Differentiated thyroid carcinoma

Prof. S. Deivanayagam MSProfessor & HOD of Surgery Madras Medical College

Carcinoma of ThyroidCa. Thyroid - Types : -Primary / secondaryFollicular cell-derivedPapillary thyroid cancerFollicular thyroid cancerAnaplastic thyroid cancerLymphocyte derivedLymphomaC-Cell derivedMedullary thyroid cancerSecondary breast, colon, melanomaDifferentiated Thyroid Ca. : -85% of all thyroid cancersDerived from follicular cellsTypesPapillary carcinomaFollicular carcinomaMixed Papillary FollicularHurthle cell carcinoma

Etiology & Risk factors : -Male sexPrevious neck irradiationFor Hodgkins lymphoma Papillary ca.Pre-existing lesionsMNG Follicular ca.Hashimotos Papillary ca. (controversial)Iodine deficiency Follicular caFamily H/OFamilial Syndromes

Familial Non-Medullary Thyroid ca : -

Clinical Features : -MC presentation Painless swelling in the neckPainDysphagiaStridorRapid enlargementHoarseness of voice (most important)Dyspnoea, Hemoptysis (late & rare)Lateral aberrant thyroid lymphnode mets in papillary ca. thyroidPulsatile 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 malignanciesCommonly metastasize to neck nodesDistant metastasis uncommonMinimal 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 : -TypesFollicular variantTall cellColumnar cellDiffuse sclerosingPoor PrognosisInsularBreaking of capsule

PTC Pathology : -Gross : -Multi-focalUnencapsulated but often has pseudocapsuleMicroscopic : -Closely packed PapillaePsammoma bodiesOval or elongated pale staining nuclei with ground glass appearance Orphan Annie eye cellsPapillae : -

Psammoma bodies : -

Orphan Annie Cells : -

Orphan Annie : -

Investigations : -USG neckTo identify the lesionTo categorize the noduleTo detect associated lymphadenopathyTo take guided FNACFNACBest first line diagnostic procedure for papillary ca.Thyroid function testPTC Prognostic Systems : -AGES Age, Grade, Extent & SizeAMES Age, Mets, Extent & SizeGAMES Grade, Age, Mets, Extent & SizeFactorsLow RiskHigh RiskAge40 yrsSexFemaleMaleExtentIntrathyroidalExtrathyroidalMetastasisNonePresentSize4 cmGradeWell differentiatedPoorly differentiatedPTC Prognostic Systems : -DeGroots classificationClass I Intra-thyroidalCass II Cervical node metsClass III Extra-thyroidal invasionClass IV Distant metsMost important prognostic factor Age at diagnosisLymph node mets No prognostic significanceFollicular Thyroid Ca. : -Accounts for ~10% of thyroid ca.Common in femalesMean age 40 50 yrsCommon in iodine deficient areasMay coexist with MNGMetastasize to flat bones pulsatile bony secondariesLymph node metastasis uncommon

FTC Bone Mets : -

FTC Types : -Minimally invasiveCapsular invasion without involvement of surrounding parenchyma and vascular invasion (except those within tumour)Widely invasiveSurrounding parenchymal and / or vascular invasionFTC Pathology : -GrossSolitary & EncapsulatedMicroscopicWell differentiated cellsPresence of Vascular and / or capsular invasionFNAC & frozen section cannot distinguish between follicular adenoma & carcinomaMinimal tissue required - HemithyroidectomyFTC Capsular Invasion : -

TNM Classification : -Common for all differentiated thyroid carcinomasThe only TNM system to incorporate the age of the patientSeparate for differentiated, medullary and anaplastic ca.TNM for DTC AJCC 7th : -T1Tumour 2cm or less & confined to thyroidT2Tumour 2 4 cm & confined to thyroidT3Tumour >4cm or minimal extra-thyroid extension (Invasion of sternothyroid/perithyroid soft tissues)T4aInvasion of larynx, trachea, oesophagus or RLNT4bInvasion of prevertebral fascia or carotid a.TNM for DTC AJCC 7th : -N1aMetastasis to level VI nodesN1bInvolvement of unilateral/bilateral lateral group nodes(level I - V) or mediastinal nodes (level VII)M0No distant metastasisM1Distant metastasisTNM Stage Grouping : -AGE < 45 yearsIAny TAny NM0IIAny TAny NM1TNM Stage Grouping : -AGE > 45 yearsIT1N0M0IIT2N0M0IIIT1 T3N1aM0IVT4a / T4bN1bM1DTC - Treatment : -Surgery remains the main stay of treatment for DTCTypes of Surgeries : -Total thyroidectomy Removal of all thyroid tissue with preservation of parathyroidsTotal thyroidectomy remains Gold standardTotal thyroidectomy Rationale : -Total thyroidectomy Pros : -Enables usage of RAI effectivelyMakes serum Tg a sensitive marker for recurrenceEnables better removal of central compartment nodesReduces the risk of recurrenceReduces the risk of re-operationTotal thyroidectomy Cons : -Risk of RLN injury & hypocalcemiaNode management in DTC : -Without lateral group enlargement Total thyroidectomy with central compartment node dissectionWith unilateral lateral group nodes mets Total thyroidectomy with MRNDWith b/l lateral group nodes mets Total thyroidectomy with b/l MRNDProphylactic neck dissection NOT indicated

Post-op 131I adjuvant therapy : -Specific uptake into follicular cellsEmits both particles and rays rays are therapeutic while particles produce radiation toxicityIndications : -Positive radio-iodine uptake scan post total thyroidectomy

131I ablation continuedPrecautions : -Stop thyroxine for 4-6 wksTSH > 30-50 mU/L for maximal effectAvoid iodinated contrast CTs, salts & pain balmsTherapeutic dose : -Low risk pt. 30-100mCiHigh risk pt. 100-200mCiRole of Chemo & Radiotherapy : -Radiotherapy - Indications : -Unresectable diseaseMetastasis in support bones to avoid fracturesPainful metastasisNo role for routine chemotherapyDoxorubicin is commonly used mainly as a radiation sensitizer

Post-op follow up : -Suppressive dose of thyroxine till TSH 95% 10yr relapse free survivalSubsequent scans only if clinically indicatedThyroglobulin : -Level >2ng/ml suggestive of recurrence / metsTg & anti-Tg antibodies level should be measured every 6mth in first year, and then annually

Hurthle Cell Ca. : -Variant of Follicular cell ca.Women > MenAffects older age group ~65 yrsDefn. - An encapsulated group of follicular cells with at least a 75% Hurthle cell or Oncocyte componentLarge, polygonal, eosinophilic thyroid follicular cells with abundant granular cytoplasm and numerous mitochondria- Askanazy

Hurthle Cell Ca : -

Hurthle Cell Ca. continued..: -Often multicentricDiagnosis requires demonstration of capsular and / or vascular invasionRegional lymph nodes involved ~30% & is a poor prognostic indicatorDistant metastasis in ~15%More aggressive & poorer prognosisHurthle cell ca. Treatment : -Total thyroidectomy & central compartment node dissection recommendedMRND done in case of enlarged lateral nodesPost op management : -Thyroid suppressionSerum thyroglobulin measurement every 6 monthsPostoperative radioactive iodine is usually not effective (10% concentrate iodine)

Medullary Carcinoma : -Arises from Para-follicular C cells from neural crestConstitutes 3 10 % of all thyroid cancersTypesSporadicHereditary (Familial or MEN II)Clinical features: -Symptoms due to the tumourBoth lymphatic & hematogenous spread commonParaneoplastic SyndromesDue to secretion of calcitonin, VIP, serotonin and somatostatinDiarrhoea most commonMedullary Ca. - Peculiarities : -Characteristic amyloid stroma on HPEDoesnt take up radioactive iodineBoth I-131 scan and radio-iodine ablation are of no useSerum calcitonin elevation tumour markerPresence of lymph node metastasis is a poor prognostic indicator

Investigations : -FNACUSG / CT neckCalcitonin confirms the diagnosisCEA (>50% of tumours)USG abdomen & 24hr urine catecholamines to rule out pheochromocytomaAmyloid Stroma : -

Treatment : -Without neck nodes Total thyroidectomy with central compartment neck dissectionWith neck nodes Total thyroidectomy with MRND of the involved sideExternal beam RTExtra-thyroidal extension(T4 disease)Unresectable / metastatic disease as palliationFollow up serum calcitonin & CEA monitoringAnaplastic Carcinoma : -Most aggressive and fortunately rarest varietyInvariably well advanced at presentationWorst prognosisTreatment Palliative External beam RTSurgery isthumusectomy to relieve tracheal obstructionCarry Home Message : -DTC carries very good prognosis and when detected early is a curable diseaseTotal thyroidectomy with central node dissection is the gold standard treatment in both DTC & MTCMRND is optionalRAI ablation plays a key role in metastatic disease in DTCThank You