Abstract
Purpose:
To describe the clinical, imaging, histopathologic, immunohistochemical, and ultrastructural characteristics of coexistent amyloid and spheroidal degeneration-type deposits in a family with Histidine-626-Argenine Transforming Growth Factor Beta Inducible Gene (H626R TGFBI) corneal stromal dystrophy.
Methods:
Retrospective clinical-pathologic and genetic analysis of one family with H626R lattice dystrophy.
Results:
The disease showed autosomal dominant inheritance pattern by pedigree analysis. The affected individuals presented in 4th or 5th decades with progressive visual impairment and recurrent erosions. Ophthalmic examination of the 3 affected family members revealed asymmetric, thick, branching lattice-like deposits, associated with corneal haze. Sequencing of the TFGBI gene revealed a high-penetrance disease causing sequence variation (H626R CAT>CGT heterozygous). Optical coherence tomography demonstrated fusiform, poorly demarcated, hyper-echoic stromal deposits, consistent with amyloid, with focal hypo-echoic central region. Histologic evaluation of the corneal buttons from the 2 affected family members showed stromal fusiform Periodic acid-Schiff (PAS)-positive, Congo red-positive, birefringent, and keratoepithelin antibody-immunoreactive deposits, consistent with TGFBI amyloid. Few amyloid deposits contained a central nidus of spheroidal degeneration-type material. This material demonstrated autofluorescence, stained with elastic and Masson-trichrome stains, did not stain with PAS or Congo red stains, was non-birefringent, and did not immunoreact with keratoepithelin antibodies. Transmission electron microscopy confirmed the presence of peripheral amyloid fibrils with central electrodense, homogeneous, discrete spheroidal degeneration-type deposits.
Conclusions:
Presence of spheroidal degeneration-type deposits in a subset of affected patients, the variability in presentation within an individual and between the family members, the predominant anterior corneal stromal location and the non-immunoreactivity of deposits for keratoepithelin suggest that these deposits are degenerative in nature. The deposits may arise from ultraviolet light-altered proteins diffused from the limbus, which form a nidus for mutant keratoepithelin deposition in patients with the late onset H626R lattice dystrophy variant.
Keywords: 554 immunohistochemistry •
636 pathobiology