Aphthous Ulcer
(Canker Sore)

Quick Summary

Clinical Features

Painful 5-day old ulcer has diffuse red halo around it and shows new blood vessels forming in the ulcer bed, which otherwise is covered by white, fibrinoid necrotic debris.





Quick Review for Patients

The aphthous ulcer or canker sore is a very common and painful ulceration or local destruction caused by a variety of factors, especially involving the immune system, and is often a hypersensitivity reaction to a food or oral micro-organism.  The disease may run in families and ulcers usually remain less than 1 cm. in size.  Some persons have large numbers of deep ulcers and are seldom without mouth ulcers, but most have only the occasional 1-3 ulcers occurring once a month or every few months.  The ulcers usually start during the teens or twenties, but may begin in childhood or in middle age.  An attack usually lasts 5-10 days, with individual ulcers slowly enlarging over several days.  There is no effective treatment, but some patients are helped by local or systemic corticosteroids, topical or systemic tetracycline.  The mouth ulcers may be associated with blood or intestinal or skin diseases.





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Inflammatory ulceration of the oral mucosa is quite common (Table 1) and approximately 20% of adults (range in various studies: 5-66%) suffer from very painful aphthous stomatitis or canker sores, usually of the recurring variety.  At any one time 1 of every 323 adults have an active ulcer in the mouth.  Once thought to be a herpes virus infection, the entire class of canker sores is now thought to be an aggregate of a variety of disease processes, each with the ability, in its own way, to produce rapid but self-limiting destruction of mucous membranes, predominantly through immunologic and ischemic mechanisms.  In some individuals the ulcers are a secondary or hypersensitivity response to antigenic stimulus, especially foods (peanuts, tomatoes, strawberries), while in others they are a primary autoimmune disorder.  Patients with aphthae have a decreased ratio of T-helper (CD4+) cells to T-suppressor/cytotoxic (CD8+) cells in their circulation, and the ulcer bed itself has a high level of CD8+ cytotoxic cells.  While this is a likely contributor to the destruction in these ulcers, initiating causes vary from one person to the next, including: familial predisposition, allergy, nutritional imbalances, infectious agents, hormones, trauma, stress, blood dyscrasias.  Patients with AIDS are at increased risk of aphthous ulcers, most likely because of the common increased CD8+ levels resulting from a reduction of CD4+ T lymphocytes.

Certain histocompatibility antigen types, especially HLA-B12, HLA-B51 and HLA-Cw7, are associated with at least some aphthae.  This is more likely in individuals with co-morbid extra-oral diseases such as Behçet's disease (Behçet's syndrome), which is associated with HLA-B12, Crohn's disease, celiac disease and ulcerative colitis.  Cyclic neutropenia is responsible for a subgroup of aphthous stomatitis patients, with the ulcers occurring at points of minor trauma during times when the number of circulating neutrophils is low.  Stress may be indirectly responsible for canker sores, which were once called "stress ulcers," through its modulation of the immune system.  Paradoxically, tobacco smoking, with its own immune modulation, is often protective, probably because of the increased keratinization resulting from local irritation of mouth membranes.  Conversely, diseases which thin the membranes, such as deficiencies in vitamin B12, folate or iron, increase the risk of aphthae.

The subgroup of aphthous stomatitis patients who develop their ulcers in response to antigenic stimulus are experiencing immune-mediated cytotoxic destruction.  No single antigen has been identified, however, and a variety of foods and micro-organisms have been implicated.  The micro-organisms include the L forms of streptococci, cytomegalovirus, herpes simplex virus, varicella-zoster virus and adenovirus.  Recent research has shown that Behçet's disease is associated with hypercoagulation, possibly producing acute mucosal and skin ulcers via soft tissue infarction in a manner similar to deep vein thrombosis.

Clinical Features

Three clinical variations of aphthous ulceration are recognized: minor aphthous stomatitis, major aphthous stomatitis (sometimes referred to as Sutton's disease or periadenitis mucosa necrotica recurrens [PMNR]), and the much less common herpetiform aphthous stomatitis.  There are many cases which overlap these categories and it is probably best to consider the different categories as all part of a disease with a wide spectrum of clinical presentations.  

Regardless of the classification, patients are often aware of a burning or tender or tingling sensation in the area for 1-2 days prior to the appearance of the ulcer itself.  This prodromal stage is rather unique to canker sores, but may also be found in herpes labialis.  The individual ulcer begins as a round or oval area of erythema which develops a pin-point central area of white ulceration.  Over the next 3-7 days the ulcer enlarges laterally and becomes saucerized or cupped out.  As healing commences, the red halo diminishes and small punctate red areas dot the white ulcer bed (representing blood vessels from the underlying granulation tissue which have reached the surface).  Over several days the white color of the bed changes to red or pink and the area heals without scar formation.  Persons with very deep or large ulcers, i.e. with major aphthous stomatitis, may develop scars.

Mucosal ulcers are typically surrounded by an erythematous halo, indicating a normal and healthy inflammatory response (Figures 1 & 2). Often there will be a very thin line of coagulation necrosis separating the halo from the ulcer bed. Without the inflammatory halo, a nonhealing ulcer may represent a local manifestation of immunoincompetence, especially diabetes mellitus, AIDS or leukemia, or it may represent the end-stage healing of an innocuous ulcer (Figures 3 & 4).  The pain associated with these ulcers is far in excess of their size and small lesions are just as painful as large ones, although larger ulcers are more likely to contact teeth or other oral structures and, therefore, are often perceived as being more painful.

Multiple saucerized ulcers associated with moderately severe pain may represent, in addition to aphthous stomatitis, Behçet's disease, ulcerative colitis, chronic ulcerative stomatitis, or nonhealing traumatic ulceration in immunoincompetence or neutropenia. A dirty brownish/yellow ulcer bed is indicative of necrosis of underlying fat or of hemorrhage into the ulcer bed. These are seen primarily in necrotizing sialometaplasia and in purpura, leukemia and aplastic anemia.

Ulcerating oral squamous cell carcinoma is usually easy to distinguish from aphthous ulcer because it is deeply ulcerated and has an indurated, rolled border surrounding it, usually without an inflammatory halo and usually without tenderness or pain until the late stages of growth. Malignancy and granulomatous inflammation may also present as fungating growths prior to central ulceration and destruction.  Destruction of bone beneath a mucosal ulcer is a serious event.  This is not a feature of aphthae and most likely represents malignancy, Wegener's granulomatosis, lethal midline granuloma, granulomatous osteomyelitis (tuberculosis, tertiary syphilis), or noma.

A unique and quite site-specific ulceration of the gingival papillae between the teeth, acute necrotizing ulcerative gingivitis (ANUG, trench mouth) is exquisitely painful even though the necrotic ulcers remain small and localized. While normally self-limiting, ANUG in immune compromised individuals may extend to adjacent oral soft tissues to produce a life-threatening destruction of the maxillofacial region, called variously necrotizing ulcerative stomatitis, gangrenous stomatitis, cancrum oris or noma.

Pathology and Differential Diagnosis

Saucerized or aphthous-like ulcer beds consist of fibrinoid necrotic debris of the surface with abundant neutrophil dust and other cell remnants (Figure 7). This typically overlies granulation tissue with variable numbers of chronic and acute inflammatory cells, neovascularity and edema. Erythrocyte extravasation is seldom seen and if present should make one suspicious of Wegener's vasculitis, angiosarcoma or Kaposi's sarcoma. The inflammatory infiltrate should be carefully evaluated for dysplastic cells in order to rule out leukemic infiltration or MALT lymphoma, and an overwhelming predominance of plasma cells may be indicative of plasmacytoma or multiple myeloma. Filamentous bacterial colonies coated by neutrophils may be seen as a feature of oral actinomycosis and mucosal ulceration in such cases may be associated with the orifice of a fistulous tract extending deeply into underlying soft or hard tissues.

Scattered or numerous eosinophils in the granulation tissue are consistent with either traumatic eosinophilic ulcer or Langerhans cell disease. Eosinophils are decidedly rare in oral inflammatory lesions and are associated with more aggressive biological behavior than the typical saucerized ulcer; they rarely may be associated with a protozoan infection. There may be so much proliferation of granulation tissue in these types of ulcerations that the resultant fungating appearance may mimic pyogenic granuloma.

The presence of multinucleated giant cells beneath an ulcer bed is also significant and may indicate serious systemic disease or more aggressive local disease. These are discussed elsewhere in Bond's book (see granulomatous inflammations in the soft tissue section).

Fat necrosis is rarely a feature of oral inflammatory ulceration, but when present it is most likely indicative of necrotizing sialometaplasia. This localized infarction of soft tissues may have a strong chronic inflammatory cell response and is characterized by squamous metaplasia of salivary duct epithelium, fibrous replacement of acinar tissues, ductal ectasia, and edema of surrounding stroma. The pathologist must be very cautious in evaluating the islands of squamous epithelium; many of the early cases of necrotizing sialometaplasia were mistakenly diagnosed as well-differentiated squamous cell carcinoma or mucoepidermoid carcinoma and treated accordingly.

Treatment and Prognosis

There is no effective treatment for an aphthous ulcer but, fortunately, it usually heals without therapy in 6-12 days unless there is an underlying immunoincompetence or the patient suffers from major aphthous stomatitis.   Injection of IV prednisolone may be helpful, as may systemic corticosteroids and topical or systemic tetracycline therapy.  A mild anesthesia may last for 5-15 minutes (enough to get through most of a meal) with the topical application of a mixture of Maalox and liquid Benadryl or Benalyn (mixed 1:1), or a mixture of these with a Decadron elixir.  There is no malignant transformation potential to this lesion.

References (Chronologic Order)

Note: Click on underlined author's names for additional detail.

General references:

Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. Philadelphia, W. B. Saunders; 1995.

Elder D, Elenitsas R, Jaworsky C, Johnson B Jr. Lever's Histopathology of the skin, 8th edition. Philadelphia; Lippincott-Raven, 1997.

Sapp JP, Eversole LR, Wysocki GP. Contemporary oral and maxillofacial pathology. Mosby; St. Louis, 1997.

Odell EW, Morgan PR. Biopsy pathology of the oral tissues. London; Chapman & hall Medical, 1998.

Specific references:

Aozasa K, Ohsawa M, Tajima K, et al. Nation-wide study of lethal midline granuloma in Japan: frequencies of Wegener's granulomatosis, polymorphic reticulosis, malignant lymphoma and other related conditions. Int J Cancer 1989; 44:63-66.

Jaremko WM, Beutner EH, Kumar V, Kipping H, et al. Chronic ulcerative stomatitis associated with a specific immunologic marker. J Am Acad Dermatol 1990; 22:215-220.

Bagan JV, Sanchis JM, Milian MA, Penarrocha M, et al. Recurrent aphthous stomatitis: a study of the clinical characteristics of lesions in 93 cases. J Oral Pathol Med 1991; 20:395-397.

Church LF Jr, Schosser RH. Chronic ulcerative stomatitis associated with stratified epithelial specific antinuclear antibodies. A case report of a newly described disease entity. Oral Surg Oral Med Oral Pathol 1992; 73:579-582.

Field EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children: a review. Int J Paediatr Dent 1992; 2:1-10.

Grange C, Cabane J, Dubois A, et al. Centrofacial malignant granulomas: clinicopathologic study of 40 cases and review of the literature. Medicine 1992; 71:179-196.

Pedersen A, Hougen HP, Kenrad B. T-lymphocyte subsets in oral mucosa of patients with recurrent aphthous ulcerations. J Oral Pathol Med 1992; 21:176-180.

Ficarra G, Di Lollo S, Pierleoni F, Panzoni E. Actinomyces of the tongue: a diagnostic challenge. Head Neck 1993; 15:53-55.

Porter SR, Kingsmill V, Scully. Audit of diagnosis and investigations in patients with recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1993; 76:449-452.

Sobrevilla-Calvo P, Meneses A, Alfaro P, et al. Radiotherapy compared to chemotherapy as initial treatment of angiocentric centrofacial lymphoma (polymorphic reticulosis). Acta Oncol 1993; 32:69-72.

Strickler JG, Meneses MF, Habermann TM, et al. Polymorphic reticulosis: a reappraisal. Human Pathol 1994; 25:659-665.

Horning GM, Cohen ME. Necrotizing ulcerative gingivitis, periodontitis, and stomatitis: clinical staging and predisposing factors. J Periodontol 1995; 66:990-998.

Worle B, Wollenberg A, Schaller M, Kunzelmann KH, et al. Chronic ulcerative stomatitis. Brit J Dermatol 1997; 137:262-265.

Chung HS, et al. Eosinophilic ulcer of oral mucosa. Int J Dermatol 1998; 37:432

Herman WW, Whitaker SB, Williams MF, Sangueza OP. Acute actinomycosis presenting as an ulcerated palatal mass. J Oral Maxillofac Surg 1998; 56:1098-1101.

Miller M, Haddad AJ. Cervicofacial actinomycosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 85:496-508.


Table 1: Gender-specific prevalence rates per 1,000 population for selected oral masses and surface alterations in U.S. adults, ranked by total frequency. Modified from Bouquot JE. Common oral lesions found during a mass screening examination. J Am Dent Assoc 1986; 112:50-57, and Bouquot JE, Gundlach KKH. Oral exophytic lesions in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral Pathol 1986; 62:284-291.


Number of lesions per 1,000 population*








Torus palatinus 




Irritation fibroma




Fordyce granules




Torus mandibularis 9.6 7.9 8.5





Erythema, inflammatory 4.5 4.8 4.7





Epulis fissuratum




Varicosities, lingual




Fissured tongue 3.5 3.1 3.2
Benign migratory glossitis 3.4 3.0 3.1
Aphthous ulcer 3.3 3.0 3.1

Papillary hyperplasia








Herpes labialis (herpes simplex) 2.4 2.6 2.5
Traumatic ulcer 2.1 2.1 2.1
Angular cheilitis 1.8 1.9 1.9
Smokeless tobacco keratosis 4.3 0.2 1.7
Hematoma or ecchymosis 2.0 1.4 1.6

Enlarged lingual tonsil




Chronic cheek bite 0.7 1.4 1.2

Lichen planus




Squamous cell carcinoma 2.5 0.1 0.9
Amalgam tattoo 0.6 1.0 0.9

Buccal exostosis




Leaf-shaped fibroma 0.4 1.2 0.9

Median rhomboid glossitis




Hairy tongue 1.2 0.3 0.6
Nicotine palatinus 1.2 0.2 0.6
Atrophic glossitis (smooth tongue) 0.6 0.5 0.6

Epidermoid cyst




Oral melanotic macule




Oral tonsils (except lingual)




Leukoedema 0.4 0.3 0.3





Non-lingual oral tonsils








Gingival hyperplasia 0.1 0.1 0.1

Buccinator node, hyperplastic




Pyogenic granuloma




Nasoalveolar cyst








* total examined population = 23,616 adults over 35 years of age 



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