Unsuspected Systemic Amyloidosis Diagnosed by Fine-Needle Aspiration of the Salivary Gland: Case Report Tamar Giorgadze, M.D., Ph.D., 1 * Zubair W. Baloch, M.D., Ph.D., 1 Erica R. Thaler, M.D., 2 and Prabodh K. Gupta, M.D., F.I.A.C. 1 Amyloidosis of the head and neck region may represent a local amyloidoma or a manifestation of systemic disease. Involvement of major salivary glands by either primary or secondary forms of amyloidosis is very rare. We describe a case of systemic amyloid- osis that initially presented as submandibular gland mass and was diagnosed by fine-needle aspiration (FNA). A 69-year-old male presented with submandibular mass. His past medical history was significant for left forearm melanoma that was excised 6 years ago and tricuspid valve endocarditis after valvular replacement 3 months prior to FNA of the submandibular gland. The patient had no symptoms or clinical and laboratory data suggestive of amy- loidosis. FNA specimen showed salivary gland tissue and abun- dant amorphous material, which stained positive for amyloid with Congo red stain and showed typical birefringence when examined by polarized microscopy. Further workup of the patient revealed generalized amyloidosis with multiorgan involvement by the dis- ease. This case demonstrates that FNA can be a useful technique in the diagnosis of unsuspected amyloidosis. Diagn. Cytopathol. 2004;31:57–59. © 2004 Wiley-Liss, Inc. Key Words: amyloid; salivary gland; Congo red; fine-needle aspi- ration The patient was a 69-year-old male who presented with slowly growing submandibular mass. His past medical his- tory was significant for right forearm melanoma excision, coronary artery bypass grafting, permanent pacemaker, and valvular heart disease that required tricuspid and mitral valve replacement. Following this surgical procedure, the patient developed culture-negative tricuspid valve endocar- ditis and polyarticular complaints that were successfully treated with triple antibiotic regimen. Laboratory workup for the rheumatoid factors was negative. Fine-needle aspi- ration (FNA) of the submandibular mass was performed, and the onsite diagnosis was deferred. The FNA smears showed clusters and sheets of salivary gland tissue without any cytologic atypia. The most striking feature was the smear background that showed numerous irregular deposits of amorphous material that stained deep blue on Diff-Quik. These were of various size and shape with irregular contours and some of them were lined on their periphery by spindle-shaped cells. Congo red stain with adequate controls was performed and showed orange- pink staining of the amorphous material (Fig. 1). Examina- tion under polarization microscopy demonstrated apple- green birefringence typical for amyloid (Fig. 2), and the diagnosis of submandibular gland amyloidosis was ren- dered. Amyloid is an extracellular proteinaceous tissue deposit that is composed of nonbranching fibrils with an average diameter of 10 –12 nm and shows congophilia with typical apple-green birefringence when examined under the polar- ized light. Amyloid depositions, or amyloidosis, can be seen in essentially every organ. Multiple clinical and biochemi- cal forms of amyloidosis exist. Amyloidosis may represent as either primary or systemic disease. Among many causes of systemic amyloidosis are rheumatic and infectious dis- eases, malignant tumors, and some inherited and idiopathic diseases. The depositions of the amyloid in the secondary amyloidosis can be local or systemic. The distinction be- tween those two forms is very important, since the treatment options as well as prognosis are different. While the local- 1 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 2 Department of Otorhinolaryngology and Head and Neck Surgery, Uni- versity of Pennsylvania Medical Center, Philadelphia, Pennsylvania * Correspondence to: Tamar Giorgadze, M.D., Ph.D., Department of Pathology and Laboratory Medicine, Division of Cytopathology, 6 Founders Pavilion, UPENN Medical Center, 3400 Spruce Street, Philadel- phia, PA 19104. E-mail: giorgadt@uphs.upenn.edu Received 8 August 2003; Accepted 29 January 2004 DOI 10.1002/dc.20080 Published online in Wiley InterScience (www.interscience.wiley.com). © 2004 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 31, No 1 57