Diseases of the Oral Cavity

Overview

Shared entry for digestive+respiratory tracts. Mucosa: squamous epithelium over vascularised CT — keratinised(hard palate/lips/gingiva) vs non-keratinised(elsewhere). Minor salivary glands scattered; sebaceous glands only lips/buccal mucosa; lymphoid=tonsils/adenoids.

Developmental anomalies

1. Facial clefts(harelip, cleft palate) — commonest, failed facial-process fusion
2. Fordyce’s granules — sebaceous macules, lips/buccal, undeveloped till puberty
3. Leukoedema — grey-white buccal, children, intracellular oedema. NO malignant potential (contrast leukoplakia)
4. Tongue defects: macroglossia(lymphangioma/haemangioma/amyloid), microglossia/aglossia(rare), fissured/scrotal tongue(genetic, ±mild glossitis), bifid tongue(failed fusion), tongue tie(short frenum), hairy tongue(NOT true developmental — hypertrophied stained filiform papillae)

Mucocutaneous lesions

LICHEN PLANUS(interlacing whitening, buccal). Vesicular: PEMPHIGUS VULGARIS(oral lesions ALL cases, initial in ~half), PEMPHIGOID(oral+conjunctival, older women), ERYTHEMA MULTIFORME(subepithelial vesicles), STEVENS-JOHNSON(fatal severe EM variant, post-sulfa drugs), EPIDERMOLYSIS BULLOSA(hereditary, subepidermal bullae).

Inflammatory/pigmentary

STOMATITIS:

• APHTHOUS ULCERS — COMMONEST oral ulceration. Unknown etiology, triggers=stress/allergy/hormones/nutrition/GI/trauma. Painful, ≥1cm. ±Behçet’s/IBD
• HERPETIC STOMATITIS — acute, infants/children, COMMONEST primary HSV presentation. Perioral vesicles. Recurrence: stress/URI
• NECROTISING STOMATITIS(Noma/Cancrum oris) — malnourished children(kwashiorkor), post-measles, immunodeficiency. Marginal gingival necrosis→cheek cellulitis→±gangrene
• Mycotic — cervicofacial actinomycosis(commonest form, mandible angle); candidiasis/thrush(opportunistic, palatal erythema+angular cheilitis)

GLOSSITIS: acute(swollen papillae, measles/scarlet fever). Chronic non-atrophic(raw red, NO swelling — pellagra/ariboflavinosis/niacin deficiency). CHRONIC ATROPHIC(atrophied papillae, smooth raw — iron deficiency/pernicious anaemia/sprue).

SYPHILIS: primary(lip chancre), secondary(maculopapular+mucous patches), tertiary(gummas/fibrosis-hard palate/tongue), congenital(angle fissures+Hutchinson’s incisors).

TB — rare, ulcers/nodules.

HIV — opportunistic infections(candidiasis/histoplasmosis/cryptococcosis/caries/mycobacterial/herpetic/CMV/HPV), tumours(Kaposi’s sarcoma-half have intraoral lesions, SCC, NHL), others(hairy leukoplakia, recurrent aphthous ulcers).

PIGMENTARY — Addison’s, Albright syndrome, Peutz-Jeghers, haemochromatosis; naevi, melanoma, exogenous(lead sulfide).

Tumours/tumour-like lesions

A. Tumour-like (NOT true neoplasms)

Fibrous growths(inflammatory/irritative): FIBROEPITHELIAL POLYPS(trauma), FIBROUS EPULIS(gingival, post-trauma; giant cell epulis variant=women, osteoclast-like giant cells), DENTURE HYPERPLASIA(ill-fitting denture irritation).

PYOGENIC GRANULOMA — bright red vasoproliferative, lips/tongue/buccal/gingiva. Pregnancy tumour=variant.

MUCOCELE — mucous gland cystic dilatation, ruptures→extravasation inflammation.

RANULA — large mucocele, mouth floor, TRUE epithelial lining.

DERMOID CYST — mouth floor, developmental, squamous lining, wall has sebaceous/sweat glands+hair follicles.

B. Benign tumours

Resemble elsewhere: squamous papilloma, HAEMANGIOMA(tongue→macroglossia, mostly capillary), LYMPHANGIOMA(tongue→macroglossia, lips→macrocheilia; cystic hygroma=neck variant in children), FIBROMA(COMMONEST benign oral mass, pedunculated, trauma-response, NON-neoplastic), fibromatosis gingivae(unknown etiology), minor salivary gland tumours(e.g. pleomorphic adenoma — see Diseases of the Salivary Glands), GRANULAR CELL TUMOUR(mesenchymal not odontogenic, tongue, EXCLUSIVELY FEMALES, granular polyhedral cells, pseudoepitheliomatous hyperplasia of covering epithelium; congenital epulis=infant equivalent). Other rare: neurilemmoma, neurofibroma, lipoma, giant cell granuloma, rhabdomyoma, leiomyoma, plasmacytoma, osteoma, chondroma, naevi, Osler-Rendu-Weber/Sturge-Weber vascular lesions.

C. Oral leukoplakia (white lesions)

DEFINITION: white patch/plaque >5mm, CANNOT be rubbed off, doesn’t fit other diagnosis — pathologist term for epithelial thickening spanning benign→premalignant.

Incidence: MALES more. Sites(↓freq): cheek>angles of mouth>alveolar mucosa>tongue>lip>palate>floor. 4-6% show carcinomatous change; SPECKLED/NODULAR forms more likely to progress. RULE: biopsy ALL oral white patches (visual triage alone unreliable given this rate).

Etiology: shares factors with oral CA. Strongest = TOBACCO(smoking-esp pipe/cigar, improves on cessation; chewing-paan/zarda/gutka) = smokers’ keratosis/stomatitis nicotina. Other: friction(dentures/jagged teeth), alcohol, hot/spicy food. HAIRY LEUKOPLAKIA = distinct AIDS variant, hairy/corrugated, NOT linked to cancer risk (key exception).

Morphology: Gross=white/yellow/red-velvety, >5mm, circumscribed, smooth/wrinkled/speckled/nodular. Micro (2 types):

1. HYPERKERATOTIC — orderly regular hyperplasia+surface hyperkeratosis
2. DYSPLASTIC — irregular stratification, abnormal mitoses, hyperchromatism, pleomorphism, loss of polarity, individual keratinisation. Mild dysplasia=reversible(remove cause); severe=progression risk. ERYTHROPLASIA=dysplastic variant, MORE atypia, HIGHER malignancy risk. Full-thickness dysplasia=CARCINOMA IN SITU→may progress to invasive.

D. Malignant tumours

SQUAMOUS CELL (EPIDERMOID) CARCINOMA — poor prognosis mainly from LATE detection.

Incidence: 90% of oral malignancies, 5% of ALL human malignancies. Peak: UK/US=55-75yrs; INDIA=YOUNGER(40-45yrs) — India/Sri Lanka/Eastern countries high frequency, linked to betel-nut chewing+reverse smoking (region-specific habits→age-of-onset shift). Sites(↓freq): lips(lower>upper)>tongue>anterior floor>buccal mucosa(alveololingual sulcus)>palate.

Etiology:

• STRONG: tobacco smoking/chewing(via leukoplakia, MOST important), alcohol, HPV(esp 16/18/33)
• WEAK: chronic irritation(dentures/teeth), submucosal fibrosis(chilli-linked, Indians), poor hygiene, nutritional deficiency, sunlight(lip CA), radiation, Plummer-Vinson syndrome

Molecular: p16, p53, p63, cyclin D, PTEN, EGFR.

Morphology — Gross: ULCERATIVE(most frequent, indurated, everted/rolled edges) > PAPILLARY/VERRUCOUS(soft, wart-like) > NODULAR(firm, slow) > SCIRRHOUS(deep infiltration). ±leukoplakia/erythroplasia background, ±cervical nodes.

Micro: well-diff keratinising→undifferentiated. Lip+intraoral usually well-differentiated. LIP CA=FAVOURABLE prognosis(visible, accessible, less nodal spread) vs INTRAORAL=POOR prognosis(late detection, early nodal spread esp tongue/soft palate) — prognosis split explained by SITE/ACCESSIBILITY not tumour biology. VERRUCOUS CARCINOMA=very well-diff, minimal atypia, VERY GOOD prognosis (deliberate “good” outlier).

Other malignant: melanoma, lymphoepithelial carcinoma, lymphoma, malignant minor salivary gland tumours, sarcomas(rhabdomyosarcoma/liposarcoma/alveolar soft part sarcoma/Kaposi’s/fibrosarcoma), metastatic tumours.

Clinical relevance

Leukoedema vs leukoplakia = compact pair — both white, only leukoplakia has malignant potential — explains the strict “cannot be rubbed off/otherwise classified” definition (excludes benign look-alikes). Biopsy-everything rule = follows from unreliable visual prediction (4-6% transformation rate broad enough that appearance alone insufficient). India’s younger oral CA age vs West = epidemiologic case study of etiology driving age-of-onset. Lip-vs-intraoral prognosis split = site/accessibility explains outcome, not tumour biology. Verrucous carcinoma’s good prognosis = deliberate exception within a poor-prognosis cancer category.

Overview

The oral cavity is the shared entry point for digestive and respiratory tracts. Mucosa: squamous epithelium over vascularised connective tissue — keratinised over the hard palate, lips, gingiva; non-keratinised elsewhere. Minor salivary (mucous) glands are scattered throughout; sebaceous glands occur only in the lips/buccal mucosa; lymphoid tissue forms tonsils/adenoids.

Developmental Anomalies

1. Facial clefts — cleft lip (harelip) and cleft palate, alone or combined; the commonest facial developmental anomalies, from failed facial-process fusion.
2. Fordyce’s granules — symmetric, small, light yellow lip/buccal macules from sebaceous gland collections; undeveloped until puberty, common in adults.
3. Leukoedema — asymptomatic, symmetric grey-white buccal areas in children; pronounced intracellular oedema histologically; no increased malignant potential, unlike leukoplakia.
4. Tongue defects: macroglossia (enlargement, usually lymphangioma/haemangioma, sometimes amyloid); microglossia/aglossia (rare, small/absent tongue); fissured (scrotal) tongue (genetic, dorsal grooves, ± mild glossitis); bifid tongue (failed midline fusion); tongue tie (short/anteriorly-attached lingual frenum); hairy tongue (not a true developmental defect — hypertrophied, elongated, food/tobacco/oral-flora-stained filiform papillae).

Mucocutaneous Lesions

Oral lesions of skin diseases, similar morphology: lichen planus (interlacing whitening/keratosis network, mainly buccal mucosa); vesicular diseases — pemphigus vulgaris (oral lesions in all cases, initial presentation in ~half), pemphigoid (oral + conjunctival vesicles, older women), erythema multiforme (subepithelial vesicles, skin + mucosae), Stevens-Johnson syndrome (fatal severe erythema multiforme variant, post-sulfa-drug), epidermolysis bullosa (hereditary, subepidermal bullae).

Inflammatory and Pigmentary Diseases

Stomatitis (oral mucosal inflammation):

• Aphthous ulcers (canker sores) — commonest oral ulceration; unknown etiology, precipitated by emotional stress, allergy, hormonal imbalance, nutritional deficiency, GI disturbance, trauma; painful ulcers ≥1 cm; recurrent aphthae may be part of Behçet’s syndrome or IBD.
• Herpetic stomatitis — acute, infants/children; commonest primary HSV manifestation; perioral vesicles; recurrence from stress, emotional upset, URI.
• Necrotising stomatitis (Noma/Cancrum oris) — poorly-nourished children (kwashiorkor), post-measles, immunodeficiency, emotional stress; marginal gingival necrosis extending to cheek cellulitis, possibly cheek gangrene.
• Mycotic infections — cervicofacial actinomycosis (commonest form, mandible angle); candidiasis/thrush (Candida albicans, opportunistic in immunocompromised, palatal erythema, angular cheilitis).

Glossitis — acute (swollen papillae, measles/scarlet fever); chronic non-atrophic (raw red tongue, no swelling — pellagra, ariboflavinosis, niacin deficiency); chronic atrophic glossitis (atrophied papillae, smooth raw tongue — iron deficiency anaemia, pernicious anaemia, sprue).

Syphilitic lesions — primary (extragenital lip chancre), secondary (maculopapular eruption, mucous patches), tertiary (gummas/diffuse fibrosis, hard palate/tongue), congenital (angle-of-mouth fissures, Hutchinson’s incisors).

Tuberculous lesions — rare, ulcers or elevated nodules.

HIV infection — associated with opportunistic infections (candidiasis, histoplasmosis, cryptococcosis, dental caries/periodontitis, mycobacterial infection, herpetic stomatitis, CMV, HPV), tumours (Kaposi’s sarcoma — ~half of cases have intraoral lesions, squamous cell carcinoma, non-Hodgkin lymphoma), and other findings (hairy leukoplakia, recurrent aphthous ulcers).

Pigmentary lesions — melanotic pigmentation in Addison’s disease, Albright syndrome, Peutz-Jeghers syndrome, haemochromatosis; also pigmented naevi, malignant melanoma, exogenous pigmentation (e.g. lead sulfide).

Tumours and Tumour-like Lesions

A. Tumour-like Lesions

• Fibrous growths (not true tumours — inflammatory/irritative): fibroepithelial polyps (chronic-trauma reparative fibrous tissue), fibrous epulis (gingival connective tissue hyperplasia post-trauma/inflammation; giant cell epulis variant — women, osteoclast-like giant cells), denture hyperplasia (ill-fitting denture/elongated tooth irritation).
• Pyogenic granuloma — elevated, bright red, vasoproliferative inflammatory lesion (lips/tongue/buccal mucosa/gingiva); pregnancy tumour is a variant.
• Mucocele (mucous/retention cyst) — cystic mucous gland dilatation; ruptures on distension, causing mucous extravasation inflammation.
• Ranula — large mucocele on the mouth floor, true epithelial lining.
• Dermoid cyst — mouth-floor developmental malformation; stratified squamous lining; wall contains sebaceous glands, sweat glands, hair follicles.

B. Benign Tumours

Mostly resemble their counterparts elsewhere: squamous papilloma (finger-like projections, vascularised core); haemangioma (anywhere, tongue involvement → macroglossia, mostly capillary type); lymphangioma (tongue → macroglossia, lips → macrocheilia; cystic hygroma variant in children’s lateral neck; large endothelium-lined lymphatic spaces); fibroma (commonest benign oral mass, pedunculated, trauma-response, non-neoplastic); fibromatosis gingivae (unknown-etiology gingival fibrous overgrowth, occasionally covering teeth); tumours of minor salivary glands (e.g. pleomorphic adenoma — see Diseases of the Salivary Glands); granular cell tumour (formerly granular cell myoblastoma, mesenchymal not odontogenic origin, tongue-predominant, exclusively females, large polyhedral granular cells, pronounced pseudoepitheliomatous hyperplasia of covering epithelium; congenital epulis is the infant equivalent); other rare benign tumours (neurilemmoma, neurofibroma, lipoma, giant cell granuloma, rhabdomyoma, leiomyoma, solitary plasmacytoma, osteoma, chondroma, naevi, and vascular lesions of hereditary haemorrhagic telangiectasia/Osler-Rendu-Weber syndrome and Sturge-Weber syndrome).

C. Oral Leukoplakia (White Lesions)

Definition: a white patch/plaque on oral mucosa, >5 mm, that cannot be rubbed off and doesn’t fit any other diagnosable disease — reserved by pathologists for epithelial thickening ranging from entirely benign to atypical/premalignant.

Incidence: more frequent in males. Sites of predilection (descending frequency): cheek mucosa, angles of mouth, alveolar mucosa, tongue, lip, hard/soft palate, mouth floor. 4–6% show carcinomatous change; speckled/nodular forms are more likely to progress. All oral white patches should be biopsied to exclude malignancy.

Etiology: shares etiologic factors with oral carcinoma (below) — strongest association with tobacco (smoking, especially pipe/cigar, improving on cessation; and chewing — paan, paan masala, zarda, gutka); also called smokers’ keratosis/stomatitis nicotina. Other factors: chronic friction (ill-fitting dentures, jagged teeth), alcohol excess, very hot/spicy food/drink. Hairy leukoplakia — a distinct AIDS-associated variant with a hairy/corrugated surface, not linked to oral cancer risk.

Morphology: Gross — white/whitish-yellow/red-velvety, >5 mm, circumscribed, slightly elevated, smooth/wrinkled/speckled/nodular. Micro — two types:

1. Hyperkeratotic type — orderly, regular squamous hyperplasia with surface hyperkeratosis.
2. Dysplastic type — irregular epithelial stratification, focal abnormal/increased mitoses, hyperchromatism, pleomorphism, loss of polarity, individual cell keratinisation; subepithelial lymphoplasmacytic infiltrate. Severity of epithelial change indicates dysplasia severity — mild dysplasia may revert with removal of the causative factor, while severe dysplasia suggests progression risk to carcinoma. Erythroplasia is a dysplastic-leukoplakia form with more marked atypia and higher malignancy risk. Full-thickness dysplasia = carcinoma in situ, which may progress to invasive carcinoma.

D. Malignant Tumours

Squamous cell (epidermoid) carcinoma — oral cancer has a very poor prognosis largely because it is recognised/treated late.

Incidence: 90% of oral malignant tumours, 5% of all human malignancies. Peak age in the UK/US is 55–75 years; in India, notably younger (40–45 years) — oral cancer is very frequent in India, Sri Lanka, and Eastern countries, likely linked to betel-nut chewing and reverse smoking habits. Sites of predilection (descending frequency): lips (more often lower), tongue, anterior mouth floor, buccal mucosa (alveololingual sulcus region), palate.

Etiology:

• Strong association: tobacco smoking/chewing (via leukoplakia, the most important factor); chronic alcohol consumption; HPV infection (especially types 16, 18, 33).
• Weak association: chronic irritation (ill-fitting dentures, jagged teeth); submucosal fibrosis (excess chilli consumption, seen in Indians); poor orodental hygiene; nutritional deficiency; sunlight exposure (lip cancer); radiation exposure; Plummer-Vinson syndrome (upper alimentary tract atrophy).

Common molecular oncogene alterations: p16, p53, p63, cyclin D, PTEN, EGFR.

Morphology — Gross patterns: ulcerative type (most frequent — indurated ulcer, firm everted/rolled edges); papillary/verrucous type (soft, wart-like); nodular type (firm, slow-growing submucosal nodule); scirrhous type (deep-structure infiltration). All types may arise on a leukoplakia/erythroplasia background; ± enlarged cervical nodes.

Micro: ranges well-differentiated keratinising to highly undifferentiated; epithelial dysplasia often surrounds the lesion. Lip carcinoma and intraoral squamous carcinoma are usually well-differentiated. Lip carcinoma has a more favourable prognosis — visible, accessible, less frequent nodal metastasis — while intraoral squamous carcinoma has poor prognosis from late detection and early nodal metastasis, especially tongue and soft palate carcinoma. Verrucous carcinoma — a very well-differentiated variant with minimal atypia — has a very good prognosis.

Other malignant tumours: malignant melanoma, lymphoepithelial carcinoma, malignant lymphoma, malignant minor salivary gland tumours, various sarcomas (rhabdomyosarcoma, liposarcoma, alveolar soft part sarcoma, Kaposi’s sarcoma, fibrosarcoma), and metastatic tumours.

Clinical Relevance

• The leukoedema-vs-leukoplakia distinction is a compact, high-value pair: both present as white oral changes, but only leukoplakia carries malignant potential — this is precisely why the “cannot be rubbed off, cannot be otherwise classified” definitional requirement for leukoplakia matters clinically, since it excludes benign look-alikes.
• The biopsy-everything rule for oral white patches follows directly from the difficulty of visually predicting which leukoplakia will transform — speckled/nodular appearance raises suspicion, but the stated 4–6% malignant transformation rate applies broadly enough that visual triage alone is unreliable.
• India’s markedly younger oral cancer peak age (40–45 vs 55–75 in the West) is a genuinely important epidemiologic fact tracing directly back to region-specific habits (betel-nut chewing, reverse smoking) — worth remembering as a case study in how etiology drives age-of-onset shifts.
• The lip-vs-intraoral prognosis split (favourable vs poor) despite both being predominantly well-differentiated squamous cell carcinoma is explained entirely by anatomic accessibility and detection timing rather than tumour biology — a useful reminder that prognosis in oral cancer is often more about site than grade.
• Verrucous carcinoma’s excellent prognosis despite being a squamous cell carcinoma variant is worth flagging as a deliberate exception — its minimal atypia and indolent behaviour make it the “good” outlier in an otherwise poor-prognosis cancer category.

• Leukoplakia progression spectrum: hyperkeratotic → dysplastic (mild/severe) → erythroplasia → carcinoma in situ → invasive carcinoma
• Oral cavity map showing squamous cell carcinoma’s sites of predilection in descending frequency

Multiple Choice Questions (3)