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Revista Española de Cirugía Oral y Maxilofacial

On-line version ISSN 2173-9161Print version ISSN 1130-0558

Rev Esp Cirug Oral y Maxilofac vol.30 n.1 Madrid Jan./Feb. 2008




Oral nodular amyloidosis

Amiloidosis oral nodular



P. Martos Díaz1, J. Sastre Pérez2, M. Mancha de la Plata1, T. Reina3, S. Rosón Gómez1, L. Naval Gías2

1 Médico Residente de Cirugía Oral y Maxilofacial.
2 Médico Adjunto. Servicio de Cirugía Oral y Maxilofacial.
3 Médico Residente. Servicio de Anatomía Patológica.
Hospital Universitario de la Princesa. Madrid, España





Introduction. Amyloidosis is a condition characterized by the deposit of amyloid in different tissues. In the oral cavity it is usually manifested as macroglossia and, more rarely, as nodules on the surface.
Clinical case. A man had multiple myeloma that began with nodular lesions of the lower lip and tongue. As a result of these lesions, the patient was diagnosed of systemic amyloidosis by histological study.
Discussion. Amyloid nodules in the oral cavity are a rare manifestation of systemic amyloidosis. Its appearance entails the necessity to make I diagnose differential with other organizations and I diagnose of certainty is obtained by means of the histological analysis.

Key words: Lingual amyloidosis; Congo red; Amyloid nodules; Multiple myeloma; Amyloid protein.


Introducción. La amiloidosis constituye una entidad marcada por el depósito de amiloide en diferentes tejidos. En la cavidad oral se manifiesta habitualmente en forma de macroglosia, y más raramente, como nódulos dispuestos en la superficie.
Caso clínico. Varón afecto de Mieloma Múltiple, que comienza con lesiones nodulares en labio inferior y lengua. A raíz de estas lesiones, mediante estudio histológico, es diagnosticado de Amiloidosis Sistémica.
Discusión. Los nódulos amiloideos en la cavidad oral, constituyen una manifestación rara de la amiloidosis sistémica. Su aparición conlleva la necesidad de realizar un diagnostico diferencial con otras entidades y el diagnostico de certeza se obtiene mediante el análisis histológico.

Palabras clave: Amiloidosis lingual; Rojo congo; Nódulos amiloideos; Mieloma múltiple; Proteína amiloidea.



Amyloidosis is a disease of unknown etiology and is one of a group of conditions characterized by the deposit of proteins of fibrillary structure in the extracellular space of different tissues.1,2 The incidence of amyloidosis in the population is 8 people per million inhabitants a year,3 giving rise to different disorders depending on the amount deposited and the organ affected.

Amyloid protein is noteworthy due to the capacity to be identified under optical microscope by means of red Congo stain, observing apple-green birefringence under polarized light. This has been related with its ‚ β-folded configuration.4,5

The classification of amyloidosis has been difficult and debated for a long time.6 At present it is based on the chemical nature of the precursor protein. In this classification, the three main types of amyloidosis are 1) primary amyloidosis or AL, 2) familial amyloidosis due to transthyretin mutation or ATTR, and 3) secondary amyloidosis, or AA, that is associated with chronic disease or familial Mediterranean fever, in which case the patient would present recessive autosomal heredity.7

In the course of this disease, multiple tissues and organs can be involved, such as: gastrointestinal system, kidney, heart, musculoskeletal system, skin, nervous tissue. The primary cause of death is cardiac arrhythmia and renal insufficiency. 1,2

The oral cavity is involved in up to 40% of cases. This is the most common location affected, two conditions being differentiated:8,9

1. Macroglossia, which is manifested as a diffuse increase in the size of the tongue and loss of elasticity.

2. Clumps of amyloid material forming nodular lesions that may be distributed in the tongue, salivary glands, and lips.10 This variant occurs less frequently than the above symptoms.11

In the present article we report a case of primary oral amyloidosis associated with multiple myeloma that coursed with nodular lesions of the tongue and lips. We offer data on the clinical manifestations, histology, and imaging and review the literature.


Clinical case

A 57 year-old man with a history of arterial hypertension and hepatitis C was diagnosed as solitary bone plasmocytoma of the eleventh rib that evolved to multiple myeloma, Bence Jones Lambda type. The patient had been treated peritoneal dialysis for 5 years for chronic renal insufficiency secondary to nephropathy associated with multiple myeloma.

The patient consulted for several lesions of the tongue and left lower lip that had been present for 2 months and produced irritation. The examination disclosed five nodular lesions on the tip and side of the tongue and left lip. Three of the nodules were purplish in color with a slightly whitish center and the other two were lighter-colored, without a purplish tone (Figs. 1 and 2). The consistency was somewhat indurated on palpation. The nodule on the side of the tongue had a diameter of more than 1.5 cm. The largest nodule on the lip measured 1.2 cm and the rest of the nodules were smaller. One month after the oral examination, the patient had bilateral periocular purple- colored lesions (Fig. 3).

A total of 3 biopsies were made, one of the lip and two of the tongue lesions. These biopsies are described as dense deposits of hyaline, acellular, homogeneous material that occupies the entire submucosa, separating muscular bundles and affecting vascular walls. These deposits stain with Congo red (Fig. 4), presenting apple-green birefringence. Thioflavine T stain (Fig. 5) elicits a yellowish-green fluorescence. In the rest of the mucosa, mild acanthosis is observed with parakeratosis and a slight lymphoplasmocytic infiltration.

Based on these findings, a fine needle aspiration biopsy (FNAB) was ordered of the abdominal fat, which was positive for amyloid material with Congo red stain. The diagnosis of systemic amyloidosis was confirmed and different tests were made that showed a multiorganic disorder that affected the skin, nerve tissue, gastrointestinal system, heart, and kidney.

Fifteen months after the diagnosis of amyloidosis, the patient died as a result of megacolon and multiorgan failure.



Amyloidosis is a systemic disease of unknown etiology that groups a series of disorder whose primary characteristic is the deposit of a material known as amyloid.1,2 Amyloid material is constituted by proteins of abnormal fibrillary structure. It is formed by degenerated immunoglobulins or derived from an acute phase serum reactant known as amyloid A, or from products derived from keratinocytes, as a result of a local epidermal lesion that is deposited in the extracellular space of a variety of tissues.

The most modern classification of amyloidosis is based on the function of the precursor protein.7 Among the different subgroups, in primary amyloidosis, or AL, the amyloid protein consists of lightchain immunoglobulins produced by clones of plasmacytic cells, with a high percentage associated with multiple myeloma. In this group, fibrils may be deposited in the skin, liver, kidneys, digestive system, and elsewhere.

In the case reported here, the anomalous protein originates from the malignant plasmatic cells of myeloma, which gives rise to the production of an excessive amount of light chains of Lambda type immunoglobulins. This type of amyloidosis due to light chain deposit has been associated only with plasmocellular dyscrasias.1

Oral clinical manifestations of amyloidosis can occur in up to 40% of the primary forms, but are rare in secondary forms and extremely rare in localized forms. Only isolated cases of oral amyloid deposits without evidence of systemic affectation have been described in the literature.12,13

Among the oral manifestations, the most frequent a diffuse increase in the tongue that we call macroglossia. The tongue loses its elasticity, becoming increasingly stiff and larger in size. This situation can evolve to produce speech, chewing, and swallowing disorders. In advanced stages, the tongue may not fit inside the oral cavity due to its volume and may even impede ventilation.14 In these advanced cases, treatment must be surgical, consisting of partial glossectomy to alleviate the symptoms and diminish the aesthetic impact.15

Our patient did not present macroglossia, but the second disorder described in the oral cavity characteristic of this disease, although much rarer, consisting of nodular lesions of the tongue and lips. These lesions also are reported in submandibular glands. In a series published by Van der Waal et al in 2002,11 of 11 cases of amyloidosis of the oral cavity in a period of 31 years of follow-up, only 2 appeared in the form of amyloid nodules, while the remaining 9 manifested as macroglossia. These alterations consist of nodular lesions of diverse sizes, indurated on palpation, and frequently adopting a yellowish white color.16 They are distributed throughout the lingual surface, being found mainly towards the back. They also can be observed in other areas of the oral mucosa like the palate, gums, floor of the mouth and lips, as in the case of the patient described.

The differential diagnosis of amyloidosis nodules should be made with disorders like fibromas, lipomas, sarcomas, and salivary gland tumors.12 Biopsies should be made of the lesions to diagnose them by histological analysis.

The histological diagnosis of amyloidosis is based mainly on its staining characteristics. The stain most often used is Congo red, although other less frequently used, histochemical techniques exist that allow amyloid to be differentiated from other substances, such as crystal violet or methyl violet, which produces secondary fluorescence with ultraviolet light when dyed with thioflavines T or S. The diagnosis can be confirmed by electron microscopy.

Amyloidosis should be suspected in patients with underlying systemic disease of long duration, particularly those related to plasmocellular dyscrasias, among which multiple myeloma is notable due to its frequency.

Lingual amyloidosis frequently is associated with primary amyloidosis in the context of plasmocellular dyscrasias, with hyperproduction of light chains of AL immunoglobulins and systemic involvement. More than 88% of patients with primary systemic amyloidosis and the totality of patients with multiple myeloma and systemic amyloidosis present monoclonal light chains, also denominated Bence Jones protein, in serum or urine.8 Therefore, once the histological diagnosis is made, we must diagnose the extension by blood tests, electrocardiography, cardiac ultrasonography, chest radiograph, and others and assess the possible involvement of other body systems.



Among oral pathologies that course with mucosal nodules, amyloidosis is a rare condition, but it must be considered in the differential diagnosis. It must be suspected when nodular lesions occur in patients with chronic disease and in hematological disorders that course withplasmocellular dyscrasia. When amyloid lesions are found in the oral mucosa or other specific location, a battery of tests must be carried out to discover the underlying systemic disease. On the other hand, when a possible systemic amyloidosis is suspected, the search for possible lesions in the oral cavity should not be overlooked during the physical examination.



Pedro Martos Díaz
Hospital de la princesa. Servicio de Cirugía Oral y Maxilofacial.
c/ Diego de León 62
28006 Madrid, España

Recibido: 20.03.07
Aceptado: 31.10.07




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