Carcinoma of Thyroid Prof. S. Deivanayagam MS Professor & HOD of Surgery Madras Medical College

Ca. Thyroid - Types : - Primary / secondary Follicular cell-derived Papillary thyroid cancer Follicular thyroid cancer Anaplastic thyroid cancer Lymphocyte derived Lymphoma C-Cell derived Medullary thyroid cancer Secondary – breast, colon, melanoma

Differentiated Thyroid Ca. : - 85% of all thyroid cancers Derived from follicular cells Types Papillary carcinoma Follicular carcinoma Mixed Papillary – Follicular Hurthle cell carcinoma

Etiology & Risk factors : - Male sex Previous neck irradiation For Hodgkin’s lymphoma – Papillary ca. Pre-existing lesions MNG – Follicular ca. Hashimoto’s – Papillary ca. (controversial) Iodine deficiency – Follicular ca Family H/O Familial Syndromes

Familial Non-Medullary Thyroid ca : -

Clinical Features : - MC presentation – Painless swelling in the neck Dysphagia Stridor Rapid enlargement Hoarseness of voice (most important) Dyspnoea, Hemoptysis (late & rare) Lateral aberrant thyroid – lymphnode mets in papillary ca. thyroid Pulsatile bony secondaries in follicular thyroid ca.

Papillary Thyroid Ca. : - Most common type (~80%) Young females (mean age 30 - 40 yrs) Least malignant – one of the curable malignancies Commonly metastasize to neck nodes Distant metastasis uncommon Minimal or occult/microcarcinoma refers to tumours of 1 cm or less in size with no evidence of local invasiveness through the thyroid capsule or angioinvasion, and that are not associated with lymph node metastases

PTC – Neck secondaries : -

PTC – Types : - Types Follicular variant Tall cell Columnar cell Diffuse sclerosing Poor Prognosis Insular Breaking of capsule

PTC – Pathology : - Gross : - Microscopic : - Multi-focal Unencapsulated but often has pseudocapsule Microscopic : - Closely packed Papillae Psammoma bodies Oval or elongated pale staining nuclei with ground glass appearance– Orphan Annie eye cells

Papillae : -

Psammoma bodies : -

Orphan Annie Cells : -

Orphan Annie : -

Investigations : - USG neck FNAC Thyroid function test To identify the lesion To categorize the nodule To detect associated lymphadenopathy To take guided FNAC FNAC Best first line diagnostic procedure for papillary ca. Thyroid function test

PTC – Prognostic Systems : - AGES – Age, Grade, Extent & Size AMES – Age, Mets, Extent & Size GAMES – Grade, Age, Mets, Extent & Size Factors Low Risk High Risk Age <40 yrs >40 yrs Sex Female Male Extent Intrathyroidal Extrathyroidal Metastasis None Present Size <2 cm >4 cm Grade Well differentiated Poorly differentiated

PTC – Prognostic Systems : - DeGroot’s classification Class I – Intra-thyroidal Cass II – Cervical node mets Class III – Extra-thyroidal invasion Class IV – Distant mets Most important prognostic factor – Age at diagnosis Lymph node mets – No prognostic significance

Follicular Thyroid Ca. : - Accounts for ~10% of thyroid ca. Common in females Mean age 40 – 50 yrs Common in iodine deficient areas May coexist with MNG Metastasize to flat bones – pulsatile bony secondaries Lymph node metastasis uncommon

FTC – Bone Mets : -

FTC – Types : - Minimally invasive Widely invasive Capsular invasion without involvement of surrounding parenchyma and vascular invasion (except those within tumour) Widely invasive Surrounding parenchymal and / or vascular invasion

FTC – Pathology : - Gross Microscopic Solitary & Encapsulated Microscopic Well differentiated cells Presence of Vascular and / or capsular invasion FNAC & frozen section cannot distinguish between follicular adenoma & carcinoma Minimal tissue required - Hemithyroidectomy

FTC – Capsular Invasion : -

TNM Classification : - Common for all differentiated thyroid carcinomas The only TNM system to incorporate the age of the patient Separate for differentiated, medullary and anaplastic ca.

TNM for DTC – AJCC 7th : - T1 Tumour 2cm or less & confined to thyroid Tumour 2 – 4 cm & confined to thyroid T3 Tumour >4cm or minimal extra-thyroid extension (Invasion of sternothyroid/perithyroid soft tissues) T4a Invasion of larynx, trachea, oesophagus or RLN T4b Invasion of prevertebral fascia or carotid a.

Metastasis to level VI nodes TNM for DTC – AJCC 7th : - N1a Metastasis to level VI nodes N1b Involvement of unilateral/bilateral lateral group nodes(level I - V) or mediastinal nodes (level VII) M0 No distant metastasis M1 Distant metastasis

TNM – Stage Grouping : - AGE < 45 years I Any T Any N M0 II M1

TNM – Stage Grouping : - AGE > 45 years I T1 N0 M0 II T2 III T1 – T3 N1a IV T4a / T4b N1b M1

DTC - Treatment : - Surgery remains the main stay of treatment for DTC Types of Surgeries : - Total thyroidectomy – Removal of all thyroid tissue with preservation of parathyroids Total thyroidectomy remains Gold standard

Total thyroidectomy – Rationale : - Total thyroidectomy – Pros : - Enables usage of RAI effectively Makes serum Tg a sensitive marker for recurrence Enables better removal of central compartment nodes Reduces the risk of recurrence Reduces the risk of re-operation Total thyroidectomy – Cons : - Risk of RLN injury & hypocalcemia

Node management in DTC : - Without lateral group enlargement – Total thyroidectomy with central compartment node dissection With unilateral lateral group nodes mets – Total thyroidectomy with MRND With b/l lateral group nodes mets – Total thyroidectomy with b/l MRND Prophylactic neck dissection – NOT indicated

Post-op 131I adjuvant therapy : - Specific uptake into follicular cells Emits both β particles and γ rays γ rays are therapeutic while β particles produce radiation toxicity Indications : - Positive radio-iodine uptake scan post total thyroidectomy

131I ablation continued… Precautions : - Therapeutic dose : - Stop thyroxine for 4-6 wks TSH > 30-50 mU/L for maximal effect Avoid iodinated contrast CTs, salts & pain balms Therapeutic dose : - Low risk pt. – 30-100mCi High risk pt. – 100-200mCi

Role of Chemo & Radiotherapy : - Radiotherapy - Indications : - Unresectable disease Metastasis in support bones to avoid fractures Painful metastasis No role for routine chemotherapy Doxorubicin is commonly used mainly as a radiation sensitizer

Post-op follow up : - Suppressive dose of thyroxine – till TSH <0.1mU/l RAI Scanning : - 6-12mth after initial ablation If consecutively negative - >95% 10yr relapse free survival Subsequent scans – only if clinically indicated Thyroglobulin : - Level >2ng/ml – suggestive of recurrence / mets Tg & anti-Tg antibodies level should be measured every 6mth in first year, and then annually

Hurthle Cell Ca. : - Variant of Follicular cell ca. Women > Men Affects older age group ~65 yrs Defn. - An encapsulated group of follicular cells with at least a 75% Hurthle cell or Oncocyte component “Large, polygonal, eosinophilic thyroid follicular cells with abundant granular cytoplasm and numerous mitochondria” - Askanazy

Hurthle Cell Ca : -

Hurthle Cell Ca. continued..: - Often multicentric Diagnosis requires demonstration of capsular and / or vascular invasion Regional lymph nodes involved ~30% & is a poor prognostic indicator Distant metastasis in ~15% More aggressive & poorer prognosis

Hurthle cell ca. – Treatment : - Total thyroidectomy & central compartment node dissection recommended MRND done in case of enlarged lateral nodes Post op management : - Thyroid suppression Serum thyroglobulin measurement every 6 months Postoperative radioactive iodine is usually not effective (10% concentrate iodine)

Medullary Carcinoma : - Arises from Para-follicular C cells from neural crest Constitutes 3 –10 % of all thyroid cancers Types Sporadic Hereditary (Familial or MEN II)

Clinical features: - Symptoms due to the tumour Both lymphatic & hematogenous spread common Paraneoplastic Syndromes Due to secretion of calcitonin, VIP, serotonin and somatostatin Diarrhoea – most common

Medullary Ca. - Peculiarities : - Characteristic amyloid stroma on HPE Doesn’t take up radioactive iodine Both I-131 scan and radio-iodine ablation are of no use Serum calcitonin elevation – tumour marker Presence of lymph node metastasis is a poor prognostic indicator

Investigations : - FNAC USG / CT neck Calcitonin confirms the diagnosis CEA (>50% of tumours) USG abdomen & 24hr urine catecholamines – to rule out pheochromocytoma

Amyloid Stroma : -

Treatment : - Without neck nodes – Total thyroidectomy with central compartment neck dissection With neck nodes – Total thyroidectomy with MRND of the involved side External beam RT Extra-thyroidal extension(T4 disease) Unresectable / metastatic disease as palliation Follow up – serum calcitonin & CEA monitoring

Anaplastic Carcinoma : - Most aggressive and fortunately rarest variety Invariably well advanced at presentation Worst prognosis Treatment – Palliative External beam RT Surgery – isthumusectomy to relieve tracheal obstruction

Carry Home Message : - DTC carries very good prognosis and when detected early is a curable disease Total thyroidectomy with central node dissection is the gold standard treatment in both DTC & MTC MRND is optional RAI ablation plays a key role in metastatic disease in DTC

Thank You