Special Surgery 3. Malignant Diseases of the Thyroid Gland and Treatment

I. General Diagnostic Approach

Clinical Suspicion and Physical Examination

• Most thyroid cancers present as thyroid nodule or cervical lymph node
• Most patients are euthyroid
• Suspicious history: childhood neck irradiation, family thyroid cancer, MEN2, rapid growth in elderly patient
• Suspicious signs:

• Hard, firm, irregular or fixed nodule
• Cervical lymphadenopathy
• Hoarseness → recurrent laryngeal nerve paresis until proven otherwise
• Dysphagia, dyspnea, stridor → local invasion/compression

• Palpation: stand behind patient, ask patient to swallow
• Assess: size, consistency, solitary/multinodular, mobile/fixed, central/lateral cervical lymph nodes
• Laryngoscopy: hoarseness, previous neck surgery, or before thyroid cancer surgery

Laboratory Tests

• TSH first; FT4/T3 if TSH abnormal

• Hyperthyroidism: increased T3/T4, decreased TSH
• Primary hypothyroidism: decreased T3/T4, increased TSH

• Calcitonin + CEA: suspected/confirmed medullary thyroid carcinoma
• Thyroglobulin: not primary nodule diagnosis; follow-up marker after thyroidectomy for differentiated thyroid cancer

Imaging and Cytology

1. Ultrasound

• First-line imaging for thyroid nodule and cervical lymph nodes
• Distinguishes solid, cystic and mixed nodules
• Suspicious US features:

• Hypoechoic solid nodule
• Microcalcification
• Irregular border, absent halo
• Taller-than-wide shape
• Extrathyroidal extension
• Suspicious lymph node: round shape, loss of hilum, cystic change, microcalcification

• Suspicious nodule/lymph node → US-guided FNAB

2. FNAB

• Gold-standard initial cytology for suspicious thyroid nodule
• Diagnoses many papillary, medullary and anaplastic cancers
• Follicular adenoma vs follicular carcinoma cannot be separated reliably by FNAB
• Follicular carcinoma diagnosis needs histology: capsular and/or vascular invasion

3. Scintigraphy

• Main indication: low TSH / suspected autonomous nodule
• Hot nodule: autonomous hormone production → malignancy risk low
• Cold nodule: non-secreting tissue → cyst, adenoma or cancer → US/FNAB
• Diffuse homogeneous uptake: Graves-Basedow disease pattern

4. CT / MRI

• Not routine for every nodule
• Use if advanced disease suspected: retrosternal spread, tracheal/esophageal invasion, bulky nodes, distant metastasis, anaplastic cancer

II. Papillary Thyroid Carcinoma

Definition / Etiology

• Most common thyroid cancer, about 80%
• Derived from follicular epithelial cells
• May occur at any age; female predominance
• Risk factor: previous ionizing radiation exposure
• Common alterations: RET/PTC, NTRK fusion, BRAF mutation

Clinical Features / Pathology

• Slow-growing firm thyroid nodule; can be solitary, multifocal or bilateral
• May present first as cervical lymph node metastasis
• May be well-circumscribed/encapsulated or infiltrative
• Microscopy:

• Branching papillae with fibrous/fibrovascular stroma
• Orphan Annie eye nuclei, nuclear grooves, intranuclear inclusions
• Psammoma bodies

• Metastasis: lymphatic → cervical lymph nodes
• Prognosis: excellent, especially young/localized disease

Treatment

• Lobectomy: small, unifocal, intrathyroidal, low-risk tumor
• Total/near-total thyroidectomy: large, multifocal/bilateral, extrathyroidal extension, nodal/distant metastasis, or need for radioiodine/follow-up
• Clinically involved lymph nodes → compartment-oriented lymph node dissection
• Central neck dissection: central nodal disease
• Lateral neck dissection: proven lateral nodal metastasis
• Radioiodine ablation/therapy I-131: residual tissue, iodine-avid metastasis, recurrence or high-risk disease
• Levothyroxine: hormone replacement + TSH suppression

III. Follicular Thyroid Carcinoma

Definition / Etiology

• Second most common thyroid cancer, about 10-15%
• Derived from follicular epithelial cells
• More common in women; peak age 40-60 years
• More frequent in iodine-deficient areas

Clinical Features / Pathology

• Slow-growing firm thyroid nodule, often solitary
• Microscopy: follicular pattern similar to normal thyroid
• Key malignant sign: capsular and/or vascular invasion
• FNAB limitation: follicular neoplasm needs histology to prove carcinoma
• Metastasis: hematogenous → lung, bone, liver
• Prognosis: good, but worse than papillary carcinoma

Treatment

• Diagnostic lobectomy may be first step for follicular neoplasm
• Total thyroidectomy: widely invasive, large or high-risk carcinoma
• Completion thyroidectomy: carcinoma found after lobectomy and risk profile indicates it
• Lymph node dissection only for clinically involved nodes
• Radioiodine therapy: iodine-avid residual/metastatic or high-risk disease
• Levothyroxine: replacement + risk-adapted TSH suppression

IV. Medullary Thyroid Carcinoma

Definition / Etiology

• Neuroendocrine thyroid cancer
• Derived from parafollicular C cells → calcitonin secretion
• Sporadic or hereditary
• Hereditary forms: RET mutation, MEN2A/MEN2B

• MEN2A: medullary thyroid carcinoma + pheochromocytoma + primary hyperparathyroidism
• MEN2B: medullary thyroid carcinoma + pheochromocytoma + mucosal neuromas/marfanoid habitus

Clinical Features / Pathology

• Firm thyroid nodule or cervical lymphadenopathy
• Often multifocal/bilateral in hereditary disease
• Calcitonin excess may cause diarrhea/flushing in advanced disease
• Hypocalcemia is not typical despite calcitonin secretion
• Microscopy: neuroendocrine tumor pattern + amyloid deposition
• Markers: calcitonin and CEA
• Metastasis: early lymph nodes; distant spread to liver, lung, bone, brain
• Prognosis: worse than differentiated cancer; stage-dependent

Diagnosis

• Diagnosis: FNAB cytology + serum calcitonin/CEA
• RET genetic testing in every MTC patient
• RET-positive/familial disease → screen family members
• Before thyroid surgery in MEN2: exclude pheochromocytoma first

Treatment

• Total thyroidectomy + central lymph node dissection
• Lateral neck dissection: proven/suspected lateral nodal metastasis
• No radioiodine therapy → C-cell tumor does not take up iodine
• Levothyroxine: hormone replacement only, no TSH-suppression oncological effect
• Follow-up: calcitonin + CEA; rising values → residual/recurrent/metastatic disease until proven otherwise

V. Anaplastic Thyroid Carcinoma

Definition / Clinical Features

• Very rare, aggressive, undifferentiated thyroid cancer
• Usually follicular epithelial origin by dedifferentiation
• More common in elderly patients and women
• Rapidly enlarging hard neck mass
• Local invasion:

• Dysphagia, dyspnea, stridor
• Hoarseness
• Pain, skin fixation/ulceration

• Microscopy: poorly differentiated/anaplastic pleomorphic cells
• Metastasis: early nodal and hematogenous spread → lung, bone, brain
• Prognosis: very poor

Diagnosis

• Urgent FNAB/core biopsy + rapid multidisciplinary evaluation
• Assess airway immediately
• CT/MRI neck/chest: trachea, esophagus, vessels, mediastinum, metastasis

Treatment

• Airway management is often first priority; tracheostomy if needed
• Most cases are unresectable at diagnosis because of local invasion/metastasis
• Resectable + fit patient → surgery aiming R0/R1 + radiotherapy/systemic therapy
• Unresectable/metastatic → palliative radiotherapy, chemotherapy/systemic therapy, symptom control
• Not responsive to radioiodine
• Levothyroxine only if thyroidectomy performed; no useful TSH-suppression effect

VI. Postoperative Management and Follow-Up

1. Differentiated Thyroid Cancer: PTC / FTC

• Levothyroxine:

• Hormone replacement after total thyroidectomy
• Risk-adapted TSH suppression

• Radioiodine ablation/therapy only if differentiated, iodine-avid and risk-indicated
• Follow-up: neck US, serum thyroglobulin, anti-thyroglobulin antibodies

2. Medullary Thyroid Carcinoma

• Follow calcitonin and CEA
• RET mutation result guides MEN2 and family screening
• No thyroglobulin follow-up and no radioiodine therapy

3. Main Surgical Complications

• Neck hematoma → airway emergency
• Recurrent laryngeal nerve injury → hoarseness/vocal cord palsy
• External branch of superior laryngeal nerve injury → weak high-pitched voice
• Hypoparathyroidism/hypocalcemia after total thyroidectomy/central neck dissection
• Lifelong levothyroxine after total thyroidectomy