Parathyroid cancer differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Parathyroid cancer must be differentiated from other conditions presenting as a neck swelling.

Differentiating Parathyroid cancer from other Diseases

Parathyroid cancer must be differentiated from other conditions presenting as neck swelling. The differentials include the following:

Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings
Neoplasm	Hypopharyngeal cancer		Malignant	More common in males Age: 55-65 years old Incidence: < 1/100,000 in U.S. More common in Japan, India, Iran	Tobacco use Abuse alcohol consumption HPV infection Lump in the neck Odynophagia Hoarseness	−	+	Non tender cervical node	Lymphadenopathy	−	Spindle cells Nuclear atypia Basaloid cells Abundant chromatin	Neck CT scan: Soft tissue mass Irregular thickening of mucosa Necrotic region MRI: Tumors are hypointense on T1 and hyperintense on T2	Biopsy	−
	Parathyroid cancer		Malignant	Incidence: Rare Mean age : 44-54 years old Gender: Female predilection	Presents with the hyperparathyroidism Bone pains Abdominal pain Nausea and vomiting Fatigue Confusion	+	+	Lower neck mass	Tachycardia Weight loss Sweating Neck swelling	Low TSH Increased T4 and T3 Hypercalcemia	Microscopic findings: Trabecular growth pattern High mitosis Surrounding thick fibrotic bands Capsular involvement Vascular invasion is common	CT and MRI shows more frequent lower lobe involvement, vascular involvement , lymph node metastasis, and perineural involvement Bone scan may show decreasing bone density	Biopsy and histopathological examination	Hereditary syndromes MEN-2B syndrome Neurofibromatosis type 1 VHL disease
	Carotid body tumors		Benign	Age: 26-55 years Male predominance	A slow growing neck mass	+	−	Mobile Non-tender neck mass (horizontally more than vertically) Pulsatile Bruit may be present	Change in voice Dizziness Tinnitus Headache	Rasised catecholamine levels	Microscopically they are extra-adrenal paragangliomas	Doppler ultrasound, CT, MRI and angiography is used to visualize the tumor Metaiodobenzylguanidine (MIBG) testing	Histopathology analysis and catecholamine levels	−
	Paraganglioma		Benign (Majority) Malignant (rare)	Age 50-70 years More in females	May be an accidental finding depending on their secretory nature or present with following symptoms: Palpitation Tremor Pulse-like vibratory sense Headache Change in voice Vertigo Catecholamine secreting paragangliomas presents with : Hypertension Headache Sweating Tachycardia	−	−	No visible mass Located deep in the the neck along the glossopharyngeal nerve	−	Biochemical testing may show catecholamine metabolites in serum or urine samples	Highly vascular tumors that involves nerves around vessels Gross findings: Fleshy tumor Pink to red-brown to gray in color Associated with hemorrhage or fibrosis Microscopic findings: Round or polygonal cells Nests or trabecular structures inside the capsule	Ultrasound Computed tomography Magnetic resonance imaging Angiography metaiodobenzylguanidine (MIBG) 18F-fluoro-2-deoxyglucose Positron emission tomography (FDG-PET)	Imaging and serum catecholamine analysis	−
Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings
Neoplasm	Schwannoma		Benign	Rare tumor Incidence: 1-10%	Slow growing mass Localized neural deficit depending on the site of peripheral nerve involved Vagus nerve or superior cervical sympathetic chain involvement (most common locations)	+	±	Multiple Slow growing nodules on the skin	Vagal involvement: Hoarseness Dysphagia Sympathetic nerve involvement may present as Horner's syndrome: Dilated pupil Decrease sweating Dropping eyelid Vestibular nerve involvement & Hearing impairment (most common)	May be normal	Encapsulated neural tissue growth	Resembling Carotid body tumor on CT MRI and MRI angiography confirm the diagnosis	Imaging	neurofibromatosis type II
	Lymphoma		Benign or malignant	Age: Predilection for older age Mean age: 55	Insidious onset slow growing lymph nodes Non-specific systemic B symptoms: Fever Night sweats Weight loss) Rash Waxing and waning lymphadenopathy Abdominal fullness	−	±	Multiple chain lymphadenopathy Hepatosplenomegaly Ascites Crackles heard on chest auscultation	Rash and pruritus	Pancytopenia Hypercalcemia Hyperuricemia (increased cell turnover) Monoclonal immunoglobulin (M-spike) Raised LDH levels	On complete node analysis four patterns are described: Nodular/follicular Diffuse pattern Transition from a nodular to a diffuse pattern in adjacent nodes Transition from a lower to a higher grade of involvement within a single node	Imaging to stage the disease Positron emission tomography with computed tomography is preferred over MRI	Lymph node biopsy coupled with cytometry	Infections due to cytopenias With acquired form of C1 inhibitor deficiency patients may develop angioedema
	Liposarcoma		Malignant	Rare tumor Age: Relatively in older age Gender: No gender predilection	Mobile mass Few symptoms until they grow enough to compress the surrounding structures Symptoms of neural deficit, pain, tingling, or skin changes	±	−	Mobile soft mass Intact overlying skin Blue discoloration due to intra-lesion hemorrhage	Intact skin and normal color	Normal	Gross examination: Bulk of yellow colored fat tissue Microscopic features: Adipose tissue containing lipoblasts Atypical nucleus pushed to side by intracytoplasmic vacuoles Tissue biopsy may show histological sub-groups: Well-differentiated Myxoid/round cell Pleomorphic liposarcomas	Imaging not usually required for diagnosis May show deeper invasion Ultrasound shows homogeneous hyperechoic mass	Biopsy and histopathology analysis	−
Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings
Neoplasm	Lipoma		Benign	Genetic predisposition Unspecific gender or age association	One or multiple soft, painless skin nodules May causes pain or compressive symptoms	±	−	Mobile soft nodule Intact overlying skin	Normal	Normal	Diagnoses is usually clinical Tissue biopsy may show: Bundle of well-demarcated lipocytes Single nuclei aligned to the side Intra-cytoplasimic fat granules	Diagnosis is usually clinical ultrasound is used to differentiate lipoma from other benign lesions such as: Epidermoid cyst A ganglion	Clinical evaluation	Multiple lipomas Associated with familial multiple lipomatosis
	Glomus vagale, glomus jugulare tumors		Benign	Rare tumor	Painless slowly enlarging mass in the neck	−	±	Non-compressible Firm Non-tender swelling No thrill or bruit Normal overlying skin	Secretory tumors May have compressive signs such as: Dysphagia Hoarseness Cranial nerves deficits Horner's syndrome	Normal	Glomus tumors arise from Non Chromaffin cells histopathology reveals "salt and pepper" chromatin On immunohistochemistry tumor cells show chromogranin and S-100 positivity	MRI (Imaging of choice): Typical appearance of the tumor along vagus nerve Ultrasonography (early stage of diagnosis): Isoechoic to hypoechoic well defined tumor CT: Vascularity of the tumor Biochemical testing: Shows secretary nature of the tumor	Imaging and Metaiodobenzylguanidine (MIBG) testing	−
	Metastatic head and neck cancer		Malignant	Depends on the nature of metastatic tumor	Asymptomatic Painless lymphadenopathy Supra clavicular fullness in case of stomach cancer metastasis	−	±	Non-tender mass in the neck Non-tender lymphadenopathy	Majority of metastatic head and neck cancer Metastatise from GIT and lungs	Vary depending on the underlying cancer	Histology of primary cancer	CT and MRI to see extent of tumor	Biopsy and histopathology of the primary site of tumor	−
Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings
Other	Laryngeal cancer		Benign/Malignant	Older males Younger patients with HPV infection or smoking history	Neck mass Hoarseness Throat pain Snoring Obstructive sleep apnea	±	±	Examination of neck and oral cavity may show : mass lymphadenopathy Examination of laryngeal cancer is done using flexible laryngoscopy under anesthesia.	Smoking is the most common risk factor Smoking with alcohol increases the risk Oropharyngeal cancers presenting with neck masses are associated with human papillomavirus (HPV) infection	HPV testing may show HPV infection	FNA of neck mass Followed by biopsy of laryngeal cancer Show type cancer cells	CT, MRI and PET are used to see local infiltration by cancer Also to see distant metastases. Panendoscopy is done to see extent of the tumor.	Laryngoscopy and biopsy	−
	Arteriovenous fistula		Benign/Malignant	Depends on the risk factors	Expanding neck mass Headaches Dizziness Neurological sequels	−	−	Pulsating neck mass Bruit	May be associated with vasculopathies metastatic invasion of vessels and neck surgery		Varies depending on the etiology	MR angiography	MR angiography	−
	Thyroid nodule/ Goiter		Benign/ Malignant	Female predominance Young age (benign causes) Old age (malignant etiology)	Growing painless neck mass in front of neck Weight loss Palpitation Hoarseness Irritability	±	±	Painless Non-tender Asymmetrical neck mass in front of neck With smooth overlying skin Nodular surface Depending on the type: May be mobile Adherent to the underlying structure Lymphadenopathy in case of malignant features	Goiter is most commonly associated with iodine deficiency	Normal to low TSH levels in case of malignancy High TSH levels in case of goiter	FNA is done in case of goiter Core biopsy is performed if malignancy is suspected	USG: Shows nodular or non- nodular lesions in Thyroid US is better than CT. Thyroid radionuclide imaging: Shows radioiodine uptake Cold in case of malignancy Cold or hot in case of goiter.	Biopsy and histopathology of nodules	−
Category	Diseases		Benign	Demography	History	Pain	Dysphagia	Mass exam	Others	Lab findings	Histopathology	Imaging	Gold standard diagnosis	Associated findings