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: munar-ques@ogm.jazztel.es

Amyloid, December 2008; 15(4): 272–274

ISSN 1350-6129 print/ISSN 1744-2818 online � 2008 Informa Healthcare USA, Inc.

DOI: 10.1080/13506120802525061

Am

yloi

d D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y U

nive

rsity

of

Cal

ifor

nia

Irvi

ne o

n 11

/07/

14Fo

r pe

rson

al u

se o

nly.

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

Am

yloi

d D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y U

nive

rsity

of

Cal

ifor

nia

Irvi

ne o

n 11

/07/

14Fo

r pe

rson

al u

se o

nly.

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.

References

1. Palha JA, Moreira P, Oloffson A, Lundgren E, Saraiva MJ.

Antibody recognition of amyloidogenic transthyretin variants

in serum of patients with familial amyloidotic polyneuropathy.

J Mol Med 2001;78:703–707.

2. Garret JA. Amyloid deposits in the nose and maxillary sinuses.

Arch Otolaryngol 1968;87:103–104.

3. Mufarrij AA, Busaba NY, Zaytoun GM, Feiner HD. Primary

localized amyloidosis of the nose and paranasal sinuses. A case

report with immunohistochemical observations and a review

of the literature. Am J Surg Pathol 1990;14:379–383.

4. Heinritz H, Kraus T, Iro H. Localized amyloidosis in the area

of head-neck. A retrospective study. HNO 1994;42:744–749.

5. Kobayashi T, Taguchi O, Yasui H, Hataji O, Yoshida M,

Kobayashi H, Gabazza EC, Adachi Y. A case of amyloidosis of

the tracheobronchial tree and inferior nasal concha. Nihon

Kyobu Gakkai Zasshi 1997;35:1378–1382.

6. Pang KP, Chee LW, Busmanis I. Amyloidoma of the nose in a

pediatric patient: a case report. Am J Otolaringol 2001;

22:138–141.

7. Patel A, Pambuccian S, Maisel R. Nasopharingeal amyloi-

dosis. Am J Otolaringol 2002;23:308–311.

8. Biewend ML, Menke DM, Calamia KT. The spectrum of

localized amyloidosis: a case series of 20 patients and revision

of the literature. Amyloid 2006;13:135–142.

9. Dubey SP, Mehra YN, Banerjee AK, Mann SBS, Garg K,

Nehru VI. Nasal involvement in systemic amyloidosis. J

Laryngol Otol 1988;102:1153–1155.

10. Lim JS, Lebowitz RA, Jacobs JB. Primary amyloidosis

presenting as a nasopharyngeal mass. Am J Rhinol 1999;13:

209–212.

11. Hidaka H, Ikeda K, Oshima T, Ohtani H, Suzuki H, Takasaka

T. A case of extramedullary plasmacytoma arising from the

nasal septum. J Laryngol Otol 2000;114:53–55.

274 Letter to the Editor

Am

yloi

d D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y U

nive

rsity

of

Cal

ifor

nia

Irvi

ne o

n 11

/07/

14Fo

r pe

rson

al u

se o

nly.