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ISSN : 1225-1577(Print)
ISSN : 2384-0900(Online)
The Korean Journal of Oral and Maxillofacial Pathology Vol.50 No.3 pp.53-61
DOI : https://doi.org/10.17779/KAOMP.2026.50.3.001

Traumatic Ulcerative Granuloma with Stromal Eosinophilia of the Oral Cavity: Clinicopathological Analysis from a 25-Year Single-Institution Experience

Ho-A Shin, Seong-Doo Hong, Jae-Il Lee, Hye-Jung Yoon*
Department of Oral Pathology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea
* Correspondence: Hye-Jung Yoon, Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea Tel: +82-2-740-8682 Email: hyejyoon@snu.ac.kr ORCID: 0000-0002-3534-3295

May 28, 2026 May 29, 2026 May 30, 2026

Abstract


Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare distinctive ulcerative lesion of the oral mucosa that is generally considered to be associated with trauma. Clinically, it may mimic malignant ulcerative lesions, making accurate diagnosis particularly important. This retrospective study analyzed 64 patients diagnosed with TUGSE at the Department of Oral Pathology, Seoul National University Dental Hospital over a 25-year period from 2000 to 2025. Clinical information and histopathologic findings were analyzed through review of medical records and pathological slides. Among the 64 cases, 38 patients (59.4%) were male and 26 (40.6%) were female, with a mean age of 47 years (range, 8–86 years). The tongue was the most commonly affected site, accounting for 37 cases (57.8%), followed by the buccal mucosa and the floor of the mouth. Biting-related trauma was considered the most likely etiologic factor in 22 cases (34.3%). All lesions showed spontaneous healing following biopsy. Histopathologically, all cases demonstrated proliferation of granulation tissue beneath the ulcerated epithelium accompanied by infiltration of chronic inflammatory cells. Prominent eosinophilic infiltration extending deeply into the underlying muscle layer was a characteristic finding. 33.7% of the lesions were initially suspected to be malignant or potentially malignant lesions prior to biopsy, suggesting that histopathologic examination is essential for the accurate diagnosis and appropriate management of TUGSE.


Traumatic ulcerative granuloma with stromal eosinophilia , TUGSE , Eosinophil , Oral cavity

구강에서 발생한 간질성 호산구증가증을 동반한 외상성 궤양성 육아종: 25년간의 단일 기관 경험에 근거한 임상병리학적 분석

신호아, 홍성두, 이재일, 윤혜정*
서울대학교 치의학대학원 구강병리학 교실

초록

    Ⅰ. INTRODUCTION

    Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare reactive benign lesion occurring in the oral mucosa1. Although the exact pathogenesis of TUGSE remain unclear, trauma has been identified as a contributing factor in many reported cases2. Clinically, TUGSE usually presents as a solitary ulcer with delayed healing3. The tongue is the most commonly affected site, and the ulcer may occasionally present with induration or raised, rolled margins. These clinical features may closely resemble malignant lesions such as oral squamous cell carcinoma (OSCC), making differential diagnosis challenging. The ulcer surface is usually covered by a yellowish-white pseudomembrane or exudate, and the associated pain ranges from asymptomatic to moderate or severe4. A history of repetitive trauma, including biting, sharp tooth margins, prosthetic irritation, occlusal abnormalities, psychological disorders associated with tics, and parafunctional habits, is frequently reported. In infants, TUGSE has also been described within the spectrum of Riga-Fede disease5. Histopathologically, the lesion characteristically shows surface ulceration with underlying proliferation of granulation tissue and deep inflammatory stromal infiltration. Various chronic inflammatory cells are observed in the lesion, particularly abundant eosinophils. This inflammatory infiltrate may extend into the submucosa, salivary glands, and muscle layer3, and deep inflammatory extension may lead to degeneration of the muscle tissue2.

    Although studies on TUGSE have continued to be reported, most publications have been limited to single case reports or small case series. To the best of our knowledge, this study represents one of the largest cohorts of TUGSE cases reported to date and systematically describes the clinical and histopathologic characteristics of 64 TUGSE cases of the oral cavity. Through this analysis, we aim to improve understanding of the major features of this disease and provide useful guidance for its diagnosis and treatment planning.

    Ⅱ. MATERIALS AND METHODS

    Cases diagnosed as traumatic granuloma, traumatic ulcer, traumatic ulcerative granuloma, traumatic ulcerative mucositis, eosinophilic ulcer, eosinophilic granuloma, or ulcerative eosinophilic granuloma in the Department of Oral Pathology at Seoul National University Dental Hospital between January 1, 2000, and December 31, 2025, were retrospectively reviewed. Histopathologic slides were independently reviewed by two oral pathologists. A total of 95 cases were retrieved, of which 64 were ultimately included in the study after applying the exclusion criteria. Cases were excluded if (1) the tissue specimen was insufficient for a definitive diagnosis, (2) at least mild eosinophilic infiltration was not identified, or (3) clinical information was incomplete. Cases were excluded if (1) the tissue specimen was insufficient for a definitive diagnosis, (2) at least mild eosinophilic infiltration was not identified, or (3) clinical information was incomplete. As a result, a total of 64 cases were included in the final analysis.

    Quantitative assessment of eosinophilic infiltration was performed under high-power fields (HPFs; ×400 magnification), and the mean value from the two observers was calculated. Areas showing the highest density of eosinophilic infiltration were first identified by low-power examination, and the average number of eosinophils per HPF was determined from at least three representative fields. Based on criteria adapted from previous studies,6 eosinophilic infiltration was semi-quantitatively classified as mild (0–20 eosinophils/HPF), moderate (20–40 eosinophils/HPF), or severe (>40 eosinophils/HPF).

    Clinical information was obtained through review of electronic medical records (EMRs) and clinical photographs, including sex, age, lesion location, clinical course, traumatic etiologic factors, associated systemic diseases, and clinical diagnosis. Lesion healing and recurrence were evaluated based on follow-up records documented in the EMR system. Cases lost to follow-up after suture removal following biopsy were excluded from the analyses of healing and recurrence. Complete healing was defined as complete resolution of the lesion following the initial surgical procedure during the follow-up period. Recurrence was defined as the reappearance of an ulcerative lesion at the same anatomical site after initial treatment. This retrospective study was granted exemption by the Institutional Review Board of Seoul National University Dental Hospital (approval No. ERI26033).

    Ⅲ. RESULTS

    The clinical characteristics of the 64 TUGSE cases are summarized in Table 1, and the initial clinical diagnoses are categorized in Table 2.

    1. Age, Gender

    Patient age ranged from 8 to 86 years, with a mean age of 47 years. There was a male predominance, with 38 male patients (59.4%) and 26 female patients (40.6%).

    2. Etiology

    A history of trauma was identified in 65.6% of patients. The most common cause was biting-related trauma in 34.3% of cases, followed by irritation from sharp tooth margins in 20.3% and denture-related trauma in 6.2% of cases. Eruption-related trauma, trauma caused by extrusion, and irritation from retained roots were each observed in 1 case. The possible involvement of underlying systemic diseases should also be considered. Our cohort included several patients with systemic diseases that have been relatively infrequently reported in the literature. Associated conditions included autoimmune diseases [Behçet disease (n=1) and granulomatosis with polyangiitis (GPA) (n=1)], psychiatric disorders [schizophrenia (n=1)], epilepsy (n=1)], neurodevelopmental and behavioral disorders [tic disorder (n=2), attention-deficit/hyperactivity disorder (ADHD) (n=2), and autism spectrum disorder (ASD) (n=2)], cognitive impairment [mild cognitive impairment (n=1) and dementia (n=1)], intellectual disability (n=2), severe cerebral palsy-related disability (n=2), tuberculosis (n=2), and xerostomia (n=3).

    3. Location, size, and clinical course

    The tongue was the most commonly affected site, accounting for 37 cases (57.8%). Among tongue lesions, the lateral border was the most frequently involved site (23 cases), followed by the ventral surface (6 cases), dorsal surface (4 cases), and the tongue tip and anterior tongue (1 case each). In 2 cases, the precise location could not be determined. The buccal mucosa was involved in 19 cases (29.7%), followed by the floor of the mouth in 3 cases (4.7%). Other sites included the alveolar mucosa, lingual mucosa, retromolar area, and hard palate. Lesion size ranged from 0.3 to 2.5 cm (mean, 1 cm), and lesion duration varied from 6 months to 24 months.

    With the exception of one case presenting with simultaneous bilateral lesions and the other case with metachronous bilateral lesions occurring on opposite sides, all remaining lesions were solitary. The ulcer base was covered by a yellowish-white fibrinous exudate. Ulcers ranged from shallow crateriform lesions to deeply ulcerated lesions, and some cases demonstrated associated granulation tissue proliferation arising from the ulcer base. White keratotic borders and elevated ulcer margins were observed in many cases (Fig. 1). Pain was reported in 62.5% of cases. All cases with available follow-up data showed spontaneous healing. Recurrence was observed in only one case.

    4. Initial clinical diagnosis

    The most common initial clinical diagnosis was a simple ulcerative or inflammatory lesion in 37 cases (37.8%), followed by OSCC in 30 cases (30.6%), reactive lesions in 16 cases (16.3%), benign tumors in 7 cases (7.1%), and potentially malignant disorders in 3 cases (3.1%). These findings indicate that although TUGSE is frequently recognized clinically as a benign lesion, differentiation from malignant disease remains an important clinical consideration.

    5. Histopathologic findings

    Most cases showed formation of a superficial fibrinopurulent membrane over the ulcer surface. Chronic inflammatory cell infiltration composed of lymphocytes, plasma cells, and macrophages was observed within the underlying connective tissue, accompanied by varying degrees of eosinophilic infiltration. Among the 64 lesions, eosinophilic infiltration was classified as mild in 25 cases (39.1%), moderate in 12 cases (18.8%), and severe in 27 cases (42.2%). Eosinophils diffusely infiltrated from the subepithelial connective tissue into the adjacent minor salivary glands and deep muscle layer, and in some cases, associated degenerative changes of muscle fibers were observed (Fig. 2).

    Ⅳ. DISCUSSION

    TUGSE is a relatively rare lesion of the oral mucosa whose etiology and pathogenesis have not yet been fully elucidated. In the literature, it has been described under a variety of terms, including sublingual granuloma, traumatic granuloma, eosinophilic granuloma, eosinophilic ulcer, and ulcerative eosinophilic granuloma7-8. Sublingual granuloma, which has been primarily reported in infants, was first clinically described by Riga in 1881 and later histologically characterized by Fede in 1890, leading to the designation of Riga-Fede disease9-10. This condition typically occurs in newborns with natal or early erupted mandibular incisors, in whom repetitive traumatic irritation during breast-feeding results in traumatic ulceration of the lingual frenum. Similar lesions have also been reported in adults under various names. In 1983, Elzay proposed the unifying term “traumatic ulcerative granuloma with stromal eosinophilia”. Although he initially intended to avoid the term “granuloma” because the lesion does not represent true granulomatous inflammation, he retained the terminology in consideration of its widespread use in the literature5.

    While our study noted a male predominance, previous literature reports conflicting findings, including similar sex distribution2 and female predominance11. Consequently, no definitive sex predilection has been established for TUGSE. The mean age of the patients in our study was 47 years, consistent with previous studies reporting a mean age of 49 years6. The tongue is the most common site for TUGSE, accounting for 82.6% of cases in Shen et al.6 (predominantly the dorsal surface and tip) and 68.4% in Fonseca et al.2 (dorsal surface and lateral border). Similarly, tongue lesions in this study mostly affected the lateral border and dorsal surface. In agreement with Shen et al.6, the buccal mucosa was the second most frequent site in this study. Although TUGSE typically presents as a solitary ulcer, our cases exhibited multiple lesions: a contralateral metachronous lesion in the patient with Behçet disease and bilateral lesions in the patient with GPA. Specifically, the patient with Behçet disease initially developed a buccal mucosa lesion, followed a year later by a pharyngeal arch lesion. This metachronous pattern supports the findings of Sugaya et al.12, who reported a primary tongue lesion followed by a subsequent hard palate lesion, suggesting that new TUGSE lesions can arise at different oral sites over time. Clinically, the differential diagnosis of TUGSE is important because it may closely resemble infectious ulcers or ulcerative lesions associated with OSCC. In the present study, approximately 33% of patients underwent biopsy because the lesion was clinically suspected to represent a malignant or potentially malignant lesion. Although TUGSE is a benign lesion, it may present with induration and elevated or rolled borders, which can lead to clinical misdiagnosis as a malignant neoplasm13. Therefore, biopsy is essential for accurate diagnosis in cases of persistent ulcerative lesions, particularly those accompanied by induration or elevated margins. TUGSE generally shows complete resolution following elimination of the traumatic stimulus3. In the present study, most cases with available follow-up data showed spontaneous healing after biopsy, except in several patients in whom elimination of the source of irritation was delayed or difficult due to intellectual disability or severe neurologic impairment. Recurrence in TUGSE is considered uncommon; however, one recurrent case was identified in the present study one year after the initial lesion. This finding is consistent with the report by Shen et al.6, who observed recurrence in only one case among 34 analyzed patients. Taken together, TUGSE is characterized by rare recurrence and a highly favorable prognosis.

    Histopathologically, eosinophilic infiltration in our cases was predominantly concentrated within the submucosa and superficial muscle rather than the deep muscle layer, consistent with the findings of Shen et al.6 Similar to their study, we classified eosinophilic infiltration as mild, moderate, or severe. However, a limitation of this approach is that counting eosinophil numbers on HE-stained sections is subject to interobserver variability. Therefore, it is currently difficult to accurately assess the relationship between the degree of eosinophilic infiltration and clinical features, including recurrence. Future studies using immunohistochemical markers specific for eosinophils or their secretory products may allow more objective and quantitative assessment of eosinophilic activity and facilitate investigation of the clinical significance of eosinophilic infiltration in TUGSE.

    The exact etiology of TUGSE has not yet been clearly established, although traumatic irritation is generally considered the most likely contributing factor. Sharp tooth margins, ill-fitting dentures, and even biopsy procedures performed for leukoplakia have been suggested as possible causes1-2. Nevertheless, not all reported cases have shown a clear association with traumatic injury14-15. In the present study, an association with traumatic irritation was identified in 65.6% of cases. In addition to simple local trauma, involuntary masticatory dysfunction, oral parafunctional habits, and psychiatric disorders were also identified as possible contributing factors. The etiology in the remaining cases remains unclear, although abnormal immune responses may contribute to persistent inflammation and impaired wound healing, resulting in chronic ulcer formation. In our patients with Behçet disease and GPA, delayed healing after localized mucosal injury caused by prosthetic irritation was observed. This may be related to abnormal autoimmune conditions or impaired inflammatory responses in those systemic conditions. Persistent chronic ulceration associated with xerostomia may also be related to increased friction and repetitive microtrauma due to decreased salivary lubrication and protective function16. Nevertheless, the pathogenic mechanisms underlying TUGSE arising from these various conditions remain poorly understood.

    The role of eosinophils, particularly regarding wound healing and cell-mediated immunity has drawn increasing attention. Elovic et al. previously proposed that eosinophils regulate normal tissue repair by producing TGF-α and TGF-β, which drive epithelial proliferation and tissue remodeling17. However, their subsequent analysis of 12 TUGSE cases revealed a lack of TGF-α and TGF-β1 expression despite dense eosinophilic infiltration, suggesting that this growth factor deficiency underlies delayed healing in TUGSE. Conversely, Bagh and Ali reported strong positive expression of TGF-β1 in all examined TUGSE cases18. These conflicting findings indicate that the chronic delayed healing of TUGSE cannot be attributed solely to insufficient eosinophil-derived growth factors, suggesting the involvement of alternative pathophysiologic mechanisms. Moreover, El-Mofty et al. and Hirshberg et al. suggested that TUGSE represents a cell-mediated immune response to unidentified antigens introduced via trauma1,15. Supporting this, immunohistochemical studies show an infiltrate predominantly composed of cytotoxic T lymphocytes, mast cells, and macrophages. These cells likely secrete cytokines (e.g., IL-1, IL-5, TNF) that recruit eosinophils1,15. Upon activation, recruited eosinophils release cytotoxic granule proteins—such as major basic protein and eosinophil peroxidase—which participate in microbial defense but can also induce severe tissue toxicity and injury19-21. As a result, the ulcer may fail to heal properly and persist as a chronic lesion. However, the precise mechanisms linking eosinophil activation and degranulation to deep muscle destruction in TUGSE remain unclear, warranting further investigation into cytokine profiles and degranulation patterns in tissue samples from a large cohort.

    Ⅴ. CONCLUSION

    This study comprises a relatively large data set of oral TUGSE cases within the current literature. Thus, our clinicopathological findings offer useful evidence to better understand the disease spectrum and assist clinicians in crucial differential diagnoses, such as distinguishing TUGSE from malignancies. Nevertheless, because its pathogenesis is not yet fully understood, future investigations focusing on the roles of eosinophils and stromal cells in impaired wound healing, regeneration, and immune responses are warranted to clarify the definitive pathogenesis of TUGSE.

    Figure

    KAOMP-50-3-53-Fig1.jpg

    Clinical photographs of TUGSE. (A) A well-demarcated oval ulcer is observed on the lateral border of the tongue, showing a depressed crateriform ulcer surface with slightly elevated whitish margins. (B) An irregularly shaped ulcer is present on the lateral border of the tongue. The ulcer surface is covered by a yellowish-white fibrinous pseudomembrane with surrounding erythema. (C) An ulcer is observed on the buccal mucosa with hyperkeratotic rolled border. (D) A relatively extensive ulcer is observed on the floor of the mouth, resembling OSCC.

    KAOMP-50-3-53-Fig2.jpg

    Histopathological features of TUGSE. (A) Surface ulceration is present over an elevated mucosal lesion, with underlying proliferation of inflammatory granulation tissue (H&E stain; x40). (B) Chronic inflammatory cells composed of eosinophils, lymphocytes, and histiocytes infiltrate between muscle bundles, accompanied by degeneration of muscle fibers (H&E stain, x200). (C) In the floor of mouth, prominent infiltration of lymphocytes and eosinophils is observed around and within the minor salivary glands, resulting in interlobular fibrosis (H&E stain, x400). (D) Marked eosinophilic infiltration is observed within the deep muscle layer (H&E stain, x400).

    Table

    Demographics and Clinical Characteristics of Patients with TUGSE (N=64)

    *Note. Because multiple clinical features could be recorded for a single patient, the total number of clinical features exceeded the total number of patients.

    Provisional clinical diagnoses recorded in 64 cases of TUGSE

    Multiple clinical diagnoses were permitted per patient. Percentages were calculated using the total number of clinical diagnoses as the denominator (n = 98), not the number of patients (n = 64).

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