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Paul Dieffenbach
Gillian Lieberman, MD
1
Radiological Diagnosis and Radiological Diagnosis and Treatment of Papillary Thyroid Treatment of Papillary Thyroid
CarcinomaCarcinoma
Paul Dieffenbach – HMS III
Gillian Lieberman, MD
September 2006
Paul Dieffenbach
Gillian Lieberman, MD
2
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
Paul Dieffenbach
Gillian Lieberman, MD
3
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
Paul Dieffenbach
Gillian Lieberman, MD
4
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.
Paul Dieffenbach
Gillian Lieberman, MD
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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.
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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?
BIDMC PACSBIDMC PACS
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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)
Paul Dieffenbach
Gillian Lieberman, MD
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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
BIDMC PACS
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Paul Dieffenbach
Gillian Lieberman, MD
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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.
BIDMC PACS
BIDMC PACS
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Paul Dieffenbach
Gillian Lieberman, MD
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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
BIDMC PACSBIDMC PACS
Paul Dieffenbach
Gillian Lieberman, MD
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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).
BIDMC PACS
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.
BIDMC PACS
Demonstration Pt: Thyroid Scintigraphy
Paul Dieffenbach
Gillian Lieberman, MD
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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.
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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Patient AJ: Thyroid UltrasoundPatient AJ: Thyroid Ultrasound
BIDMC PACSBIDMC PACS
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
Paul Dieffenbach
Gillian Lieberman, MD
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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
BIDMC PACS
BIDMC PACS
BIDMC PACS
Paul Dieffenbach
Gillian Lieberman, MD
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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
BIDMC PACS
BIDMC PACS
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
25
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.
Paul Dieffenbach
Gillian Lieberman, MD
26
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
BIDMC PACS
Paul Dieffenbach
Gillian Lieberman, MD
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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
BIDMC PACS
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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
Paul Dieffenbach
Gillian Lieberman, MD
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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.
Paul Dieffenbach
Gillian Lieberman, MD
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AcknowledgementsAcknowledgements
Dr. Alice Fisher
Dr. Gillian Lieberman
Dr. Janneth Romero
Pamela Lepkowski
Larry Barbaras – our Webmaster
Many Thanks!Many Thanks!