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 Table of Contents  
Year : 2015  |  Volume : 7  |  Issue : 6  |  Page : 420-423  

Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited

1 Department of Oral Pathology, Madha Dental College and Hospital, Kundrathur, India
2 Department of Oral Pathology, Faculty of Dentistry, Asian Institute of Medicine Science and Technology (AIMST) University, Malaysia
3 Department of Pedodontics, Faculty of Dentistry, Asian Institute of Medicine Science and Technology (AIMST) University, Malaysia
4 Private Dental Practitioner, Sai Raghav Dental Clinic, West Mambalam, Chennai, Tamil Nadu, India
5 Private Dental Practitioner, Sree Sai Dental Care, Kolapakkam, Chennai, Tamil Nadu, India

Date of Submission28-Apr-2015
Date of Decision28-Apr-2015
Date of Acceptance22-May-2015
Date of Web Publication1-Sep-2015

Correspondence Address:
Dr. R Sarangarajan
Department of Oral Pathology, Madha Dental College and Hospital, Kundrathur
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-7406.163474

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Oral ulcers are a common symptom in clinical practice. Among various causative factors, different types of ulcers in oral cavity exist. Among this, traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) appears to be quite neglected by the clinicians due to the limited knowledge and awareness. On reviewing with a detailed approach to titles and abstracts of articles eliminating duplicates, 40 relevant articles were considered. Randomized studies, review articles, case reports and abstracts were included while conference papers and posters were excluded. Of importance, TUGSE cases been reported only to a minimal extent in the literature. Lack of its awareness tends to lead clinicians to a misconception of cancer. Thus, this particular lesion needs to be differentiated from other malignant lesions to provide a proper mode of treatment. The present article reviews various aspects of the TUGSE with emphasis on the clinical manifestation, pathogenesis, histological, and immunohistochemical study. This study provides the clinician contemporaries, a humble expansion to their knowledge of the disease, based on the searched literature, enabling a more comprehensive management of this rare occurrence.

Keywords: CD30+, lymphoproliferative disorders, oral ulcer, Riga-Fede disease, traumatic ulcerative granuloma with stromal eosinophilia, ulcerative granuloma

How to cite this article:
Sarangarajan R, Vaishnavi Vedam V K, Sivadas G, Sarangarajan A, Meera S. Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited. J Pharm Bioall Sci 2015;7, Suppl S2:420-3

How to cite this URL:
Sarangarajan R, Vaishnavi Vedam V K, Sivadas G, Sarangarajan A, Meera S. Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited. J Pharm Bioall Sci [serial online] 2015 [cited 2022 Aug 19];7, Suppl S2:420-3. Available from:

One frequently encounters oral ulcers in a clinical scenario. Owing to several predisposing factors, diverse types of ulcers occur in the oral cavity. [1],[2] Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a reactive benign and self-limiting lesion of the oral mucosa exhibiting puzzling pathogenesis. [3],[4],[5] This lesion was first suggested by Popoff (1956) in adults. [6] Shortly, this lesion was named as Riga-Fede disease in infants and children by Riga (1881) clinically and later, by Fede (1890) histologically. [3]

Traumatic ulcerative granuloma with stromal eosinophilia used to be known widely among the clinicians as eosinophilic granuloma of the soft tissue, [7] traumatic granuloma of the tongue, ulcerative eosinophilic granuloma, [8],[9] eosinophilic ulcer, TUGSE, eosinophilic ulcer of the oral mucosa, [10],[11],[12] ulcerated granuloma with eosinophilicum of the tongue, [7] ulcerated granuloma eosinophilicum diutinum of tongue [5] (a spectrum of granuloma faciale), Riga-Fede disease (infants). [13],[14],[15],[16] In half the number of cases, it is seen with ulceration next to trauma, resembling carcinoma and lymphoma, a basic tool to re-examine has been felt.

   Sources of Data and Research Top

Data sources

On reviewing with a detailed approach to titles and abstracts of articles eliminating duplicates, 40 relevant articles were considered. These articles were found in PubMed, Science Direct, Scopus and Google Scholar from first reported TUGSE case till date were evaluated. Randomized studies, review articles, case reports and abstracts were included while conference papers and posters were excluded.

   Review of Literature Top


The pathogenesis of TUGSE still remains controversial. [17] Among all etiological factors, mucosal trauma [4] (external or internal physical, chemical; thermal or electrical) appears to be the major instigating factor of this lesion. Previous literature states that not all TUGSE lesions are induced by trauma. Clinical and histological presentation is, as an ulcerated lesion with a massive immune response. The inflammatory infiltrate in TUGSE exhibits sheets of atypical mononuclear cells (predominantly T-cell lymphocyte population), eosinophils, macrophages/histiocytes, and few plasma cells. [4] In earlier studies, immunohistochemistry revealed these atypical mononuclear cells to be belonging to the macrophage and myofibroblast lineage. More recent studies point toward the T lymphocytic function of these cells immunohistochemically, with positivity against all T-cell specific antigens. [18],[19],[20],[21] Of late, TUGSE is agreed upon as a reactive lesion dominated by predominant clonal T-cell population. However this lesion requires more attention, owing to its tendency to mimic malignancy. [22],[23] The exact role of these inflammatory cells to produce such an exaggerated inflammatory response mimicking a malignancy is still unknown. Correlating various studies, this appears similar to a hypersensitivity type reaction (predominant T-cell infiltration exhibiting a delayed type of cell-mediated immunity).

Traumatic ulcerative granuloma with stromal eosinophilia is evoked in most cases, by a traumatic antigen, wherein existing macrophages and histiocytes act as antigen presenting cells. Various antigens include toxins, viral, microorganisms, endogeneous degradation products or foreign proteins. [3],[4] On release of cytokines, the predominant cells of eosinophils and lymphocytes are recruited to the submucosal tissue. [4],[7] However, previous studies suggest that the exact presence of eosinophils remains controversial, as most of the traumatic ulcers are devoid of eosinophilic infiltration. On the contrary, certain other authors have concluded that there is increased prevalence of histiocytes and eosinophils than lymphocytes suggesting the aggressiveness of TUGSE. [5] This process of cyclic reaction continues with increase in proliferating T-cells by release of cytokines/toxic products by the degranulating eosinophils. [3],[4],[7] The accumulation of all these inflammatory cells along with the varied spectrum of cytokines results in tissue damage.

In addition, studies also depict that a response resulting from an exaggerated mast cell-eosinophil reaction may arise similar to that noticed in the pathogenesis of type 1 hypersensitivity reaction. Degranulating mast cells releases several mediators like eosinophil chemotactic factor, aryl sulfates arid histamines, and major basic proteins, eventually causing tissue destruction. [4]

What is interesting to the researchers, is the uniqueness of TUGSE in being a slow self-healing ulcer with atypical mononuclear cells and massive eosinophilia. Eosinophils appear to be a reactive tissue response to an unknown antigen entering via mucosal trauma. The delayed healing process may be attributed to the decreased synthesis of transforming growth factor, released by the eosinophils in the inflammatory infiltrate of TUGSE as compared to the eosinophils in other traumatic ulcers. [8] Furthermore, eosinophils produces a spectrum of cytokines, like tumor necrosis factor, which induces further tissue damage.

   Discussion Top

Traumatic ulcerative granuloma with stromal eosinophilia presents as a chronic slow progressive lesion (commonly fourth to sixth decade). [24] This lesion occurs following missing or malposed teeth, partial denture. Predominantly, TUGSE appears to be more common in males than females (1.6:1) which may exist from 1-week to several weeks. It appears as a red lesion in oral mucosa with rolled, elevated and indurated margins with central areas of fibrinopurulent membrane mimicking squamous cell carcinoma. [25],[26],[27] Even though, tongue [28],[29],[30] is the most common site, other regions like buccal mucosa, vestibular mucosa, gingiva, lip, [31] mucobuccal fold, retromolar area, and palate [32] also may exhibit TUGSE. Histopathologically, TUGSE exhibits ulceration with diffuse polymorphic inflammatory infiltrate (exhibiting epitheliotropism) extending from the superficial epithelium into the deep connective tissue. This dense chronic inflammatory infiltrate includes small round T-lymphocytes, large atypical mononuclear cells, granular macrophages, B-lymphocytes massive eosinophils, plasma cells, and histiocytes in the superficial layer and deep muscle layers. [33],[34],[35] Proliferating endothelial cells, blood vessels and focal areas of necrosis are seen scattered throughout the lesion. However, presence of massive eosinophilia is not mandatory in this lesion.

A TUGSE lesion often seen in infants (Riga-Fede disease) occurs within 1-week to 1-year. [13] Mucosal lesions are often caused by repetitive traumatic damage due to backward and forward motions of the tongue over the erupting lower incisors, natal or neonatal teeth. The anteroventral, dorsal, and sublingual surfaces of the tongue are usually affected. [14],[15]

Rarely, this lesion has also been termed as atypical histiocytic granuloma as studies have shown diffuse scattered atypical large mononuclear cells (large cells with irregular nuclear contours, fine chromatin, small nucleoli, and abundant cytoplasm) in a background of diffuse inflammatory cell infiltrate. [36],[37] This picture exhibits a reminiscent of squamous cell carcinoma. Immunohistochemically, most of these mononuclear cells show CD30, CD3 and T-cell intracytoplasmic antigen 1 (T-cell lineage markers) positivity for T-cells, while few are positive for CD68 macrophages/histiocytic origin and 10-50% cells show Ki-67 with high degree of production. [7],[8],[23] Some endothelial cells demonstrate von Willebrand factor positivity. Literature also previously stated that mononuclear cells show factor XIII positivity suggestive of dendritic cells and vimentin positive suggestive of myofibroblasts. [17]

Regarding the existence of predominantly CD30+, what remains unresolved is whether this lesion TUGSE is just a benign oral counterpart of CD30+ lymphoproliferative disease (LPD) or a reactive benign primary lesion or just a histological simulator of CD30+ LPD. This requires further studies to be proved. Immunohistochemical studies are slightly in favor of TUGSE being a benign oral counterpart of primary cutaneous CD30+ LPDs. Confusion however persists, as CD30+ is expressed on B and T lymphocytes, not only in malignancies, but also in many other lymphoproliferative disorders. [38],[39] The polymerase chain reaction of T-cell receptor gene gamma with monoclonality is suggested for a more definitive diagnosis. [40]

Differential diagnosis includes primary sypilitic chancre, CD30+ LPD, malignant T lymphoma, angiolymphoid hyperplasia with eosinophilia, langerhans cell histiocytosis, pseudolymphoma, metastatic tumors, Kimura's disease, salivary gland tumors, lymphomatoid papulosis. [3],[7],[9],[17] The mere presence of eosinophils should differentiate from insects/parasites, granuloma faciale, allergic reactions, angiolymphoid hyperplasia with eosinophilic lymphoid granuloma, eosinophilic fascitis, eosinophilic granuloma, and histiocytosis X. [4],[9]

Traumatic ulcerative granuloma with stromal eosinophilia lesions are treated with antibiotics like penicillin, removal of traumatic agents, followed by excision if still persistent. Appropriate management of the offending tooth is suggested in case of Riga-Fede disease. [4] Other modes of treatment include 0.1% triamcinolone acetonide mouthwash, oral antibiotics, steroids (topical/systemic), electrocoagulation, irradiation, and liquid nitrogen. [9] Due to the aggressiveness of the lesion, though a few cases show a retarded healing phase, majority of them show a rapid healing following surgery. Prognosis of TUGSE is normally favorable, yet a long term follow up to at least 2 years is mandatory.

   Conclusion Top

The presence of TUGSE is rare in the oral cavity. This condition likely represents a group of related disorders with overlapping clinical and histopathologic features. We, as clinicians, must have adequate knowledge regarding TUGSE pathogenesis, and perform biopsy for a histological analysis along with a background immunohistochemistry techniques, to rule off other neoplastic lesions at a very early stage.

   References Top

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