Thyroid malignancy

Zeeshan

• 66/M• c/o swelling in front of neck for 10 years• c/o Diplopia for the past 3 months

• No rapid increase in size

• No hyperthyroid/hypothyroid symptoms

• No voice change

O/E

• There was a 3x2 cm • size, hard swelling in • the right lobe of • thyroid, which • moved up • with deglutition.• No nodes

Triple assessment

• Clinical assessment – Size, fixity, character on palpation

• FNAC

• Imaging – USG neck

History

• Rapid increase in size

• Childhood radiation

• Family h/o thyroid cancer

• Syndromes (MEN 2, Cowden’s, FAP)

Examination

• Fixed hard mass

• Obstructive symptoms

• Voice change

• Cervical lymphadenopathy

FNACA – Macrofollicle

B- Macrofollicle broken apart

AdenomaMicrofollicle with little or no colloid in backgroundNo clumping or pleomorphism

Follicular carcinomaMicrofollicles, No colloidClumping, pleomorphism presentCells not arranged in follicles

Hurthle cell neoplasmLarge polygonal cells with abundant oxyphilic cytoplasm

Papillary carcinomaNuclei have clefts, grooves and holesIntranuclear inclusions – Orphan annie eye

Medullary carcinomaSpindle shaped cells – occasional RED cystoplasmic inclusionsAmyloid stroma

Bethesda classification

• Benign • FLUS/AUS• Follicular neoplasm• Suspicious for malignancy• Malignancy• Nondiagnostic

FLUS/AUS

• Cells have mild nuclear atypia

• Equal number of micro/macrofollicles

• Extensive oncocytic change BUT not enough to characterise as HURTHLE cell neoplasm

USG Neck

Our patient

• A well defined heterogenous solid nodule with calcification in the right lobe . The skull lesion on the left is similar in appearance to the thyroid lesion Findings are highly suspicious of malignancy * Three small isohypoechoic nodules in the left lobe -Probably benign * Suspicious left level 4 node measuring

6.3 mm. No other significant cervical nodes

TIRADS (Thyroid imaging reporting and data system)

TIRADS Interpretation

1 Normal thyroid gland

2 Benign lesion

3 Probably benign lesion

4 a,b,c Suspicious of malignancy

5 Probably malignant (>80% risk)

6 Biopsy proven malignancy

TIRADS 4 a,b,c

• Marked hypoechoic nodule• Solid component• Microlobulations/ irregular margins• Microcalcifications• Taller than wider shape

• TIRADS 4 a – One suspicious feature (5-10%)• TIRADS 4 b – Two suspicious features • TIRADS 4 c – Three to four suspicious features

- Tirads 4b,c – 10-80% risk of malignancy

Thyroid malignancy

MALIGNANT

PRIMARYFollicular epithelium – DifferentiatedFollicular caPapillary ca

Follicular epithelium – UndifferentiatedAnaplastic carcinoma

Parafollicular cells - Medullary ca

Lymphoid cells – Lymphoma

IncidenceTumor Relative incidence

Papillary carcinoma 60

Follicular carcinoma 20

Anaplastic carcinoma 10

Medullary carcinoma 5

Malignant lymphoma 5

Papillary carcinoma

Follicular carcinoma

Medullary carcinoma

Presentation Younger age

M:F – 1:2.5

Older age (40 – 60)MIFC/ WIFCM:F -

Sporadic/ Familial/MEN 2A,B

Metastases Common at presentationLymph node – MC site

Poor prognosis

Hematogenous

Common at presentation (50%)Lymph node

Gene NTRK, RET, BRAF

RAS oncogene RET

Tumor marker

None None CalcitoninCEA

Papillary carcinoma Follicular carcinoma

Medullary carcinoma

Types Follicular InsularTall cellInsular Diffuse sclerosing

Hurthle cell carcinoma

MEN IIAMEN IIBFMTC

Radioiodine Concentrates radioiodine

Concentrates radioiodine

Does NOT concentrate radioiodineRESISTANT to RT, chemo

Patient risk factor

• Age :- Males – 45 years- Females – 50 years

• H/O neck irradiation• Signs of invasive nature

Tumor risk factors

• Distant metastases

• Vascular invasion

• Capsular invasion

• Tumor size

• Early recurrence

AJCC staging

Risk stratification

• A – Age• G – Grade • E – Extent • S – Size

• A – Age• M – Metastases• E – extent • S - Size

• MACIS• M – Metastases• A – Age• C – Completeness of resection• I –Invasiveness • S - Size

ATA

Treatment

Differentiated thyroid cancer- GOAL of intial therapy

• To remove the primary tumor and involved lymph nodes

• To minimize treatment and disease related morbidity

• To permit accurate staging of the disease

• To facilitate postoperative iodine treatment

Surgery in Differentiated thyroid cancer

- Primary tumor >1 cm

- Presence of regional/ distant mets

- Prev h/o neck irradiation

- First degree relative with thyroid ca

- Age >45 yrs.

Basis of treatment in MTC

• Does NOT take up Radioiodine

• Does NOT respong to Thyroid suppression

• In 90% of hereditary forms MULTICENTRIC In 20% of sporadic forms

• Nodal metastases are present in > 70% of palpable disease

Advantages of Total thyroidectomy

• Radioactive iodine scan and Tg levels on follow-up

• Most PTC multicentric

• Recurrence rates lower

• Re-operative Sx higher morbidity

Indication of hemithyroidectomy

• Tumor < 1cm

• No nodal/distant metastases

• No adverse patient risk factors

No role for hemithyroidectomy in Hurthle cellMedullary Ca

Lymph node dissection - Differentiated Ca thyroid

Disease Treatment

PTC with no nodal spread TT

PTC with nodal spread TT + CCND + Unilateral MRND

Follicular carcinoma with no nodal spread

TT

Follicular carcinoma with lymphnodal spread

TT + CCND + Unilateral MRND

Surgery in DTC

Surgery in MTC

Follow-up of patients• High risk group :- Whole body scan- Thyroglobulin levels- USG neck

• Low risk group :- Thyroxine suppression therapy TSH levels < 0.1 mU/L Thyroxine 2.2 – 2.5 mcg/Kg body weight for 5 yrs

When to do a WBS?

• Do a radioiodine scan in - High risk patients- Tumor size > 1cm- LVI/PNI present

- Timing : 45 days after stopping T4 2 weeks after stopping T3- AIM : To achieve TSH > 30 mU/dl

Radioiodine scan

• I123/ I131

• Low iodine diet prior to scan

• Done 1 week post radioiodine therapy

• Oral I131 administration – 2-5 mCi

WBSMultiple metastatic deposits

Tg levels

• 95% of patients with distant metastases have elevated Tg levels

• Best time to evaluate Tg – when patient is hypothyroid in evaluation for WBS

• Tg >> WBS in predicting metastatic disease

• Level > 2mg/ml significant

Recurrence in DTC

• Radioiodine ablation

• Dosage 150 – 200 mCi

• Follow up with atleast 2 negative scans

Recurrence in MTC

• EBRT

• Chemotherapy – Doxorubicin NOT EFFECTIVE

• Interferon a

• Surgery – Tissel described “microdissection” Extensive lymph nodal clearance

Metastatic carcinoma thyroid

• Persistent / Recurrent disease in the neck : Surgical debulking

• Invasion of upper aerodigestive tract : Sx + RI ablation/ RT

Pulmonary metastases

Bony metastases

• Bone mets- Insensitive to I131 therapy

Brain metastases

• Incidence – 0.15 – 0.30%

• Treatment of choice – Surgical excision in view of neurologic symptoms

• External RT - Pain

Mediastinal lymph nodal metastases

• Surgical excision

Role of Chemotherapy

• Metastatic disease – 10- 15 % respond to Alkylating agents 20 – 33% response to Bleomycin/Adriamycin

• Indication:Tumors not amenable to - Radioiodine- RT

Role of RT

• Painful osseous mets

• Bone mets not amenable to Sx - Vertebral column - Base of skull

Our patient

• Underwent

TT + CCND + Left MRND

Biopsy report• Total thyroidectomy specimen: Multifocal follicular

variant of papillary carcinoma, right and left lobes. Maximum tumour size is 3.3 cm in right lobe and 1 cm in left lobe. Capsular invasion, present in right lobe. There is no lymphovascular or perineural invasion. Tumour is 0.2 cm from the nearest inked margin in left lobe and <0.1 cm in right lobe.

• Perithyroidal extension, not seen. • Separately sent left MRND: • 9 lymphonode, free of tumour. • mpT2N0.

CT brain

Plan

• To D/W neurosx regarding feasability of resection

• WBS booked