Download - Finding of vascular amyloid TTR in inferior nasal concha in a patient with FAP TTRVal30Met
LETTER TO THE EDITOR
Finding of vascular amyloid TTR in inferior nasal concha in a patientwith FAP TTRVal30Met
MIGUEL MUNAR-QUES1, JACINTO MARTINEZ-NADAL2,
JOSE JUAN TORRES-ROVIRA3, MANEL SOLE4, JOSE MARIA ZABAY-BECERRIL1, &
JUANA MARIA MULET-FERRER1
1Grupo de Estudio de la Paf, Majorca, Spain, 2Servicio de O.R.L. Hospital Universitario Son Dureta, Majorca, Spain,3Servicio de Anatomıa Patologica, Clınica Juaneda, Majorca, Spain, and 4Servicio de Anatomıa Patologica, Hospital Clınic,
Universidad de Barcelona, Spain
Keywords: Hereditary amyloidosis, familial amyloid polyneuropathy, amyloid TTR, liver transplantation, nasal polyp
Abbreviations: FAP¼ familial amyloid polyneuropathy; TTR¼ transthyretin; LTX¼ liver transplantation
AbstractWe report the case of a female patient with familial amyloid polyneuropathy (FAP) who demonstrated TTR amyloiddeposition in the inferior nasal conchal vessels.
To our knowledge this location has not been described previously in FAP; in addition, it was detected in a patient who hadundergone successful liver transplantation (LTX) 4 years earlier.
The amyloid deposition was found incidentally during examination of a right nasal obstruction caused by a nonspecificinflammatory polyp. Small focal deposits of amyloid TTR were observed on deep thick walled vessels, contrasting with themassive deposition reported in neoformed vessels in amyloidomas. This amyloid was clearly deposited between the onset ofFAP and LTX and had probably decreased since the graft.
If amyloid deposition is frequent in inferior nasal concha in FAP, this location could be a suitable biopsy site.
Case report
In 1998, a 58-year-old Majorcan woman developed
paresthesia in both feet. She later noted loss of tactile
sensation and pain in the same zone with very slow
progression to her legs.
She was visited for the first time at 60 years of age.
She had a family history of familial amyloid
polyneuropathy (FAP) in a maternal relative. The
distal loss of sensation had a stocking distribution.
There were no motor disturbances. Plantar and
tendon reflexes were normal. Electromyography
showed a chronic axonal polyneuropathy predomi-
nantly affecting sensory nerves in lower limbs. No
cardiac, renal or ocular amyloidosis was found.
Genomic and proteomic analyses classified her as
heterorozygous TTR Val30Met. Abdominal fat pad
biopsy with prior Congo red staining and polariza-
tion microscopy revealed amyloid deposition. For
this reason, liver transplantation (LTX) was recom-
mended and was performed in December 2000, 1
year after the first visit. The outcome was excellent.
The graft was well-tolerated and neurological symp-
tomatology showed a slow but progressive improve-
ment. Moreover, a direct enzyme-linked
immunosorbent assay (ELISA) with the monoclonal
antibody Mab 39-44 demonstrated the disappear-
ance of the variant from the plasma [1].
Four years after LTX, in October 2004, while in
good general health and with a marked improve-
ment of neurological symptoms, she was seen for a
5-month history of nasal discharge and obstruction
of the right side of her nose. She also reported
mild epistaxis on the same side over the previous 5
days.
An anterior rhinoscopy showed a mass occupy-
ing the right side of the nasal fossa. It was well
delimited, very vascularised and hard to the touch.
Its origin was not clear. The left side of the nasal
fossa and the palate were normal. No posterior
Correspondence: Dr. Miguel Munar-Ques, Grupo de Estudio de la PAF, Plaza Olivar 5, 07002 Palma de, Mallorca, Spain. Tel: þ971-713155.
Fax: þ971-213696. E-mail: [email protected]
Amyloid, December 2008; 15(4): 272–274
ISSN 1350-6129 print/ISSN 1744-2818 online � 2008 Informa Healthcare USA, Inc.
DOI: 10.1080/13506120802525061
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discharge was present. A rhinosinusal scan was
performed as a nasal tumour was suspected. It
showed blockage of the right nostril because of the
enlargement of the inferior nasal concha. A nasal
biopsy of the mass was performed under local
anesthesia. Congo red staining and polarization
microscopy revealed chronic non-specific inflam-
mation of the nasal mucosa with small amyloid
deposits in deep vessels.
Nasal instillation of fluticasone and local applica-
tion of mucipirone cream was prescribed for one and
half months. The mass decreased in size and at the
last visit the nasal fossa was normal.
Immunohistochemical analysis was performed to
determine the kind of amyloid. The specimen
consisted of several polypoid fragments of nasal
mucosa, with a fibroedematous stroma showing focal
inflammatory infiltrate and ulceration (Figure 1).
Deeper areas corresponding to the base of the polyp
contained several thick-walled vessels, some of
which showed focal amyloid deposits (Figure 2).
No amyloid deposition was identified in newly
formed vessels either in stroma of the inflammatory
polyp.
Immunohistochemical analysis was performed
using antibodies against Amyloid A (1:1000), kappa
and lambda light chains (1:64) and TTR (1:2000)
purchased from DAKO. Antigen retrieval was
performed using formic acid for TTR and citrate
for the remaining markers. The ENVISION1
method was used for all antibodies. Amyloid deposits
were positive for TTR. Amyloid A and light chains
were negative.
Although the patient presented with a mass in the
right nasal fossa, this was, in fact, not an amyloid
tumour, but a non-specific inflammatory polyp
arising on mucosa containing vessels previously
involved by amyloid.
Discussion
Amyloid deposits in nasal concha have been de-
scribed in only a few patients and the majority are
localised amyloidosis (amyloidomas). In the few
cases in which amyloid have been typed, it was
amyloid AL [2–8].
In a literature search of systemic amyloidosis
patients we did not find amyloid deposits in nasal
concha in any FAP patients (TTR amyloidosis) and
only in three patients with immunoglobulin amyloi-
dosis (AL amyloidosis) [9–11].
In our patient, the deposition was detected
incidentally when she presented right nasal obstruc-
tion due to a nonspecific inflammatory polyp.
Pathological examination confirmed small deposits
in deep thick- walled vessels, but not in newly
formed vessels either in stroma of the polyp, thus
excluding a new onset amyloid deposition. This
case contrasts with the massive deposits involving
both vessels and stroma usually found in amyloi-
domas. We consider it raises the possibility of
finding amyloid in biopsies performed for other
reasons in FAP patients, even in specimens from
brain tumour resection (Guimaraes, personal com-
munication).
Involvement of nasal mucosa by vascular amyloid
TTR has not been previously reported, although its
occurrence is not surprising because this type of
amyloidosis typically involves vessels with a wide-
spread distribution.
The disappearance of the plasmatic variant and the
excellent outcome suggests to us that the deposition
in the present case had previously been larger but
had diminished after LTX.
If the inferior nasal concha was confirmed as a
frequent location of amyloid in FAP, it could be an
optimal site for biopsy as it provides easy access and
can be performed under local anesthesia.
Figure 1. Fragment of inflammatory polyp. Arrows indicate thick-
walled vessels in the base of the polyp that were involved by
amyloid (H&E6 20).
Figure 2. Focal amyloid deposition in vascular walls, stained with
TTR (6250).
Letter to the Editor 273
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Acknowledgements
This work was partially funded by a research grant
from Asociacion Valverdena de la Enfermedad de
Andrade (Valverde del Camino, Huelva). Our most
sincere gratitude to Prof. Antonio Guimaraes for his
collaboration.
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274 Letter to the Editor
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