HISTOLOGICAL FINDINGS

The histological examination revealed deposits of weakly eosinophilic, hyaline homogeneous material in the sub-mucosal connective tissue and also perivascular; these deposits stain positively with Congo red with a pink appearance and showed apple-green birefringence under polarized light.

As no other organ appeared involved, the final diagnosis was of primary oral amyloidosis; the patient was send to the specialists and underwent chemotherapy. No follow-up data are available.

 

DISCUSSION

Amyloidosis, first described by Eanes and Glenner in 1968 by using the x-ray diffraction properties of amyloid, is a multisystemic disorder which rarely involve an isolated organ. Pathogenesis of amyloidosis appears to be multifactorial finally resulting in the production of altered proteins (two different components: amorphous proteic deposition of linear fibrils with an diameter of about 7.5 to 10 nm and a beta-pleated sheet fibrils) and deposition in the extra-cellular matrix.

Many different classification systems have been proposed in the past till to the current classification which is based on the biochemical composition of the fibril protein subunit and the plasma precursor proteins.

Three major types of amyloidosis are defined: 1) AL form observable in primary and idiopathic amyloidosis, when there is no associated disease or it has been also associated with plasma cell dyscrasia; fibrils are derived from the N-terminal region of monoclonal light or heavy chains, consisting of a portion of the variable region; affected patients typically produced urinary free monoclonal light chains (Bence-Jones proteinuria); 2) AA amyloidosis, characterized by the deposition of a 76 amino acid molecule derived from an acute phase reactant, the serum amyloid A (SAA protein) produced in response of chronic inflammatory processes (e.g. tuberculosis, reumathoid arthritis or familial mediterranean fever); 3) the third type consists of a group of autosomal dominant diseases characterized by some inheritable variant of proteins which caused the production of amyloid fibrils (the most common mutations occur in transthyretin, apolipoprotein A-1, fibrinogen and gelsolin); patients present significant neuropathic involvement, also defined as familial amyloidotic polyneuropathies.

Other subtypes of amyloidosis are correlated to the ageing, Alzheimer’s disease and haemodialysis.

Systemic involvement is related to the stage of disease and the type of amyloid. The kidney is the more affected site (33% to 40% of patients) in patients with AL, followed by the heart, liver (25%), the gastrointestinal mucosa, peripheral nerves axons with demyelinization, wall of blood vessel with following vascular fragility and muscle with consequent muscular hypertrophy.

According to the literature, a diagnosis of amyloidosis is strictly related to the amyloid detection in the biotic tissues thought false-positive are frequent because of collagen and elastic fibrils may retain Congo red staining.

Although oral involvement in amyloidosis is rare, it is often the first sign of diseases above all in patients affected by multiple myeloma or other monoclonal gammapathies; the tongue is the most frequently involved site (30 % of cases) with typical  bilateral yellowish nodules on  the borders which create difficulties in speaking, chewing and swallowing; salivary glands are involved in the 10% of cases with a characteristic major glands enlargement which rarely caused xerostomia, while oral mucosa is reported to be affected in the 3.6% of the cases; petechiae, multiple yellowish nodules, ecchymoses and hemorrhagic bullae may also be found; gingiva usually appears normo-coloured and normo-trofic though the tissues is extensively infiltrated. The treatment of amyloidosis is directed toward the specific type of the disease. The eradication of the amyloidogenic clone by chemotherapy is indicated in AL amyloidosis. Melphalan, colchicines, prednisolone, thalidomide, etarnacept, vincristine, adriamycin and other agents were advocated singular or in association in different clinical trials. The treatment of AA form of disease is directed toward the causal therapy of the inflammatory disease. The prognosis essentially depends on the involved organs and the survival varies between 4 months and 2 years.

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