not necessarily crystalline in appearance [11] and that the deposits may resemble certain genetically determined diseases of the cornea (corneal dystrophies) [7, 11] A penetrating keratoplasty is often indicated to restore vision in patients with immunoglobulin deposition in the cornea. The deposits may, however, recur in the graft.

Conclusion(s):
The cornea may be affected in conditions associated with hypergammaglobulinemia such as a monoclonal gammopathy of uncertain significance and multiple myeloma.

References:
  1. Beebe WE, Webster RG Jr. Spencer WB. Atypical corneal manifestations of multiple myeloma: a clinical and immunohistochemical report. Cornea 1989; 8:274-280.

  2. Cherry PMH, Kraft S, McGowan H., et al. Corneal and conjunctival deposits in monoclonal gammopathy. Can J Ophthalmol 1983; 18:142-149.

  3. Hill JC, Mulligan GP. Subepithelial corneal deposits in IgG lambda myeloma. Br J. Ophthalmol 1989; 73:552-554.

  4. Klintworth GK, Bredehoeft SJ, Reed JW. Analysis of corneal crystals in multiple myeloma. Am J Ophthalmol 1978; 86:303-313.

  5. Kyle R, Rajkumar S. Monoclonal gammopathies of undetermined significance: a review. Immunological Reviews 2003;194:112-39.

  6. Miller KH, Green WR, Stark WJ, et al. Immunoprotein deposition in the cornea. Ophthalmology 1980; 87: 944-950, 1980.

  7. Moller H, Ehlers N, Bojsen-Moller M, Ridgeway A. Differential diagnosis between granular corneal dystrophy Groenow type I and paraproteinemic crystalline keratopathy. Acta Ophthalmologica 1993; 71:552-5.

  8. Rodrigues MM, Krachmer JH, Miller SD, Newsome DA. Posterior corneal crystalline deposits in benign monoclonal gammopathy: a clinicopathologic case report. Arch Ophthalmol 1979; 97:124-128.

  9. Schelonka L, Ogawa G, O'Brien T, Green W> Acute unilateral corneal immunoprotein deposition in IgM monoclonal gammopathy. Arch Ophthalmol 2000;118:125-6.

  10. Sekundo W, Seifert P. Monoclonal corneal gammopathy: topographic considerations. German Journal of Ophthalmology 1996; 5:262-7.

  11. Spiegel P, Grossniklaus HE, Reinhart WJ, Thomas RH. Unusual presentation of paraproteinemic corneal infiltrates. Cornea 1990; 9:81-85.

  12. Steuhl K, Knorr M, Rohrbach J, et al. Paraproteinemic corneal deposits in plasma cell myeloma. Am J Ophthalmol 1991; 111:312-8.

  13. Yassa NH, Font RL, Fine BS, Koffler BH. Corneal immunoglobulin deposition in the posterior stroma: a case report including immunohistochemical and ultrastructural observations. Arch Ophthalmol 1987; 105:99-103.