Eosinophilic Sialodochitis Identified in Duct Remnant After Submandibular Gland Resection

ABSTRACT

Eosinophilic sialodochitis (ES) is an increasingly recognized cause of recurrent sialadenitis but likely remains underdiagnosed as it is commonly considered to be nonspecific chronic sialadenitis. ES is likely increasing in prevalence in association with the growing number of allergic diseases and should be considered in patients presenting with multiple episodes of salivary gland pain and swelling refractory to conventional treatment. We highlight this difficulty in diagnosis with a report of ES established following Wharton duct remnant swelling after submandibular gland (SMG) resection for stone removal with photographic, histopathologic, and radiographic analysis.

Key Points

• Eosinophilic sialodochitis (ES) is likely underdiagnosed and should be considered in patients with atopy and recurrent salivary gland swelling refractory to standard treatments.

• Sialolithiasis, Sjögren's syndrome, and IgG4‐related disease are important diagnostic confounders that must be systematically excluded.

• ES may persist as a ductal disease after gland resection, underscoring the importance of recognizing the duct remnant as a site of recurrence.

1. Introduction

Since Kussmaul's first description in 1879, recurring episodes of salivary gland swelling associated with mucus plugs and eosinophils have been described by many names [1]. Initially termed sialodochitis fibrinosa, the naming of this condition has changed with our evolving knowledge [2]. This rare condition, more recently termed eosinophilic sialodochitis (ES), typically presents with recurrent salivary gland swelling and pain due to obstruction of ducts with eosinophilic, mucus plugs [3]. We report a case of ES with a unique clinical presentation including radiologic, photographic, and pathologic analysis. Coexisting sialolithiasis, a positive SS‐A antibody, and prior gland resection each obscured the underlying eosinophilic process in this case, highlighting the need to systematically consider and exclude differential diagnoses, including Sjögren's syndrome, IgG4‐related sialadenitis, and chronic obstructive sialadenitis.

2. Case Report

A 71‐year‐old female presented to clinic with abnormal taste and stringy, yellow secretions on the left side of her mouth. Past medical history was notable for cardiac disease, allergic rhinitis, and asthma. She denied a history of other autoimmune disorders.

A right submandibular gland (SMG) resection had been performed 4 years prior to our intervention at an outside hospital for swelling and severe pain due to an obstructive salivary stone. Six months prior to her presentation at our clinic, she developed swelling and yellow discharge from her left submandibular duct persisting despite antibiotics.

Outside computed tomography (CT) imaging demonstrated two calculi and ductal dilatation in the left SMG. Ultrasound imaging confirmed sialolithiasis and illustrated a heterogeneous gland suggesting possible Sjögren's syndrome. Immunological testing showed a positive antinuclear antibody titer and SS‐A antibody. Rheumatoid factor and SS‐B antibody results were within normal limits.

Two weeks after her initial presentation to our clinic, sialanedoscopy identified sufficient ductal stenosis to preclude effective transoral stone removal, necessitating left SMG resection. At that time, histopathologic examination of the gland and duct showed significant fibrosis, chronic inflammation, ductal dilatation along with a 6‐mm stone in the hilum and no report of eosinophilic infiltration.

Five months later, she developed an enlargement in the left floor of her mouth persisting despite antibiotics leading to our re‐evaluation for ongoing swelling and discomfort. Ultrasound with sonopalpation revealed an anteriorly located tubular, hypoechoic prominence in the left floor of the mouth consistent with an enlarged Wharton's duct (Figure 1) [4].

Figure 1.

Ultrasound demonstrating hypoechoic structure casting a shadow consistent with the known region of the mass with sonopalpation further delineating a hypoechoic structure measuring 14.9 mm.

Ductoplasty under local anesthesia in clinic permitted removal of a 6.5‐cm aggregate of gelatinous, firm material with the gross appearance of inspissated ductal contents, consistent with the characteristic eosinophilic mucus plugs of ES (Figure 2). Grocott's methenamine silver (GMS) stain was negative for any fungal forms. Histopathology identified mucus, necro‐inflammatory debris, and numerous eosinophils. On a follow‐up phone call a few days later, the patient reported that she was doing well and had no further issues.

Figure 2.

Removal of obstruction from marsupialized Wharton's duct (A, B). Dilated duct remnant (C). Mucus and necro‐inflammatory debris (D).

Based on increased recognition of the disorder now termed ES, re‐examination of the resected SMG identified parenchyma with dilated ducts, periductal lymphocytic inflammation with numerous eosinophils, and periductal fibrosis (Figure 3). Intraepithelial eosinophils were focally identified in ductal epithelium. Inspissated mucus containing eosinophils and calcifications were identified within the dilated ducts. Smaller interlobar ducts were similarly affected. Based on the history, imaging, operative, and histopathologic evaluation, it was concluded that this case was consistent with ES.

Figure 3.

Hematoxylin–eosin‐stained sections from SMG resection: Duct with inspissated mucin and stone at ×4 magnification (A). Periductal fibrosis with intraepithelial mucin containing eosinophils at ×20 magnification (B). Dilated duct with periductal and rare intraepithelial eosinophils at ×20 magnification (C). Mucin with eosinophils at ×40 magnification (D).

3. Discussion

ES is an increasingly recognized cause of recurrent sialadenitis, yet it continues to be difficult to diagnose in routine practice. ES remains unfamiliar to many clinicians with diagnostic criteria not yet fully standardized [2, 5]. In addition, its nonspecific symptomatology overlaps with more well‐established conditions, such as sialolithiasis, Sjogren's syndrome, IgG4‐related disease, and the less common Kimura disease [2].

In this case, the positive SS‐A antibody and history of sialolithiasis presented diagnostic confounders. Although SS‑A positivity raised concern for Sjögren's syndrome, she lacked sicca symptoms, and histopathology demonstrated eosinophilic rather than lymphoplasmacytic inflammation [6]. The positive SS‐A finding most likely reflected background autoimmunity that can occur in other inflammatory states.

We interpreted the sialolithiasis in this case to more likely be a consequence rather than the cause of the underlying eosinophilic process [2].

This patient's history of allergic rhinitis and asthma is consistent with the well‐established association between ES and atopic disease. The underlying Th2‐mediated inflammatory pathway shared across asthma, allergic rhinitis, and ES likely drives eosinophil recruitment into the ductal submucosa through IL‐4, IL‐5, and IL‐13 signaling [1, 3].

ES should be suspected in patients with recurrent salivary swelling, atopic comorbidities, trigger‐related flares, and poor response to prior treatments. Laboratory evaluation may include assessment for peripheral eosinophilia (CBC with differential) [7]. Imaging may reveal chronic inflammation and ductal dilatation. Endoscopic or operative evaluation can show mucinous debris and sialoliths. Distal ductal biopsy demonstrating periductal eosinophilic infiltration can support the diagnosis.

Antibiotics are often prescribed for recurrent salivary gland pain and swelling. This may address secondary bacterial infection, but it is not expected to address the underlying eosinophilic inflammation felt to be allergic in origin. Suggested management includes massage, sialagogues, anti‐allergic therapy, and glucocorticoids [5]. Sialendoscopic irrigation and dilation or gland resection may provide relief. Sialoadenectomy has been reported as a successful treatment of ES [5]. Our case highlights that ES can recur in the duct remnant after gland removal, reinforcing the concept that ES may be more of a ductal disease rather than a glandular disease. Reports have demonstrated effective management with immunomodulatory therapies targeting the Th2 pathway. McCarty et al. noted marked symptomatic improvement over 6 months in a patient with ES involving all 4 major salivary glands following initiation of dupilumab, an IL‐4 receptor antagonist [3]. Similarly, González et al. described sustained clinical remission after 10 months of benralizumab therapy, an IL‐5 receptor monoclonal antibody [8].

To our knowledge, ES presenting after salivary gland resection for stone removal is uncommon in medical literature. Operative, radiologic, and histopathologic observations can provide confirmation of ES and limit antimicrobial or surgical escalation.

Author Contributions

Edward Tannenbaum: concept and design, acquisition, analysis, or interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, administrative, technical, or material support. Claire Orth: acquisition, analysis, or interpretation of data, critical revision of the manuscript for important intellectual content. Nicole Becker: acquisition, analysis, or interpretation of data, critical revision of the manuscript for important intellectual content. Henry Hoffman: concept and design, acquisition, analysis, or interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content; administrative, technical, or material support.

Ethics Statement

Institutional review board approval was not required as this manuscript describes a single retrospective case report anonymously.

Conflicts of Interest

Hendry Hoffman Research Consultant for Everis, Institutional Primary Investigator for MeiraGtx and Primary Investigator for RiboX; Advisory Board for RiboX; author for UpToDate. The remaining authors declare no conflicts of interest.

Data Availability Statement

All available data have been shared with readers in the format of this case report.