Thyroid Cancer

• Ionizing radiation; (particularly during childhood): mostly associated with papillary carcinoma
• Iodine deficiency: higher frequency of follicular carcinoma
• Genetic factors
  • Medullary carcinoma: associated with MEN2 (RET gene mutations) or familial medullary carcinoma
  • Papillary carcinoma: associated with RET/PTC rearrangements and BRAF mutations
  • Follicular carcinoma: associated with RAS mutation
  • Undifferentiated/anaplastic carcinoma: associated with TP53 mutation

• Approximately 80% of cases
• Most common in young women
• Peak age: 30–50 years
• Present as asymptomatic nodules or metastasis to cervical lymph nodes
• Advanced disease: hoarseness, cough, dyspnea
• Associated with familial adenomatous polyposis , Cowden syndrome
• Least aggressive; very good prognosis if detected early
• Histopathologic features
  • Psammoma bodies (round calcified structure within papillae

• 10% of cases
• Women > men
• Peak age: 40–60 years
• Seen in areas of iodine deficiency
• Painless, slow-growing thyroid nodule
• Cold nodules on scintigraphy
• Commonly spreads hematogenously to lungs or bones
• Typically, regional lymph nodes are not involved.
• Associated with Cowden syndrome
• Good prognosis if detected early

• Approximately 1-2% of cases
• Most common in women
• Average age: 65 years
• ¼ of patients have past history of or coexisting differentiated carcinoma.
• Rapid growth → local compression
• Most have spread beyond the thyroid on presentation
• Spreads via lymphatics and bloodstream
• Poor prognosis

• < 10%of cases
• MEN2: Cases occur in young patients.
• Sporadic and familial cases peak at age 40–60 years.
• Can present as a neck or lymph node mass
• Also can manifest with:
  • Diarrhea , flushing (calcitonin and from tumor-secreted vasoactive intestinal peptide (VIP), prostaglandin and serotonin)
  • Cushing’s syndrome due to adrenocorticotropic hormone (ACTH)
• Other biomarker: carcinoembryonic antigen (CEA)
• Associated with MEN2 syndrome
• Familial type: more aggressive

• Physical Examination: Presence of nodule.
• Blood Tests: Thyroid function tests.
• Ultrasound: To characterize the nodule.
• Fine-Needle Aspiration Biopsy (FNAB): Definitive diagnosis.
• Genetic Testing: For medullary carcinoma.

• Initial Approach
  • Physical examination: palpable thyroid nodule, cervical lymphadenopathy
  • TSH levels ➜ First test for thyroid nodule
    • Low TSH → suggests hyperfunctioning nodule → thyroid scintigraphy
    • Normal/High TSH → proceed with ultrasound
• Thyroid Ultrasound
  • Features suggesting malignancy:
    • Hypoechoic nodule
    • Microcalcifications (especially in papillary carcinoma)
    • Irregular margins
    • Taller than wide shape
    • Increased vascularity
• Fine Needle Aspiration (FNA) ➜ Definitive diagnosis
  • Indications:
    • Nodules > 1 cm with suspicious ultrasound features
    • Any size nodule with high-risk features or lymphadenopathy
    • Cold nodules on scintigraphy
  • Cannot distinguish follicular adenoma from carcinoma (needs surgical excision)
• Thyroid Scintigraphy (Radioiodine Uptake)
  • Indicated when TSH is low
  • Hot nodule = increased uptake → usually benign → no FNA needed
  • Cold nodule = decreased uptake → concern for malignancy → needs FNA
• Tumor Markers
  • Calcitonin: for medullary carcinoma (elevated in >95% of cases)
  • Thyroglobulin: used for monitoring after treatment of differentiated thyroid cancer
  • CEA: may be elevated in medullary carcinoma
• Additional Tests
  • Genetic testing: for suspected medullary carcinoma (RET mutations)
  • CT/MRI: for assessing local invasion or metastases

Thyroid adenomas

• Follicular adenoma (most common)
• Hürthle cell adenoma (A subtype of follicular adenoma that is treated similarly to it)
• Toxic adenoma
• Papillary adenoma (least common)

Follicular adenoma

• It is a benign encapsulated tumor of the thyroid gland that is surrounded by a thin fibrous capsule.
• Follicular adenoma is the most common type of thyroid adenoma.
• 10–15% of follicular neoplasms are malignant.

Clinical features

• Often presents as a slow-growing solitary nodule
• Patients are typically euthyroid.
• In rare cases, patients can manifest with clinical features of hyperthyroidism (∼ 1% of follicular adenomas develop into toxic adenomas).

Diagnostics

• Follicular adenoma is a histopathological diagnosis. Cytology alone cannot distinguish between adenoma and carcinoma.
• Thyroid function tests: TSH is typically normal.
• Thyroid ultrasound: may show sonographic signs of malignancy or appear benign
• FNAC
  • Cannot distinguish between follicular adenoma and carcinoma
• Confirmatory test
  • Surgical excision (e.g., hemithyroidectomy ) with histologic analysis (A complete histopathological examination of the tumor is needed to rule out capsular and vascular invasion before establishing a diagnosis of follicular adenoma. Frozen-section analysis cannot always distinguish between follicular adenoma and carcinoma in all cases and its significance in the management of follicular adenomas is controversial.)