A Case of Eosinophilic Sialodochitis with Right Submandibular Sialolithiasis and Hyperdense Material along Wharton’s Duct

1. Introduction and Clinical Significance

Eosinophilic sialodochitis (ES), also known as sialodochitis fibrinosa, is a rare disease characterized by the formation of fibrinous plugs within the salivary ducts, resulting in impaired salivary flow and recurrent swelling of the salivary glands. Histopathological examination typically reveals mucous plugs containing eosinophils and Charcot-Leyden crystals, as well as eosinophilic infiltration around the major salivary gland ducts [1]. A recent review reported that most patients with ES were atopic and that 75.4% had allergic rhinitis [2]. Elevated serum IgE levels and peripheral blood eosinophilia in some patients suggest possible involvement of type I allergic mechanisms. Baer’s criteria (Table 1), which includes clinical and pathological findings, is commonly used for the diagnosis. Characteristic imaging findings of ES include salivary duct dilatation and swelling of the salivary glands [3,4]. Rare cases associated with sialoliths or calcifications have also been reported [5]. However, to our knowledge, no previous report has clearly described a high-attenuation area along the salivary duct on computed tomography (CT) suggestive of eosinophilic mucin retention within the duct in ES.

Here, we report a case of ES that initially presented as right submandibular sialolithiasis and showed a high-attenuation area within the right Wharton’s duct on preoperative CT. In this case, histology revealed numerous eosinophils and Charcot-Leyden crystals not only within the lumen of Wharton’s duct but also within the sialolith. This case may provide useful insights into the relationship between eosinophilic inflammation, CT findings, and sialolith formation in patients with ES.

2. Case Presentation

The patient was a 56-year-old woman who visited a local clinic with a chief complaint of recurrent swelling and pain in the right submandibular region. Her medical history included allergic rhinitis. Physical examination revealed right submandibular swelling with tenderness on palpation. Laboratory tests showed a white blood cell count of 8460 cells/µL, with eosinophils accounting for 7.9%, and an IgE level of 113.5 IU/mL. Serum antigen-specific IgE testing using the View Allergy 39 (a multiple-allergen-specific IgE screening test) showed positivity for Japanese cedar pollen and house dust mites, with values of 1.49 IU/mL and 10.61 IU/mL, respectively. Laboratory findings ruled out differential diagnoses associated with recurrent submandibular swelling, including Sjögren’s syndrome, IgG4-related salivary gland disease, and Kimura’s disease (Table 2).

Cervical ultrasonography (US) revealed a calcified lesion with acoustic shadowing in the right submandibular gland (Figure 1A). CT confirmed an 11 mm × 14 mm × 16 mm sialolith in the gland (Figure 1B, C). Both US and CT revealed dilatation of Wharton’s duct (Figure 1D-F). Based on these findings, intraductal pus retention secondary to chronic submandibular sialadenitis associated with sialolithiasis was initially suspected. Because spontaneous expulsion was considered difficult owing to the location and size of the stone, a right submandibular gland resection was performed.

Histopathological examination of the resected specimen using hematoxylin and eosin staining revealed a sialolith at the hilum of Wharton’s duct (Figure 2A). Periductal fibrosis, fragments of ductal epithelium, and lymphocytic and eosinophilic infiltration around the ducts were also observed (Figure 2B). Notably, after decalcification of the sialolith, numerous eosinophils and Charcot-Leyden crystals were observed both around and within the sialolith (Figure 2C, D).

Soon after surgery, the patient developed frequent pain and swelling of the right floor of the mouth, with expulsion of a brownish jelly-like secretion from the Wharton’s duct. US and CT revealed dilatation of the right Wharton’s duct, and CT showed a high-attenuation area within the duct, with no obvious residual sialolith (Figure 3A-C). Similar findings were retrospectively identified on preoperative CT, and ductal dilatation was considered unlikely to be caused by the sialolith itself or by chronic submandibular sialadenitis.

Intraoral examination revealed a mucous plug extruding from the right Wharton’s duct (Figure 4A). The plug was collected as a specimen, and ductal cannulation with saline irrigation revealed dilatation of the ductal orifice (Figure 4B, C). Papanicolaou staining of the mucous plug revealed numerous eosinophils and Charcot-Leyden crystals (Figure 4E). Clusters of eosinophils and an anucleate crystal-like structure were also observed in the mucous plug (Figure 4F). As the clinical and histological findings fulfilled Baer’s criteria (Table 1), the patient was diagnosed with eosinophilic sialodochitis.

Physical extraction of mucous plugs and anti-allergic medications, including bilastine (20 mg) and montelukast (10 mg), were administered for 3 months but showed limited efficacy. Therefore, ductal irrigation with saline and corticosteroids was initiated. The irrigation consisted of 2 mL of normal saline and 0.1 mL of triamcinolone acetonide 40 mg/mL. After steroid irrigation, the mucous plug discharge markedly decreased. Following two additional steroid irrigations at 6-month intervals, the patient’s symptoms remained well controlled with self-extraction of residual mucous plugs and saline irrigation every 3 months during 18 months of follow-up.

3. Discussion

Eosinophilic sialodochitis (ES), previously known as eosinophilic sialodochitis (sialodochitis fibrinosa), is a rare inflammatory disease of the salivary glands that primarily affects the excretory ducts of the major salivary glands. ES was first described by Kussmaul in 1879. It is characterized by recurrent painful swelling of the salivary glands and mucous plugs containing leukocytes and Charcot-Leyden crystals. Baer’s criteria (Table 1) are the most commonly used diagnostic criteria [1]. A recent review, which included cases that did not fully meet these criteria after excluding related disorders, identified 309 previously reported cases since 2000 [2].

ES is reported to occur more often in women and commonly involves the bilateral parotid glands, although unilateral cases and cases involving the submandibular gland have also been described [2]. In the present case, the patient had recurrent swelling of the right floor of the mouth and discharge of viscous secretions from the orifice of Wharton’s duct, containing numerous eosinophils and Charcot-Leyden crystals. The patient also fulfilled all of Baer’s criteria [1], including blood test results, histopathological findings, and medical history. Therefore, the patient was diagnosed with eosinophilic sialodochitis.

In the present case, mucous plug-related symptoms became clinically apparent after submandibular gland resection. Previous reports have described submandibular gland excision as a surgical treatment for ES involving the submandibular gland; however, mucous plug symptoms have also become evident postoperatively [5,6]. In contrast, long-term disease control has been achieved in cases treated with additional or simultaneous resection of the affected salivary duct [6,7]. These findings suggest that the salivary duct, rather than the gland itself, may be the primary site involved in the pathogenesis of ES. A recent review summarized treatment options for ES, including conservative ductal interventions (saline and/or steroid irrigation, mechanical dilatation, and drain placement), medical therapy (antihistamines, leukotriene receptor antagonists, and systemic corticosteroids), and surgical excision of the involved gland and duct [2]. Among these approaches, conservative ductal interventions have been associated with the highest long-term success rates among currently available treatments. The favorable outcomes of local therapies targeting the salivary duct further support the central role of ductal involvement in the pathogenesis of ES. In the present case, submandibular gland resection was considered unavoidable because of the presence of a large intraglandular sialolith in the submandibular gland. Although medical treatment is effective, ductal resection may be considered if the disease becomes refractory.

In many cases of ES, concomitant allergic disease, elevated eosinophil counts and IgE levels, and numerous eosinophils in ductal secretions have been reported [8]. Eosinophilic inflammation associated with type I allergy is considered to contribute to the pathogenesis of this disease. In the present case, although the total IgE level was not markedly elevated, the patient had peripheral blood eosinophilia and a history of allergic rhinitis. Recent studies have suggested that eosinophilic ETosis (EETosis) may be involved in the pathogenesis of ES [6]. ETosis is a form of cell death observed in granulocytes, including neutrophils and eosinophils, in which extracellularly released chromatin and granule proteins form web-like structures [9,10]. EETosis is thought to contribute to the formation of viscous eosinophilic mucin in type 2 inflammatory diseases, such as allergic bronchopulmonary aspergillosis (ABPA) [11], eosinophilic chronic rhinosinusitis (ECRS) [12], eosinophilic otitis media [13]. The viscous mucus plug with numerous eosinophils and Charcot-Leyden crystals observed in the present case may support the presence of a similar mechanism of eosinophilic mucin formation in sialodochitis fibrinosa.

An important feature of the present case was the high-attenuation area along the right Wharton’s duct on the CT scan. Viscous eosinophilic mucin in ABPA and ECRS appears as high-attenuation areas on CT [11,12]. In particular, as a characteristic finding of ABPA, high-attenuation mucus (HAM) is defined as mucus with a CT value of 70 Hounsfield units (HU) or higher, which helps distinguish it from mucus plugs associated with other diseases [14]. In contrast, the imaging findings of sialodochitis fibrinosa reported to date mainly include ductal dilatation and salivary gland swelling [3,4]. In the present case, the high-attenuation area along Wharton’s duct corresponded to the site from which viscous secretions containing eosinophils and Charcot-Leyden crystals were discharged. The CT value of this mucous plug was consistently 70 HU or higher both before and after surgery, suggesting that it could be regarded as a HAM. This finding raises the possibility that eosinophilic mucin retained within the salivary duct may appear as a high-attenuation area on CT in some ES cases.

Another characteristic feature of this case is that ES was identified during the evaluation of right submandibular sialolithiasis in the patient. ES associated with sialolithiasis is rare, with only a limited number of cases reported in the literature [5].Although the mechanism of sialolith formation remains unclear, the aggregation of sialomicroliths [15,16], anatomical factors of the salivary ducts [17,18], and changes in the biochemical composition of saliva [19] are considered to be involved in its formation. Sialomicrolith itself has been reported in normal salivary glands of asymptomatic individuals [18]. A recent ultrastructural study showed that sialoliths consist of three layers: a central nidus, an intermediate compact zone, and a peripheral multilayered zone [20]. The authors proposed that bacterial infection and biofilm formation in the central nidus, promoted by ductal congestion, may facilitate the aggregation of sialomicroliths and subsequent sialolith formation. In addition, neutrophil ETosis has been suggested to promote calcium-based crystal formation [21]. In the present case, sialomicrolith-like structures were observed within mucous plugs, along with eosinophil clusters and Charcot-Leyden crystals. These findings suggest that viscous secretions and crystalline components associated with eosinophilic inflammation may contribute to salivary stasis and act as a nidus for microcalcifications.

This study has several limitations. First, this report describes only a single case; thus, further accumulation of cases and pathological studies are required to confirm our findings. Second, the direct continuity between the sialolith removed from the submandibular gland and the secretions discharged from Wharton’s duct postoperatively could not be demonstrated pathologically. Third, the involvement of eosinophilic ETosis was not confirmed by immunohistochemistry and was inferred only from the pathological findings. These issues should be addressed in future research.

4. Conclusions

We report a case of ES identified during the evaluation of right submandibular sialolithiasis, which showed a high-attenuation area along the right Wharton’s duct on CT. The presence of numerous eosinophils and Charcot-Leyden crystals in the discharged material suggests that eosinophilic mucin retained within the salivary duct may appear as a high-attenuation area on CT. These findings may have contributed to salivary stasis and sialolith formation. This case provides useful insights into the imaging findings and pathophysiology of ES.