eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Eosinophilic Ulcer: Differential Diagnoses & Workup

Author: Faizan Alawi, DDS, Assistant Professor, Department of Dermatology, Section of Dermatopathology, Hospital of the University of Pennsylvania
Coauthor(s): Paul D Freedman, DDS, Section Chief of Oral Pathology, Assistant Director, Assistant Professor of Surgery, Department of Dental Medicine, The New York Hospital, Cornell University Weill Medical College
Contributor Information and Disclosures

Updated: Oct 2, 2009

Differential Diagnoses

Angiolymphoid Hyperplasia with Eosinophilia
Noncandidal Fungal Infections of the Mouth
Cancers of the Oral Mucosa
Oral Manifestations of Drug Reactions
Chronic Granulomatous Disease
Oral Manifestations of Systemic Diseases
Contact Dermatitis, Allergic
Oral Pyogenic Granuloma
Contact Dermatitis, Irritant
Sarcoidosis
Cutaneous Tuberculosis
Squamous Cell Carcinoma
Kimura Disease
Syphilis
Langerhans Cell Histiocytosis
Traumatic Ulcers
Metastatic Neoplasms to the Oral Cavity
Viral Infections of the Mouth
Necrotizing Sialometaplasia
Wegener Granulomatosis

Other Problems to Be Considered

Noma (necrotizing stomatitis)
Atypical herpes stomatitis (in patients who are immunocompromised)

Workup

Procedures

  • The clinical presentation and history often suggest the cause and nature of eosinophilic ulcers; however, many cases can resemble ulcerative squamous cell carcinoma. However, if the origin of the lesion is not obvious or if eosinophilic ulcer does not respond to conservative therapy, biopsy under local anesthesia is indicated.
  • For small lesions, excisional biopsy may be performed; however, incisional biopsy is recommended for larger ulcers.
  • In general, a biopsy specimen of an eroded or ulcerated area should include a portion of the adjacent intact epithelium.

Histologic Findings

Microscopic sections typically show ulcerated stratified squamous epithelium with underlying granulation tissue characterized by an invasive, dense, mixed cellular infiltrate composed mainly of sheets of large mononuclear cells with pale nuclei and numerous eosinophils. The eosinophils, including many cells that show evidence of degranulation, usually infiltrate deep into the subjacent skeletal muscle, dissecting through and separating the muscle fibers. Degenerating muscle, interfascicular fibrosis, and regenerative myocytes may be identified.

The adjacent surface epithelium may be normal or hyperplastic and occasionally hyperkeratotic. Numerous capillaries, often lined by plump endothelial cells, are usually seen deep to the ulcer. This vascular hyperplasia may lead to surface elevation, which gives the lesion a clinically raised appearance.

Immunohistochemical studies have demonstrated that the large mononuclear cells include 2 phenotypically distinct cell types: CD68-positive histiocytes and factor-XIIIa–positive submucosal dendrocytes in varying ratios. Longer-standing lesions may have more dendrocytes than histiocytes; however, this finding is controversial.

Typically, small T lymphocytes are scattered throughout the connective tissue, and a minority of these cells are of the CD4 phenotype. Usually, B cells are scarce. Neutrophils are often clustered within and near the base of the ulcer; mast cells, occasional plasma cells, and focally scattered S-100–positive histiocytes also are seen. An increased number of dendritic Langerhans cells may be identified in the epithelium immediately adjacent to the ulcer.

Smooth muscle actin and muscle-specific actin tests usually fail to highlight any of the cells in the connective tissue (except endothelial cells). This finding suggests that myofibroblasts are not an integral component of the cellular proliferation.

Although cellular atypia or mitoses are not typical findings, in rare cases, large atypical cells and mitotic figures may be scattered throughout the cellular infiltrate, creating a pseudolymphomatous pattern. These lesions are termed atypical histiocytic granulomas.

Immunohistochemical studies are often necessary to rule out lymphoma. In some cases, these atypical lesions recur and are subsequently determined to be CD30-positive T-cell non-Hodgkin lymphoma.7

The histologic differential diagnosis may include lymphoma, Langerhans cell disease, angiolymphoid hyperplasia with eosinophilia, and Kimura disease. Immunohistochemical studies may be necessary to confirm the diagnosis.

Low-power view showing an ulcerated surface epith...

Low-power view showing an ulcerated surface epithelium with a dense cellular inflammatory infiltrate underlying the mucosal surface (original magnification X40). Courtesy of Dr Paul D. Freedman.

Low-power view showing an ulcerated surface epith...

Low-power view showing an ulcerated surface epithelium with a dense cellular inflammatory infiltrate underlying the mucosal surface (original magnification X40). Courtesy of Dr Paul D. Freedman.


Cellular infiltrate composed mainly of large mono...

Cellular infiltrate composed mainly of large mononuclear cells, including histiocytes and submucosal dendrocytes, eosinophils, and scattered T lymphocytes (original magnification X400). Courtesy of Dr Paul D. Freedman.

Cellular infiltrate composed mainly of large mono...

Cellular infiltrate composed mainly of large mononuclear cells, including histiocytes and submucosal dendrocytes, eosinophils, and scattered T lymphocytes (original magnification X400). Courtesy of Dr Paul D. Freedman.


Inflammatory infiltrate extending through and bet...

Inflammatory infiltrate extending through and between muscle bundles (original magnification X400). Courtesy of Dr Paul D. Freedman.

Inflammatory infiltrate extending through and bet...

Inflammatory infiltrate extending through and between muscle bundles (original magnification X400). Courtesy of Dr Paul D. Freedman.


More on Eosinophilic Ulcer

Overview: Eosinophilic Ulcer
Differential Diagnoses & Workup: Eosinophilic Ulcer
Treatment & Medication: Eosinophilic Ulcer
Follow-up: Eosinophilic Ulcer
Multimedia: Eosinophilic Ulcer
References

References

  1. Segura S, Pujol RM. Eosinophilic ulcer of the oral mucosa: a distinct entity or a non-specific reactive pattern?. Oral Dis. May 2008;14(4):287-95. [Medline].

  2. Elzay RP. Traumatic ulcerative granuloma with stromal eosinophilia (Riga-Fede's disease and traumatic eosinophilic granuloma). Oral Surg Oral Med Oral Pathol. May 1983;55(5):497-506. [Medline].

  3. Bhaskar SN, Lilly GE. Traumatic granuloma of the tongue (human and experimental). Oral Surg Oral Med Oral Pathol. Aug 1964;18:206-18. [Medline].

  4. 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. Jun 1996;81(6):672-81. [Medline].

  5. Gerbig AW, Zala L, Hunziker T. Tumorlike eosinophilic granuloma of the skin. Am J Dermatopathol. Feb 2000;22(1):75-8. [Medline].

  6. Chawla O, Burke GA, MacBean AD. The eosinophilic ulcer revisited. Dent Update. Jan-Feb 2007;34(1):56-7. [Medline].

  7. Rosenberg A, Biesma DH, Sie-Go DM, Slootweg PJ. Primary extranodal CD3O-positive T-cell non-Hodgkins lymphoma of the oral mucosa. Report of two cases. Int J Oral Maxillofac Surg. Feb 1996;25(1):57-9. [Medline].

  8. Pilolli GP, Lucchese A, Scivetti M, Maiorano E, Favia G. Traumatic ulcerative granuloma with stromal eosinophilia of the oral mucosa: histological and immunohistochemical analysis of three cases. Minerva Stomatol. Jan-Feb 2007;56(1-2):73-9. [Medline].

  9. 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. Jun 1993;75(6):716-22. [Medline].

  10. Gopalakrishman R, Miloro M, Allen CM. Indurated ulceration of the tongue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Aug 1996;82(2):119-21. [Medline].

  11. Mezei MM, Tron VA, Stewart WD, Rivers JK. Eosinophilic ulcer of the oral mucosa. J Am Acad Dermatol. Nov 1995;33(5 Pt 1):734-40. [Medline].

  12. Movassaghi K, Goodman ML, Keith D. Ulcerative eosinophilic granuloma: a report of five new cases. Br J Oral Maxillofac Surg. Feb 1996;34(1):115-7. [Medline].

  13. Neville BW, Damm DD, Allen CM. Oral and Maxillofacial Pathology. ed. Philadelphia, Pa: WB Saunders; 1995:213-22.

  14. Regezi JA, Zarbo RJ, Daniels TE, Greenspan JS. Oral traumatic granuloma. Characterization of the cellular infiltrate. Oral Surg Oral Med Oral Pathol. Jun 1993;75(6):723-7. [Medline].

Further Reading

Keywords

eosinophilic ulcer, oral eosinophilic ulcer, oral ulcer, oral mucosa ulcer, traumatic ulcerative granuloma with stromal eosinophilia, TUGSE, traumatic granuloma, Riga-Fede disease in infants, ulcerated granuloma eosinophilicum diutinum, eosinophilic granuloma of soft tissue, EU, oral ulcer

Contributor Information and Disclosures

Author

Faizan Alawi, DDS, Assistant Professor, Department of Dermatology, Section of Dermatopathology, Hospital of the University of Pennsylvania
Faizan Alawi, DDS is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology
Disclosure: Nothing to disclose.

Coauthor(s)

Paul D Freedman, DDS, Section Chief of Oral Pathology, Assistant Director, Assistant Professor of Surgery, Department of Dental Medicine, The New York Hospital, Cornell University Weill Medical College
Paul D Freedman, DDS is a member of the following medical societies: American Academy of Oral and Maxillofacial Pathology and American Dental Association
Disclosure: Nothing to disclose.

Medical Editor

Donald Belsito, MD, Clinical Professor, Department of Internal Medicine, Division of Dermatology, University of Missouri at Kansas City; Private Practice, American Dermatology Associates, LLC
Donald Belsito, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, Dermatology Foundation, Kansas Medical Society, Noah Worcester Dermatological Society, Phi Beta Kappa, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Drore Eisen, MD, DDS, Consulting Staff, Department of Dermatology, Dermatology Research Associates of Cincinnati
Drore Eisen, MD, DDS is a member of the following medical societies: American Academy of Dermatology, American Academy of Oral Medicine, and American Dental Association
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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