Oral cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

Overview

There are different types of cancers of the oral cavity and oropharynx. It is important that they are differentiated from one another.

Oral cancer differential diagnosis

The table below outlines the different types of tumors/cancers present in the oral cavity and oropharynx and how they can be differentiated from one another.

Type of cancer	Subtype	ICD-O Code	Epidemiology	Etiology	Localization	Clinical features	Diagnostic procedures
Squamous cell carcinoma Basaloid squamous cell carcinoma Papillary squamous cell carcinoma Spindle cell carcinoma Acantholytic squamous cell carcinoma Acantholytic squamous cell carcinoma Adenosquamous carcinoma	Verrucous carcinoma	8051/3	Older males 5th and 6th decades of life Males are affected more often than females	Tobacco smoking and alcohol Chronic smokeless tobacco HPV 16 and 18	Lip SCC arise almost exclusively on the lower lip Buccal mucosa Upper and lower gingiva Hard palate Anterior two-thirds of the tongue, including dorsal, ventral and lateral surfaces, and the floor of mouth	Often asymptomatic or may present with vague symptoms and minimal physical finding	Biopsy shows: Thickened club-shaped papillae and blunt stromal invaginations of well-differentiated squamous epithelium with marked keratinization
Lymphoepithelial carcinoma		8082/3	0.8-2% of all oral or oropharyngeal cancers	EBV	Tonsil and tongue(90%) Palate and buccal mucosa (others)	Intraoral mass, which may be ulcerated. Some tumors can be bilateral	Biopsy chows: Syncytial sheets and clusters of carcinoma cells with vesicular nuclei Prominent nucleoli and ill-defined cell borders A rich lymphoplasmacytic infiltrate is present
Epithelial precursor lesions	---	---	---	Smoking	Seen in the entire digestive tract	White patches (leukoplakia) Red patches (erythroplasia/erythroplakia) Mixed red and white lesions	Biopsy shows: Hyperplasia Dysplasia / squamous intraepithelial neoplasia / atypical hyperplasia Carcinoma in-situ
Proliferative verrucous leukoplakia and precancerous conditions	---	---	Average age at diagnosis is 62 years Women are more commonly affected (ratio, 4:1)	Unknown	Buccal mucosa in women Tongue in men.	An aggressive form of oral leukoplakia with considerable morbidity and strong predilection to malignant transformation	Biopsy shows: Extensive, thick, white plaques Hyperplasia and dense hyperkeratosis Verrucous surface with hyperkeratosis, hypergranulosis and a dense inflammatory infiltrate in the corium
Papillomas	Squamous cell papilloma and verruca vulgaris		Common in children and in adults in the 3rd to 5th decades Almost equal sex incidence with a slight male predominance	HPV sub-types 2, 4, 6, 7,10, and 40	Any oral site may be affected mostly: Hard and soft palate Labial mucosa Tongue Gingiva	Soft, pedunculated lesions formed by a cluster of finger-like fronds or a sessile, dome-shaped lesion with a nodular, papillary or verrucous surface	Biopsy shows: Exophytic and comprise folds of hyperplastic stratified epithelium Cluster of finger-like projections
	Condyloma acuminatum		2nd and 5th decade with a peak in teenagers and young adults	HPV- most common sub-types: 6, 11, 16 and 18	Labial mucosa Tongue Palate	Painless, rounded, dome-shaped exophytic nodules 15 mm in diameter Have a broad base and a nodular or mulberry-like surface that is slightly red, pink or of normal mucosal color. Lesions may be multiple and are then usually clustered	Biopsy shows: Several sessile, cauliflower-like swellings forming a cluster
	Focal epithelial hyperplasia	---	Disease of children, adolescents and young adults	HPV sub types: 13 and 32	All areas of the oral cavity Labia Buccal mucosa Tongue	Multiple asymptomatic lesions Soft rounded or flat plaque-like sessile swelling. Usually pink or white in color 2-10 mm in diameter	Biopsy shows: Rounded sessile swelling formed by a sharply demarcated zone of epithelial acanthosis Koilocytes similar to those of squamous papilloma are usually present “Mitosoid bodies”, which are nuclei with coarse clumped heterochromatin resembling a mitotic figure
Granular cell tumor	---	9580/0	Arise in all age groups, with a peak between 40 and 60 years Females are affected more often than males with an M/F ratio of 2:1	No etiological factors are known	Tongue is the most common single site Buccal mucosa Floor of oral cavity Palate Salivary gland	Lesion presents as a smooth, sessile mucosal swelling 1-2 cm in diameter with a firm texture The overlying epithelium is of normal color or may be slightly pale	Biopsy shows: Plump eosinophilic cells with central small dark nuclei and abundant granular cytoplasm
Keratoacanthoma	---	8071/1	Occurs more often in whites Twice as frequent in men as in women	Associated with uptake of carcinogens (e.g. via particular smoking habits)	Skin of the face, including the lips Mucocutaneous linings may also be involved	Verrucous, speckled or ulcerated lesions Deep projections, which extend through minor salivary glands and underlying bone	Biopsy shows: Verrucous surface, keratinized clefts and penetrating squamous rete processes Minimal atypia seen
Papillary hyperplasia	---	---	Affects all age groups	Associated with: Wearing ill-fitting dentures Xerostomia Individuals with a high-arched palate HIV infection	Palate	Asymptomatic nodular or papillary mucosal lesion	Biopsy shows: Parakeratinisation or less frequently orthokeratinisation
Median rhomboid glossitis	---	---	---	Associated with chronic candidal infection	Dorsum of the tongue at the junction of the anterior two-thirds and posterior third	Forms a patch of papillary atrophy in the region of the embryological foramen caecum	Biopsy shows: Psoriasiform hyperplasia Areas of pseudoepitheliomatous hyperplasia Atypia may be present
Salivary gland tumors	Acinic cell carcinoma	8550/3	2-6.5% of all intra-oral salivary gland tumors Age range from 11-77 years, with a mean of 45 years Male to female ratio of 1.5:1	Unknown	Buccal mucosa Upper lip Palate	Tumors usually form non-descript swellings	Biopsy shows: Solid sheets of epithelium with secretory material Ductal differentiation in tumors
	Mucoepidermoid carcinoma	8430/3	9.5-23% of all minor gland tumors	Unknown	Palate (most common site) Buccal mucosa Lips: upper>lower Floor of oral cavity Retromolar pad	Asymptomatic Bluish, domed swellings that resemble mucoceles or haemangiomas High-grade tumors result in ulceration, loosening of teeth, paraesthesia or anaesthesia	Low power microscopy shows low-grade tumor with both cystic and solid areas and an inflamed, fibrous stroma
	Adenoid cystic carcinoma	8200/3	42.5% of minor gland tumors	Unknown	Tongue Tonsil Oropharynx Cheek Lips Retromolar pad and gingiva	Slow growing sub-mucosal masses and ulceration may be seen, particularly in the palate Pain, or evidence of nerve involvement, is usually only present in advanced tumors	Predominantly solid variant shows peri- and intraneural invasion
	Epithelial-myoepithelial carcinoma	8562/3	---	Unknown	---	---	---
	Clear cell carcinoma, NOS	8310/3		Unknown	---	---	---
	Basal cell adenocarcinoma	8147/3	Rare in minor glands	Unknown	Palate Buccal mucosa Lip	Asymptomatic, smooth or lobulated sub-mucosal masses	Microscopically similar to basal cell adenocarcinomas of the major gland
	Cystadenocarcinoma	8450/3	32% developed in the minor glands	Unknown	Palate Lips Buccal mucosa Tongue and retromolar regions	Slow growing and painless but somepalatal tumors may erode the underlying bone-causing sinonasal complex	---
	Salivary duct carcinoma	8500/3	Rare in minor salivary glands Age range is 23-80 years (mean is 56 years)	Unknown	Palate (65%) Buccal mucosa and vestibule (19%) Tongue (8%) Retromolar pad (4%) and upper lip (4%)	Tumors form painless swellings but many in the palate can be painful and ulcerated or fungated withmetastases to regional lymph nodes	The range of microscopical appearances is similar to that seen in the major glands
Salivary gland adenomas	Pleomorphic adenoma	8940/0	40-70% of minor gland tumors	Unknown	Palate Lips Buccal mucosa	Painless, slow-growing, submucosal masses, but when traumatized may bleed or ulcerate	Biopsy shows cellular, and hyaline or plasmacytoid cell
	Myoepithelioma	8982/0	42% of minor gland tumors	Unknown	Palate of younger individuals	---	---
	Basal cell adenoma	8147/0	20% of minor gland tumors	Unknown	Upper lip Buccal mucosa	---	They are histologically similar to those in major glands.
	Cystadenoma	8149/0	7% of benign minor gland tumors	Uknown	Lips Cheek Palate	---	---
Kaposi sarcoma	---	---	Classic (elderly men of Mediterranean/East European descent) Endemic (middle-aged adults and children in Equatorial Africa, who are not HIV infected) Iatrogenic (Immunosuppressed, post-transplant) AIDS-associated (HIV-1 infected individuals)	HHV-8 Immunologic, genetic, and environmental factors	Skin (most common) Mucosal membranes, such as oral mucosa, lymph nodes and visceral organs	Purplish, reddish-blue or dark brown macules Plaques and nodules that may ulcerate	Biopsy of all 4 types show: Vascular slits and sparsely distributed lymphocytes
Lymphangioma	---	9170/0	Pediatric lesions Present at birth or during the first years of life Appear mostly in the head and neck area but may be found in any other part of the body	Developmental malformation Genetic abnormalities Turner's syndrome	Tongue	Circumscribed painless swelling Soft and fluctuant on palpation Irregular nodularity of the dorsum of the tongue	Biopsy shows: Thin-walled, dilated lymphatic vessels of different size, which are lined by a flattened endothelium
Ectomesenchymal chondromyxoid tumour of the anterior tongue	---	---	Age range varies from 9-78 years No distinct sex predilection.	Unknown	---	Asymptomatic, slow growing solitary nodule in the anterior dorsal tongue	Biopsy shows: Round, cup-shaped, fusiform, or polygonal cells with uniform small nuclei and moderate amounts of faintly basophilic cytoplasm Some tumors may show nuclear pleomorphism, hyperchromatism, and multinucleation
Focal oral mucinosis (FOM)	---	---	The lesion affects all ages Rare in children There is no distinct sex predilection.	Unknown	Gingiva (most common site) Palate Cheek mucosa Tongue	Asymptomatic fibrous or cystic-like lesion	Histopathology is characterized by: Well-circumscribed area of myxomatous tissue Fusiform or stellate fibroblasts Absent or sparse reticular fibers Mucinous material shows alcianophilia at pH 2.5
Congenital granular cell epuli	---	---	Affects newborns Females are affected ten times more often than males	Etiology uncertain	Maxilla Mandible	Solitary, somewhat edunculated fibroma-like lesion, attached to the alveolar ridge near the mid-line	Ultrasound for prenatal diagnosis Immuno-histochemically, the tumor cells are positive for vimentin and neuron specific enolase No reactivity with cytokeratin, CEA, desmin, hormone receptors or S-100
Hematolymphoid tumors	Non-Hodgkin lymphoma	---	Second most common cancer of the oral cavity	There is no known etiology in most patients Underlying immunodeficiency state (e.g. HIV Infection) Strong association with EBV	Palate Tongue Floor of mouth Gingiva Buccal mucosa Lips Palatine tonsils Lingual tonsils Oropharynx	NHL of the lip presents with: Ulcer Swelling Discoloration Pain Paresthesia Anesthesia Loose teeth	Biopsy shows: Large cells with predominantly round nuclei and membrane-bound nucleoli, consistent with centroblastic morphology. Predominantly medium-sized cells with abundant pale cytoplasm. Large cells with round or multilobated nuclei
	Langerhans cell histiocytosis	9751/1	---	Associated with: Eosinophilic granulomas Multifocal multisystem disease	Jaw bone Intra-oral soft tissues Gingiva Palate Floor of mouth Buccal mucosa Tonsil	Common oral symptoms include: Swelling Pain Gingivitis Loose teeth Ulceration	Biopsy shows ovoid Langerhans cells with deeply grooved nuclei, thin nuclear membranes and abundant eosinophilic cytoplasm
	Hodgkin lymphoma		---	Strongly associated with Epstein- Barr Virus	Waldeyer ring, particularly the palatine tonsil Oropharynx Alveolar crest of mandible Maxillary gingiva	Most patients present with localized disease (stage I/II), with Chronic tonsillitis or tonsillar enlargement with or without enlarged cervical lymph nodes	---
	Extramedullary myeloid sarcoma	9930/3	---	History of acute myeloid leukaemia, predominantly in the monocytic or myelomonocytic sub-types	Palate Gingiva	Isolated tumor-forming intra-oral mass	Biopsy shows an Indian-file pattern of infiltration
	Follicular dendritic cell sarcoma / tumour	9758/3	Tumor of adulthood Affects wide age range	History of underlying hyaline-vascular Castleman disease	Tonsil Palate Oropharynx	The patients usually present with a painless mass	Biopsy usually exhibits borders and comprises: Fascicles Whorls Nodules Storiform arrays Diffused sheets of spindle to ovoid tumor cells sprinkled with small lymphocytes
Mucosal malignant melanoma	---	8720/3	0.5% of oral malignancies Incidence 0.02 per 100,000	No known etiological factors associated with oral melanoma	80% arise: Palate Maxillary alveolus or gingivae Mandibular gingiva Others: Buccal mucosa Floor of mouth Tongue	Asymmetric with irregular outlines Macular pigmentation Nodular growth Ulceration Melanosis	Biopsy: S100 positive Negative for cytokeratins More specific markers include: HMB45 Melan-A or anti-tyrosinase

References

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