Introduction
Amyloid rarely involves the head and neck region, and occurs even less frequently in the nasal and nasopharyngeal area.Reference Kramer and Som1–Reference Heinritz, Kraus and Iro31 We report the first case in the English literature of nasopharyngeal amyloidosis secondary to multiple myeloma.Reference Kramer and Som1–Reference Ling, Bai-qiang, Xu and Zhu24 We aim to raise awareness of the unusual complications of amyloid. Therefore, we include a literature review of nasopharyngeal amyloidosis, with the intention of increasing awareness of the diagnosis and management of this rare disease.Reference Kramer and Som1–Reference Ling, Bai-qiang, Xu and Zhu24
Case report
A 61-year-old man presented to the ENT out-patient department with a two-month history of left nasal obstruction, loss of sense of smell and left-sided conductive hearing loss. His past medical history included multiple myeloma, diagnosed three years previously, with associated mediastinal lymphadenopathy. There was a medical history of allergic rhinitis.
A large, left-sided nasal polyp and polypoidal mass on the right middle turbinate was visualised on nasopharyngoscopy. Visualisation of the overlying external eustachian orifice revealed no significant findings. Tympanometry of the left ear demonstrated otitis media with effusion. Pure tone audiometry revealed a mild to moderate, mixed hearing loss in the left ear and a moderate, high frequency loss in the right ear.
The patient was treated with topical steroids and listed for excision and biopsy of the nasal cavity polyp and left myringotomy.
Myringotomy findings revealed an effusion.
Nasal cavity biopsies revealed eosinophilic, proteinaceous material with a mixed infiltrate of plasma cells (acute and chronic) (see Figure 1). Staining of the amorphous material with Congo red demonstrated pale congophilia with apple-green birefringence when viewed under high intensity, cross-polarised light. Immunohistochemical analysis established a diagnosis of λ light chain amyloid. No computed tomography (CT) scan was performed at this stage.
Fig. 1 Photomicrograph of nasal cavity biopsy specimen, showing diffuse material staining with Congo red (×100).
Three months later, the patient was admitted to the accident and emergency department with a three-day history of progressively worsening epistaxis and deterioration of hearing in the left ear. Examination demonstrated re-growth of the left-sided nasal polyp. The patient was listed for resection of this mass under general anaesthetic.
On examination six weeks after this procedure, there was recurrence of the amyloid tumour, which now extended to the posterior wall of the nasopharynx.
At this stage, the patient's paraprotein levels had risen from 35 to 36.5 g over the previous three months, and he was referred to the National Amyloid Centre. There, the patient's mediastinal lymphadenopathy was thought clinically to be almost certainly secondary to amyloid infiltration, and the patient was thus diagnosed with secondary amyloidosis.Reference O'Sullivan and Muller32 A serum amyloid precursor scan, performed to search for other secondary amyloid deposits, found no other tissue to be involved by amyloid.
Following an increase in bone marrow plasma cells from 22 to 70 per cent, three months after his nasopharyngeal amyloid resection, the patient commenced chemotherapy with the vincristine, adriamycin and dexamethasone regime, for his myeloma. Unfortunately, the chemotherapy did not reduce the aggression of the neoplasm. A CT scan performed three months later (Figure 2) showed an invasive mass present in the left maxillary antrum, ethmoids and sphenoidal air sinuses. The mass extended into the middle cranial fossa with associated bone destruction of the left maxillary antrum, ethmoids, pterygoid plates, greater wing of the sphenoid, pituitary fossa and part of the clivus. The posterior fossae and orbits remained largely unaffected.
Fig. 2 Axial computed tomography scan with contrast, demonstrating invasion of nasopharyngeal amyloid tumour in the left maxillary antrum, ethmoids and sphenoidal air sinuses.
In light of the progression of the multiple myeloma, the patient's chemotherapy regime was changed to cyclophosphamide, thalidomide and dexamethasone. This led to an improvement, and over a period of six months his paraprotein levels reduced from 13 g/l to 31 g/l; however, a new CT scan showed that the nasopharyngeal amyloidosis continued to penetrate into nearby structures, as in the previous scan.
At this point, a trial of localised radiotherapy to the nasopharyngeal amyloid mass was introduced. A CT scan taken after several cycles of radiotherapy (without contrast due to unknown renal status) showed a decrease in nasopharyngeal amyloid (Figure 3).
Fig. 3 Axial computed tomography scan without contrast, demonstrating a reduction in the nasopharyngeal amyloid tumour mass following localised radiotherapy.
Discussion
Myeloma is a monoclonal plasma cell tumour with an incidence of 40 per million in the UK population, and accounts for 1 per cent of all cancers in the Western World.Reference Smith, Wisloff and Samson33, Reference Kumar, Abbas Abul and Fausto34 It is an incurable, multi-system disease, postulated to be caused by a cytogenetic error late in B cell differentiation, originating in the bone marrow, and often complicated by subsequent anaemia and bone marrow failure.Reference Bird and Cavenagh35 Amyloidosis occurs as a complication of multiple myeloma in 5–15 per cent of patients.Reference Bird and Cavenagh35
Amyloid is a non-branching, fibrillar protein which is resistant to proteolysis and thus remains deposited in most intracellular regions.Reference Kumar, Abbas Abul and Fausto34 Amyloid deposition complicates many chronic diseases.Reference Smith, Wisloff and Samson33 Over-accumulation of amyloid results in amyloidosis, defined as a pathological accumulation of protein fibrils between cells in various tissues and organs of the body. Clinically, amyloidosis can be categorised as primary, when associated with some immunocyte dyscrasia, or secondary, when occurring as a complication of an underlying chronic inflammatory or tissue destructive process. Hereditary or familial amyloidosis constitutes a separate, albeit heterogeneous group with several distinctive patterns of organ involvement.Reference Kumar, Abbas Abul and Fausto34
Amyloid fibrils associated with a plasma cell dyscrasia are derived from the N-terminal region of monoclonal immunoglobulin light chains and are classified as Amyloid Light chain (AL) amyloid deposition.Reference Bird and Cavenagh35 Common clinical presentations of amyloid include nephrotic syndrome, restrictive cardiomyopathy and sensorineual neuropathy.Reference Singer36
Head and neck amyloidosis is rare. There have been 28 case reports of nasal or nasopharyngeal amyloidosis deposits in the English language literature between 1928 and 2004.Reference Kramer and Som1–Reference Ling, Bai-qiang, Xu and Zhu24 Only three of these cases occurred secondary to systemic amyloidosis.Reference Elcock and Grimaldi5, Reference Dubey, Mehra, Banerjee, Mann, Garg and Nehru9, Reference Zundel, Pyle and Voytovich16 Elcock and Grimaldi reported the case of a 72-year-old woman with known Waldenstrom's macroglobulinaemia presenting with epistaxis, nasal obstruction and a mass in the nasal cavity.Reference Elcock and Grimaldi5 Dubey et al. described a 64-year-old woman with systemic primary amyloidosis presenting with increasing nasal obstruction, epistaxis and progressive widening of the dorsum of the nose.Reference Dubey, Mehra, Banerjee, Mann, Garg and Nehru9 In this case, anterior rhinoscopy revealed a pale, polypoid, friable mass at the level of the middle turbinate in both nasal cavities. Zundel et al. gave an account of a 56-year-old man with known systemic amyloidosis and renal failure presenting with intermittent epistaxis; on examination, the patient had near-total perforation of the nasal septum.Reference Gean-Marton, Kirsch, Gilbert Vezina and Weber11
Nasal and nasopharyngeal amyloidosis affects both genders, with a wide age range of reported cases (eight to 86 years). The most common presenting complaint is nasal obstruction due to the tumour invading the nasal chamber, followed by epistaxis. In several reports, the amyloid tumour has been described as polypoidal, firm and submucosal.Reference Kramer and Som1–Reference Ling, Bai-qiang, Xu and Zhu24 Some cases, all of which involved localised amyloidosis, had amyloid masses described as yellowish or whitish and hard.Reference Zakzouk8, Reference Lesserman and Finn14, Reference Dominguez, Wienberg, Claros, Claros and Vila15, Reference Lim, Lebowitz and Jacobs17, Reference Pitkaranta and Malmberg18, Reference Fatterpeckar, Kao, Chen, Som and Chin22 Excluding one case,Reference Dominguez, Wienberg, Claros, Claros and Vila15 all these descriptions were associated with a relevant ENT past surgical history.Reference Zakzouk8, Reference Lesserman and Finn14, Reference Lim, Lebowitz and Jacobs17, Reference Pitkaranta and Malmberg18, Reference Fatterpeckar, Kao, Chen, Som and Chin22 These patients may perhaps have had localised primary amyloid secondary to surgical or medical intervention.
Nasopharyngoscopy and CT scanning have been performed in cases of nasal and nasopharyngeal amyloidosis from 1984 onwards.Reference Prathap, Looi and Prasad6 Prior to this, several reports described the use of sinus X-rays to visualise the amyloid mass.Reference Garrett3–Reference Elcock and Grimaldi5 Magnetic resonance imaging (MRI), which enables more detailed visualisation, has been featured in case reports from 2000 onwards.Reference Pitkaranta and Malmberg18, Reference Pang, Chee and Busmanis20
The radiological appearance of focal amyloidosis is non-specific. Computed tomography scans show amyloid as a well defined, radiopaque, high attenuation, soft tissue mass associated with calcification. Fatterpeckar et al. (who described a case of localised nasopharyngeal amyloidosis) noted a ‘fluffy’ appearance in the bone adjacent to the amyloid, leading them to postulate that deposition of proteinaceous amyloid fibrils in the submucosal layers of the sinonasal cavities incited an osteoblastic reaction, resulting in the fluffy bone appearance.Reference Fatterpeckar, Kao, Chen, Som and Chin22 Pang et al. reported a CT appearance of bilateral turbinate masses with osteotic changes.Reference Pang, Chee and Busmanis20 Magnetic resonance imaging characteristics are described in one case report only, as consisting of a hypo-intense, soft tissue mass with low to intermediate signal intensity in both T1- and T2-weighted images, making amyloid difficult to differentiate from muscle tissue.Reference Pitkaranta and Malmberg18
Histological examination of biopsied material using congo staining has previously been the method of choice for amyloid diagnosis.Reference Johner, Widen and Sahgal4–Reference Ling, Bai-qiang, Xu and Zhu24 Immunohistochemical techniques, first implemented in 1990 and included in several reports thereafter, enable the biochemical diagnosis of amyloid as either systemic or localised.Reference Mufarrij, Busaba, Zaytoun, Gallo and Feiner10, Reference Panda, Sharma, Mann and Radotra13, Reference Lesserman and Finn14, Reference Lim, Lebowitz and Jacobs17, Reference Pang, Chee and Busmanis20
The recently developed SAP scan was used in the current case to demonstrate the location and quality of amyloid deposits in organs throughout the body. Radiolabelled SAP component, specifically and quickly localises to amyloid deposits, in direct relation to the amount of amyloid present. Thus diagnosis and quantification of whole body deposits by whole body scintigraphy is realised via SAP. Unfortunately, the reliability of the test is questionable, as hollow or moving organs cannot be assessed. Tsikoudas et al. used SAP scanning to rule out the possibility of systemic amyloidosis.Reference Tsikoudas, Martin-Hirsch and Woodhead19
Nasal and nasopharyngeal amyloidosis may be resected surgically. Thirteen out of a possible 26 articles available for review describe resection of nasal or nasopharyngeal amyloidosis.Reference Kramer and Som1, Reference Ottosen2, Reference Elcock and Grimaldi5, Reference Simpson, Strong, Skinner and Cohen7–Reference Dominguez, Wienberg, Claros, Claros and Vila15, Reference Pitkaranta and Malmberg18 Only one of the three patients with secondary amyloidosis underwent surgical resection, as the remaining patients were unsuitable for surgical intervention owing to their poor health status.Reference Elcock and Grimaldi5, Reference Dubey, Mehra, Banerjee, Mann, Garg and Nehru9, Reference Zundel, Pyle and Voytovich16 Earlier cases used comparatively extensive surgical methods. Ottosen performed a conchotomy, and Garrett used a Caldwell–Luc procedure to perform a rhinotomy.Reference Ottosen2, Reference Garrett3 However, in a recent report a patient was treated with a turbinectomy, although one must note that she had previously defaulted and that, in the interim, the tumour had grown considerably in size.Reference Pang, Chee and Busmanis20 There is evidence that a conservative surgical approach to nasal and nasopharyngeal amyloidosis improves outcomes. Lesserson and Finn found that their previous attempt to remove an amyloid tumour (i.e. transoral removal via laser with forceps punch biopsy) resulted in amyloid recurrence on bilateral sides of the palate, particularly on pressure areas of the palate.Reference Lesserman and Finn14 Their subsequent surgical intervention avoided the traction used in their earlier approach and was performed transnasally under local anaesthetic and intravenous sedation. Three years' follow up revealed no recurrence of disease.Reference Lesserman and Finn14
Most of the case reports located failed to prevent recurrence of amyloid tumour by surgical methods.Reference Kramer and Som1–Reference Ling, Bai-qiang, Xu and Zhu24 Some omitted follow-up details,Reference Kramer and Som1, Reference Ottosen2, Reference Garrett3, Reference Zakzouk8, Reference Mufarrij, Busaba, Zaytoun, Gallo and Feiner10, Reference Tsikoudas, Martin-Hirsch and Woodhead19 and several reported ill patients who died soon afterwards.Reference Garrett3, Reference Elcock and Grimaldi5, Reference Dominguez, Wienberg, Claros, Claros and Vila15, Reference Lim, Lebowitz and Jacobs17
• Nasal or nasopharyngeal amyloidosis is a rare cause of epistaxis
• Treatment is surgical to achieve symptomatic relief, although recurrence is common
• A conservative surgical approach may be associated with a slower rate of recurrence
• Chemotherapy has not been shown to be of benefit in the treatment of nasopharyngeal amyloidosis; however, in the presented case radiotherapy produced useful remission
The cyclophosphamide-thalidomide-dexamethasone chemotherapy regime slowed progression of multiple myeloma in our patient; however, it did not ameliorate the symptoms or signs of amyloidosis. We thought it possible that reduction in the rate of plasma cell production could in turn reduce the amyloid produced and subsequently deposited in the nose and nasopharynx. One other case report, of localised nasal and nasopharyngeal amyloidosis, describes a female with Non-Hogkins lymphoma for whom chemotherapy was introduced as empirical treatment. After 45 days of melphalan, the trial was abandoned owing to non-progression of symptoms.Reference Johner, Widen and Sahgal4
The current case represents the first report of nasal and nasopharyngeal amyloidosis (either systemic or localised) treated with localised radiotherapy. Several cycles of localised radiotherapy led to a dramatic decrease in the size of the amyloid tumour (see Figure 3), with an associated improvement in symptoms and signs. Perhaps this could be considered in future cases of nasal or nasopharyngeal amyloidosis.
Conclusion
Nasal or nasopharyngeal amyloidosis is a rare cause of epistaxis and/or nasal obstruction in cases of known, chronic illness. It may be associated with a past history of surgical or medical ENT conditions. Immunohistochemical techniques now enable a definitive diagnosis. A SAP scan is suitable as a supportive investigation for assessing the extent of spread of systemic amyloidosis in visceral organs. Computed tomography and MRI imaging (although non-specific for nasal or nasopharyngeal amyloidosis) enables evaluation of disease progression. Treatment by surgical excision provides symptomatic relief, but there is a high incidence of recurrence. In the presented case, localised radiotherapy decreased the mass of the nasopharyngeal amyloid tumour.
