Tongue cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2] Mohammed Abdelwahed M.D[3]

Overview

Tongue cancer must be differentiated from other diseases that cause malignant lesions of the oral cavity and from non-neoplastic lesions of the oral cavity, such as lymphoma, sarcoma,, metastatic tumor, malignant salivary gland tumors, tuberculosis, scarlet fever, syphilis, papilloma, lipoma, leiomyoma, neurofibroma, schwannoma, granular cell tumor, benign migratory glossitis, Hairy tongue, pemphigus, erythema multiforme, mucous membrane pemphigoid, vitamin B deficiency, amyloidosis, diabetes mellitus, hypothyroidism, acromegaly.

Differential Diagnosis

The differential diagnosis for a squamous cell carcinoma of the tongue is essentially that of other malignant lesions of the oral cavity as well as a few non-neoplastic lesions. It includes the following:

Other malignancies:

• Lymphoma
• Sarcoma
• Metastatic tumor
• Malignant salivary gland tumors

Infections:

• Tuberculosis
• Scarlet fever
• Syphilis

Benign neoplasm:

• Papilloma
• Lipoma
• Leiomyoma
• Neurofibroma
• Schwannoma
• Granular cell tumor

Idiopathic:

• Benign migratory glossitis
• Hairy tongue
• Pemphigus
• Erythema multiforme
• Benign mucous membrane pemphigoid

Metabolic causes:

• Vitamin B deficiency
• Amyloidosis
• Diabetes mellitus
• Hypothyroidism
• Acromegaly

		Location	Clinical presentation		Investigations	Others
			Symptoms	Signs
Infections	Tuberculosis (TB)	Dorsum	Primary TB symptoms: night fever, sweating, bloody cough, and loss of weight Painful tongue ulcers	Ulcer: irregular outline, undulated borders, and covered with a yellowish-gray, and fibrinous layer	Culture and biopsy Chest x-ray for primary infection Tuberculin skin test
	Scarlet fever	Dorsum	Fever, malaise, headache, pharyngitis Red skin rash Swelling of tongue, white and red coating	Heavy gray-white coating Enlargement of the fungiform papillae, which appear as multiple red dots Dots disappear with time	Throat swab and culture Rapid streptococcal antigen tests	Mainly in children due to group A streptococcal infection
	Syphilis	Dorsum	Single or multiple painless masses or ulcers according to the stage White patches of leukoplakia Symptoms of generalized syphilis in secondary and tertiary stages especially generalized lymphadenopathy	The primary stage The lingual chancre is a solitary, painless, slightly raised, well-demarcated ulcer Enlarged, painless, regional lymph nodes The secondary stage: The mucous patches are slightly raised, grayish-white, and usually surrounded by a red halo If the lesion is scraped, it leaves a raw, bleeding surface The third stage: The gumma appears as a painless, elastic mass that subsequently undergoes central necrosis and ulceration Atrophy of the papillae Frequently associated with leukoplakia, which has a tendency to undergo malignant transformation	Dark-field illumination reveal the causative organism Rapid plasma reagin Venereal Disease Research Laboratory
Benign neoplasms	Papilloma	Dorsum and lateral borders	Painless slowly growing mass	Warty surface or consist of hyperkeratotic finger-like projections Sessile or pedunculated, pink to white color	Biopsy
	Lipoma	Dorsum and lateral borders	Painless slowly growing mass	Soft, sessile, and yellowish	Biopsy
	Leiomyoma	Dorsum	Painless slowly growing mass	Small, single or multiple, circumscribed mass	Biopsy
	Schwannoma	Dorsum and lateral borders	Painless slowly growing lesions, may be painful	Firm, submucosal mass	Biopsy
	Neurofibroma	Dorsum and lateral borders	Slowly growing multiple nodules Unilateral macroglossia	Tongue may show multiple nodules or there may be a more diffuse involvement causing unilateral macroglossia	Biopsy
	Granular cell tumor	Dorsum	Painless, firm, slwoly growing nodules	Submucosal nodules with a yellowish or pinkish color	Biopsy
Malignant neoplasms	Squamous cell carcinoma	Lateral borders	Painless ulcer or exophytic mass. History of heavy use of alcohol and tobacco	The lesion has an ulcerated appearance with rolled borders around a necrotic center It frequently resembles a traumatic ulcer	Biopsy Computed tomography
	Malignant salivary gland tumors	Ventral and dorsum	Slow-growing, painless mass		Submueosal mass May ulcerate in the later stages
	Metastatic tumor	Base of tongue	Painful mass Dysphagia Symptoms of primary tumor	Mass in tongue base Cachexia and loss of appetite Signs of primary tumor	Mass in tongue base Cachexia and loss of appetite Signs of primary tumor	Subtypes: Mucoepidemoid tumors Acinic cell tumors Adenocarcinomas
	Sarcoma	Palate and tongue	Painless slowly growing mass Dysphagia and weight loss	Reddish or bluisb macules that then coalesce to form purplish nodules and may get ulcerated	Biopsy	Subtypes:  Fibrosarcoma Alveolar soft-part sarcoma Rbabdomyosarcoma Leiomyosarcoma Synovial sarcoma Chondrosarcoma Neurogenic sarcoma Kaposi's sarcoma
Idiopathic	Benign migratory glossitis	Dorsum	Painless redish ulcerative lesions	The lesions appear as one or more irregularly shaped, reddish areas of depapillation surrounded by a narrow, whitish zone of regenerating papillae
	Hairy tongue		Tongue color changes	Hypertrophy of the filiform papillae Tongue color will vary from yellowish-white to brown or black		Risk factors: Tobacco Radiation therapy
Metabolic	Diabetes mellitus	Dorsum	Burning and dryness White plaques on the dorsum of tongue due to Candidal infection in uncontrolled cases	Lingual papillary atrophy	Throat swab Blood glucose level HBA1C
	Hypothyroidism		Dry mouth Difficulties in eating and speaking Tongue swelling	Tongue protrusion Macroglossia	TSH level T3 and T4 levels
	Acromegaly	Generalized	Swollen tongue Lingual indentations	Hyperplasia of the epithelium and connective tissue Macroglossia Spacing and labial tilting of the teeth	Serum IGF-1 concentration Oral glucose tolerance test
	Vitamin B deficiency	Dorsum	Redness in the tip and margins of the tongue Swelling of the tongue Indentations of the teeth Associated neurological symptoms due to niacin and B12 deficiency	Atrophy of both the filliform and fungiform papillae	Serum vitamin B12 and folate levels CBC and blood smear
	Amyloidosis	Lateral borders	Enlarged tongue Decrease in lingual mobility Difficulty in chewing, swallowing and speaking	Generalized induration Yellowish nodules	Tongue biopsy Abdominal fat pad biopsy  Monoclonal pattern on serum protein electrophoresis (SPEP)
Immunologic disorders	Benign mucous membrane pemphigoid	Generalized	Women over the age of 50 Painful bullae or ulcerations	Yellow or hemorrhagic bullae on an erythematous background Bullae rupture leaving a fibrin-covered ulceration	Biopsy Indirect immunofluorescence Autoantibodies against BP180, BP230, laminin 332
	Erythema multiforme	Generalized	It occurs primarily in young men	Small, erythematous plaque that then becomes a vesicle, quickly rupture and become confluent, shallow erosions covered by a pseudomembrane of necrotic tissue	The cause of this disorder is an infectious disease such as Herpes simplex, Coxsackie virus, or drug therapy
	Pemphigus	Generalized		Bullae rupture soon after formation to produce ulcers (pemphigus vulgaris) Fungoid vegetations develop on the base of these ulcers (pemphigus vegetans)	ELISA for antibodies to the BP180 NC16A Biopsy