Thyroid Neoplasms

Muhammad Haris Aslam Janjua

Resident, Surgical Unit I

SIMS/Services Hospital, Lahore

OUTLINE IntroductionEpidemiologyEtiologyPathophysiologyClinical presentationWorkupStagingTreatment FollowupPrognosisCase Presentation

Introduction

Most common endocrine tumour

Responsible for about 6 deaths per million persons annually

It accounts roughly for about 0.5% of all cancers in men and 1.5% of all cancers in women

5% of all thyroid nodules are malignant

Single nodule more likely to be malignant than multiple nodules

Classification of Thyroid Neoplasms

Benigni)Follicular adenoma.

ii)Hurthle cell adenoma

iii)Colloid adenoma(commenest)

Malignant

(dunhill classification)

Differenciated

i) Papillary Carcinoma (80%)

ii) Follicular Carcinoma (10%)

iii) Hurthle cell carcinoma (3%)

iv) Papillofollicular carcinoma

Undifferenciated

i)Anaplastic carcinoma (1-2%)

Medullary Carcinoma (5-10%)

Malignant lymphoma (~1%)

Secondaries from colon, kidney, Melanoma

Woolner classificationPapillary

carcinoma

Occult primary<1.5cm intrathyroidal extrathyroidal

• Other variants of papillary carcinoma include• Tall cell• Insular• Columnar• Diffuse sclerosing• Clear cell • Trabecular and• Poorly differenciated

*Micropapillary carcinoma is a tumour, clinically not detectable or less than 1cm with no evidence of local invasiveness through the

thyroid capsule or angioinvasion.....

Epidemiology Annual incidence is 0.5 to 10 per 100,000 persons

Highest Incidence Northren america

Female to male ratio is 3:1

Differenciated carcinomas peaks in 3rd and 4th Decadeof life

Medullary thyroid carcinoma peaks in 5th and 6th

decade

Anaplastic carcinomas peaks in 7th and 8th decade.

Epidemiology

In Pakistan thyroid cancer is responsible for 1.2% cases of all malignant tumors

Papillory thyroid carcinoma iodine sufficient areas

Medullary thyroid carcinoma iodine deficient areas

Prevalence according to age

Carcinoma Age group

a) Papillary Thyroid carcinomab) Medullary thyroid carcinoma

associated with MEN type 2.

Children

a) Follicular thyroid carcinomab) Anaplastic carcinomac) Sporadic Medullary thyroid

carcinoma

Elderly

Etiology

Endodermally derived Follicular cells

• Papillary

• Follicular

• anaplastic

Neuroendocrine derived calcitonin producing C cells

• Medullary thyroid carcinomas

Thyroid cancer Arises from 2 types of Cells

Thyroid lymphomas Intrathyroid lymphoid Tissue

Sarcomas connective tissue of thyroid gland

Etiology

Radiation* Papillary thyroid carcinoma Signal most imp factor in differenciated carcinoma is irradiation of

thyroid under 5 years of age

Pre-existing Multinodular goiterFollicular Carcinoma.

Hashimotos thyroiditisPapillary Thyroid carcinoma

Familial

*Increased incidence of thyroid carcinoma among children following exposure to ionising radiation after Chernobyl nuclear disastor in Ukraine in 1986

*Radiotherapy received in adolescents for Hodgkins lymphoma may predispose to PTC

Familial cancer syndromes involving non medullary thyroid cancer

Syndrome Thyroid tumorCowdens syndrome FTC and rarely PTC and hurthle

cell tumors

FAP PTC

Werners syndrome PTC, FTC , Anaplastic Cancer

Carney complex type 1 PTC, FTC

McCune Albright syndrome PTC Clear cell

Medullary carcinoma multiple endocrine neoplasia (MEN) 2A or 2B syndrome, as well as familial MTC (FMTC) syndrome..

Genes implicated in thyroid tumorigenesis

Cancer Oncogenes Tumour suppressorgenes

Papillary thyroid Carcinoma

RET, MET, TRK1,RAS,BRAF

p53

Medullarythyroid carcinoma

RET

Follicularcarcinoma

Ras, PAX8/PPAR P53, PTEN

Anaplastic BRAF p53.

Pathophysiology

Commonest site junction of isthmus with one of the lateral lobes

TypesToxic solitory nodule

Non toxic solitory nodule

Pathophysiology

GROSS Soft , firm, hard, cystic. Solitory /multinodular Contain brownish black fluid

Microscopy Nuclear groves Orphan annie eye nuclei characteristic Psamomma bodies (50%)

Spread Slowly progressive and less aggressive Spread through lymphatics Most commonly to lungs followed by bone,

liver and brain Blood spread less often

Orphan annie is strip cartoon character with empty circled eyes

Lymph node involvement in Papillary carcinoma

Central compartment(Level 6) medial to the carotid sheaths on both sides, from the hyoid bone superiorly to the sternal notch inferiorly

Jugular lymph node chains (levels 2-4)

posterior triangle of the neck (level 5)

Pathophysiology

Types InvasiveBlood spread common

Non invasiveBlood spread not common

Typical features Capsular invasion Angioinvasion

Spread More aggressive tumour. Through blood into bones*, lungs,

liver. Occasional spread to lymph nodes

in neck (10%)

*Bone secondaries typically vascular , warm , pulsatile, localised, commonly in skull, long bones, ribs

Pathophysiology

Variant of Follicular carcinoma according to WHO 75-100% of the tumor is composed of Hürthle cells,

also known as oxyphilic, oncocytic, Askanazy, or large cells

Large, polygonal follicular cells abundant granular acidophilic cytoplasm

Differ from follicular cancer inMultifocal and bilateral(30%)Donot take radio iodine(5%)More likely to metastasize to local nodes (25%) and distant

metastasisAssociated with higher mortality rate( ~20 % in 10 years)

Pathophysiology

GROSS Firm and whitish

Microscopy Sheats of cells with marked heterogenicity

Spread One of the Most aggressive thyroid malignancy

Spread through lymphatics commonly to lungs, brain and bones

Arise from de-differenciation of differenciated thyroid carcinoma

Pathophysiology

Types Sporadic(75%) Familial (25%)

Gross Well circumscribed Unencapsulated

Microscopy Amyloid stroma wherein malignant cells are dispersed

Calcitonin in amyloid on immnunochemistry

Spread Mainly to lymph nodes (60%) MCT associated with MEN type IIB

with pheochromocytoma (sipple syndrome) is MOST AGGRESSIVE

Features of Medullary Thyroid Cancer Syndromes

Syndrome Manifestations

MEN2A MTC, pheochromocytoma, primaryhyperparathyroidism, lichen planus amyloidosis

MEN2B MTC, pheochromocytoma, Marfanoid habitus,mucocutaneous ganglioneuromatosis

Familial MTC MTC

MEN2A andHirschsprung'sdisease

MTC, pheochromocytoma, primaryhyperparathyroidism, Hirschsprung's disease

Pathophysiology

Most common non hodgkin B cell lymphomas.

Commonly arise from chronic lymphocytic thyroiditis

Chronic antigenic lymphocyte stimualtion lymphocyte transformation

Presentation

HistoryMost commonPainless, palpable, solitary

thyroid nodule.

Solitory nodules presenting before 30 years and after 60 years increased chances of malignancy

Nodules in males higher chances of malignancy

Rapidly growing nodule is an ominous sign of malignancy.......

History

• Hoarseness involvement of the recurrent laryngeal nerve and vocal fold paralysis.

• Dysphagia impingement of the digestive tract

• Heat intolerance and palpitations suggest autonomously functioning nodules.

Carcinoma Clinical Features

Papillary thyroid carcinoma

Slow growing painless mass Discrete neck lymph nodes (40 %) Lateral aberrant thyroidcervical lymph

node invaded by metastatic cancer Compression featureuncommon

Follicular carcinoma Solitory thyroid nodules with history of rapid size increase and long standing goiter

Tracheal compressionstridor +ive Berrys sign*advanced malignancy Dyspnoea, hemoptysis and chest pain

when there are lung secondaries Pulsatile secondaries in skull and long

bones Cervical lymphadenopathyuncommon Signs and symptoms of thyrotoxicosis

*Infiltration of carotid sheath and absence of carotid pulsations James berry is a surgeon who named it

Secondaries in skull from thyroid primary ( well localised, warm pulsatile vascular tumour with underlying bone erosion).

• Anaplastic carcinoma

Carcinoma Clinical features

Anaplastic carcinoma Long standing neck mass >5cm which enlarges rapidly , may be painful

Tracheal obstruction stridor Hoarseness and dysnea common (50%) Vocal cord paralysis(30%) Hard Mass fixed to surrounding structures , may be

ulcerated,cervical mets (40%) +ive berry’s sign

Medullary thyroid carcinoma

Develops in superolateral part of thyroid lobes Neck mass with palpable cervical lymphadenopathy (15

to 20%) Paincommon Local invasion dysphagia, dysnea, dysphonia Sporadic unilateral(80%) Familial bilateral (90%)

Clinical presentation of thyroid cancer patients in Pakistan--AKUH experience,

• Thyroid cancer is a more aggressive disease in Pakistan, with majority of patients presenting with multinodular goiters, and a significant number have lymph node metastases. A higher degree of vigilance and a lower threshold for fine needle aspiration (FNA) is needed while evaluating patients with thyroid goiter......

Physical examination

Features suggestive of malignancy in a solitory nodule include

Any nodule can be malignant ( hard, firm, cystic,small,large,asymtomatic)

Rapid onset/rapid recent increase in size

Hoarseness of voice/dysphagia/ stridor/dyspnea

Fixity of the nodule

Palpable neck nodes

Head and neck examination with careful attention to the thyroid gland and cervical lymph nodes, as well as indirect laryngoscopy.

Thyroid paradox

Cellular tumours are soft and cystic tumors are firm and hard

Observed in papillary carcinoma of thyroid

Differential diagnosis of CA thyroid

• Multinodular goiter

• Reidels thyroiditis– Presents as hard fixed swelling.May have local

invasion and fibrosis but is BENIGN.

• Thyroid adenoma– Follicular- colloid , embroyal, fetal

– Hurthle cell

• Thyroid cyst

• Only one nodule palpable in MNG

Workup

Fine needle aspiration biopsy

Laboratory investigation

Imaging studies

Fine Needle Aspiration Biopsy

Most important diagnostic tool. Safe and minimally invasive

Ultrasonographic guidance increases the accuracy of FNAB

Gharib and Goellner (1993) found that 69% of FNAB results were benign, 4% were malignant, 10% were indeterminate, and 17% were nondiagnostic.

Sensitivity 83% Specificity 92%False-positive rate was 2.9%, and their false-

negative rate was 5.2%.

Fine Needle Aspiration Biopsy

Fine needle aspiration biopsy

• Complications• Minor hematoma and ecchymosis most common

• Puncture of the trachea, carotid artery, or jugular vein may occur

– Can be managed by applying local pressure

FNAB

• Limitation

• Difficult to differenciate between follicular adenoma and carcinoma on cytology as it depends upon capsular and angioinavision

Options in Follicular carcinoma Frozen section biopsy Hemithyroidectomy Trucut biopsy Danger of hemmorhage and injury to trachea, recurrent

laryngeal nerve and vessels

*Except in patients with history of external radiation or family history of thyroid cancer

Workup

• Laboratoty investigation• Serum TSH levels

– Low level suggests autonomously functioning nodule (usually benign)

– Dosnt rule out malignancy

• Serum calcitonin levels– Highly suggestive of MTC if increased– More senstive marker than CEA

• PCR assays for germline mutations in the RET proto-oncogene– Diagnostic in Familial medullary thyroid carcinoma

Laboratoty investigation

• Pentagastrin-stimulated calcitonin used as tumor markers to monitor patients who have been treated for MTC

• Serum thyroglobulin levels

– Cannot differenciate between benign and malignant disease

– Used in patients who underwent total thyroidectomy * for thyroid cancer

– Patients undergoing non operative managment of thyroid nodule

*increased levels indicate recurrence

Laboratoty investigation

• Urinary VMA, metanephrine and catecholamine– To rule out coexisting Pheochromocytoma in MTC

• Serum levels of CEA– Increased in MTC but nonspecific

– Better indicator of prognosis than Calcitonin

• New patients with MTC should be screened for RET point mutations, pheochromocytoma and HPT.

Imaging studies

Ultrasonography

Highly sensitive for thyroid nodules

Can depict nodules only a few millimeters in size

Can detect non palpable thyroid nodules

Differenciate solid from cystic nodules

Can detect adjacent lymphadenopathy

Ultrasonography

• Features suggestive of malignancy on USG include

– Fine stippled calcification

– Enlarged regional lymph nodes

• Used to follow the size of suspected benign nodules

Ultrasonograpy

Thyroid nodule with few, easily countable microcalcifications

Solid, hypoechoic, and coarse central calcificationsLater proved to be medullary carcinoma

Workup

Radio iodine studies Recommended in patients having Follicular CA on FNAB and

suppressed TSH.

Determine functional status of a nodule

• Based on radioisotope studies nodule can be Hot

Autonomous toxic nodule

Warm Normally functioning

Cold Non functioning nodule (likely to be malignant but not always)

Thyroid Scan showing cold nodule Thyroid scan showing hot nodule

Workup

• 111 indium octreotide scanning MTC (70 %sensitive)

Xrays• CXR and Xray skull to rule out metastatic deposits

– Skull mets more likely in Follicular carcinoma

CT scanning and MRI

– used to evaluate soft-tissue extension of large or suspicious thyroid masses into the neck, trachea, or esophagus.

– To assess metastases to the cervical lymph nodes

X-ray of skull showing a couple of painless, progressively increasing swellings in the occipitoparietal region of the scalp.

World J Radiol. 2012 June 28; 4(6): 286-290.

Staging TNM Classification of Thyroid Tumors

Papillary or Follicular Tumors

• Stage TNM

• <45 y

• I Any T, any N, M0 (cancer in thyroid only)

• II Any T, any N, M1 (Distant metastasis)

• ≥45 y

• I T1, N0, M0

• II T2, N0, M0

• III T3, N0, M0; T1–3, N1a, M0

• IVA T4a, N0–1a, M0; T1–4a, N1b, M0

• IVB T4b, any N, M0

• IVC Any T, any N, M1

Medullary Thyroid Cancer• Stage TNM• I T1, N0, M0• II T2–3, N0, M0• III T1–3, N1a, M0• IVA T4a, N0–1a, M0; T1–4a, N1b, M0• IVB T4b, any N, M0• IVC Any T, any N, M1

Anaplastic Cancer• Stage TNM• IVA T4a, Any N, M0• IVB T4b, Any N, M0• IVC Any T, Any M, M1

DefinitionsPrimary tumor (T)

• TX = Primary tumor cannot be assessed

• T0 = No evidence of primary tumor

• T1 = Tumor ≤2 cm in diameter, limited to thyroid

• T2 = Tumor >2 cm but <4 cm in diameter, limited to thyroid

• T3 = Tumor >4 cm in diameter, limited to thyroid, or any tumor with minimal extrathyroidal invasion

• T4a = Any size tumor extending beyond capsule to invade subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent

• laryngeal nerve, or intrathyroidal anaplastic cancer

• T4b = Tumor invading prevertebral fascia, or encasing carotid artery or mediastinal vessels; or extrathyroidal anaplastic cancer

Regional lymph nodes (N)—include central, lateral cervical, and upper mediastinal nodes

• NX = Regional lymph nodes cannot be assessed

• N0 = No regional lymph node metastasis

• N1 = Regional lymph node metastasis

• N1a = Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes)

• N1b = Metastases to unilateral, bilateral, or contralateral cervical or superior mediastinal lymph nodes

• Distant metastasis (M)

• MX = Distant metastases cannot be assessed

• M0 = No distant metastasis

• M1 = distant mets present

Staging

Stage 1 Malignancy is intrathyroidal

Stage 2 Cervical nodal metastasis

Stage 3 Extrathyroidal invasion

Stage 4 Distant metastasis

*Applicable in all thyroid malignancies but mainly used in follicular carcinoma

Prognostic indicators in PTC

Classify patients into LOW RISK and HIGH RISK groups

AGES scoring system

• Age, Grade, Extrathyroidal invasion and Size.– LOW RISK patients are

• Young <40 years

• Well differenciated tumor

• No mets

• Small primary lesions (<4cm)

– HIGH RISH include• Older >40 years

• Poorly differenciated tumor

• Distant metastasis

• Large primary lesion >4cm

MACIS scoring system

Post operative system modified from AGES

• Include Metastasis, Age , Completeness of excision, extrathyroidal Invasion and Size.

• The final prognostic score was defined as– MACIS = 3.1 (if aged less than or equal to 39 years) or 0.08 x

age (if aged greater than or equal to 40 years), + 0.3 x tumor size (in centimeters), +1 (if incompletely resected), +1 (if locally invasive), +3 (if distant metastases present).

AMES Scoring system

• Proposed by Cady

• Include Age, Metastasis, Extent of primary tumour, Size

• LOW RISK include– Age <40 in men and <50 in women

– No mets

– No extrathyroidal invasion

– Size <5 cm

• HIGH RISK include– Age > 40 in men and >50 in women

– Distant mets +ive

– Extrathyroidal invasion

– Size >5cm

Tid Bits

Lymph node involvement does not alter the prognosis of papillary carcinoma of thyroid.

All scoring systems catagorise the patient asHigh risk of death i.e 40 % in 20 years

Low risk of death i.e 1 % in 20 years

Low risk is acheived by complete clearance of macroscopic tumor during first surgery

Lymph node levels in neck

Unilateral thyroid lobectomy is recommended

Cyst persist after 3 attempts for aspiration

Cyst >4cm

Complex cyst with solid and cystic components higher chances of malignancy (15 %)

Papillary thyroid carcinoma

HIGH RISK or BILATERAL Total or near total thyroidectomy

Minimal papillary carcinoma in thyroid specimen

Unilateral thyroid lobectomy and isthmectomy

Large , Locally aggressive/ metastatic tumours

Total thyroidectomy with excision of adjacent involved structures if necessary and appropriate nodal surgery followed by radioablation with long term TSH suppression

Modified Radical neck dissection type III is done in case of lymph node involvement

Low risk groupsPoints in favour of total thyroidectomy Point in favour of lobectomy

Enables the use of RAI to detect and treat residual thyroid tissue/mets

Lobectomy has less complication rate

Makes serum Tg level more sensitive for recurrent or persistent disease

Recurrence in remaining tissue is unsual (5%) and mostly curable by surgery

Removes contralateral occult cancer as sites of recurrence ( 85% bilateral)

Tumour multicetricity has littleprognostic significance

Reduces recurrence risk and improved survival

Prognosis is comparable to total thyroidectomy

Decreases the 1 % risk of progression to anaplastic cancer

Reduces rate of re-operation and complication

Generally total or near total thyroidectomy is recomended in low risk groups provided complication rates are low <2 %

Indication of total thyroidectomyNCCN guidelines

If any present If all present (thyroidectomy/lobectomy)

Age <15y or >45y Age 15 – 45 y

Radiation history No radiation history

Known distant mets No distant mets

Bilateral nodularity No nodularity

Extrathyroidal invasion No extrathyroidal invasion

Tumour > 4cm Tumour <4 cm

Cervical lymph node mets No cervical lymph nodes mets

Aggressive variant No aggressive variant

• Prophylactic lateral neck node dissection is NOT recommended in PTC

– Cancer dosnt metastatise systemically from lymph nodes

– Micrometastasis can be ablated by RAI therapy

Residual disease Post operatively

• TSH + Tg and antithyroglobulin antibodies – 2 to 12 weeks post operatively

• Total body RAI imaging– Suspected or proven RAIEBRT

– Adequate RAI uptake Radioiodine treatment and post treatment I131 imaging

• If no imaging performed EBRT

• In all these cases suppress TSH with Levothyroxine.

• Using the Surveillance, Epidemiology, and End Results (SEER) database, one study compared the overall survival (OS) and cause-specific survival (CSS) of 23,605 subjects with papillary or follicular thyroid cancer treated with local excision, lobectomy, near-total thyroidectomy, or total thyroidectomy.

• The 10-year OS and CSS results concluded that total thyroidectomy resulted in improved survival over other techniques– Poorer outcomes were associated with age, stage

T3/T4 disease, positive nodes, and tumor size

Metastatic disease

• CNS Neurosurgical resection and/or image guided EBRT

• BONE Surgical paliation ( weight bearing extremities and/or RAI treatment and/or EBRT– bisphosphonate or denosumab therapy– Embolization of mets

• Other than CNS surgical resection and/or EBRT of selected mets and/or radioiodine – Best supportive care

Follicular carcinoma• Follicular lesion on FNAB thyroid lobectomy (80 % are

adenomas)

• Total thyroidectomy is recommended in– Older patients– Lesion >4cm ( cancer risk is 50 %)

• Intraoperative frozen section examination if– Evidence of vascular or capsular invasion– Adjacent lymphadenopathy is present

• If non diagnostic then hemithyroidectomy is done and sent for histopathology

• Thyroid specimen follicular carcinoma total thyroidectomy

• Nodal mets therapeutic neck dissection

Hurthle cell carcinoma

• Unilateral lobectomy and isthmectomy

• Invasive total thyroidectomy + central neck node removal

• Modified radical neck dissection if lateral nodes are involved

• TSH suppression

Rediffereciating therapies such as retinoic acid and PPAR gamma have shown some benefit in these tumors but require futher

research

Post operative management of DTC

Radioiodine scanning and ablation

• RAI ablation is recommended in

– All patients with stage 3 and 4 disease

– All Patients with stage 2 disease <45 years

– Usually in patients >45 years and stage 2 disease

– Stage 1 disease with

• Aggresive histology

• Nodal mets

• Multifocal disease

• Extrathyroidal or vascular invasion

• More senstive than xray/ CT in detecting metastatic disease

• Less senstive than Tg level except in Hurthle cell Tumours

• 4-6 weeks after thyroidectomy, hypothyroid can be induced by discontinuing replacement (T4 for 4 weeks or T3 for 2 weeks) to obtain high serum TSH levels.

• A diagnostic dose of131 I or123 I is given initially.

• Whole-body scanning is performed to detect any tissue taking up radioiodine.

• If any normal thyroid remnant or metastatic disease is detected, a therapeutic dose of131 I is administered to ablate the tissue.

• If a treatment dose of131 I is required, diagnostic thyroid scanning is repeated after 6 months after initial treatment,

• If the diagnostic scan Positive additional therapeutic dose is given. Process is repeated until the diagnostic scan is negative

Role of recombinant human TSH

• Thyrogen stimulation avoids the discomfort of patients having to discontinue thyroid replacement– t4 stopped 1 day before TSH stimulation

Recent advances

• Sorafenib* (Nexavar) was approved in November 2013 for differentiated thyroid

cancer (DTC) that is refractory to radioactive iodine treatment.

• *Sorafenib is a small molecular inhibitor of several tyrosine protein kinases

Thyroid suppression

• Used after thyroidectomy and radioablation

• Reduces tumoural growth and recurrence rates

• Suppressive dose is 0.3 mg OD lifelong

• TSH levels should be < 0.1 mU/L

External beam radiotherapy

• Used in unresectable, locally invasive or recurrent disease

• In bone mets to decrease

– Risk of fractures

– Bone pain

Chemotherapy

• Generally has no role

• Doxorubicin is used as radiation sensitizer in patients undergoing external beam radiation

Medullary thyroid carcinoma

• If pheochromocytoma present operated first• Total thyroidectomy is the treatment of choice

with bilateral central neck node dissection

• Palpable cervical lymph nodesmodified radical neck dissection

• Tumour >1 cm ipsilateral Prophylactic modified radical neck dissection– If +ive than contralateral node dissection is done

Medullary thyroid carcinoma

• If unresectable– Tumour debulking to reduce symptoms– External beam radiation

Recent advances Tyrosine kinase inhibitors Imitanib Zactima (reduces calcitonin and CEA levels

Anti CEA monoclonal antibody Labetuzumab

Laproscopic Radiofrequency ablation For Liver mets >1.5 cm (palliative)

• If patient is hypercalcemic at thyroidectomy

– Only enlarged parathyroid gland is removed

• RET mutation carrier total thyoroidectomy

– MEN2A before 6 years

– MEN2B before 1 year

• Central neck node dissection

– Avoided in calcitonin negative and normal USG exam

– Done prophylactically in calcitonin positive and if USG suggests cancer

• Maintenance dose of L-thyrosine

• All family members of patients with MTC should be evaluated with serum calcitonin (

genetic evaluation can also be done ) and if it is high they should undergo prophylatic

thyroidectomy ......

Anaplastic carcinoma

• If resectable

– Adjuant chemoradiotherapy

• Adriamycin is used for chemo.

• Tracheostomy and isthemectomy to relieve airway obstruction in unresectable cases

Lymphomas

• Mainstay Chemotherapy

– CHOP ( Cyclophosphamide, Doxorubicin, vincristine, and prednisolone)

• Radiotherapy may also be given

• Thyroidectomy and nodal resection to alleviate airway obstruction

Differenciated thyroid carcinoma

Throglobulin levels Thyroglobulin is a useful marker of tumor recurrence

because well-differentiated thyroid cancers synthesize thyroglobulin

• After total thyroidectomy levels should be– <2 ng/ml if taking t4– <5ng/ml if hypothyroid– Levels >2ng/ml suggest metastatic or persistant normal tissue.

(>95%)

• Tg and Tg antibodies measuresd initially 6 months interval then annualy if disease free.

Follow up imaging

• In low risk and –ive TSH stimulated Tg and cervical USG routine whole bodyscan is not recommended after first post operative scan

• After remnant ablation routine whole body scan after 6 to 12 months is recommended

Cervical USG • To evaluate thyroid bed and lymph node 6 to 12 months

post thyroidectomy then annually for 4 to 5 years

FDG PET SCAN• If RAI and USG normal but Tg remain elevated

Medullary thyroid carcinoma

• Annual measurements of calcitonin and CEA levels.

• Regular USG , CT , MRI if required

• FGD PET scans

– Superior to other radionuclide based studies

Management of recurrence

• Localised

– Surgical excision

• Non localised

– 131 I radioablation

– External beam radiotherapy

Stage Age < 45 Age > 45Local

RecurrenceDistant

Recurrence10 year Survival

I Any T Any N M0 T1 N0 M0 5.5% 2.8% 98%

II Any T Any N M1 T2 N0 M0 7% 7% 89%

III - T3 N0 M0T1-3 N1a M0

27% 13.5% ~82%

IVa - T4a N0 M0T1-4 N1b M0

IVb - T4b N0-1b M0

IVc - Any T Any N M1 60.9% 100% 50%

• This table is extrapolated from a number of sources including the American Cancer Society, The National Cancer Institute,

and the National Comprehensive Cancer Network, among others

According to stage

According to cancer type

5-Year Survival for Papillary Thyroid Cancer

Stage 5-Year Survival

I Nearly 100%

II Nearly 100%

III 93%

IV 51%

5-Year Survival for Follicular Thyroid Cancer

Stage 5-Year Survival

I Nearly 100%

II Nearly 100%

III 71%

IV 50%

5-Year Survival for Medullary Thyroid

Cancer

Stage 5-Year Survival

I Nearly 100%

II 98%

III 81%

IV 28%

Papillary carcinoma• Good prognosis• Age is most important factor

AGES systemAGES Prognostic score = 0.05 × age (if age ≥40)

+ 1 (if grade 2)+ 3 (if grade 3 or 4)+ 1 (if extrathyroid)

+ 3 (if distant spread)+ 0.2 × tumor size (cm maximum diameter)

AGES score Survival (20-yr)

≤3.99 99%

4-4.99 80%

5-5.99 67%

≥6 13%

• Survival by AMES risk-groups (20-yr)

Low risk 99%

High risk 61%

• Survival by MACIS score (20-yr)MACIS score Survival

<6 99%

6-6.99 89%

7-7.99 56%

≥8 24%

Follicular carcinoma

• Cumulative mortality is – 15% at 10years

– 30 % at 20 years

• Poor prognosis is associated with– Age >50

– Tumour size > 4cm

– High tumor grade

– Marked vascular and extrathyroidal invasion

– Distant metastasis

Medullary thyroid carcinoma

• 10 yr survival rate is 80 %

• Decreases to 45 % with lymph node involvement

• From best to worst prognosis

– Non MEN familial MEN 2A sporadic MEN2B

• MEN2B has survival rate of 35 % at 10 years

Anaplastic carcinoma

• Few patients survive 6 months beyond diagnosis

Lymphomas • Depends upon

• Histologic grade• Tumour within thyroid or disseminated

• Overall 5 yr survival rate is 50 %• Extrathyroidal disease lower survival

rates

Patient education

• Patients who discover a neck deformity or thyroid lumps or have a history of prior

exposure to ionizing radiation must consult their physician

Case Presentation• A 40 year old male, resident of Chichawatni, electrician by profession

presented with complain of swelling on the right side of neck for 3 months.

• Swelling was gradual in onset, progresively increasing in size and number. Noticed by the patient by self palpation.

• Associated with

– Hoarseness of voice

– Anorexia and weightloss for last 1 month

• No h/o pain, fever, palpitation, sweating, heat/cold intolerence, dysphagia, dysnea, radiation exposure , sleep disturbance or neck trauma.

• Past medical and surgical history unremarkable except HCV infection (7 years)

• Drug history : Took interferon injections for 6 months for HCV.

• Personel history : Non smoker, non addict

• Socio economic History: Lower class with 7000/ month income.

• Family history : Mother is diabetic .

• Allergic history: Not significant .

General physical examination• A middle aged male of lean physique sitting comfortably on

bed well oriented in time place and person– B.P= 130/90 mmHg– Pulse= 90/ min regular rhythm, volume and character– Resp rate = 14/min – Temp= 98.6 F– Weight =50 kg BMI=16.03

• Bilateral cervical lymphadenopathy– Right Post triangle nodes– Bilateral along anterior border of sternocleidomastoid– Bilateral supraclavicular nodes

• Right axillary medial group of lymph nodes are also palpable

• No Pallor, cyanosis, jaundice, clubbing or edema

Local examination

• A 3*2 cm soft, globular, nontender, nonfluctuant, non pulsatile, normothermic swelling on the right side of anterior triangle that moves upward with deglutition.

• Not fixed to overlying skin but fixed to underlying tissues ,with smooth surface and irregular borders but no prominent veins, pulsations or stridor.

• Carotid pulse palpable i.e berry’s sign –ive

Systemic examination• No eye signs

• CNS : GCS= 15/15 intact

• CVS : S1 + S2 + 0

• Chest : NVB + 0

• Abdomen: Soft nontender, no viceromegaly, Liver span = 12 cm in midclavicular line, bowel sounds present

Investigation

• Laboratory investigation: – CBC, LFTS, RFTS, and COAGULATION is NORMAL– Thyroid function test are normal

• FNAC– Thyroid nodule

• Nuclear overlapping, nuclear groves with papillary cores suggestive of Papillary carcinoma of thyroid

• No inclusion or psamomma bodies

– Cervical lymph node• Sheets of pleomorphic cells with nuclear grooves against

hemorrhagic background

Imaging studies

• CT scan of neck with I/V contrast

– Large heterogenous enhancing mass involving right side of isthmus and right lobe of thyroid with extrinsic compression of trachea.

– Calcification also noted in mass

– Multiple enlarged lymph nodes in right axilla, supraclavicular and cervical region

– Oro/hypopharynx and larynx appear normal. Esophagus is normal. Great vessels in the neck are un remarkable

• 99m Tc MDP bone scan:– Normal ( homogenious and bilateral symmetrical tracer

distribution)

• CHEST X RAY:– Normal

• Indirect laryngoscopy:– Bilateral normal mobile vocal cords

Plan• Total thyroidectomy with neck block dissection

followed by lifelong thyroid hormone replacement therapy

Intraoperative findings

Level IIb , III , IV and V lymph node chains with pericapsular fibrosis invading carotid sheath.

Right lobe hard fixed infiltrating right wall of trachea

Hard fixed mass extending retrosternally and fixed with trachea....

Procedure done

• Modified radical neck dissection

– Accessory nerve saved . Internal jugular vein and sternocleidomastoid removed

• Left lobectomy and isthmectomy + right nodulectomy