Author: Grindle, Christopher R; Curry, Joseph M; Cantor, Joshua P; Malloy, Kelly M; Pribitkin, Edmund A; Keane, William M
Date published: May 1, 2011
Journal code: ENTJ
While numerous reports of amyloidosis of the upper airway exist, localized amyloidosis of the oropharynx is exceptionally rare. Biopsy is necessary to make the diagnosis, and it is important to rule out systemic disease. Treatment options include expectant management and surgical resection, with the latter being reserved for symptomatic cases. Continued regular follow-up is necessary to look for recurrence. We report a new case of localized oropharyngeal amyloidosis of the AA type.
A 29-year-old woman was referred to our department for evaluation of a right-sided oropharyngeal mass. The mass had been initially noticed 4 years earlier and evaluated by an outside otolaryngologist. At that time, the lesion was biopsied and the findings were consistent with an amyloid deposit. Further workup- including urinalysis, a complete blood count and blood chemistry panel, protein electrophoresis, and chest x-ray- found no evidence of systemic amyloidosis.
During the 6 months preceding the patient s presentation to our institution, she had noticed an increase in the size of the lesion, as well as associated mild dysphagia and odynophagia. She denied any constitutional symptoms or weight loss, and she was otherwise healthy. Her family history was negative for lymphoproliferative disorder and amyloidosis.
Examination in our office revealed a bulky, yellow, submucosal mass on the right lateral oropharyngeal wall that extended over the posterior pillar into the tonsillar fossa (figure 1). The mass was firm but mobile on palpation. There was no palpable adenopathy in the neck. Nasopharyngolaryngoscopy confirmed these findings, and it identified no other lesions. Computed tomography (CT) and magnetic resonance imaging (MRI) detected a solid, apparently noninvasive 2.2 ? 3.2 ? 2.6-cm mass on the right tonsil and lateral pharyngeal wall with coarse calcifications (figure 2).
Given the increased size of the lesion and her new symptoms, the patient elected to undergo surgical excision. She was taken to the operating room, where she underwent a right tonsillectomy and resection of the mass with a local advancement flap. She recovered without complication. Pathologic analysis identified the mass as a nodular amyloid lesion, as the pathognomonic apple-green birefringence was seen on Congo red staining (figure 3). Immunohistochemistry identified the mass as a non-AL-type amyloid lesion.
At the 2-year follow-up, the patient was doing well with no evidence of recurrence.
First described in 1 842 by Rokitansky1 and so named by Virchow2 in 1 85 1 , amyloidosis is an idiopathic phenomenon that occurs as a result of an extracellular deposition of normally soluble proteins (amyloids) in an abnormal fibrillar form. In the upper aerodigestive tract, the most common site is the larynx. Only a few cases of localized amyloidosis of the tonsil or pharyngeal wall have been previously reported.
Several classifications of amyloidosis have been proposed. Early classification systems were based on organ involvement as the distmguishing feature. Then in 1956, Symmers classified amyloidosis into five categories based on other characteristics as localized, primary, secondary, familial, and multiple myeloma-associated.3 Further work has since identified 20 biochemically distinct types of amyloid, on which contemporary classification systems are based. The various amyloids were then designated with a capital A (for amyloid) followed by an abbreviation for the fibril protein. For example, an amyloid with an immunoglobulin light chain is designated AL, and an amyloid with serum amyloid A is designated AA. In 1980, Glenner4,5 described a tiered clinicopathologic classification based on (1) the type of protein in the deposit, (2) the precursor protein from which the abnormal protein arises, and (3) the clinical disease process as described by Symmers3 (e.g., AL/kappa/primary).
While amyloidosis has been considered to be an idiopathic disease, increasing evidence points to an immunocyte-derived etiology. Two theories have been suggested for the immunogenic origin of amyloid. The first suggests a plasma cell immunoglobulin response to inhaled antigens, and the second suggests an inability to clear excessive or abnormal immunoglobulins produced by monoclonal lymphoid tissue.6
Localized amyloidosis is usually associated with the AL type of amyloid. AL-type amyloidosis can occur alone and it can be associated with lymphoproliferative disorders such as multiple myeloma or Waldenstrom macroglobulinemia. In our patient, immunoglobulin light-chain immunohistochemistry was negative, as was flow cytometry. Instead, pathology identified nodular amyloidosis, which is associated with the AA type of amyloid.6 This type of amyloid has been associated with underlying chronic inflammation, and it may complicate other disorders, including rheumatoid arthritis and periodic fever syndromes.
In the upper aerodigestive tract, two types of infiltration occur: diffuse subepithelial infiltration and tumor nodule infiltration. Amyloid tumor nodules occur more commonly in the nasopharynx and larynx, while subepithelial infiltration predominates elsewhere.6 To the best of our knowledge, only 10 cases of localized oropharyngeal amyloidosis have been previously reported since 1933.69 Among these cases, 5 included the presence of amyloid plaques within the tonsil, and the other 5 involved localized tumor-like deposits called amyloidomas that emanated from the tonsil. As is evident in figure 1, the lesion in our patient appeared to arise from the posterolateral oropharyngeal wall, from whence it grew anteriorly into the tonsillar fossa.
While amyloidosis of the upper aerodigestive tract is typically a localized lesion, it is considered prudent to work up the patient for systemic involvement. In our patient, urine and serologic evaluations, as well as chest x-ray, revealed no evidence of systemic disease.
The standard treatment for localized amyloid lesions of the upper aerodigestive tract is surgical resection. Recurrence is not uncommon, and multiple surgeries may be required.6 Our patient exhibited no evidence of recurrence 24 months out from surgery.
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Christopher R. Grindle, MD; Joseph M. Curry, MD; Joshua P. Cantor, MD; Kelly M. Malloy, MD; Edmund A. Pribitkin, MD; William M. Keane, MD
From the Division of Otolaryngology, Nemours/Aifred I. duPont Hospital for Children, Wilmington, Del. (Dr. Grindle); the Department of Otolaryngology, Thomas Jefferson University Hospital, Philadelphia (Dr. Curry, Dr. Cantor, Dr. Pribitkin, and Dr. Keane); and the Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia (Dr. Malloy). The case described in this article occurred at the Department of Otolaryngology, Thomas Jefferson University Hospital.
Corresponding author: Christopher R. Grindle, MD, Division of Otolaryngology, Nemours/Aifred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19803. Email: cgrindle@ nemours.org