Event Abstract

Mandibular and cheek swelling revealing the diagnosis of localized amyloidosis

  • 1 University of Turin, Department of Oncology, Italy
  • 2 Ospedale San Luigi Gonzaga, Hematology Division, Italy

Aim. Amyloidosis is a progressive metabolic disease characterized by abnormal deposits of the amyloid protein in one or more organs. The term was coined by Virchow in 1854 in order to describe abnormal extracellular material seen in the liver during an autopsy. The amyloidogenic protein is the basic component of about 25 different protein structures that can misfold and aggregate in insoluble beta-pleated-sheet structures, which are deposited in the extracellular space of different tissues and finally cause functional impairment.This disease may be acquired or hereditary. Also, it can be restricted to a single organ, where the amyloid is both produced and deposited, such as the lungs, the brain, or the skin (localized form) with an excellent prognosis, or may affect many organs of the body, leading to significant morbidity and mortality (systemic form). Amyloidosis can be classified according to its cause: primary, secondary and familial. Primary systemic amyloidosis, also known as amyloid light-chain (AL) amyloidosis, is thought to be related with monoclonal gammopathies, in which amyloid-forming immunoglobulin light chains are produced. AL amyloidosis is associated with plasma cell dyscrasia and multiple myeloma; the most commonly affected organs are the kidneys, the liver, the heart and the nerves [2]. Familial transthyretin-associated (ATTR) amyloidosis derives from a group of autosomal-dominant diseases where the onset of mutations in protein coding genes leads to deposition of amyloid fibrils in adult age. In this case, the aberrant protein is transthyretin, a transport protein for thyroxine able to bind retinol. Other hereditary forms of amyloidosis involve mutations in other serum proteins, such as apolipoprotein A1, fibrinogen, and gelsolin. Secondary amyloidosis due to chronic diseases (e.g. rheumatoid arthritis and chronic infections) is due deposition of serum amyloid A, an acute-phase protein produced in response to inflammation. Another type of secondary amyloidosis may occur in patients undergoing dialysis. In these patients, β-2 microglobulin, which is part of the Class I major histocompatibility complex antigen, fails to pass the dialysis membrane, resulting in the formation of amyloid fibrils Localized amyloidosis in the head and neck is a rare and generally benign condition. The most common sites of involvement are the thyroid, the larynx and subglottis, whereas in the oral cavity, amyloidosis usually tends to involve the tongue or buccal mucosa. The particularity of our case is linked to the anatomical subsite of onset that coincides with the mandibular bone marrow in just one month and in a team approach to reach the correct diagnosis. Materials and Methods. A 81 year-old male no smoker suffering for hypertension and carotid vasculopathy, diabetes complicated by severe renal failure and lower limb vasculopathy in pharmacological treatment, was admitted to our Oral Medicine and Oral Oncology Clinic on January 2018 with a chief complaint of swelling at the left mandible. The patient referred the onset of a fast-growing asymptomatic swelling from one month, he already assumed an antibiotic therapy (clarithromycin 250 mg), without any improvement. At the clinical observation a large swelling involving the left cheek and submandibular region was observed. On palpation a firm enlargement of the posterior vestibular side of the left mandible was perceived. The intraoral examination revealed a huge submucosal mass partially ulcerated involving the mandible, the mucobuccal fold and the cheek. Incisional biopsy and imaging were performed in the diagnostic process. The pathological assessment revealed the presence of protein infiltrate with few inflammatory cells and no alteration of the overlying mucosa. Due to allergy and poor general conditions of the patient computer tomography (CT) magnetic resonance (MR) imaging were acquired without contrast medium. They showed a large mass of 56x32x58 mm, with a massive mandibular bone involvement, while the masticatory muscles and the parotid did not show evident involvement. Laterocervical lymphadenopathies were not appreciated. Still lacking a complete definitive diagnosis a fine needle aspiration biopsy (FNAB) under ultrasound guidance was performed in order to have deeper tissue sampling from the mandibular mass. Results. The pathological assessment showed the presence of plasmacells (CD20-, CD3-, CD138+) with secretory capacity mainly formed of kappa chains, moreover the red Congo staining highlighted the deposition of amyloid. The joint assessment of such results allowed the diagnosis of plasmacellular kappa dyscrasia with amyloid deposition. The following hematological evaluation included a total body CT and a bone marrow biopsy (BMB). The BMB ruled out an involvement by clonal plasma cells; while the CT showed a multifocal involvement with osteolytic lesions of the left humeral metaphysis, the right humeral condyle and a pathological fracture of the eighth costal arch. Even in absence of further FNABs such findings were diagnoses as multiple amyloid bone involvement. Velcade and cyclophosphamide were administered at a lower dosage than usual due to the systemic conditions of the patient. On May 2018, after administration of the second cycle of chemotherapy, the patient had spontaneous suppuration from the intraoral mass in absence of systemic signs or symptoms of infection. Such feature jointly to the lack of response in mass reduction, suggested a potential mandibular pathological fracture. Chemotherapy was temporarily stopped and an antibiotic therapy was performed. Due to the known renal failure, amoxicillin clavulanate 875 + 125 mg (3 times daily) and metronidazole 250mg (twice daily) were administered. The CT of the facial bones ruled out the mandibular fracture, highlighting multiple colliquative areas, likely related to chemotherapy. The antibiotic therapy gave an improvement of local sign of infection and chemotherapy was restarted. Discussion. A diagnosis of amyloidosis is usually made on the basis of clinical presentation; a tissue biopsy is then performed to confirm the diagnostic hypothesis and to obtain a definitive diagnosis. Bennhold introduced the Congo red stain in 1922, and showed the characteristic red staining of amyloid in normal light. Apple-green birefringence with polarized light microscopy, however, is now the gold standard for diagnosis. The nature of amyloid deposition in the oral cavity has long been the subject of controversy. In presence of systemic amyloidosis, the tongue is the most frequently reported intraoral location of amyloid deposition. Moreover, when systemic amyloidosis is suspected, even in absence of oral signs of amyloid deposition, an incisional biopsy aiming to find out amyloid deposition in minor salivary glands can be performed. Local amyloidosis of the jaws’s bone is an extremely rare condition that can present as an unspecific nodular mass. Dentists, oral surgeons, radiologist, haematologist, pathologists as well as general practitioners should be able to cooperate for the diagnosis, treatment and follow-up. Histologic examination is the first step towards diagnosis, integrated by immunohistochemistry test. The diagnosis of localized amyloidosis should always be followed by blood tests, a bone marrow biopsy, echocardiography and digestive endoscopy to rule out systemic amyloidosis or any other haematological/immunological disorder or organ dysfunction. There is no consensus on the management of local amyloidosis due to their lack of morbidity. Surgical treatment of localized forms is indicated in case of functional impairment due to the presence of the mass.


1. Virchow VR. Ueber einem Gehirn und Rueckenmark des Menschen auf gefundene Substanz mit chemischen reaction der Cellulose. Virchows Arch Pathol Anat. 1854;6:135–138. 2. Mollee P, Renaut P, Gottlieb D, Goodman H. How to diagnose amyloidosis. Intern Med J. 2014;44(1):7–17 3. Pentenero M, Davico Bonino L, Tomasini C, Conrotto D, Gandolfo S. Localized oral amyloidosis of the palate. Amyloid. 2006 Mar;13(1):42-6.

Keywords: Amyloidosis, Mandible, Localised oral amyloid, Fine needle aspiration biopsy, Hematological disorder

Conference: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.

Presentation Type: Poster Presentation

Topic: Oral Diseases

Citation: Val M, Marino R, Guglielmelli T, Familiari U and Pentenero M (2019). Mandibular and cheek swelling revealing the diagnosis of localized amyloidosis. Front. Physiol. Conference Abstract: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine.. doi: 10.3389/conf.fphys.2019.27.00061

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Received: 05 Nov 2018; Published Online: 09 Dec 2019.

* Correspondence: Dr. Matteo Val, University of Turin, Department of Oncology, Turin, Piedmont, 10124, Italy, matteo.val@outlook.it