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Salivary Gland Imaging in Sjogren's Syndrome

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Salivary Gland Imaging in Sjogren's Syndrome REVIEW Salivary gland imaging in Sjogren’s syndrome Susan I Lemon, Sjogren’s syndrome (SS) is a systemic connective tissue disease characterized by a Steven G Imbesi & progressive immune-mediated impairment of the exocrine glands. The high prevalence in Alexander R Shikhman† the general population of sicca and other symptoms mimicking SS has increased the need †Author for correspondence for accurate tools in its diagnosis. Imaging may be substantially helpful in this regard, as Scripps Clinic, Member of the well as in the assessment of acute and chronic complications of the disease. A future Division of Rheumatology, MS113, 10666 North Torrey, application of salivary imaging in SS may be guiding therapeutics by enabling Pines Road, La Jolla, radiographic monitoring of treatment responsiveness. This review of salivary gland imaging CA 92037, USA in SS summarizes the types of information yielded by currently available modalities and Tel.: +1 858 554 8562; suggests their proper clinical application. It emphasizes recent advances in noninvasive Fax: +1 858 554 6763; imaging, including magnetic resonance sialography, ultrasonography and nuclear [email protected] medicine techniques. Sjogren’s syndrome (SS) is a systemic connective atrophic and, finally, destroyed [8]. Eventually, the tissue disease characterized by a progressive only remaining ductal epithelium consists of iso- immune-mediated impairment of the exocrine lated cell clusters of epithelial and myoepithelial glands [1,2]. Common clinical manifestations of cells surrounded by a dense lymphocytic infiltra- exocrine involvement in SS include keratocon- tion (a benign lymphoepithelial lesion) [9]. These junctivitis sicca, xerostomia and episodic glandu- pathological changes lead to salivary gland hypo- lar swelling. SS affects 1–4 million people in the function, including decreased salivary gland flow, USA, has a significant female predominance and increased saliva viscosity, as well as abnormal sali- has a peak incidence between the ages of 40 and vary biochemistry, bactericidal and fungicidal 60 years [3]. properties [10]. Salivary gland involvement in SS Salivary glands are one of the key target organs may manifest clinically as recurrent gland swelling, affected by SS [4]. Morphologically, normal salivary xerostomia, increased frequency of dental caries glands consist of secretory units, which include and oral candidiasis, gingival recession, fissuring of acini (cells producing primary secretion), myo- the tongue, angular cheilitis, halitosis, dysphagia epithelial cells (cells moving secretions toward the and hoarseness of voice [3]. excretory duct), the intercalated ducts (the ducts Although minor salivary gland biopsy yielding lined with low cuboidal epithelial cells rich in car- a focus score of 1 or greater is still considered a bonic anhydrase and secreting bicarbonate into the diagnostic gold standard for SS, salivary gland ductal lumen while absorbing chloride from the imaging has significant value in the evaluation of lumen), the striated ducts (the ducts lined with SS owing to the disease predilection for glandu- simple cuboidal epithelial cells absorbing Na+ from lar involvement [11]. Imaging may help to cor- the lumen and secreting K+ into the lumen), and rectly classify patients with sicca symptoms by the excretory ducts (ducts lined with simple cuboi- differentiating between SS versus non-SS causes dal epithelium proximally and stratified cuboidal of dryness. It can be used to differentiate palpa- or pseudostratified columnar epithelium distally ble or painful salivary gland abnormalities of SS and not performing any modification of the from other conditions in the differential diagno- saliva). While lymph nodes are commonly present sis (Box 1). Specifically, different imaging modali- Keywords: computed within the parotid glands, lymphoid infiltrates are ties lend valuable information about salivary tomography, imaging, absent in all normal salivary tissue [5–7]. anatomy and/or function. Conventional modali- magnetic resonance imaging, The pathomorphological hallmark of SS is ties have included sialography and scintigraphy. magnetic resonance sialography, positron emission lymphocytic infiltration of the salivary glands with In recent years, there has been considerable tomography, salivary glands, predominantly CD4+ T cells [1]. In the early stages development in the use of ultrasonography and scintigraphy, sialography, of SS, lymphocytic infiltration results in thinning magnetic resonance imaging (MRI) for the eval- Sjogren’s syndrome, ultrasound and fragmentation of the connective tissue reticu- uation of salivary glands. The current review lum of the terminal or intercalated duct walls. As summarizes published data on imaging modali- part of the disease progresses, this accumulation continues, ties used in differential diagnosis and functional the serous acini become surrounded, compressed, assessment of salivary glands in SS. 10.2217/17460816.2.1.83 © 2007 Future Medicine Ltd ISSN 1746-0816 Future Rheumatol. (2007) 2(1), 83–92 83 REVIEW – Lemon, Imbesi & Shikhman Box 1. Differential diagnosis of salivary involvement in scanning. These tests provide a unique functional Sjogren’s syndrome. assessment by displaying flow and distribution of radioactive tracer but the considerable expense • Benign sialectasis and need for a local isotope-producing cyclotron • Sialolithiasis limits their practicality. • Chronic sialadenitis •Infection – Bacterial (i.e., Staphylococcus aureus), viral (i.e., HIV, hepatitis C virus Sialography and mumps) Sialography is an invasive test performed by can- •Tumors nulating the main ducts of major salivary glands • Granulomatous diseases via their oral mucosal orifices and infusing con- – Tuberculosis, nontuberculous Mycobacterium, sarcoidosis, syphilis, trast retrograde to the usual direction of salivary cat-scratch fever and fungal infections flow. Stensen’s duct of the parotid gland enters • Vasculitis (Wegener’s granulomatosis) the mouth along the buccal mucosa adjacent to •Sialosis the upper second molar, and Wharton’s duct of – Diabetes mellitus, alcoholism, hypothyroidism, malnutrition, diuretics the submandibular gland drains into the floor of and psychotropics • Chronic graft-versus-host disease the mouth near the frenulum. The main interc- • Amyloidosis alated ducts branch into peripheral ducts which • Eating disorders end in acini. Sialography outlines salivary duct anatomy and provides reliable results in the diag- Modalities nosis of SS that challenge the current gold stand- Plain sialography and MRI provide anatomical ard of minor salivary gland biopsy. Secretory detail via static images but do not assess function sialography adds the ability to perform functional (Table 1). MRI offers advantages over sialography assessment of salivary glands (Table 1). Sialography including its noninvasive nature and ability to is included in both the Japanese and European provide high-resolution images of salivary gland Community criteria for the diagnosis of SS [13]. parenchyma. Sialography shows salivary duct Sialography of parotid and submandibular architecture, but is an invasive procedure which glands readily differentiates the pseudosialectasis can be painful and, particularly in the setting of of SS from chronic sialadenitis, sialolithiasis, acute sialadenitis, predispose to infection and granulomatous conditions, tumors and the sia- induce obstruction. Nuclear medicine techne- loses (Box 1). Historically, SS signature sialo- tium-99m pertechnetate (99mTc)-based scinti- graphic staining pattern was that of patent, graphy yields dynamic information by nondilated main ducts with diffusely uniform quantifying salivary flow rates but does not pro- punctuate or globular collections throughout the vide anatomical information. Ultrasound (US) is gland [14]. These collections were thought to be a modality which boasts relatively inexpensive, noninvasive acquisition of structure and func- Table 1. Characteristics of imaging tion. High-resolution US images are now readily modalities in Sjogren’s syndrome. available with the use of modern very-high fre- quency transducers. Combination techniques, Modality Anatomy Function such as magnetic resonance (MR) sialography Sialography (+) (-) and sialographic sonography, have been devel- Secretory (+) (+) oped with hopes of increasing diagnostic accu- sialography racy in SS (Table 2). These modalities allow Scintigraphy, PET (-) (+) simultaneous imaging of the parenchyma and PET-CT (+) (+) ducts [12]. While sialographic sonography has not yet been developed for clinical use, MR sialogra- MRI, MR (+) (-) sialography phy is being increasingly utilized clinically. Scinti- graphy and high-resolution power Doppler US Dynamic MR (+) (+) provide objective functional assessments of sali- Sialography vary glands, which can be used as outcome meas- US (+) (-) ures in SS clinical trials. The breadth of nuclear Power Doppler US (+) (+) medicine evaluation of salivary gland involve- +: Informative; -: Noninformative. ment in SS extends beyond conventional scinti- CT: Computed tomography; MRI: Magnetic resonance graphy to positron emission tomography (PET), imaging; PET: Positron emission tomography; PET-computed tomography (CT) and 67Gallium US: Ultrasound. 84 Future Rheumatol. (2007) 2(1) futurefuture sciencescience groupgroup Salivary gland imaging in Sjogren’s syndrome – REVIEW Table 2. Sensitivity and specificity of imaging modalities for However, with the advent of MR sialography, a
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