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 Table of Contents  
Year : 2021  |  Volume : 11  |  Issue : 1  |  Page : 64-67

Traumatic ulcerative granuloma with stromal eosinophilia: Uncommon or misdiagnosed?

1 Ministry of Health Malaysia, Penang, Malaysia
2 Department of Oral Medicine and Radiology, Penang International Dental College, Penang, Malaysia
3 Department of Oral Pathology, Penang International Dental College, Penang, Malaysia

Date of Submission04-May-2020
Date of Decision05-Oct-2020
Date of Acceptance25-Mar-2021
Date of Web Publication9-Aug-2021

Correspondence Address:
Dr. Shalini Subramanian
No. 45, Jalan USJ 4/1A, 47600 Subang Jaya, Selangor Darul Ehsan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijohs.ijohs_12_20

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Oral ulcers with different presentations and etiologies are common findings in a dental clinical practice. Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare, solitary, self-limiting lesion that may persist from weeks to months. Its indurated margins combined with its rapid development and delayed healing are often confused with oral malignancy and are frequently neglected or more concerningly misdiagnosed by clinicians due to limited knowledge and awareness. The cause, although still rather debated, is believed to be trauma. We present a case of TUGSE in a 65-year-old Chinese male who presented with a history of a painful, nonhealing ulcer of 2 months in duration on the labial mucosa. The ulcer clinically mimicked oral squamous cell carcinoma clinically. There was no evidence of lymph node involvement. With the patient's history and excisional biopsy results, the lesion was diagnosed as TUGSE.

Keywords: Eosinophilic ulcer, immunohistochemistry, Riga–Fede disease, traumatic ulcer, traumatic ulcerative granuloma with stromal eosinophilia

How to cite this article:
Subramanian S, Krishnan A, Telang LA, Telang A. Traumatic ulcerative granuloma with stromal eosinophilia: Uncommon or misdiagnosed?. Int J Oral Health Sci 2021;11:64-7

How to cite this URL:
Subramanian S, Krishnan A, Telang LA, Telang A. Traumatic ulcerative granuloma with stromal eosinophilia: Uncommon or misdiagnosed?. Int J Oral Health Sci [serial online] 2021 [cited 2021 Nov 28];11:64-7. Available from: https://www.ijohsjournal.org/text.asp?2021/11/1/64/323522

  Introduction Top

Oral ulcers are one of the most common and peculiar tell-tale signs of an orodental or systemic disease. They can be termed as a silent feature of any existing pathology. One of these is traumatic ulcerative granuloma with stromal eosinophilia (TUGSE), a rather enigmatic lesion.[1],[2]

TUGSE is a benign, rapidly growing ulcerative lesion of the oral cavity with a typically self-limiting course.[3] It can last over a span of several weeks to months. Many names have been used to describe TUGSE such as eosinophilic granuloma, eosinophilic ulcer, Riga–Fede disease (in infants and children), and atypical histiocytic granuloma.[4] TUGSE has been reported to be found to affect various sites in the oral cavity, the most common being the tongue.

Popoff was the first to report this condition among adults in 1956. A similar presentation in infants is called the Riga–Fede disease.[5] The etiology of this lesion is not known, but mucosal trauma that includes physical, chemical, thermal, and electrical injuries is considered the most plausible factor. The exact pathogenesis of TUGSE, however, is highly controversial.[1] This lesion presents most commonly as a solitary ulcer with rolled or indurated margins and may persist from weeks to months if the causative factor is not removed.

Histologically, TUGSE usually involves the superficial mucosa but may also extend to the deeper muscle layers and is characterized by a diffuse polymorphic inflammatory infiltrate rich in eosinophils. This in some cases may be accompanied by large atypical mononuclear cells, whose origins are debatable.[6] Even microscopically, TUGSE can be confused with malignancy due to its relative frequency of atypical cells in the stroma.[7]

  Case Report Top

A 65-year-old Chinese male patient reported to the outpatient department with the chief complaint of a painful, nonhealing ulcer of 2 months in duration on the upper right labial mucosa. The ulcer gradually increased in size over the past 2 months to the size it was at the time of visit.

The patient is known to have arthritis, psychotic problems, hypertension, and diabetes mellitus and is a carrier of hepatitis B. At the time of examination, he was on calcium supplements, antihypertensives, antipsychotics (Largactil), and antivirals (lamivudine). Habit history was not relevant.

His general physical examination revealed no significant findings. Extraoral examination was unremarkable, and no lymphadenopathy was noted. On intraoral examination, a solitary ulcer of about 0.8 cm in diameter with raised borders was seen on the labial mucosa in relation to a sharp, attrited upper right canine, which highlighted trauma as a possible causative factor. The floor of the ulcer appeared to be necrotic and yellowish in color, and no fresh bleeding was seen. The entire lesion appeared to be punched out with surrounding bluish mucosa [Figure 1]. On palpation, the floor of the lesion as well as the surrounding mucosa was tender. The base was found to be uniformly indurated up to 2 mm beyond the margins of the ulcer. The size of the lesion on palpation was confirmed to be about 1 cm in diameter.
Figure 1: Punched out appearance of a solitary ulcer with raised borders, necrotic base, and bluish margins

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With the above clinical findings, the lesion was provisionally diagnosed as a traumatic ulcer. Extraction of the traumatic tooth was done with the physician's consent. An excisional biopsy of 1 cm × 1 cm was done and sent for histopathological examination. Neither intraoperative nor postoperative complications were encountered.

On microscopic examination, the submitted section showed a bit of soft tissue composed of an overlying nonkeratinized epithelium, a large ulcerated area, and underlying connective tissue. The ulcer was lined by a fibrinopurulent membrane that was infiltrated by neutrophils. Connective tissue under the ulcer showed fibrocellular stroma densely infiltrated by numerous eosinophils, lymphocytes, plasma cells, and histiocytes. Other findings included endothelium-lined blood capillaries of varying sizes, inflammatory changes in minor glands, muscle fibers, and areas of extravasated red blood cells (RBCs). No evidence of significant atypia was observed in the regional cell population [Figure 2].
Figure 2: Microscopy showing infiltration of fibrocellular stroma by eosinophils, lymphocytes, plasma cells, and histiocytes (H and E, ×10)

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Based on the histopathological findings, the case was diagnosed as TUGSE. The lesion healed following excisional biopsy in about 2 weeks, and there was no recurrence in the follow-up period of one year and in the patient's subsequent biannual dental visits. The lesion was not subjected to immunohistochemical analysis as there was no recurrence. Prognosis was good.

  Discussion Top

TUGSE is a unique, benign lesion of the oral cavity that is often clinically and microscopically confused with malignancy. It has been reported to occur most frequently in patients between 41 and 60 years of age[3] although it has also been reported to show a bimodal age distribution with the first peak at an early age (childhood) and the second peak at a later age in the fiftieth to sixtieth decade of life.[4] Gender predilection for this lesion varies greatly, with some studies showing a greater inclination toward males. For example, in a study of 34 cases of oral TUGSE by Shen et al., the male-to-female ratio was reported at 1.83:1.[3] Observations by Fonseca et al. in a study of 19 cases showed a 1.38:1 male-to-female ratio.[8] However, a study by El-Mofty et al. showed a slightly greater predominance in females with a male-to-female ratio of 1:1.5.[9] Some studies have also proven the male-to-female ratio as 1:1 which was observed in the study conducted by Elzay that included 41 patients with TUGSE, proving no gender predilection.[4]

Clinically, this lesion presents as a solitary ulcer with raised borders, and an indurated base, mimicking lesions such as squamous cell carcinoma and fungal or bacterial ulcers and is mostly found to be painful. Interestingly, submucosal masses and multifocal lesions have also been mentioned in the literature.[10] Lymphadenopathy has been reported to be rare.[9],[11],[12],[13] The ulcer in our case had similar clinical characteristics. TUGSE is most commonly found on the tongue in about 60%–80% of the cases. Other commonly affected sites include the buccal mucosa, vestibular mucosa, floor of the mouth, retromolar area, gingiva, alveolar mucosa, lip, labial frenum, and palate.[4],[12],[14]

Many hypotheses have been proposed in the development of TUGSE which includes trauma and viral and toxic agents. It was first suggested by Elzay that the pathogenesis of TUGSE highly likely was a result of a form of trauma that allowed the movement of microorganisms, toxins, or foreign protein into the connective tissue.[4] The exact cause for TUGSE is still somewhat controversial, but the most common cause reported is direct trauma, mostly from sharp cusp tips or marginal edges, ill-fitting dentures, overhanging restorations, impacted teeth, and history of trauma (accidental biting, etc.).[4],[9],[12] The duration of the lesion ranges from weeks to months (years in a handful of cases) as long as the cause remains unresolved.[15]

TUGSE is a distinct clinical entity which mimics oral squamous cell carcinoma but histologically is a benign 1–6 granulomatous lesion associated with stromal eosinophilia.[16] Histopathologically, apart from ulceration, granulation tissue that consisted of neutrophils, plasma cells, histiocytes, and varying number of eosinophils has been noted like in our case.[3],[4] The infiltration of eosinophils is found to be most dense either in the superficial muscle layers or in the admixture of lymphocytes and plasma cells and scattered around in the deeper layers.[3] Our slides showed eosinophils, mainly concentrated in the superficial layers. As the main pathogenesis of TUGSE is believed to be trauma, it can be interpreted that the trauma leads to ulceration, therefore allowing the ingress of foreign bodies as suggested by Elzay causing an exaggerated inflammatory reaction that releases eosinophils.[4] The importance of cell-mediated immunity in the pathogenesis was highlighted by El-Mofty et al.[9]

Among the differential diagnoses suggested through observations are squamous cell carcinoma, atypical histiocytic granuloma, Langerhans cell histiocytosis, lymphocyte-rich CD30+ lymphoproliferative disorders, and angiolymphomatoid hyperplasia with eosinophilia. These differential diagnoses were made based on the strictures of the lesion within the oral cavity, macroscopical presentations, age, histopathology, and immunochemistry.[17]

A variety of treatment modalities have been suggested for TUGSE. Many have reported that the self-limiting nature of this lesion allows it to heal within a span of 2 weeks to 3 months once the causative factor has been removed.[3] The reason for this delayed healing is observed by Elovic et al. to be the lack of synthesis of transforming growth factors by the infiltrating eosinophils. They also state that a surgical intervention seems to “reactivate” a normal healing process leading to uneventful healing following complete excision of the lesion.[14] Many have reported successful healing with no recurrence following surgical excisions.[3],[9],[11],[15] Complete healing was also seen in our case just 2 weeks after the excisional biopsy with no recurrence through follow-up. Recurrence is very rare although it has not been unreported.[3],[9] Ficarra et al. reported a case with multiple recurrent episodes of ulcers occurring mainly on the buccal mucosa and gingiva that lasted up to a month before undergoing slow healing subsequent to repeated incisional biopsies.[18]

Other treatment modalities such as prescription of oral and topical corticosteroids and topical mouthwashes, as well as curettage and cryotherapy, have also been reported to be used in managing TUGSE.[11],[12] Our patient was not prescribed topical or systemic steroids. In the case that the lesion had recurred or healed poorly, a re-evaluation and further biopsy would have been mandatory.

TUGSE may heal spontaneously following the removal of the causative factor, especially factors such ill-fitting dentures and sharp or malpositioned teeth. An incisional biopsy should be performed for a definitive diagnosis. Prognosis is relatively good, and effective follow-up measures are required to ensure complete and uneventful healing.

  Conclusion Top

The diagnosis of TUGSE was obtained based on both clinical and histopathological examination and evaluation. The pathogenesis of this condition remains indeterminate and its histogenesis questionable. In general, this condition is self-healing with a benign course.

As many cases have been reported to date, it is possible that TUGSE is more common than believed, and it in fact goes undiagnosed, misdiagnosed, or under-reported. As oral diagnosticians, TUGSE should be part of our differential diagnoses when facing similar solitary long-standing ulcers with everted and indurated margins, especially with significant history like trauma as it mimics squamous cell carcinoma almost entirely and may be missed out or mistreated if not diligently captured.

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.


We would like to thank Dr. Vinay Marla, oral pathologist.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Alobeid B, Pan LX, Milligan L, Budel L, Frizzera G. Eosinophil-rich CD30+lymphoproliferative disorder of the oral mucosa. A form of “traumatic eosinophilic granuloma”. Am J Clin Pathol 2004;121:43-50.  Back to cited text no. 1
Hirshberg A, Amariglio N, Akrish S, Yahalom R, Rosenbaum H, Okon E, et al. Traumatic ulcerative granuloma with stromal eosinophilia: A reactive lesion of the oral mucosa. Am J Clin Pathol 2006;126:522-9.  Back to cited text no. 2
Shen WR, Chang JY, Wu YC, Cheng SJ, Chen HM, Wang YP. Oral traumatic ulcerative granuloma with stromal eosinophilia: A clinicopathological study of 34 cases. J Formos Med Assoc 2015;114:881-5.  Back to cited text no. 3
Elzay RP. Traumatic ulcerative granuloma with stromal eosinophilia (Riga-Fedes Disease and Traumatic Eosinophilic Granuloma). Oral Surg Oral Med O 1983;55:497-506.  Back to cited text no. 4
Abdullah BH. Traumatic ulcertive granuloma with stromal eosinophilia (a clinicopathological study of 18 cases). J Baghdad Coll Dent 2011;23:59-64.  Back to cited text no. 5
Gagari E, Stathopoulos P, Katsambas A, Avgerinou G. Traumatic ulcerative granuloma with stromal eosinophilia: A lesion with alarming histopathologic presentation and benign clinical course. Am J Dermatopathol 2011;33:192-4.  Back to cited text no. 6
Brasileiro BF, Alves DB, Andrade BA, Vargas PA, León JE, Almeida OP. Traumatic ulcerative granuloma with stromal eosinophilia of the palate showing an angiocentric/angiodestructive growth pattern. Contemp Clin Dent 2012;3:S109-11.  Back to cited text no. 7
Fonseca FP, de Andrade BA, Coletta RD, Vargas PA, Lopes MA, de Almeida OP, et al. Clinicopathological and immunohistochemical analysis of 19 cases of oral eosinophilic ulcers. Or Surg Med Pa 2013;115:532-40.  Back to cited text no. 8
El-Mofty SK, Swanson PE, Wick MR, Miller AS. Eosinophilic ulcer of the oral mucosa. Report of 38 new cases with immunohistochemical observations. Oral Surg Oral Med Oral Pathol 1993;75:716-22.  Back to cited text no. 9
Vélez A, Alamillos FJ, Dean A, Rodas J, Acosta A. Eosinophilic ulcer of the oral mucosa: Report of a recurrent case on the tongue. Clin Exp Dermatol 1997;22:154-6.  Back to cited text no. 10
Boffano P, Gallesio C, Campisi P, Roccia F. Traumatic ulcerative granuloma with stromal eosinophilia of the retromolar region. J Craniofac Surg 2009;20:2150-2.  Back to cited text no. 11
Gao S, Wang Y, Liu N, Li S, Du J. Eosinophilic ulcer of the oral mucosa: A clinicopathological analysis. Chin J Dent Res 2000;3:47-50.  Back to cited text no. 12
Mortazavi H, Safi Y, Baharvand M, Rahmani S. Diagnostic features of common oral ulcerative lesions: An updated decision tree. Int J Dent 2016;2016:7278925.  Back to cited text no. 13
Elovic AE, Gallagher GT, Kabani S, Galli SJ, Weller PF, Wong DT. Lack of TGF-alpha and TGF-beta 1 synthesis by human eosinophils in chronic Oral ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:672-81.  Back to cited text no. 14
Salisbury CL, Budnick SD, Li S. T-cell receptor gene rearrangement and CD30 immunoreactivity in traumatic ulcerative granuloma with stromal eosinophilia of the oral cavity. Am J Clin Pathol 2009;132:722-7.  Back to cited text no. 15
Sivapathasundharam B, Lavanya S. Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE). J Oral Maxillofac Pathol 2005;9:30.  Back to cited text no. 16
  [Full text]  
Marszałek A, Neska-Długosz I. Traumatic ulcerative granuloma with stromal eosinophilia. A case report and short literature review. Pol J Pathol 2011;62:172-5.  Back to cited text no. 17
Ficarra G, Prignano F, Romagnoli P. Traumatic eosinophilic granuloma of the oral mucosa: A CD30+(Ki-1) lymphoproliferative disorder? Oral Oncol 1997;33:375-9.  Back to cited text no. 18


  [Figure 1], [Figure 2]


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