Thyroid nodules are abnormal growths in the thyroid gland that affect approximately 50% of the population. While most nodules are benign, thyroid cancer can develop in around 5% of cases. The main types of thyroid cancer are papillary, follicular, medullary, and anaplastic. Papillary carcinoma is the most common type, making up around 80% of thyroid cancers. It often spreads via lymphatic vessels and has an excellent prognosis with treatment. Follicular carcinoma also has a good prognosis but is more likely to metastasize hematogenously. Medullary carcinoma develops from parafollicular cells and can be hereditary. Anaplastic carcinoma is the most aggressive and

1. Thyroid Nodules and Cancer
By Lara Masri
4th year medical student
Sources : Step up, Amboss

2. Outlines
 Thyroid nodules
 Definition
 Etiology
 Diagnosis
 Thyroid cancers
 Papillary
 Follicular
 Medullary
 Anaplastic

3. • Definition
• Thyroid nodules are abnormal growths within the thyroid gland.
• They are present in approximately 50% of the general population but only palpable
in 5–10% of the population.
• They are more common in women, especially in iodine-deficient regions
• Their incidence increases with age
• Incidental finding on imaging
• Carotid ultrasound
• Neck or chest CT
• Major clinical concern: thyroid cancer
• Cause of about 4 to 10% nodules
• To be detectable on palpation, a nodule must be at least 1 cm in diameter

4. Etiology
Benign thyroid nodules (∼ 95% of cases)
• Thyroid adenomas
• Follicular adenoma (most common)
• Hürthle cell adenoma
• Toxic adenoma
• Papillary adenoma (least common)
• Thyroid cysts
• Dominant nodules of multinodular goiters
• Hashimoto thyroiditis
Malignant thyroid nodules (∼ 5% of cases)
Types
1. Thyroid carcinoma
2. Thyroid lymphoma
3. Metastatic cancer from breast/renal carcinoma (rare)

5. Red flags for thyroid cancer
o Patient characteristics
o Male sex
o Age: < 14 years or > 70 years
o History of radiation to the head or neck
o Family history of:
o MEN2 syndrome
o Differentiated thyroid cancer (i.E., Papillary, follicular,
or medullary thyroid cancer)
o Gardner syndrome
o Symptoms
o Rapid growth of thyroid nodule
o Recent onset of persistent hoarseness, dysphagia, or
dyspnea
o Palpatory findings
o Firm or hard nodule
o Fixed nodule
o Cervical lymphadenopathy
o solid nodule on thyroid ultrasound or a cold nodule on thyroid
scintigraphy

6. Diagnosis
TSH : may be normal, elevated or low
• Elevated TSH: associated with a higher risk of malignancy in thyroid nodules
• Low TSH: indication for thyroid scintigraphy
Thyroid ultrasound
• Differentiates a solid from a cystic nodule; most cancers are solid.
• Can identify nodules 1 to 3 mm in diameter.
• Cystic masses larger than 4 cm in diameter are not malignant.
• Cannot distinguish between benign and malignant thyroid nodules
suspicion for malignancy and require further evaluation with FNAC:
1. Solid
2. hypoechoic nodules with irregular margins
3. Microcalcifications
4. taller-than-wide shape
5. extrathyroidal growth
6. cervical lymphadenopathy

7. Thyroid scintigraphy
 Indication: thyroid nodules in a patient with low TSH
 Contraindications: pregnant and breastfeeding women
 Findings and interpretation
• Cold nodule (hypofunctioning nodule): Evaluate for indications for FNAC of thyroid
nodules with ultrasound.
• Hot nodule (hyperfunctioning nodule): rarely malignant, FNAC not recommended
• Solitary hot nodule: toxic adenoma
• Multiple hot nodules: toxic multinodular goiter

8. FNAC
• FNA has a sensitivity of 95% and a specificity of 95%.
• 5% false-negative results, so follow up with periodic FNA if thyroid nodularity
persists.
• FNA is reliable for all cancers (papillary, medullary, anaplastic) except
follicular.
• Patient should first be evaluated with ultrasound and TSH level.
• This is the only test that can reliably differentiate between benign and
malignant nodules.
• FNA findings:
1. Probable cancer (15%) : Most of these are really cancers. Surgery is
indicated.
2. Indeterminate (19%) : A thyroid scan should be performed, and if the lesion
is “cold” by the scan, surgical resection is indicated because about 20% of
these lesions are found to be malignant.
3. Benign (66%) : Most of these are benign. Observe for 1 year, then follow up
with an ultrasound.
4. Follicular neoplasm : Surgery is recommended because it is difficult to
distinguish between benign and malignant follicular cells on histology.

10. Thyroid cancer
 Malignant tumor that arises from either the thyrocytes or the parafollicular cells of
the thyroid gland.
 common in women
 30–50 years of age
 Risk factors : red flags for thyroid cancer
Thyroid
carcinoma
differentiated
papillary
follicular
Undifferentiated
medullary
anaplastic

11. Papillary Carcinoma:
 Most common form thyroid cancer (~ 80%)
 Increased risk with prior radiation exposure
 Median age at diagnosis is 51 years
 Presents as thyroid nodule
 Diagnosis made after fine needle aspiration (FNA)
 spread via lymphatics  Distant metastasis is rare
 Excellent prognosis
 Treated with Total thyroidectomy
 Post-operative T4 (levothyroxine) to Prevent hypothyroidism, Prevent TSH rise  cancer
growth
 Psammoma bodies

12. Follicular Carcinoma:
o Malignancy of follicular epithelial cells account for 15% of all thyroid
cancers.
o Similar to follicular adenoma
o Invades fibrous capsule
o FNA cannot distinguish between adenomas/cancer; rather we need a
tissue sample for diagnosis (frozen section ) .
o Many similarities with papillary carcinoma
o Diagnosed at age 51 year old
o The main risk factor is history of radiation
o Treated with surgery (thyroidectomy) and postoperative iodine
ablation
o Prognosis is worse than papillary carcinoma; spreads via a haematogenous
route.
o Distant metastasis occur in 20% of patients.

13. Hurthle cell carcinoma
• 3–10% of all well-differentiated thyroid cancers
• Often classified as subtype of follicular carcinoma
• Thyroid histopathology: hyper cellularity with a predominance of Hurthle cells
(large, polygonal epithelial cell with eosinophilic granular cytoplasm as a result of
numerous altered mitochondria)
• Hurthle cells are nonspecific and also observed in Hashimoto thyroiditis, Graves
disease, previously-irradiated thyroid glands, and in Hurthle cell adenoma (no
vascular or capsular invasion; no metastasis)
• They are also found in the parathyroid glands, salivary glands, and kidneys

14. Medullary Carcinoma:
• Accounts for 2% to 3% of all thyroid cancers
• One-third sporadic, one-third familial, one-third associated with MEN II
• Cancer of para-follicular cells (C cells)
• Produces calcitonin:
• Lowers serum calcium
• Normally minimal effect on calcium levels
• Treatment: total thyroidectomy , Modified radical neck dissection is also indicated
when there is lymph node involvement (most cases).
• Most patients have bilateral disease
• Serial calcitonin monitoring

15. MEN Syndromes:
Multiple Endocrine Neoplasia
• Gene mutations
• Autosomal dominant
• Cause multiple endocrine tumors
• MEN 2A and 2B associated with
medullary carcinoma
• Caused by RET oncogene mutation

16. Anaplastic Carcinoma:
Undifferentiated Carcinoma
• Occurs in elderly
• Highly malignant - invades local tissues
• Dysphagia (esophagus)
• Hoarseness (recurrent laryngeal nerve)
• Dyspnea (trachea)
• Don’t confuse with Riedel’s (“rock hard”
thyroid/young pt)
• Poor prognosis
• Treatment: surgery (local disease only),
chemotherapy and radiation

17. Carcinoma Characteristics Distribution Peak
Incidence
Papillary
thyroid
carcinoma
 Most common type of thyroid cancer
 Palpable lymph nodes due to metastatic spread by lymph
 May be multifocal
 Very good prognosis
70-80% 30-50
years
Follicular
thyroid
carcinoma
 Hematogenous metastasis especially to
o Lungs
o Bone (lytic lesions)
 Rarely multifocal
 Vascular and capsular invasion
 Good prognosis, more malignant than papillary
15% 40-60
years
Anaplastic
thyroid
carcinoma
 Rapid local growth
 Symptoms of compression of the structures of the neck
(e.g. dysphagia, dyspnea)
 Lymphatic and hematogenous metastasis
 Very poor prognosis
5% >60
Years
Medullary
carcinoma
 From Parafollicular cells
 Sometimes a genetic predisposition → multiple endocrine neoplasia
type 2 (MEN2) ,Sporadic , familial
 Produces calcitonin
 Diarrhea and facial flushing
2-3% 50-60
years

18. Prognosis
Thyroid cancer 5-year survival rate
Papillary > 90%
Follicular 50–70%
Medullary 50%
Anaplastic 5–14%