Multiple transthyretin (TTR) mutations have recently been identified and implicated
in the development of familial systemic amyloidoses, but early diagnosis of these
disorders is still largely unresolved. We investigated the presence and tissue distribution
of TTR-derived amyloid in skin biopsies of a 59-year-old woman carrying the 'Hungarian-type'
mutation of TTR (Asp18Gly). Clinical symptoms involved severe central nervous system
dysfunction without signs of polyneuropathy, also referred to as the 'central form'
of TTR-related systemic amyloidosis. Skin biopsy was also evaluated as a tool in order
to diagnose this type of TTR amyloidosis. Biopsy samples were collected from the infra-axillary
region. Light microscopy using Congo red and polarized light was used to diagnose
amyloid deposits. Subsequently, electron microscopic analysis was performed to correlate
the amyloid deposits with vicinal dermal structures. The amyloid class was determined
by means of immunocytochemistry. TTR amyloid was primarily localized to lymphatic
microvessels in the present case, whereas arterioles were devoid of TTR amyloid deposits.
In addition, the well-known association of TTR amyloid with neural structures along
the erector pilorum and around the sebaceous and serosal (sweat) glands was also evident.
Electron microscopic analysis of amyloid deposits revealed characteristic amyloid
fibrils that were irregular in shape, and exhibited a heterogeneous density and a
random deposition pattern. Immunocytochemistry confirmed the cutaneous accumulation
of TTR amyloid. In conclusion, amyloid deposits were abundantly present in the skin
of a patient with 'Hungarian-type' TTR amyloidosis; skin biopsy seems to be appropriate
for the diagnosis of this disorder. We showed that besides the erector pilorum, sweat
glands and nerve terminals, lymphatic microvessels are also severely infiltrated by
TTR amyloid. Whether these pathological alterations can exclusively be found in 'Hungarian-type'
TTR amyloidosis should still be investigated. If such changes are not specific for
the Asp18Gly mutation, they may be considered as diagnostic markers for 'central'
TTR amyloid disorders.
