Medullary thyroid cancer differential diagnosis

Medullary thyroid cancer must be differentiated from anaplastic thyroid carcinoma, papillary thyroid carcinoma, paraganglioma, carcinoid tumor, and Hurthle cell carcinoma.

• Medullary thyroid cancer must be differentiated from the following:

• Anaplastic thyroid carcinoma
• Papillary thyroid carcinoma
• Hurthle cell carcinoma
• Paraganglioma
• Carcinoid
• Metastatic Melanoma

Disease Name	Age of Onset	Gender Preponderance	Signs/Symptoms	Imaging Feature(s)	Macroscopic Feature(s)	Microscopic Feature(s)	Laboratory Findings(s)	Other Feature(s)	Microscopic Appearance
Medullary Thyroid Cancer[1][2][3][4]	Incidence increases with age More common in the 3rd to 4th decades of life	Both genders are affected equally	Solitary thyroid nodule Mostly affects upper lobe of thyroid gland Possible systemic symptoms due to hormonal secretion by the tumor Cervical lymphadenopathy	On ultrasound: Solitary hypoechoic nodule with or without calcification Imaging features are not characteristic of this cancer	Single non-encapsulated mass Gray-tan color	Sheets of cells in an amyloid stroma	Secretes calcitonin Normal thyroid function tests Carcinoembryonic antigen (CEA) may be used as a tumor marker Rarely negative for calcitonin	Can be part of MEN 2A and 2B syndrome Can be associated with RET mutation
Papillary Thyroid Cancer[5][6][4]	More common in the 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	On ultrasound Solitary mass with an irregular outline Located in the sub-capsular region High vascularity Imaging features are not characteristic of 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 tests can be normal Serum thyroglobulin can be used as a tumor marker	History of radiation to the head and neck BRAF and/or RET mutation may be present The most common type of thyroid cancer
Follicular Thyroid Cancer[6][4][7]	Peak incidence at 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	On ultrasound: Solid hypoechoic nodule with a peripheral halo indicating fibrous capsule Irregular margin Imaging features are not characteristic of this cancer	Single encapsulated nodule Thick and irregular capsule Can be cystic or hemorrhagic in appearance	Invades thyroid capsule and vasculature Uniform follicles	Thyroid function tests can be normal Serum thyroglobulin can be used as a tumor marker	RAS mutation may be present PAX8–PPARγ translocations
Anaplastic Thyroid Cancer[8][9][10]	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 Can present with signs/symptoms of metastasis Constitutional symptoms may be present Hard nodular goiter without tenderness	On ultrasound: Solid hypoechoic nodule with a peripheral halo indicating fibrous capsule Irregular margin Imaging features are not characteristic of this cancer	Solid tumor with areas of necrosis and hemorrhage Infiltrative pattern	Undifferentiated, devastatingly aggressive variant of papillary/follicular thyroid cancer	Normal thyroid function tests	Poor prognosis May be associated with TP53 mutation
Follicular Adenoma[11]	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
Multinodular Goiter[12]	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 tests	Benign condition
Thyroid Lymphoma[13] [14][15][16]	Affects adults or elderly	More common among women	Rapidly enlarging mass/nodule of thyroid Compressive symptoms may be present Constitiutional symptoms can be present in 10% P/E:Firm, hard thyroid Fixed to the nearby structures Immobile even during swallowing Cervical or supraclavicular lymphadenopathy may be present	On ultrasound: Hypoechogenic appearance Difficult to distinguish from chronic thyroiditis	Thyroid nodule/mass Fixed to adjacent tissue Firm texture	It is of B cell lineage in the majority of cases Dffuse, large B-cell lymphomas is the most common subtype Marginal zone lymphoma is the second most common type	No specific test Some patients may have hypothyroidism Patients can also have antibodies against thyroid peroxidase or thyroglobulin	Preexisting chronic autoimmune (Hashimoto’s) thyroiditis is a known risk factor for this condition