Case 7 -

Crystalloids in Salivary Glands Ritu Nayar Northwestern University Feinberg School of Medicine Chicago, IL

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Definition: Crystalloids are defined as non-birefringent material without any recognizable internal structure, whereas a crystal is a birefringent, solid formed by a repeating, three dimensional pattern of molecules. Case 7 - Figure 1 Papanicolaou, low power Case 7 - Figure 2 Papanicolaou, high power Case 7 - Figure 3 Diff-Quik, medium power Case 7 - Figure 4 Cell block, low power Incidence: Crystalloids have been observed in "5% of routine postmortem sections of the parotid gland", in chronically inflamed submandibular glands, and frequently in Warthins tumor. In the largest series to date (Saenz-Santamaria), 15 cases were found in a total of 347 (4.3%) FNA's of salivary gland done for clinically apparent lesions A variety of crystalline structures can be seen in cytologic and histologic preparations from the salivary glands. These include tyrosine (or tyrosine-rich) crystalloids amylase (nontyrosine) crystalloids collagenous crystalloids calcium oxalate crystals intraluminal crystalloids Usually only the tyrosine and amylase crystalloids are encountered in FNA specimens Amylase Crystalloids: Cytomorphology: Highly variable in size, ranging from 5 to 200 microns. They are seen in various geometric shapes, including rectangular, needle shaped, plate-like and rhomboid. In FNA specimens, they typically fragment. They are non-birefringent structures that stain bright orange on Papanicolaou stain, deep blue on Diff Quik and pink on H&E. They are often seen admixed with histiocytes and/or inflammatory cells. Multinucleated histiocytes can show engulfed crystalloids. Granulation tissue and reactive ductal cells, fragments of benign acinar and squamous metaplasia can all be seen. Histologic follow up has shown dilated ducts and/or cystic lumens containing crystalloids, often lined by oncocytic cells and associated sialolithiasis. Presentation: In salivary glands, they are found most often in association with inflammation- sialadenitis or infection - and were proposed as a marker of non-neoplastic salivary gland disease. They have also been described in lymphoepithelial cysts, unilocular cysts and in association with Warthins tumor. Patients with sialadentis and crystalloids, often tend to be Caucasian, older and present with salivary gland swelling. More often than not, the clinical suspicion is a neoplasm. A subset of patients will show response to antibiotic treatment, leading Johnson, et al to speculate on the possible role of bacteria in the genesis of amylase crystalloids. However recurrences have been reported, in spite of antibiotic therapy, as has spontaneous regression. Composition: On energy-dispersive X-ray analysis, sulfur and carbon have been demonstrated as the major components and due to absence of inorganic crystals they are presumed to be protein in nature. Etiology: Due to the high sulfur content it has been suggested that nontyrosine crystalloids may be precipitates from saliva supersaturated by sulfur-containing compounds. They have also been described to stain with monoclonal antibody to alpha amylase on cytologic/ histologic preparations. Furthermore, there are reports of the binding of human salivary amylase to streptococcal species- such binding may initiate crystallization. In cases with oncocytic epithelium (metaplastic or neoplastic), it has been suggested that non-tyrosine crystalloids may be the product of oncocytic cell secretion. Some authors have suggested that non tyrosine crystalloids may be directly involved in the formation of calculi responsible for sialolithiasis. Tyrosine Crystalloids: Cytomorphology: Size range is 30-60 microns, they are floret or sunburst shaped, non-birefringent structures that stain orange on Papanicolaou stain, whitish on Diff Quik and pink on H&E. They are also positive with Millons stain. Presentation: In salivary glands, they are found most often in association with pleomorphic adenoma (PA), but have also been described in association with adenoid cystic carcinoma and polymorphous low grade carcinoma. In PA, they are located preferentially in myxoid stroma, near myoepithelial cells. Etiology: Suggested by some that tyrosine crystalloids are secreted by neoplastic stromal or myoepithelial cells. The fact that they are much more common in African American patients, have led to the hypothesis that they may be linked to tyrosine in pigment metabolism. NOTE: No specific type of crystal or crystalloid structure should be considered as a non-cellular marker for any specific salivary gland pathology. It is essential to identify and interpret a well preserved and well stained diagnostic cellular component in the FNA specimen before a final diagnosis is rendered Liesegang Rings Etiology: Raphael E Liesegang, first described the phenomenon where concentric ring like precipitates form when one ionic salt diffuses through a second ionic salt suspended in a semisolid gel matrix. LRs are formed by the complex interplay of diffusion, chemical reaction and precipitation. Morphology: LRs vary greatly in size, from 7-800 micron. LR show concentric lamellations, somewhat similar to Psammoma bodies. Histochemical stains for mucin, calcium, iron, glycogen and amyloid are negative. Associations: Described throughout nature and in a variety of human tissues, especially in chronic cystic lesions that are inflamed, necrotic or hemorrhagic. Specimen types reported to show LRs include urine, breast, renal cysts, skin adnexal tumors, head and neck masses, endometriosis and miscellaneous infectious lesions. Differential Diagnosis: Parasites such as the giant kidney worm, Dioctophyma renale. This can be distinguished from LR based on less variable size (60-80 micron) and characteristic sculpting of the shell References: Pantanowitz L, Goulart R, Cao JQ. Salivary gland crystalloids. Diagn Cytopathol 2006; 34(11): 749-750. Saenz-Santa maria J, Catalina-Fernandez I, Fernandez-Mera JJ. Sialadenitis with crystalloid formation: fine needle aspiration cytodiagnosis of 15 cases. Acta Cytol 2003; 47: 1-4. Nasuti JF, Gupta PK, Fleisher HR, et al. Nontyrosine crystalloids in salivary gland lesions: Report of seven cases with fine needle aspiration cytology and follow up surgical pathology. Diagn Cytopathol 2000; 22: 167-171 Granter SR, Renshaw AA, Cibas EE, et al. Non tyrosine crystalloids in fine needle aspiration specimens of the parotid gland: a report of 2 cases and review of the literature. Diagn Cytopathol 1999; 20: 44-46 Gupta RK, Green C, Fauk R, et al. Fine needle aspiration cytodiagnosis of sialadenitis with crystalloids. Acta Cytol 1999; 43: 390-392. Johnson F, Oertel Y, Ammann K. Sialadenitis with crystalloid formation: a report of six cases diagnosed by fine needle aspiration. Diagn Cytopahol 1995; 12: 76-748 Jayaram G, Khurana N, Basu S. Crystalloids in a cystic lesion of the parotid gland: diagnosis by fine needle aspiration. Diagn Cytopathol 1993; 9: 70-71. Jayaram G, Khurana N, Basu S. Crystalloids in a cystic lesion of teh parotid gland: diagnosis by fine needle aspiration. Diagn Cytopathol 1993; 9: 70-71. Thackray AC, Lucas RB. Tumors of the major salivary glands. AFIP atlas of tumor pathology, fascicle 10, 2nd series. Washington DC. Armed forces Institute of Pathology, 1974:9-10. Tandler B. Ultrastructure of chronically inflamed human submandibular glands. Arch Pathol Lab Med 1977; 101: 425-431 Tandler B, Shipkey FH. Ultrastucture of Warthins tumor II. Crystalloid. J Ultrastruct Res 1964; 11: 306-314. Ro JY, MacKay B, Batsakis JG, et al. Intraluminal crystalloids in malignant salivary gland tumors. J Laryngol Otol 1987; 101: 1175-1181 Shum C, Ali S. Liesegang rings in renal cyst fluid. Diagn Cyopathol 2005; 34(5): 348-349.