Radiological Diagnosis and Treatment of Papillary …eradiology.bidmc.harvard.edu/LearningLab/central/...Paul Dieffenbach Gillian Lieberman, MD 1 Radiological Diagnosis and Treatment

Paul Dieffenbach

Gillian Lieberman, MD

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Radiological Diagnosis and Radiological Diagnosis and Treatment of Papillary Thyroid Treatment of Papillary Thyroid

CarcinomaCarcinoma

Paul Dieffenbach – HMS III


September 2006

Paul Dieffenbach


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Presentation OutlinePresentation Outline

• Overview– Epidemiology– Anatomy

• CT scan in Thyroid CA• Ultrasonography and

Ultrasound-guided FNAB

• Scintigraphy

• Nuclear Medicine– Post-operative

Radioiodine Ablation– Follow-up WBS and

ablation Tx

• PET and PET-CT

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Overview of Papillary Carcinoma Overview of Papillary Carcinoma • Incidence

– ~210,000 in 2005; 2.5:1 F/M– 75% of Thyroid tumors, ~1%

of US malignancies

• Typical presentation:Solitary thyroid Nodule

• Prognosis– All comers: cancer-related

mortality of 6%– Risk Factors (AMES)

• Age (>40 in men, 50 in women)• Mets (outside of neck)• Extent—soft tissue invasion (5x)• Size (2-3.9cm =6%, 4-6.9cm =

16%, >7cm = 50%)

• Metastases– Local Nodes 80%

• Half microscopic• Not diagnostic

– Local invasion• Soft tissue 5-35%• Vascular: 5-10%

– Distant• 10% of patients• Lung (2/3), Bone

(1/4), other

http://www.georgetown.edu/dml/educ/path/cpc/endo_thyroid/09.html

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Anatomy of the ThyroidAnatomy of the Thyroid• Composed of two lateral lobes connected by an

isthmus w/ variable presence of a pyramidal lobe

• Isthmus rests at 2nd-4th laryngeal cartilages– Superior poles can rise normally to the level of the larynx– Inferior poles can descend to 5th-6th laryngeal cartilage– Exact size, location of thyroid tissue somewhat variable

• Dimensions of lateral lobes: normally 4-8cm long, 1.5-2cm wide, and less than 2-2.5cm deep

• Thyroid is bound anteriorly by the infrahyoid, laterally by sternothyroid muscles (and carotid sheath), posteriorly by the larynx, and medially by the larynx and inferior constrictor.

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Brief Anatomy of the Neck (Ant. View)Brief Anatomy of the Neck (Ant. View)

Thyroid• Pyramid• Isthmus• Lateral Lobes

Arteries• Brachiocephalic

– Occasional thyroid ima (or from arch)

• Common Carotid• External Carotid

– Superior Thyroid artery

Nerve• Vagus• Recurrent Laryngeal

Strap Muscles• Thyrohyoid• Cricothyroid• Sternothyroid,

Infrahyoid (anterior)

Airway• Larynx• Trachea

Veins• Internal Jugular

– Drains superior, middle thyroid veins

• Brachiocephalic– Usually drains inferior

thyroid veins (variable)

Henry Gray (1825–1861). Anatomy of the Human Body. 1918.

http://www.bartleby.com/107/272.html#i1174

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Introduction: Patient ASIntroduction: Patient AS

Our Patient AS is an 83 y/o woman with a history of coronary artery disease complaining of >2yrs cough + “need to clear throat,” occasional difficulty swallowing that has been getting slightly worse over time

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Patient AS: Barium SwallowPatient AS: Barium Swallow

PA L Lat Oblique

Barium SwallowRound, smooth, extrinsic indentation

Esophagus is deviated to the right and slightly anteriorly over 2-3cm

Ddx R Lower Neck Mass• Thyroid Nodule

• Lymph node enlargement • Infection, lymphoma, inflammatory (sarcoid), mets

• Tracheal masses

• Soft tissue tumors

What follow-up imaging is indicated?

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Patient AS: Neck CTPatient AS: Neck CT

Enlarged R thyroid w/ 2x3cm heterogeneous mid-thyroid nodule

Small round hypodense L lower pole lesion w/ nearby small semi- calcified nodule (both <1cm)

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* Normal Appearance of Thyroid Tissue on CT

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CT in Thyroid Carcinoma I :CT in Thyroid Carcinoma I : Determination of Likely Thyroid LesionDetermination of Likely Thyroid Lesion

Signs of Thyroid Origin• Anatomic continuity

– Local spread of tumor more common than distant metastasis

• Superior mediastinal mass (usually anterior)– Ddx: Teratoma, thymoma, thyroid, (terrible) lymphoma

• Deviation of trachea, esophagus – Large thyroid lesions have significant mass effect

• Focal calcification, heterogeneity (iodine, cysts)• High HU (~100)• Increased density after contrast bolus• Prolonged contrast enhancement

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CT in Thyroid Carcinoma II :CT in Thyroid Carcinoma II : Evaluation of Known Thyroid LesionEvaluation of Known Thyroid Lesion

Indications for CT in Thyroid Carcinoma

• Generally indicated in thyroid masses >3cm • Characterization of laryngeal/tracheal or esophageal invasion• Assess blood vessel, nerve involvement for surg. planning• Detection of local metastases

– Most useful post-surgery and radioiodide ablation for mets that are not iodine avid

• Detection of non-local metastases

Notes

• Contrast should not be given before scintigraphy, TSH evaluation, or shortly before radioiodide WBS/ablation

• CT is not sensitive or specific for determining malignancy of intrinsic thyroid nodules

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Our Patient AS was sent to Our Patient AS was sent to Ultrasound for further Ultrasound for further

characterization and likely characterization and likely biopsy of thyroid nodules biopsy of thyroid nodules

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Thyroid Ultrasonography IThyroid Ultrasonography I• Technique

– 5-15MHz high resolution transducer– Patient lies supine w/ neck hyperextended

• Indications– Characterize/verify physical exam findings– Search for nodules in high risk population (radiation exposure)– Follow up multinodular disease– Detect recurrent tumor post-operatively– Guidance of fine needle aspiration biopsy (FNAB)– Guidance of ETOH ablation

• Why not a screening tool?– Diagnostic yield low– Time consuming– Morbidity, patient anxiety involved (FNAB)– Relatively low morbidity, mortality of thyroid CA in current practice

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Thyroid Ultrasonography IIThyroid Ultrasonography II Nodule CharacterizationNodule Characterization

US Features of nodules:

• Internal Consistency• Echogenicity• Margin Regularity• Presence of macro- or

micro-calcifications• Peripheral Sonolucent

Halo• Presence & distribution

of blood-flow signals

Pathological Ddx thyroid nodule:• Colloid Nodule• Adenoma

– Adenomatous hyperplasia of thyroid

– Follicular adenoma– Parathyroid adenoma

• Thyroid Carcinoma– Papillary, follicular, anaplastic,

medullary, Hurthle cell• Cyst

– Simple Thyroid cyst (uncommon)– Degenerating adenoma or

necrotic carcinoma• Metastasis (very uncommon)

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US: Benign FeaturesUS: Benign Features• Homogeneous hyperechogenicity

(<1% malignant) or isoechogenicity with regular lucent halo

• Cystic lesion with no solid mass present (rare)

• Lack of vascularization (especially central)

• Multinodularity of lesions– Less of an effect than previously

thought (improved detection?)– Dominant lesion in multinodular goiter

carries same risk as single nod

• Eggshell calcification• Hypo- or isoechoic w/distal

enhancement +/- lateral acoustic shadowing

• Regular Margins 2 Demonstration Patients with enlarged thyroids containing multiple small nodules by physical exams

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US: Suspicious FeaturesUS: Suspicious Features• Irregular or poorly defined margins• Microcalcifications

– <2mm in diameter– Psammomas

• Same-side lymphadenopathy• Invasion of adjacent structures• Significant vascularization

– Esp. central or chaotic• Hypoechogenic solid lesions with

incomplete/irregular halo and w/o distal enhancement

Mildly increased RiskMildly increased Risk– Other calcifications (non-eggshell)– Heterogeneous internal structure– Complex cystic lesions

2 demonstration patients evaluated for nodules noted on physical examination. Neither of these nodules were the ones initially noted. Both turned out to be papillary carcinoma.

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Patient AS: Ultrasound ResultsPatient AS: Ultrasound Results

• Heterogeneous structure, echogenicity

• Incomplete halo• Microcalcifications• Poorly defined superior

margin

• Small nodule w/ fairly large calcifications & posterior shadowing

• Neighboring hypoechogenic region (cystic appearing) w/ solid portion along medial wall

• Clear margins

Rt mid 2.5 X 2.1cm nodule Lt Lower 1.5 X 1cm nodule


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UltrasoundUltrasound--guided FNABguided FNABUltrasound accuracy• 90% of biopsied nodules benign current

practice has low specificity

Indications• Any nodule with more than one suspicious

sign• Any solitary nodule• Dominant nodule in multinodular goiter• Incidentalomas? Controversial

Not indicated• Benign-appearing non-dominant nodules• “Hot nodules” by Thyroid scintigraphy

– This study of uptake w/ I-123 done less frequently for nodules unless patient has low TSH (suggesting hyperfunctioning thyroid).

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Patient AS -- FNAB

This patient presented with a large neck nodule. Scintigraphy with 300Mci I-123 revealed a cold nodule in the right lower lobe.

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Demonstration Pt: Thyroid Scintigraphy

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Patient AS FollowPatient AS Follow--upup

• Both right mid-lobe nodule and left thyroid nodule were positive for papillary carcinoma.

• The patient has been recommended for surgical consultation, and has begun her pre-operative work-up.

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Introduction: Patient AJIntroduction: Patient AJ

Our Second Patient, AJ, is a 42 y/o woman with a history of type II DM and a new finding of multinodular thyroid on physical examination

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Patient AJ: Thyroid UltrasoundPatient AJ: Thyroid Ultrasound


Right-sided 17 x 12mm Nodule– Isoechoic– Distal enhancement– Lateral acoustic shadowing– Clear halo– Slight heterogeneity– Avascular– Clear margins

FNAB Diagnosis: C/w mixed micro- & macrofollicular lesion

Left-sided 15 x 6mm Nodule– Hypoechoic– Clear Margins– No acoustic shadowing or distal

enhancement– No halo– Chaotic hypervascular pattern

FNAB Diagnosis: Papillary Ca

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Patient 2: CXR and Chest CTPatient 2: CXR and Chest CTSmall concerning lesions in R lower lobe on CXR Neck & Chest CT for further characterization

Chest CT Results:

• No mediastinal, hilar, axillary lymphadenopathy

• Small bilateral subpleural noncalcified nodules measuring 3, 4, & 6mm

• Ddx: Metastatic Disease, non-specific nodules

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Multiple Pulmonary Multiple Pulmonary MicronodulesMicronodules

on CXR and CTon CXR and CT

Companion Patient 1: 64 y/o woman initially p/w Hx of hoarseness, neck discomfort, now s/p thyroidectomy, pre-op for further tumor debulking

– Substernal anterior-superior mediastinal mass extending into neck & causing tracheal displacement

– Diffuse pulmonary micronodules (<5mm) w/ occasional macronodular met

Ddx Diffuse micronodules w/ near-random distribution:

– Metastases (especially thyroid!)– Miliary TB– Miliary Sarcoidosis– Disseminated Histiocytosis

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Patient AJ: Total ThyroidectomyPatient AJ: Total Thyroidectomy

Findings• Direct sternohyoid invasion• 7/28 nodes positive for malignant tumor

– All visually involved lymph nodes dissected

• Uncomplicated Re-implantation of parathyroid gland

The Patient was referred to Nuclear Medicine for radioiodine ablation

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Radionuclide Ablation I : UsesRadionuclide Ablation I : UsesIndications• Post total thyroidectomy for thyroid carcinoma

– All patients >45– All patients with primary tumor >1.5cm at resection– All patients with any sign of extra-thyroid disease

Justification• Allows destruction of residual thyroid tissue• Can identify and potentially treat previously unknown

metastases• Clears normal thyroid tissue to allow follow-up whole body

scans– Normal thyroid uptake very strong compared to tumor

uptake, so recurrence can not be monitored by radionuclide scanning without thyroidectomy and ablation

• Improves value of thyroglobulin measurement– An increase in thyroglobulin levels after radionuclide

ablation is a highly specific marker for recurrence

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Radionuclide Ablation II : MethodRadionuclide Ablation II : MethodAdministration of 131I• Beta-emitter – 190keV betas – 90% absorbed within 0.8mm of source• Some gamma emission (fortunate for detection)

Induction of thyroid & tumor uptake• TSH > 25mU/L – 2 strategies: iodine withdrawal, rhTSH

Scanning prior to ablation• Can be useful for dosimetry• Must avoid “stunning”

– Reduction in uptake due to radiation injury• Small doses (1.3-1.5mCi) of I-123 now generally used, but 3-

5mCi I-131 works as well

Scanning post-ablation• Always obtain scan within a week post-ablation• Generally most sensitive indicator of metastatic disease.

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Radioiodide Whole Body ScanRadioiodide Whole Body Scan

• Residual thyroid tissue or cervical lymph nodes noted in resection cavity

• Normal uptake seen in salivary glands, liver, kidneys, bladder

• Patient went on to have negative follow-up radioiodine scans I-123 scan (pre-ablation) I-131

(post ablation)

Companion Patient 2: 57 y/o male w/ poorly Companion Patient 2: 57 y/o male w/ poorly differentiated papillary CA s/p total thyroidectomydifferentiated papillary CA s/p total thyroidectomy

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Patient AJ: Radioiodine Whole body Scan Patient AJ: Radioiodine Whole body Scan Six Days PostSix Days Post--AblationAblation

• Two well-defined foci of uptake within the lower neck– c/w residual thyroid

tissue or lymph node involvement

• Multiple bilateral foci of uptake within the lungs– c/w metastases

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Patient AJ FollowPatient AJ Follow--upup

The patient is now 3 months post- ablation. She will undergo another I- 123 scan and ablation (if necessary) in the next few months

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FollowFollow--up Radionuclide Scans and Ablations I : up Radionuclide Scans and Ablations I : Indications and LimitationsIndications and Limitations

Indications• Repeat scan in all

patients w/ post- operative ablation every 6-12 months until two negative scans (97% relapse free survival)

• Repeat ablation if any abnormal uptake sites

Limitations• Limited tumor uptake

– Poorly differentiated tumor– Tumor Progression /

Response

• Large foci– <1cm lymph mets 76%

treated in 3 rounds, 20% in larger

Suggests large focus Tx w/ surgical resection or radiation therapy

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FollowFollow--up Radionuclide Scans and Ablations II : up Radionuclide Scans and Ablations II : Complications and PrognosisComplications and Prognosis

Complications• Nausea, gastric pain, neck edema,

sialadenitis• Transient impairment of spermato-

genesis, transient ovarian failure• Mildly increased risk salivary gland

tumors, other tumor types

Favorable Prognostic Variables• Age (<40)• Extent of tumor

– Lack of visualization on standard radiographs

– Micronodular vs. macronodular• Differentiation of tumor• I-131 uptake• Lack of 18-FDG uptake

Bottom Line: 10 yr Survival•Complete response – 93%

•Incomplete response – 14%

Age<40 w/ micronodular mets: 96% 10 year survival

Age>40 w/macronodular mets: 7% 10 year survival

Other: 63% 10 year survival

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The Latest in Thyroid Imaging: PETThe Latest in Thyroid Imaging: PET--CTCT

Axial fused PET/CT at baseline and follow-up in a patient with suspected recurrent thyroid cancer and rising thyroglobulin level. Abnormal FDG uptake is seen in the sternum on both scans

Baseline – SUV = 8 7 Month follow-up – SUV =27

From Fukui et. al, Seminars in Ultrasound, CT, and MRI, 24(2), 2003.

What is PET-CT?• Co-registered F-18 fluorodeoxyglucose (FDG) positron emission scan and CT imaging

• PET-FDG scan for increased glucose uptake is specific for recurrent neoplasm

• CT co-registration gives increased utility to low-resolution PET scan• Better structural resolution to guide therapy

• Of particular utility in small spaces like the neck

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PETPET--CTCT ––

The New Player for Bad ActorsThe New Player for Bad ActorsIndications• High risk patients to scan for metastases

– E.g. Companion patient 2 (age, poorly differentiated CA)

• Thyroglobulin positive patients w/ neg. I-131 WBS– PET scanning with 18-FDG has been shown to be highly sensitive (~85%) in

pts with negative I-131 scans poorly differentiated CAs

• Prognosis and staging of metastatic disease• Determine relationship of tumor to vital structures, guiding planned

biopsy, resection, or radiation tx• Monitoring Response to therapy

Limitations• Not sensitive to all thyroid carcinomas• Non-therapeutic• Limited Scanner Resolution

– Misses lesions smaller than 1cm unless extensive uptake• Requires interval of 4 months after radiation therapy

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Review of Imaging Modalities in Review of Imaging Modalities in Papillary Thyroid CancerPapillary Thyroid Cancer

• CT– Determines extent of

soft-tissue invasion, distant metastases

– Normally indicated in persons with nodules >3cm, abnormalities on pre-op plain-film

• Ultrasonography– Mainstay for intrinsic

nodule characterization– Provides guidance for

fine-needle aspiration biopsy diagnostic method of choice

• Scintigraphy– Determines nodule iodine

uptake– Indicated in persons with low

TSH

• Radionuclide WBS, ablation– Therapeutic treatment for

distant mets, recurrent disease– Allows visualization of functional

tumor burden in well- differentiated cancers

• PET-CT– New tool for staging and

monitoring of high risk patients with poorly differentiated disease

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ReferencesReferences1. Fukui MB, Blodgett TM, Meltzer CC. PET/CT imaging in recurrent head and neck cancer. Semin Ultrasound CT MR. 2003 Jun;24(3):157-63.2. Klain M, Ricard M, Leboulleux S, Baudin R, Schlumberger M. Radioiodine therapy for papillary and follicular thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2002 Aug;29 Suppl 2:S479-85. 3. Larson SM, Robbins R. Positron emission tomography in thyroid cancer management. Semin Roentgenol. 2002 Apr;37(2):169-74.4. Pacini, F. Follow-up of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2002 Aug;29 Suppl 2:S492-65. Heitzman, ER. Mediastinum: Radiologic Correlations With Anatomy and Pathology. Springer Publishing, New York, NY. 1988.6. Bradley WG, Merritt CR, Reeder MM. Reeder and Felson’s Gamuts in Radiology: Comprehensive lists of Roentgen Differential Diagnosis. Springer Publishing, New York, NY. 2004.7. Meller J, Becker W. The continuing importance of thyroid scintigraphy in the era of high- resolution ultrasound. Eur J Nucl Med Mol Imaging. 2002 Aug;29 Suppl 2:S425-38.8. Zhuang H, Kumar R, Mandel S, Alavi A. Investigation of thyroid, head, and neck cancers with PET. Radiol Clin North Am. 2004 Nov;42(6):1101-11, viii.9. Gooding GA. Sonography of the Thyroid and Parathyroid. Radiol Clin North Am. 1993 Sep;31(5):967-979.10. Butch RJ, Simeone JF, Mueller PR. Thyroid and Parathyroid Ultrasonography. Radiol Clin North Am. 1985 March;23(1):57-63.11. Solbiati L, Cioffi V, Ballaratti E. Ultrasonography of the neck. Radiol Clin North Am. 1992 Sep;30(5):941-54. 12. Gritzmann N, Koischwitz D, Rettenbacher T. Sonography of the Thyroid and Parathyroid Glands. Radiol Clin North Am. 2000 Sep;38(5):1131-45.13. Sandler MP, Delbeke D. Radionuclides in Endocrine Imaging. Radiol Clin North Am. 1993 July;31(4):909-19.14. Weber A:, Randolph G, Aksoy FG. The thyroid and parathyroid glands. CT and MR imaging and correlation with pathology and clinical findings. Radiol Clin North Am. 2000 Sep;38(5):1105-29.15. Sherman S. Overview of Papillary Thyroid Carcinoma. UptoDate Online, 2006.16. Ross, DS. Diagnostic approach to and treatment of thyroid nodules. UptoDate Online, 2006.17. Sherman S. Radioiodide treatment of differentiated thyroid cancer. UptoDate Online, 2006.

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AcknowledgementsAcknowledgements

Dr. Alice Fisher

Dr. Gillian Lieberman

Dr. Janneth Romero

Pamela Lepkowski

Larry Barbaras – our Webmaster

Many Thanks!Many Thanks!

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Radiological Diagnosis and Treatment of Papillary …eradiology.bidmc.harvard.edu/LearningLab/central/...Paul Dieffenbach Gillian Lieberman, MD 1 Radiological Diagnosis and Treatment