BRIEF REPORT
Eosinophilic Ulcer of the Oral Mucosa: Report of a Case With Multiple Synchronous Lesions Katerina Damevska, MD, MSc, Gorgi Gocev, MD, and Suzana Nikolovska, MD, PhD
Abstract: Eosinophilic ulcer of the oral mucosa is considered to be a benign, reactive, and self-limiting lesion, with unclear pathogenesis, manifesting as a rapidly developing solitary ulcer. We report the case of a 52-year-old man who presented with 4 synchronous ulcerations of the tongue. Histopathological examination showed polymorphic inflammatory infiltrate, rich in eosinophils, involving the superficial mucosa and the deeper muscle layer. Immunohistochemical analysis revealed single CD30+ cells scattered within an inflammatory infiltrate. All the lesions began to regress spontaneously within 1 week after biopsy. A 4-year follow-up showed no recurrence. Key Words: eosinophilic ulcer, multiple lesions, oral mucosa, spontaneous regression (Am J Dermatopathol 2014;36:594–596)
INTRODUCTION Eosinophilic ulcer of the oral mucosa (EUOM) is a rare clinicopathological entity with unclear pathogenesis, manifesting as a rapidly developing solitary ulcer.1 In infants, this condition is called Riga–Fede disease, whereas in adults, the most common terms used in the last decade are EUOM and traumatic ulcerative granuloma with stromal eosinophilia.2,3 Clinically, EUOM manifests as an ulcer with elevated margins or sometimes as raised and indurated submucosal mass. It is argued, however, that the indurated mass is the first stage of the development of the ulcer.3 The lesion may show a peripheral erythema, a white or yellowish base and fibrinous membrane on the surface.4 Although the tongue is the most common location, the lips, buccal mucosa, palate, gingival, floor of the mouth, and retromolar region may also be affected.1,5 This condition is characterized by the formation of a single ulcer. However, cases with multiple lesions, although uncommon, have been reported.6,7 An oral ulcer usually occurs as a single episode, with the duration ranging from several weeks to several months, and heals without significant complications.1 In this article, we report a case of multifocal eosinophilic ulcer of the tongue with complete spontaneous regression after biopsy.
From the University Clinic of Dermatology, The Ss. Cyril and Methodius University, Skopje, Macedonia. The authors declare no conflicts of interest. Reprints: Katerina Damevska, MD, MSc, University Clinic of Dermatology, The Ss. Cyril and Methodius University, Bul. Koco Racin 26/27, 1000, Skopje, Macedonia (e-mail: [email protected]). © 2014 Lippincott Williams & Wilkins
594
| www.amjdermatopathology.com
CASE REPORT In September 2008, a 52-year-old previously healthy man was referred to the department of dermatology for evaluation of painful tongue ulcerations, of 6 weeks’ duration. All the lesions occurred simultaneously within a few days. The medical history was insignificant. No trauma preceded the appearance of the lesions. He also denied ingestion of any drugs and application of topical products. Previously, he has been treated with systemic antibiotics and topical antifungal with no improvement. The oral examination revealed 4 indurate lesions on the dorsal and lateral surface of the tongue, with central ulceration, covered by a white pseudomembrane. The size of the lesions ranged from 0.8 to 2.2 cm (Figs. 1, 2). On palpation, the lesions were firm and painful. There were no other cutaneous or mucosal lesions present. There was no regional lymphadenopathy. The initial diagnostic impression was that the ulcerations were because of an infection, that is, ulcus durum, and malignancy, that is, metastatic cancer. Laboratory tests (complete blood count, hepatic and renal functions, fasting glucose, Erythrocyte Sedimentation Rate, and C-reactive protein) were normal. The serological investigations for sexually transmitted diseases (Hepatitis B virus, HIV, Venereal Disease Research Laboratory test, and Treponema pallidum hemagglutination assay) were negative. Incisional biopsy was performed from the central part of ulcerated lesion on dorsal site of the tongue. Histopathological examination showed ulcerated surface and dense diffuse infiltrate composed mainly of eosinophils, plasma cells, and large mononuclear cells. The infiltrate extended deep into the musculature of the tongue (Figs. 3, 4). Immunohistochemical analysis revealed single CD30+ cells scattered within an inflammatory infiltrate (Fig. 5). Because of a scant biopsy sample, we were unable to test for other markers. The clinical and histological findings were consistent with EUOM. All the lesions began to regress spontaneously within 1 week after biopsy, without any additional treatment. Within 3 weeks, it was almost completely healed (Fig. 6). A 4-year follow-up showed no recurrence.
DISCUSSION EUOM is considered to be a benign, reactive, and selflimiting lesion. The pathogenesis of EUOM is poorly understood. Many hypotheses have been proposed, focusing mainly on trauma. The injury is identified, however, in less than 50% of cases.4 Likewise, in the current case, there was no previous trauma. Elzay3 argues that the presence of multiple ulcers excludes trauma as the only predisposing factor.3 Velez et al2 have suggested that in some predisposed individuals, trauma is only a contributing factor in the development of EUOM.4 The most common presentation of EUOM is a single ulcer. Two or more lesions can coexist at the time of diagnosis (synchronous) or develop consequently (metachronous). Metachronous lesions are rare but have been reported.2,4,6–11 Simultaneous lesions are extremely rare.7,12 To our knowledge, Am J Dermatopathol Volume 36, Number 7, July 2014
Am J Dermatopathol Volume 36, Number 7, July 2014
FIGURE 1. Ulcerated lesions involving the dorsal and lateral part of the tongue. Largest ulcer measuring approximately 2.2 cm.
this is the first reported case of EUOM with 4 synchronous lesions of the tongue. Histologically, the lesion is characterized by a deep, eosinophil-rich mixed inflammatory infiltrate. The histological differential diagnosis may include many lesions that exhibit significant tissue eosinophilia, such as Langerhans cell histiocytosis, Kimura disease, angiolymphomatoid hyperplasia with eosinophilia, atypical histiocytic granuloma, certain types of lymphomas, pseudolymphoma, allergic reactions, and parasitic diseases.13 Despite the histological similarities, these entities have considerably different clinical and histochemical features. Eosinophils are a source of numerous cytokines and growth factors; thus, in principle, they can display both proinflammatory and anti-inflammatory activities. Moreover, the diverse spectrum of cytokines produced by eosinophils could cause the delayed healing of the ulcers.14 Some studies have reported the presence of CD30 antigens, claiming that EUOM is a simulator of CD30+ lymphoproliferative disorders.4 In pathological conditions, CD30
FIGURE 2. Ulcer with elevated borders and fibrinous surface on the left lateral border of tongue. 2014 Lippincott Williams & Wilkins
Eosinophilic Ulcer of the Oral Mucosa
FIGURE 3. Low-power photomicrograph showed ulcerated mucosa with a dense cellular infiltrate extending into the deeper underlying soft tissues and between striated muscle fibers. Hematoxylin and eosin stain; original magnification, ·40.
is found at variable levels in different lymphomas of B-cell or T-cell derivation. Nonetheless, it occurs as well in many nonneoplastic cutaneous disorders such as atopic dermatitis, adverse drug reaction, scabies, molluscum contagiosum, and insect bites.15 Hirshberg et al1 reported that anaplastic lymphoma kinase, a marker associated with large-cell CD30+ lymphoma, was negative in 12 cases of EUOM. In the current case, only a few scattered CD30+ cells were seen within the inflammatory infiltrate. Gagari et al16 argue that CD30 typing would not be of any additional diagnostic value to the patient with biopsy-proven EUOM. Spontaneous regression of EUOM is a phenomenon that has been observed by many authors.5,13–16 Although the term spontaneous implies “without apparent cause,” a review of case reports demonstrates that regression generally coincides with diagnostic biopsy. The regression occurred 1–6 weeks after the biopsy.5,13–16 The present case remitted
FIGURE 4. High-power photomicrograph showed numerous eosinophils admixed with lymphocytes and mononuclear cells infiltrating between muscle fibers of the tongue. Hematoxylin and eosin stain; original magnification, ·400. www.amjdermatopathology.com |
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Damevska et al
Am J Dermatopathol Volume 36, Number 7, July 2014
observed for several weeks, awaiting spontaneous regression before surgical and other therapies.16,17 In summary, we present the case of a rare and generally little-known entity that is significant by its clinical and histopathological similarity to other causes of oral ulceration. The clinical aspects of the described case reinforces the possibility of multiple lesions of EUOM. Considering the benign nature and spontaneous healing possibility of EUOM, a “wait and see” policy should be considered as the treatment of choice after a diagnosis is histopathologically confirmed. REFERENCES FIGURE 5. CD30-labeled section showing single CD30+ cells scattered within the inflammatory infiltrate.
spontaneously as well after biopsy without any additional treatment. However, the clinical feature of the current report is specific because complete spontaneous regression of all lesions subsequent to biopsy of one was observed. Notwithstanding, there is a possibility that regression was because of the activation of an immune response stimulated by surgical intervention. Numerous therapeutic approaches have been tested, including surgical excision, intralesional corticosteroids, curettage, and cryotherapy.4 However, in our case, diagnostic biopsy of 1 lesion was followed by simultaneous regression of all lesions. This supports the view that EUOM may be
FIGURE 6. Complete spontaneous regression 3 weeks after biopsy.
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| www.amjdermatopathology.com
1. Hirshberg A, Amariglio N, Akrish S, et al. Traumatic ulcerative granuloma with stromal eosynophilia: reactive lesion of the oral mucosa. Am J Clin Pathol. 2006;126:522–529. 2. Velez A, Alamillos F-J, Dean A, et al. Eosinophilic ulcer of the oral mucosa: report of a recurrent case on the tongue. Clin Exp Dermatol. 1997;22:154–156. 3. Elzay RP. Traumatic ulcerative granuloma with stromal eosinophilia (Riga-Fede disease and traumatic eosinophilic granuloma). Oral Surg Oral Med Oral Pathol. 1983;55:497–506. 4. Segura S, Pujol RM. Eosinophilic ulcer of the oral mucosa: a distinct entity or a non-specific pattern? Oral Dis. 2008;14:287–295. 5. Boffano P, Gallesio C, Campisi P, et al. Traumatic ulcerative granuloma with stromal eosinophilia of the retromolar region. J Craniofac Surg. 2009;20:2150–2152. 6. Garcia M, Pagerols X, Curcó N, et al. Eosinophilic ulcer of the oral mucosa: 11 cases [in French]. Ann Dermatol Venereol. 2002;129:871–873. 7. Doyle JL, Geary W, Baden E. Eosinophilic ulcer. J Oral Maxillofac Surg. 1989;47:349–352. 8. El-Mofty SK, Swanson PE, Wick MR, et al. Eosinophilic ulcer of the oral mucosa. Report of 38 cases with immunohistochemical observations. Oral Surg Oral Med Oral Pathol. 1993;75:716–722. 9. Fonseca FP, de Andrade BA, Coletta RD, et al. Clinicopathological and immunohistochemical analysis of 19 cases of oral eosinophilic ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115:532–540. 10. Ficarra G, Prigano F, Romagnoli P. Traumatic eosinophilic granuloma of the oral mucosa: a cd30 (Ki-1) lymphoprolifeative disorder. Oral Oncol. 1997;33:375–379. 11. Alobeid B, Pan LX, Milligan L, et al. Eosinophil-rich CD30+ lymphoproliferative disorder of the oral mucosa. A form of ’traumatic eosinophilic granuloma’. Am J Clin Pathol. 2004;121:43–50. 12. 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;132:722–727. 13. Gopalakrishman R, Miloro M, Allen CM. Indurated ulceration of the tongue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82:119–21. 14. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006; 24:147–174. 15. Cepeda L, Pieretti M, Chapman S, et al. CD30-positive atypical lymphoid cells in common non-neoplastic cutaneous infiltrates rich in neutrophils and eosinophils. Am J Surg Pathol. 2003;27:912–918. 16. Gagari E, Stathopoulos P, Katsambas A, et al. Traumatic ulcerative granuloma with stromal eosinophilia: a lesion with alarming histopathologic presentation and benign clinical course. Am J Dermatopathol. 2011;33: 192–194. 17. Bortoluzzi MC, Passador-Santos F, Capella DL, et al. Eosinophilic ulcer of oral mucosa: a case report. Ann Stomatol (Roma). 2012;3:11–13.
2014 Lippincott Williams & Wilkins
Eosinophilic Ulcer of the Oral Mucosa: Report of a Case With Multiple Synchronous Lesions Katerina Damevska, MD, MSc, Gorgi Gocev, MD, and Suzana Nikolovska, MD, PhD
Abstract: Eosinophilic ulcer of the oral mucosa is considered to be a benign, reactive, and self-limiting lesion, with unclear pathogenesis, manifesting as a rapidly developing solitary ulcer. We report the case of a 52-year-old man who presented with 4 synchronous ulcerations of the tongue. Histopathological examination showed polymorphic inflammatory infiltrate, rich in eosinophils, involving the superficial mucosa and the deeper muscle layer. Immunohistochemical analysis revealed single CD30+ cells scattered within an inflammatory infiltrate. All the lesions began to regress spontaneously within 1 week after biopsy. A 4-year follow-up showed no recurrence. Key Words: eosinophilic ulcer, multiple lesions, oral mucosa, spontaneous regression (Am J Dermatopathol 2014;36:594–596)
INTRODUCTION Eosinophilic ulcer of the oral mucosa (EUOM) is a rare clinicopathological entity with unclear pathogenesis, manifesting as a rapidly developing solitary ulcer.1 In infants, this condition is called Riga–Fede disease, whereas in adults, the most common terms used in the last decade are EUOM and traumatic ulcerative granuloma with stromal eosinophilia.2,3 Clinically, EUOM manifests as an ulcer with elevated margins or sometimes as raised and indurated submucosal mass. It is argued, however, that the indurated mass is the first stage of the development of the ulcer.3 The lesion may show a peripheral erythema, a white or yellowish base and fibrinous membrane on the surface.4 Although the tongue is the most common location, the lips, buccal mucosa, palate, gingival, floor of the mouth, and retromolar region may also be affected.1,5 This condition is characterized by the formation of a single ulcer. However, cases with multiple lesions, although uncommon, have been reported.6,7 An oral ulcer usually occurs as a single episode, with the duration ranging from several weeks to several months, and heals without significant complications.1 In this article, we report a case of multifocal eosinophilic ulcer of the tongue with complete spontaneous regression after biopsy.
From the University Clinic of Dermatology, The Ss. Cyril and Methodius University, Skopje, Macedonia. The authors declare no conflicts of interest. Reprints: Katerina Damevska, MD, MSc, University Clinic of Dermatology, The Ss. Cyril and Methodius University, Bul. Koco Racin 26/27, 1000, Skopje, Macedonia (e-mail: [email protected]). © 2014 Lippincott Williams & Wilkins
594
| www.amjdermatopathology.com
CASE REPORT In September 2008, a 52-year-old previously healthy man was referred to the department of dermatology for evaluation of painful tongue ulcerations, of 6 weeks’ duration. All the lesions occurred simultaneously within a few days. The medical history was insignificant. No trauma preceded the appearance of the lesions. He also denied ingestion of any drugs and application of topical products. Previously, he has been treated with systemic antibiotics and topical antifungal with no improvement. The oral examination revealed 4 indurate lesions on the dorsal and lateral surface of the tongue, with central ulceration, covered by a white pseudomembrane. The size of the lesions ranged from 0.8 to 2.2 cm (Figs. 1, 2). On palpation, the lesions were firm and painful. There were no other cutaneous or mucosal lesions present. There was no regional lymphadenopathy. The initial diagnostic impression was that the ulcerations were because of an infection, that is, ulcus durum, and malignancy, that is, metastatic cancer. Laboratory tests (complete blood count, hepatic and renal functions, fasting glucose, Erythrocyte Sedimentation Rate, and C-reactive protein) were normal. The serological investigations for sexually transmitted diseases (Hepatitis B virus, HIV, Venereal Disease Research Laboratory test, and Treponema pallidum hemagglutination assay) were negative. Incisional biopsy was performed from the central part of ulcerated lesion on dorsal site of the tongue. Histopathological examination showed ulcerated surface and dense diffuse infiltrate composed mainly of eosinophils, plasma cells, and large mononuclear cells. The infiltrate extended deep into the musculature of the tongue (Figs. 3, 4). Immunohistochemical analysis revealed single CD30+ cells scattered within an inflammatory infiltrate (Fig. 5). Because of a scant biopsy sample, we were unable to test for other markers. The clinical and histological findings were consistent with EUOM. All the lesions began to regress spontaneously within 1 week after biopsy, without any additional treatment. Within 3 weeks, it was almost completely healed (Fig. 6). A 4-year follow-up showed no recurrence.
DISCUSSION EUOM is considered to be a benign, reactive, and selflimiting lesion. The pathogenesis of EUOM is poorly understood. Many hypotheses have been proposed, focusing mainly on trauma. The injury is identified, however, in less than 50% of cases.4 Likewise, in the current case, there was no previous trauma. Elzay3 argues that the presence of multiple ulcers excludes trauma as the only predisposing factor.3 Velez et al2 have suggested that in some predisposed individuals, trauma is only a contributing factor in the development of EUOM.4 The most common presentation of EUOM is a single ulcer. Two or more lesions can coexist at the time of diagnosis (synchronous) or develop consequently (metachronous). Metachronous lesions are rare but have been reported.2,4,6–11 Simultaneous lesions are extremely rare.7,12 To our knowledge, Am J Dermatopathol Volume 36, Number 7, July 2014
Am J Dermatopathol Volume 36, Number 7, July 2014
FIGURE 1. Ulcerated lesions involving the dorsal and lateral part of the tongue. Largest ulcer measuring approximately 2.2 cm.
this is the first reported case of EUOM with 4 synchronous lesions of the tongue. Histologically, the lesion is characterized by a deep, eosinophil-rich mixed inflammatory infiltrate. The histological differential diagnosis may include many lesions that exhibit significant tissue eosinophilia, such as Langerhans cell histiocytosis, Kimura disease, angiolymphomatoid hyperplasia with eosinophilia, atypical histiocytic granuloma, certain types of lymphomas, pseudolymphoma, allergic reactions, and parasitic diseases.13 Despite the histological similarities, these entities have considerably different clinical and histochemical features. Eosinophils are a source of numerous cytokines and growth factors; thus, in principle, they can display both proinflammatory and anti-inflammatory activities. Moreover, the diverse spectrum of cytokines produced by eosinophils could cause the delayed healing of the ulcers.14 Some studies have reported the presence of CD30 antigens, claiming that EUOM is a simulator of CD30+ lymphoproliferative disorders.4 In pathological conditions, CD30
FIGURE 2. Ulcer with elevated borders and fibrinous surface on the left lateral border of tongue. 2014 Lippincott Williams & Wilkins
Eosinophilic Ulcer of the Oral Mucosa
FIGURE 3. Low-power photomicrograph showed ulcerated mucosa with a dense cellular infiltrate extending into the deeper underlying soft tissues and between striated muscle fibers. Hematoxylin and eosin stain; original magnification, ·40.
is found at variable levels in different lymphomas of B-cell or T-cell derivation. Nonetheless, it occurs as well in many nonneoplastic cutaneous disorders such as atopic dermatitis, adverse drug reaction, scabies, molluscum contagiosum, and insect bites.15 Hirshberg et al1 reported that anaplastic lymphoma kinase, a marker associated with large-cell CD30+ lymphoma, was negative in 12 cases of EUOM. In the current case, only a few scattered CD30+ cells were seen within the inflammatory infiltrate. Gagari et al16 argue that CD30 typing would not be of any additional diagnostic value to the patient with biopsy-proven EUOM. Spontaneous regression of EUOM is a phenomenon that has been observed by many authors.5,13–16 Although the term spontaneous implies “without apparent cause,” a review of case reports demonstrates that regression generally coincides with diagnostic biopsy. The regression occurred 1–6 weeks after the biopsy.5,13–16 The present case remitted
FIGURE 4. High-power photomicrograph showed numerous eosinophils admixed with lymphocytes and mononuclear cells infiltrating between muscle fibers of the tongue. Hematoxylin and eosin stain; original magnification, ·400. www.amjdermatopathology.com |
595
Damevska et al
Am J Dermatopathol Volume 36, Number 7, July 2014
observed for several weeks, awaiting spontaneous regression before surgical and other therapies.16,17 In summary, we present the case of a rare and generally little-known entity that is significant by its clinical and histopathological similarity to other causes of oral ulceration. The clinical aspects of the described case reinforces the possibility of multiple lesions of EUOM. Considering the benign nature and spontaneous healing possibility of EUOM, a “wait and see” policy should be considered as the treatment of choice after a diagnosis is histopathologically confirmed. REFERENCES FIGURE 5. CD30-labeled section showing single CD30+ cells scattered within the inflammatory infiltrate.
spontaneously as well after biopsy without any additional treatment. However, the clinical feature of the current report is specific because complete spontaneous regression of all lesions subsequent to biopsy of one was observed. Notwithstanding, there is a possibility that regression was because of the activation of an immune response stimulated by surgical intervention. Numerous therapeutic approaches have been tested, including surgical excision, intralesional corticosteroids, curettage, and cryotherapy.4 However, in our case, diagnostic biopsy of 1 lesion was followed by simultaneous regression of all lesions. This supports the view that EUOM may be
FIGURE 6. Complete spontaneous regression 3 weeks after biopsy.
596
| www.amjdermatopathology.com
1. Hirshberg A, Amariglio N, Akrish S, et al. Traumatic ulcerative granuloma with stromal eosynophilia: reactive lesion of the oral mucosa. Am J Clin Pathol. 2006;126:522–529. 2. Velez A, Alamillos F-J, Dean A, et al. Eosinophilic ulcer of the oral mucosa: report of a recurrent case on the tongue. Clin Exp Dermatol. 1997;22:154–156. 3. Elzay RP. Traumatic ulcerative granuloma with stromal eosinophilia (Riga-Fede disease and traumatic eosinophilic granuloma). Oral Surg Oral Med Oral Pathol. 1983;55:497–506. 4. Segura S, Pujol RM. Eosinophilic ulcer of the oral mucosa: a distinct entity or a non-specific pattern? Oral Dis. 2008;14:287–295. 5. Boffano P, Gallesio C, Campisi P, et al. Traumatic ulcerative granuloma with stromal eosinophilia of the retromolar region. J Craniofac Surg. 2009;20:2150–2152. 6. Garcia M, Pagerols X, Curcó N, et al. Eosinophilic ulcer of the oral mucosa: 11 cases [in French]. Ann Dermatol Venereol. 2002;129:871–873. 7. Doyle JL, Geary W, Baden E. Eosinophilic ulcer. J Oral Maxillofac Surg. 1989;47:349–352. 8. El-Mofty SK, Swanson PE, Wick MR, et al. Eosinophilic ulcer of the oral mucosa. Report of 38 cases with immunohistochemical observations. Oral Surg Oral Med Oral Pathol. 1993;75:716–722. 9. Fonseca FP, de Andrade BA, Coletta RD, et al. Clinicopathological and immunohistochemical analysis of 19 cases of oral eosinophilic ulcers. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115:532–540. 10. Ficarra G, Prigano F, Romagnoli P. Traumatic eosinophilic granuloma of the oral mucosa: a cd30 (Ki-1) lymphoprolifeative disorder. Oral Oncol. 1997;33:375–379. 11. Alobeid B, Pan LX, Milligan L, et al. Eosinophil-rich CD30+ lymphoproliferative disorder of the oral mucosa. A form of ’traumatic eosinophilic granuloma’. Am J Clin Pathol. 2004;121:43–50. 12. 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;132:722–727. 13. Gopalakrishman R, Miloro M, Allen CM. Indurated ulceration of the tongue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;82:119–21. 14. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006; 24:147–174. 15. Cepeda L, Pieretti M, Chapman S, et al. CD30-positive atypical lymphoid cells in common non-neoplastic cutaneous infiltrates rich in neutrophils and eosinophils. Am J Surg Pathol. 2003;27:912–918. 16. Gagari E, Stathopoulos P, Katsambas A, et al. Traumatic ulcerative granuloma with stromal eosinophilia: a lesion with alarming histopathologic presentation and benign clinical course. Am J Dermatopathol. 2011;33: 192–194. 17. Bortoluzzi MC, Passador-Santos F, Capella DL, et al. Eosinophilic ulcer of oral mucosa: a case report. Ann Stomatol (Roma). 2012;3:11–13.
2014 Lippincott Williams & Wilkins
