The Epidemic of Thyroid Nodules: Which Should Undergo Fine Needle Aspiration?

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The Epidemic of Thyroid Nodules: Which Should Undergo Fine Needle Aspiration?

  1. 1. The Epidemic of Thyroid Nodules: Which Should Undergo Fine Needle Aspiration? Jill E Langer, MD Associate Professor of Radiology And Endocrinology Co-Director of the Thyroid Nodule Clinic Hospital of the University of Pennsylvania DC Metro Radiological Society
  2. 2. Overview • Review the histologic and sonographic appearance of thyroid nodules • Assess the ability of sonography to predict that a nodule is malignant or to predict that it is benign • Review the recommendations for FNA of thyroid nodules as developed by The Society of Radiologists in US Thyroid Consensus Committee* *Frates MC et al, Radiology, December 2005
  3. 3. The Clinician Perspective • About 5 % of the adult US population will have a nodule that is palpable on physical exam of the neck – The vast majority of palpable nodules are over 1 cm • The ATA recommendation is to measure a serum TSH ( to exclude a functioning nodule) The risk of cancer • Perform an FNA in palpable nodules is 5 to 10%
  4. 4. The Clinical Perspective: Cancer risk is increased if • The nodule is hard and • Has a hereditary fixed syndrome – +/- rapid growth – MEN 1 • The patient presents – MEN 2 A and B with hoarseness and/or – Familial Adult Polyposis lymphadenopathy syndrome – Cowden’s syndrome • The patient is under 15 years old or over 60 • Familial papillary and medullary cancers • Has a history of prior radiation exposure
  5. 5. Sonographic Thyroid Nodule • “Nodule”- one or more areas of the thyroid with a different echotexture than surrounding parenchyma • Most nodules are not true tumors but hyperplastic regions of the thyroid • Most thyroid nodules are detected “incidentally” 5 mm non palpable nodule
  6. 6. Focal Thyroid Lesions on Ultrasound • Benign hyperplastic nodules (at least 70 to 80%) • Benign thyroid adenoma (10 %) • Thyroid carcinoma ( 5 to 12 %) – Papillary carcinoma (70-80%)-includes mixed papillary and follicular carcinoma – Pure Follicular Carcinoma (10 to 15%) – Medullary Carcinoma (5 to 10%) – Anaplastic carcinoma (<1%) • Focal area of thyroiditis (1 to 5%) • Unusual lesions: Intrathyroidal parathyroid, true cyst, metastatic disease
  7. 7. How common are thyroid nodules in the United States on Ultrasound? Ultrasound/autopsy Palpation Mazzaferri, N Engl J Med 1993
  8. 8. What nodules can’t we feel? Ultrasound vs. Palpation 35 # Nodules found by US 30 25 42% 20 Nodules MISSED by palpation 15 50% Nodules FOUND by palpation 10 5 94% 0 < 1cm 1-2cm >2cm Nodule size by US Brander, J Clin Ultrasound 1992
  9. 9. Thyroid sonography should be performed in all patients with one or more suspected thyroid nodules. USPSTF Recommendation B Management guidelines for patients with thyroid nodules and differentiated thyroid cancer, ATA Task Force, David Cooper, Chair, Thyroid, 2006 Thyroid ultrasound . . . is mandatory when a nodule is discovered at palpation European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium, Eur J Endocrinol 2006 In all patients with palpable thyroid nodules or MNG, US should be performed AACE/AME guidelines for clinical practice for the diagnosis and management of thyroid nodules, Endocrine Pract 2006
  10. 10. The “epidemic” of thyroid nodules • Commonly detected on US (also CT, MR) – 10 to 67% of US exams in asymptomatic adult patients – Additional non-palpable nodules are noted in over 50% of patients with palpable nodules • Risk of malignancy is the same for non- palpable nodules as for palpable nodules *Ross DS, J Clin Endo Metab, 2002 Ezzat, S et al, Arch Intern Med, 1994; Tan GH et al, Ann Intern Med, 1997;Marqusee E et al, Ann Intern Med, 2000
  11. 11. What not biopsy all nodules detected by sonography? • Direct effects: – Health care resources; up to 67% of the population has nodules – The vast majority of nodules are benign; thyroid cancer is relatively uncommon ( 25,000 cases/yr in US) – Many benign nodules would undergo FNA to detect the few malignancies Cooper DS et al, Thyroid, 2006
  12. 12. What not biopsy all nodules detected by sonography? • Direct effects: – Most of the newly diagnosed thyroid cancers are the smaller cancers – Most thyroid cancer does not act in an aggressive manner such that the overall mortality from thyroid cancer has not changed despite the marked increase in rate of US- guided FNA Cooper DS et al, Thyroid, 2006; Davies JAMA 2006
  13. 13. How common is thyroid cancer in the United States? 0-1.0cm 1.1-2.0cm 2.1-5.0cm Davies, JAMA 2006 >5.0cm 295:2164
  14. 14. Nodule size threshold for FNA • Papillary thyroid microcarcinomas – Occult or incidentally detected papillary thyroid cancers under 10-15mm (WHO) – PTMCs noted in 0.45 to 13% on autopsy in USA • Size threshold for most labs of 8 or 10 mm for FNA, in the absence of metastatic disease (LNs) or local invasion 1Machens A et al, Cancer 2005; 2 Ross DS, J Clin Endo Metab, 2002
  15. 15. F NA Pap-CA
  16. 16. What not biopsy all nodules detected by sonography? • Indirect effects: • Patients with non-diagnostic and “indeterminate” or follicular neoplasm FNA results (20 to 35% of all FNAs) are typically referred for surgery; over 80% are benign nodules (follicular adenomas and hyperplastic nodules) Cooper DS et al, Thyroid, 2006
  17. 17. What thyroid nodules detected “incidentally” should undergo FNA?? “incidentally” means a non- palpable nodule in a patient without risk factors for thyroid cancer
  18. 18. PET positive thyroid nodules • PET positive nodules are noted on 0.1 to 4.3% of all PET scans • A PET positive nodule has a 14 to 40 % chance of being malignant – Higher rates if microcarcinomas are included • False positives include diffuse or patchy, focal uptake in thyroiditis Kind DL et al, Oto-Head and Neck Surgery, 2007
  19. 19. PET Positive nodule
  20. 20. What is the risk of malignancy for nodules detected by sonography? Are there sonographic features that help stratify the risk that a nodule is a malignancy?
  21. 21. Features associated with malignancy • Lymphadenopathy/local invasion • Micro -calcifications • Coarse calcifications in a solid nodule • Markedly hypoechoic echotexture • Hypoechoic echotexture with solid consistency • Irregular, infiltrating margins • Intranodular flow in association with hypoechogenicity/irregular margins/Ca++ • Absence of a halo
  22. 22. Invasion of capsule and metastatic lymphadenopathy CA Sagittal view of left lobe Trv view of left lateral neck 11 mm Papillary Thyroid Carcinoma
  23. 23. Papillary thyroid cancer: Lymph node metastases IJV CCA Entirely cystic Solid with Ca++ IJV Mixed cystic and solid CA
  24. 24. Neck Node Classification Central Neck Paratracheal LNs Pre-laryngeal LNs (Levels 6 and 7) Lateral Neck Anterior and Posterior Cervical LNs (Levels 2,3,4 and 5) Som P et al, AJR 2003
  25. 25. Localization of nodal mets in 119 pts having thyroidectomy and bilateral cervical neck dissection (61% LN+) 100 85% Contralateral node Lymph nodes location (%) 90 80 involvement in 18% 63% of patients with 70 60 unilateral tumors 50 40 30 22% 15% 20 10 0 Level VI Level VI + Level VI Lateral Lateral alone alone Mirallie et al, World J Surg 1999
  26. 26. Lateral cervical lymph nodes • Important to evaluate prior to surgery • If sonographically suspicious LNs are noted, perform FN of the LN • If positive lateral nodes, a modified radical neck LN dissection is performed at the time of thyroidectomy • Most common place for “recurrence” in patients following thyroidectomy
  27. 27. Microcalcifications • Multiple bright punctate (under 1 mm) echoes without shadowing • Most specific sign of malignancy (85-95%) • Pitfall: colloid in a hyperplastic nodule- reverberation artifact Papillary carcinoma Hyperplastic nodule
  28. 28. Mixed population of calcifications Multifocal calcified papillary cancer Mixed coarse and microcalcifications
  29. 29. Microcalcifications κ =0.91 100 Median sensitivity 45% 90 Median specificity 87% 80 70 Sensitivity (%) 60 50 40 30 20 10 0 Brkljacic J Clin Ultrasound 1994; Takashima J Clin Ultrasound 1994; Rago Euro J Endorinol 1998; Cerbone Horm Res 1999; Kim AJR 2002; Papini J Clin Endocrinol Metab 2002; Nam-Goong Thyroid 2003;Cappelli Clin Endocrinol 2005; Frates, J Clin Endocrinol Metab 2006; Peccin J Endocrinol Invest 2003; Weinke J Ultrasound
  30. 30. Coarse calcifications • Coarse calcifications are common in multinodular goiters secondary to dystrophic calcifications in long standing benign nodules • When present in a solitary nodule have malignancy rates approaching 75% Khoo ML, Arch Oto Head Neck Surg 2002
  31. 31. Coarse calcification: Medullary thyroid cancer • Typically a hypoechoic, unencapsulated lesion • Mean size 20 mm • Up to 90% are calcified – 53% coarse calcifications – 42% micro-calcifications Gorman B et al, Radiology, 1987
  32. 32. Medullary carcinoma: paratracheal lymphadenopathy 12 mm Medullary Carcinoma Sagittal view of left lobe Metastatic paratracheal LNs
  33. 33. Peripheral calcification Complete, regular Interrupted or “eggshell” Papillary ca Usually benign Follicular ca
  34. 34. Calcifications Microcalcifications Coarse calcifications in (psammomatous) in papillary follicular thyroid cancer thyroid cancer
  35. 35. Hypoechoic nodules Benign hyperplastic nodule Papillary carcinoma • Most papillary cancers are hypoechoic • However, since benign nodules are much more common, most hypoechoic nodules are benign • The likelihood of a cancer increases if hypoechogenicity is combined with all solid consistency, calcifications and/or intranodular flow
  36. 36. Hypoechoic κ =0.37 100 Median sensitivity 80% 90 Median specificity 53% 80 70 Sensitivity (%) 60 50 40 30 20 10 0 Brkljacic J Clin Ultrasound 1994; Takashima J Clin Ultrasound 1994; Rago Euro J Endorinol 1998; Cerbone Horm Res 1999; Leenhardt J Clin Endocrinol Metab 1999; Kim AJR 2002; Papini J Clin Endocrinol Metab 2002; Nam- Goong Thyroid 2003;Cappelli Clin Endocrinol 2005; Frates, J Clin Endocrinol Metab 2006; Weinke J Ultrasound Med 2003
  37. 37. Evaluation of the margins • Irregular or infiltrating border is associated with malignancy, varying from 35 to 86% • High inter-observer variability
  38. 38. Anaplastic tumor: Infiltrating margins Trachea Residual normal thyroid
  39. 39. Irregular Margins κ =0.13 100 Median sensitivity 51% 90 Median specificity 77% 80 70 Sensitivity (%) 60 50 40 30 20 10 0 Takashima J Clin Ultrasound 1994; Leenhardt J Clin Endocrinol Metab 1999; Kim AJR 2002; Papini J Clin Endocrinol Metab 2002; Nam-Goong Thyroid 2003;Cappelli Clin Endocrinol 2005; Frates, J Clin Endocrinol Metab 2006; Weinke J Ultrasound Med 2003
  40. 40. Surrounding halo • Hypoechogenic thin rim surrounding the nodule (thought to represent the compressed perinodular vessels) – present – absent-suggestive of an infiltrative malignancy but often lacking in hyperplastic nodules • A thick, irregular halo is more suggestive of a neoplasm (CAPSULE --follicular or Hurthle cell carcinoma or adenoma; encapsulated papillary cancer)1 1Cerbone et al, Hormone Res 1999
  41. 41. Thin halo Thick or irregular halo sagittal sagittal Thin halo is compressed blood vessels Follicular cancer
  42. 42. Absent Halo 100 Median sensitivity 66% 90 Median specificity 62% 80 70 Sensitivity (%) 60 50 40 30 20 10 0 Brkljacic J Clin Ultrasound 1994; Takashima J Clin Ultrasound 1994; Rago Euro J Endorinol 1998; Frates, J Clin Endocrinol Metab 2006; Peccin J Endocrinol Invest 2003
  43. 43. Intra-nodular flow sagittal transverse trachea Peripheral vascularity Intra-nodular vascularity
  44. 44. Intra-nodular flow • In general there is a tendency toward increased flow increasing the risk of malignancy • The risk increases to about 30 or 40% in solid, hypervascular nodules • However, still over 50% of hypervascular nodules are benign Adenoma Hyperplastic nodule
  45. 45. Intranodular vascularity κ =0.75 100 Median sensitivity 62% 90 Median specificity 83% 80 Sensitivity (%) 70 60 50 40 30 20 10 0 Rago Euro J Endorinol 1998; Papini J Clin Endocrinol Metab 2002; Cappelli Clin Endocrinol 2005; Frates, J Clin Endocrinol Metab 2006; Weinke J Ultrasound Med 2003
  46. 46. US Prediction of Thyroid Cancer Sensitivity Specificity Microcalcifications 43% 88% Absence of halo 66% 54% Irregular margins 51% 76% Hypoechoic 80% 53% Increased intranodular flow 67% 81% MicroCa2+ + irreg margin 30% 95% MicroCa2+ + hypoechoic 26% 96% Solid + hypoechoic 68% 69% FNA 92% 84% Brkljacic J Clin Ultrasound 1994; Takashima J Clin Ultrasound 1994; Rago Euro J Endorinol 1998; Cerbone Horm Res 1999; Leenhardt J Clin Endocrinol Metab 1999; Kim AJR 2002; Papini J Clin Endocrinol Metab 2002; Nam- Goong Thyroid 2003;Cappelli Clin Endocrinol 2005; Frates, J Clin Endocrinol Metab 2006; Cap, Clin Endocrinol 1999
  47. 47. Sonographic features of Papillary thyroid cancer 100 n=259 pts 90 80 Frequency (%) 70 60 50 40 30 20 10 0 Hypoechoic Absent Irregular Solid MicroCa2+ halo margins Chan, J Ultrasound Med 2003; Yuan, Clin Imaging 2006; Jeh, Korean J Rad 2007
  48. 48. Sonographic features: Papillary vs. Mixed Papillary and Follicular thyroid cancer 100 90 * 80 Frequency (%) 70 60 * 50 40 * 30 20 * 10 0 * Hypoechoic Absent Irregular Solid MicroCa2+ halo margins Chan, J Ultrasound Med 2003; Yuan, Clin Imaging 2006; Jeh, Korean J Rad 2007
  49. 49. Can US characteristics help predict malignancy in small thyroid nodules? • Leenhardt (1999) US-FNA of 365 nodules 4-37mm (median 12mm) 16 cancers • Papini (2002) US-FNA of 402 nodules 8-15mm 31 cancers Leenhardt, J Clin Endocrinol Metab, 1999; Papini, J Clin Endocrinol Metab, 2002
  50. 50. US Prediction of Malignancy # nodules Cancers Cancers aspirated found missed Size criteria >10mm1 286/365 >10mm2 325/402 1Leenhardt, J Clin Endocrinol Metab, 1999; 2Papini, J Clin Endocrinol Metab, 2002
  51. 51. US Prediction of Malignancy # nodules Cancers Cancers aspirated found missed Size criteria >10mm1 286/365 10 (63%) 6 (37%) >10mm2 325/402 19 (61%) 12 (39%) 1Leenhardt, J Clin Endocrinol Metab, 1999; 2Papini, J Clin Endocrinol Metab, 2002
  52. 52. US Prediction of Malignancy # nodules Cancers Cancers aspirated found missed Size criteria >10mm1 286/365 10 (63%) 6 (37%) >10mm2 325/402 19 (61%) 12 (39%) US criteria Hypoechoic AND 139/365 solid1 Hypoechoic AND 125/402 irregular margins, increased vascularity, OR microCa2+2 1Leenhardt, J Clin Endocrinol Metab, 1999; 2Papini, J Clin Endocrinol Metab, 2002
  53. 53. US Prediction of Malignancy # nodules Cancers Cancers aspirated found missed Size criteria >10mm1 286/365 10 (63%) 6 (37%) >10mm2 325/402 19 (61%) 12 (39%) US criteria Hypoechoic AND 139/365 13 (81%) 3 (19%) solid1 Hypoechoic AND 125/402 27 (87%) 4 (13%) irregular margins, increased vascularity, OR microCa2+2 1Leenhardt, J Clin Endocrinol Metab, 1999; 2Papini, J Clin Endocrinol Metab, 2002
  54. 54. The Sonographic of Thyroid Nodules Hypoechoic Irreg margins No halo BENIGN ↑Vascularity BENIGN MicroCa2+ BENIGN BENIGN BENIGN BENIGN
  55. 55. Nodules which are likely benign • Entirely cystic nodule • Nearly entirely cystic nodule with no flow or calcification in the solid part (under 2 cm) • Honeycomb or spongiform nodule without calcifications (under 2 cm) • “Pseudonodules” in autoimmune thyroid disease (chronic lymphocytic thyroiditis) • Mixed cystic and solid nodules with a functioning solid component ( any size)
  56. 56. Completely cystic: Colloid cysts Comet-tail artifact
  57. 57. Mixed cystic and solid nodules • 30% of nodules have cystic change • More common in benign nodules Hyperplastic nodule • Up to 6% of papillary cancers are predominantly cystic • Usually have other features such as Ca++ or vascular flow Cystic papillary cancer
  58. 58. Predominantly Cystic Nodules: 50% or greater cystic component • up to 50% non- diagnostic rate on FNA • Target vascular areas for FNA • Indications for surgery: large cyst size (over 3 or 3.5 cm), bloody aspirate, recurrence after repeated aspirations, h/o previous irradiation
  59. 59. Acute hemorrhage into a nodule 3 months later
  60. 60. “Spongiform” or “Honeycomb” Sagittal Transverse minimal vascularity
  61. 61. Hyperplastic nodule • Area of the thyroid that is stimulated to undergo follicular hyperplasia and accumulation of colloid • Composed of follicles of various sizes and age, colloid, macrophages Hyperplastic nodule Normal thyroid
  62. 62. “Spongiform” left nodule Transverse Sagittal trachea Distinction between small calcifications and comet tail artifact from colloid is easier with a lower frequency probe 1 1Ahuja J Clin Ultrasound 1996
  63. 63. Hashimoto’s Thyroiditis: “Pseudo-nodules” Lymphocytic infiltration Fibrosis Normal follicles
  64. 64. “Pseudo-nodule”:Graves’ Disease • may have focal areas of increased echotexture • represents islands of follicular hyperplasia superimposed on a lymphocytic infiltrate
  65. 65. SRU Consensus for Sonographically Detected Nodules Solitary nodule biopsy recommendations: • Bx if microcalcifications if 10 mm or larger • Bx if solid and/or coarse calcifications if 15 mm or larger • Consider bx if mixed cystic/solid or cystic with a mural nodule and over 20 mm • Consider bx if substantial growth • Apply clinical judgment!!!! *Frates MC et al, Radiology, December 2005
  66. 66. US-guided FNA Technique • 25 gauge, 1 ½ inch BD needle • 10 cc syringe • Aseptic technique • Capillary action rather than aspiration
  67. 67. Non-diagnostic Rates of US FNA and Palpation FNA US -FNA P- FNA Takashima, 1994 4% 19% Carmeci, 1998 7% 16% Danese, 1998 4% 9% Hatada, 1998 17% 30%
  68. 68. Biopsy of a Cystic Nodule
  69. 69. Biopsy of a Calcified Nodule
  70. 70. False Negative Rates of US FNA and Palpation FNA US FNA P-FNA Carmeci, 1998 0% 0.5% Danese, 1998 0.6% 2.3% False negative specimens due to sampling error (cystic lesions or nodule was not sampled)
  71. 71. Indications for US-guided FNA • Difficult to palpate nodule • Predominantly cystic nodule • Nodule with previous non-diagnostic biopsy • Nodule with “significant” interval growth
  72. 72. FNA vs. Core Biopsy • The use of core biopsy does not improve the non-diagnostic rate of thyroid biopsies • Core does not aid in discrimination of follicular adenoma vs. carcinoma • Lower complication rate with FNA • Inability to check for cellular adequacy with core bx • Core is preferable in some less common circumstances: fibrotic tumors Nishiyama RH et al, Surgery 1986; Silverman JF et al Diagn Cytopath 1986; Pisani T et al Anticancer Res 2000
  73. 73. Cancer Rates for Solitary and Multiple Thyroid Nodules Definition FNA Ca rate of nodularity technique Sol MNG McCall I-123/histo palpation 17% 13% Belfiore I-123 palpation 5% 5% Cochand I-123/US US 13% 14% Sachamechi I-123 palpation 8% 10% Marqusee US US 7% 9% Franklyn palpation palpation 6% 1%
  74. 74. Sonographic evaluation of a multinodular gland • Incidence of cancer in patients undergoing FNA is 9.2-13% – Independent of the number of nodules detected by imaging exam • Cancer is present in the “non-dominant nodule” at least one third of patients *Frates MC et al, Radiology, December 2005
  75. 75. Multinodular Gland 1. If a patient has multiple thyroid nodules that require FNA based upon size criteria, those with the most suspicious features on US should be aspirated first 2. Nodules with similar sonographic features may be considered to be of similar histology 3. Nodules that are not biopsied can be followed and considered for FNA if they grow
  76. 76. Multinodular thyroid with one sonographically suspicious nodule Microcalcifications, Hypoechoic, Solid
  77. 77. Multinodular goiter = Multiple nodular gland Enlarged thyroid with multiple sonographically similar nodules with little or no normal parenchyma Normal parenchyma with more than one nodule
  78. 78. SRU Consensus Statement Multiple nodule biopsy recommendations: • Bx of one or more nodules using solitary nodule guidelines • May not need to perform bx if gland is diffusely enlarged and replaced by multiple sonographically similar nodules without suspicious features (true multinodular goiter)
  79. 79. American Thyroid Association Guidelines Multiple nodule biopsy recommendations: • Perform FNA of those with the most suspicious features on US first • Follow the patient by US at 6 to 18 month intervals Solitary nodule biopsy recommendations: • Biopsy if over 10 to 15 mm • Consider bx if smaller and suspicious Cooper DS et al, Thyroid, 2006
  80. 80. Role of I-123 scan • Useful if patient has low TSH to determine if hyperthyroidism is secondary to one or more functioning nodules • Useful if have nodule with Follicular Cytology on FNA; 5% will function and obviate the need for surgery
  81. 81. Follicular lesion: Increased uptake on I-123 scan Functioning nodule: no need for biopsy
  82. 82. 38y.o. woman w/2.9 transverse cm cystic left nodule, FNA→ trachea follicular neoplasm sagittal Anterior
  83. 83. 47 y.o. woman with low TSH Right sagittal Left sagittal inferior inferior
  84. 84. What nodules should we recommend for FNA?
  85. 85. The grey zone YES NO
  86. 86. Why is there a grey zone? • Small nodules may be just as likely to be thyroid cancers as larger ones - some are latent - some are clinically relevant • Cancer risk is the same for patients with multiple or solitary thyroid nodules Leenhardt J Clin Endocrinol Metab 1999; Papini J Clin Endocrinol Metab 2002; Nam-Goong Clin Endocrinol 2003; Ito World J Surg 2004; Cappelli Clin Endocrinol 2005; Marqusee Ann Intern Med 2000; Frates J Clin Endocrinol Metab 2006
  87. 87. Recommendations: What do we do at HUP TNC? • FNA all PET positive nodules • Incidental nodules detected by other imaging should have sonographic assessment to determine if malignant features are present
  88. 88. We recommend FNA if • micro Ca2+ ≥ 8mm • hypoechoic (solid) ≥ 10mm • solid ≥ 10-15mm* • complex ≥15- 20mm* • Multiple nodules: – prioritize based upon above – if multiple sonographically similar, coalescent nodules without suspicious US features, FNA largest
  89. 89. The exact role of ultrasound is still to be defined … the traditional use of ultrasound to separate cystic from solid lesions is probably outdated. Simeone, Daniels, Maloof, et al, Radiology 1982 Thanks to Susan Mandel, MD The exact role of ultrasound is still to be defined. The use of ultrasound to simply document thyroid nodules is not sufficient, we must try to identify those nodules for which FNA is indicated and those for which it is not!
  90. 90. Future Directions Society of Radiologists in Ultrasound Part II Prospective study at 10 Institutions 6000 nodules undergoing US-guided FNA • Standardization of nodule description • Stratified risk of malignancy • Reporting of nodules in a BioRads-like fashion, analogous to mammography
  91. 91. Thank you!

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