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Year : 2020  |  Volume : 31  |  Issue : 4  |  Page : 636-639
Traumatic ulcerative granuloma with stromal eosinophilia

Department of Oral and Maxillofacial Pathology and Oral Microbiology, I.T.S Centre for Dental Studies and Research, Muradnagar, Ghaziabad, Uttar Pradesh, India

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Date of Submission13-Apr-2018
Date of Decision13-Feb-2020
Date of Acceptance14-May-2020
Date of Web Publication16-Oct-2020


Oral ulcers constitute one of the most common chief complaints of patients attending any dental practice. The cause of oral mucosal ulceration is generally attributed to acute or chronic trauma from local factors. However, oral lesions may be the initial manifestation of many systemic conditions. Moreover, a group of oral ulcerative lesions have been reported to exhibit vast numbers of eosinophils and known as Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE). We present two cases of oral ulcers which on microscopic examination exhibited numerous eosinophils from ulcerated epithelium to deep into the submucosa and an exuberant lymphoid proliferation. CD15 immunohistochemical marker was used in these cases to ease the identification of the eosinophils. We also highlight the differential diagnosis of TUGSE that may manifest as oral lesions, as an important diagnostic guide for clinicians in contemporary practice.

Keywords: CD15, eosinophils, traumatic ulcerative granuloma with stromal eosinophilia (TUGSE), ulcer

How to cite this article:
Sethi A, Banga A, Raja R, Raina R. Traumatic ulcerative granuloma with stromal eosinophilia. Indian J Dent Res 2020;31:636-9

How to cite this URL:
Sethi A, Banga A, Raja R, Raina R. Traumatic ulcerative granuloma with stromal eosinophilia. Indian J Dent Res [serial online] 2020 [cited 2023 Oct 3];31:636-9. Available from:

   Introduction Top

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a chronic benign lesion of the oral mucosa. It has been known in the literature by several terms, including eosinophilic ulcer of the oral mucosa,[1]  Riga-Fede disease More Details in infants, reparative lesion of the tongue, oral traumatic granuloma, ulcerative eosinophilic granuloma and atypical histiocytic granuloma.[2],[3] Clinically, it usually manifests as an ulcer with elevated and indurated margins that may mimic squamous cell carcinoma as well as other malignant lesions. A slight female predominance has been noted, with a peak of incidence between the sixth and seventh decade and the tongue is the most commonly affected site.[4] While the ulcer often develops an adjacent white hyperkeratotic border, the underlying proliferative granulation tissue may produce an exophytic mass.[5] Microscopically, TUSGE is characterized by a dense polymorphic inflammatory infiltrate extending into the underlying muscle. The dominant cell types are small lymphocytes, macrophages, and numerous eosinophils.[1]

   Case Reports Top

Case 1

A 17-year-old male patient reported with the chief complaint of the presence of growth in the retromolar area on the right side. The patient first noticed the lesion 2 weeks before reporting to the department and recounted a gradual increase in the size of the lesion. On extraoral examination, the right submandibular lymph nodes were firm and tender on palpation. The intraoral examination revealed a well-circumscribed ovoid lesion in the right retromolar area measuring approximately 1 × 1 cm in size, yellowish-white in colour, soft in consistency and tender on palpation [Figure 1]a. The surface texture was irregular and the lesion had a white keratotic margin. Multiple, white, irregular and variably sized white patches were also observed at other oral mucosal sites such as on the right buccal mucosa, retromolar trigone, and the hard palate.
Figure 1:(a) Lesion present in the right retromolar area. (b) Stratified squamous epithelium with focal areas of ulceration (4×, Haematoxylin & Eosin stain). (c) Connective tissue exhibits the dense inflammatory cell infiltrate comprising predominantly of eosinophils (40×, Haematoxylin & Eosin stain). (d) Eosinophils infiltrating muscle bundles and surrounding blood vessels (40×, Haematoxylin & Eosin stain). (e) The cluster of eosinophils seen as intense, cytoplasmic staining using CD15 immunohistochemical marker (40×)

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The histopathological examination of the excisional biopsy showed a non-keratinized stratified squamous epithelium ulcerated at focal areas [Figure 1]b. Connective tissue was swamped with a dense inflammatory cell infiltrate consisting chiefly of large numbers of eosinophils and few lymphocytes and plasma cells [Figure 1]c. Eosinophils were evenly distributed throughout the connective tissue from the juxtaepithelial region into the submucosa, and in few areas, were arranged in compact clusters. Moderate numbers of round to ovoid cells containing scant cytoplasm and an enlarged nucleus with prominent nucleoli were seen in close proximity to the eosinophils. In the deeper areas, the eosinophils were seen to infiltrate muscle bundles [Figure 1]d. The immunohistochemical staining with CD15 antibody identified the glycolipid and glycoprotein components of the granulocyte cell surface and produced a dark brown reaction colour that assisted in examining the conspicuous eosinophilia [Figure 1]e.

Case 2

A 70-year-old female patient presented with a chief complaint of an ulcerative growth on the left side of the tongue for 20 days. She also complained of irritation due to maxillary left posterior teeth that impinged upon the growth and caused difficulty in mastication. On intraoral examination, a pale pink growth was seen in the middle third of the left lateral border of the tongue measuring approximately 1 cm both anteroposteriorly and superoinferiorly in size [Figure 2]a. On palpation, the growth was firm in consistency, non-indurated, and non-tender. An excisional biopsy was performed and a provisional diagnosis of traumatic ulcer and differential diagnosis of squamous cell carcinoma was deliberated.
Figure 2:(a) Growth on the left lateral border of the tongue. (b) Ulcerated parakeratinized stratified squamous epithelium (10×, Haematoxylin & Eosin stain). (c) Dense eosinophilic infiltrate within the connective tissue (40×, Haematoxylin& Eosin stain). (d) Eosinophils showing CD15 positivity (40×)

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The histopathology showed a parakeratinized stratified squamous surface epithelium with areas of ulceration [Figure 2]b. The underlying fibrocellular connective tissue was composed of a dense inflammatory infiltrate of eosinophils and moderate numbers of lymphocytes, plasma cells and mast cells [Figure 2]c. The eosinophils were seen as intense brown CD15 positive cells throughout the connective tissue [Figure 2]d.

   Discussion Top

Eosinophils can regulate local immune and inflammatory responses, and their accumulation in the blood and tissue is associated with several inflammatory and infectious diseases. The etiology of TUGSE remains obscure, although most authors suggest that the lesions are of traumatic origin, registered in approximately 39% of the cases.[1] The increased incidence of this lesion on the tongue, which is easily exposed to trauma, and the definitive history of trauma in most cases support the hypothesis. Moreover, trauma may introduce microorganisms, toxins, endogenous degradation products, or viral agents such as HTLV-1 and Epstein-Barr virus into the submucosa, which, in turn, may result in tissue as well as peripheral blood eosinophilia and the dense lymphoid infiltrate characteristic of TUGSE.[6],[7]

Traumatic ulcerative granuloma with stromal eosinophilia has a bimodal age distribution, generally appearing in the first 2 years of life and later in the fifth through seventh decades. The male-to-female predominance is equal.[8],[9] In most cases, TUGSE presents as a tender solitary nodule in the form of a central ulcer with indurated and rolled margins, and a yellow fibrinous base.[9],[10] In others, it may manifest hyperkeratotic white areas adjacent to the ulceration along with proliferative granulation tissue developing an exophytic mass observed after the placement of dental implants.[11] More than half the lesions develop on the dorsal or lateral surfaces of the tongue, but they may present anywhere in the oral mucosa.[8],[11] The lesion develops rapidly, typically developing in days to weeks, and although it regresses spontaneously, the lesion may take as long as up to 1 year to resolve completely.[9] It should also be noted that incision biopsy of chronic TUGSE lesions frequently leads to rapid resolution, which may be attributed to the reactivation of the “normal” healing process associated with the expression of TGF-α and β by the infiltrating eosinophils.[12]

The typical histopathological picture of TUGSE shows an ulcerated epithelium with a polymorphic inflammatory cell infiltrate that has a large predominance of eosinophils extending from the superficial epithelium to the deep layers of the muscle tissue.[8] In the aforementioned cases, eosinophils were evenly distributed throughout the connective tissue; and were localized into dense aggregates at focal areas. Likewise, the dominating cells in TUGSE may seem as a jigsaw-like destructive infiltration of the submucosa consisting of granulomatous clusters of histiocytes, atypical lymphocytes and eosinophils.[13],[14] The exact role of eosinophils in TUGSE has not been elucidated. They may be involved in the mucosal degeneration via the release of inflammatory cytokines such as tumour necrosis factor. Similarly, the lack of synthesis of transforming growth factors by eosinophils can explain the delayed healing characteristic of TUGSE.[9] Although eosinophils can be detected easily in H & E stained tissue sections owing to their tinctorial properties, immunohistochemistry with monoclonal antibodies such as CD15 can be used as a powerful tool for the identification of intact as well as degranulating eosinophils. The CD15 antigen is raised against human granulocytes. It has been shown to recognize the glycolipid and glycoprotein components of the granulocyte cell surface.[15]

The origin of the large cells buttressing the eosinophils in the lamina propria has also been a matter of debate. Immunopositivity for the macrophage marker CD68, the dendritic cellmarker, factor XIIIa, myofibroblast marker, vimentin, and CD30, which is expressed in certain hematopoietic malignancies have been reported.[16],[17] However more recently, such cases with CD30 + atypical cells have been reported to show no recurrence, spread or malignant transformation. Moreover, the atypical cells are found to be polyclonal for T-cell receptor gene re-arrangement; negating the neoplastic nature of TUGSE.[18] CD30 positive cells may also be found in many non-neoplastic cutaneous disorders, such as atopic dermatitis, drug reactions, molluscumcontagiosum, and scabies.[13],[19]

The clinical and histological picture of TUGSE must be differentiated from other eosinophil-rich lesions of the oral cavity, infectious diseases, and lesions composed of large histiocytic cells, as well as contact allergy and drug reactions [Table 1].[19]
Table 1: Differential diagnosis of traumatic ulcerative granuloma with stromal eosinophilia

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Out of all cases of TUGSE those have been reported to date, most cases have followed an uneventful benign clinical course and have resolved spontaneously after an incisional biopsy. Although the clinical picture of a tender ulcerated lesion with raised firm margins and the intraoral location of TUGSE on the lateral tongue may be alarming, the self-limiting nature of the lesion demonstrating spontaneous regression and low recurrence should be reassuring.[18] Interestingly, a commonly occurring oral lesion such as TUGSE has relatively minimal exposure in the dermatologic literature.[8],[20] Therefore, an accurate and prompt diagnosis can provide reassurance to the patient and obviate potential overtreatment. Persistent lesions can be treated after the removal of traumatic agents with oral antibiotics, steroids, electrocoagulation, irradiation, and liquid nitrogen.[10] Prognosis of TUGSE is normally favourable, yet a long-term follow-up to at least 2 years has been mandated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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Eversole LR, Leider AS, Jacobsen PL, Kidd PM. Atypical histiocytic granuloma. Light microscopic, ultrastructural and histochemical findings in an unusual pseudomalignant reactive lesion of the oral cavity. Cancer 1985;55:1722-9.  Back to cited text no. 3
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Correspondence Address:
Dr. Aashka Sethi
Department of Oral and Maxillofacial Pathology and Oral Microbiology, I.T.S Centre for Dental Studies and Research, Muradnagar, Ghaziabad, Uttar Pradesh - 201206
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijdr.IJDR_330_18

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  [Table 1]


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