Papillary thyroid cancer differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Overview

Papillary thyroid cancer must be differentiated from other diseases that cause neck mass, such as branchial cleft cyst, thyroglossal duct cyst, cystic metastasis, and multiple neurofibromas.

Differentiating Papillary thyroid cancer from other Diseases

• Other thyroid neoplasms should be considered in the absence of cavitary cervical lymph nodes.
• The differential of a cystic neck mass(es) includes:

• Thyroglossal duct cyst (only if single)
• Branchial cleft cyst (only if single)
• Cystic metastasis
• Abscess including tuberculous lymphadenitis
• Multiple neurofibromas

• Papillary thyroid cancer must be differentiated from other thyroid cancers as well as other disorders:

Disease name	Age of onset	Gender preponderance	Signs/Symptoms	Imaging Feature(s)	Macroscopic feature(s)	Microscopic feature(s)	Laboratory Feature(s)	Other Feature(s)	Microscopic appearance
Papillary Thyroid Cancer	More common in middle aged (30-50 years of age)	More commonly affects women	Asymptomatic thyroid mass or nodule Compressive symptoms such as: Difficulty swallowing/breathing Persistent cough Stridor Vocal chord paralysis Rapid enlarging mass	Ultrasound: solitary mass with an irregular outline, in the subcapsular region and with high vascularity Imaging features are not characteristic for this cancer	Solitary hypoechogenic nodule with lobulated margin which may extend into adjacent tissues Calcification may be present or not	Empty-appearing nuclei with central clearing (Orphan Annie eye) Psammoma bodies	Thyroid function test may be normal Thyroglobulin may be used as a tumor marker	History of radiation in head and neck BRAF and/or RET mutation may be present Most common type of thyroid cancer	Source:Wikimedia commons
Follicular Thyroid Cancer	Peak incidence is 40-60 years of age	More commonly affects women	Asymptomatic thyroid mass or nodule Compressive symptoms such as: Difficulty swallowing/breathing Persistent cough Stridor Vocal chord paralysis Rapid enlarging mass	Ultrasound: solid hypoechoic nodule with a peripheral halo indicating fibrous capsule Irregular margin Imaging features are not characteristic for this cancer	Single encapsulated nodule, Thick and irregular capsule May have cystic or hemorrhage	Invades thyroid capsule and vasculature Uniform follicles	Thyroid function test may be normal Serum thyroglobulin may be used as a tumor marker	RAS mutation may be present PAX8-PPAR-γ translocations	Source:Wikimedia common
Medullary Thyroid Cancer	Incidence increases with age More common in 3rd to 4th decades of life	Both genders affected equally	Solitary thyroid nodule Mostly affects upper lobe of thyroid gland Possible systemic symptoms due to hormonal secretion by the tumor Cervical lymphadenopathy	Ultrasound: solitary hypoechoic nodule with or without calcification Imaging features are not characteristic for this cancer	Single nonencapsulated mass Gray-tan color	Sheets of cells in an amyloid stroma	Secretes calcitonin Normal thyroid function test Carcinoembryonic antigen (CEA) may be used as a tumor marker Rarely negative for calcitonin	May be part of MEN 2A and 2B syndrome May be associated with RET mutation	Source:Wikimedia common
Anaplastic Thyroid Cancer	More common among older individuals Mean age at diagnosis is 65 years	More commonly affects women	Rapidly enlarging thyroid mass May manifest with compressive symptoms May present with signs/symptoms of metastasis Constitutional symptoms may be present Hard nodular goiter w/out tenderness	Ultrasound: solid hypoechoic nodule with a peripheral halo indicating fibrous capsule Irregular margin Imaging features are not characteristic for this cancer	Solid tumor with areas of necrosis and hemorrhage Infiltrative pattern	Undifferentiated, devastatingly aggressive variant of Papillary/Follicular thyroid cancer	Normal thyroid function test	Poor prognosis May be associated with TP53 mutation	Source:Wikimedia common
Follicular Adenoma	More commonly affects individuals older than 50 years of age	More commonly affects women	Asymptomatic or symptoms of hyperthyroidism	Solitary nodule which may show echogenicity or not	Solitary, spherical, and encapsulated lesion Well demarcated from the surrounding parenchyma	Uniform follicles Absence of capsular or vascular invasion	Functional adenoma: Elevated T3, T4 Decreased TSH	May be considered functional or hot May be considered non-functional or cold	Source:Wikimedia common
Multinodular Goiter	Commonly affects individuals older than 60 years of age	More commonly affects women	Thyroid enlargement Signs/symptoms of hypo/hyperthyroidism	Multiple nodules with different echogenicity Calcification may be present	Multiple thyroid nodules	Variable sized follicles Some may show papillary projections without nuclear characteristics of papillary thyroid cancer	Classified as toxic and non-toxic Toxic => hyperthyroidism Non-toxic => Normal thyroid function test	Benign condition	Source:pathology outline, case courtesy of Dr. Swati Satturwar
Thyroid Lymphoma	Affects adults or elderly	More common among women	Rapidly enlarging mass/ nodule of thyroid Compression symptoms may be present Constitiutional symptoms may be present in 10% P/E:Firm, hard thyroid Fixed to the nearby structure Immobile even during swallowing Cervical or supraclavicular lymphadenopathy may be present	Ultrasound: hypoechogenic appearance difficult to be distinguished from chronic thyroiditis	Thyroid nodule/mass fixing to adjacent tissue with a firm texture	It is of B cell lineage in the majority of cases Dffuse, large B-cell lymphomas is the most common subtype: diffuse infiltrate of B cells destroying thyroid follicles Marginal zone lymphoma is the second most common type	No specific test Some may have hypothyroidism Some may have antibody against thyroid peroxidase or thyroglobulin	Preexisting chronic autoimmune (Hashimoto's) thyroiditis is a known risk factor for this condition	Source:pathology outline, case courtesy of Dr. Mark R. Wick