Thyroid nodule: A team effort

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1 Thyroid nodule: A team effort Poster No.: C-1898 Congress: ECR 2015 Type: Educational Exhibit Authors: A. S. C. C. Germano, W. Schmitt, E. Rosado, C. Coelho, A Godinho, C. Ribeiro, R. Vieira ; Barcarena/PT, Lisboa/PT, 3 4 Amadora/PT, Lisbon/PT Keywords: Endocrine disorders, Cancer, Education, Diagnostic procedure, Decision analysis, Ultrasound, PET-CT, Nuclear medicine conventional, Thyroid / Parathyroids, Head and neck DOI: /ecr2015/C-1898 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 79

2 Learning objectives 1. Understanding the clinical relevance of endocrine data. 2. Apprehending the ultrasound features in the guidelines currently used in fine needle aspiration cytology (FNAC) thyroid nodule selection. 3. Managing to perform FNAC and correctly interpret its results. 4. Supplying the thyroid surgeon with all the information he needs to plan surgery. 5. Acknowledge nuclear medicine's role in pre and post-op thyroid evaluation Images for this section: Page 2 of 79

3 Fig. 1: Nodule, from the Latin nodulus, diminutive of nodus, possesses several meanings including those used in medicine by Plínius: small Knot, nodularity or hard tumour (1). Page 3 of 79

4 Background Thyroid nodular pathology incidence has been on the rise, adding to the patients in need of ultrasound-guided FNAC. Though the technique itself is simple, when we consider the impossibility of puncturing every single nodule we realize it is essential (particularly in multinodular conditions) for radiologists to comprehend thyroid pathology in order to select which nodules to puncture and discuss the obtained results in multidisciplinary decision meetings. However, the training of the radiologist resident does not include practice in endocrine pathology nor in thyroid surgery and only recently has nuclear medicine become a part of the young radiologist's curriculum. A basic knowledge of these subjects is essential to correctly perform and interpret thyroid ultrasound examinations and to select thyroid nodules and lymph nodes to US guided FNAC. It is also fundamental for providing a reasoned opinion in multidisciplinary group decision meetings. Findings and procedure details 1. Anatomy, pathology, function, anamnesis, physical examination data The thyroid is an endocrine gland shaped like an "H" or a "butterfly", located superficially in the visceral compartment of the neck, anterior to the trachea and bounded laterally by the carotid arteries and internal jugular veins. It is composed of two lobes, connected by a thin isthmus. A superior middle extension can be present, the pyramidal lobe. During embryological development, the thyroid gland migrates from the base of the tongue to the inferior neck position. Ectopic thyroid tissue or cysts can be present in the referred path. In ultrasound the normal thyroid should be homogeneous and more hyperechoic, than the surrounding muscles. Page 4 of 79

5 Histologically the thyroid parenchyma is composed of follicles, lined by follicular cells and filled with colloid, which contains thyroglobulin, a precursor of the thyroid hormones. Also present are parafollicular cells, or C cells, that secrete calcitonin. TRH, released by the hypothalamus, regulates the secretion of TSH by the anterior pituitary. TSH controls the secretion of T3 and T4 by the thyroid. Diseases of the thyroid gland include excessive or deficient release of thyroid hormones and nodular lesions, on which we will focus in this presentation (2). Thyroid nodules are very common, the great majority being benign. Benign nodules include hyperplasia and follicular adenomas. The most frequent malignant nodules are papillary carcinomas, followed by follicular carcinomas, medullary carcinomas and undifferentiated or anaplastic carcinomas. Rarely, there can be involvement of the thyroid gland by lymphoma, metastasis or other very rare types of carcinomas. When evaluating a patient with a thyroid nodule, either clinically evident or an incidentaloma (these have become more and more frequent, often discovered during an examination performed for an entirely different reason, such as a CT scan, an MRI or a neck Doppler ultrasound), the endocrinologist registers the patient anamnesis including possible familiar or personal risk factors, concerning symptoms such as dyspnoea, dysphagia or rapid growth, symptoms related to hyper or hypo function. The physical examination includes the size and consistency of the nodule, adherence to adjacent planes and evaluation of neck lymph node chains, searching for adenopathies Dosage of TSH is usually demanded together with FT4. 2. Guidelines, ultrasound suspicious criteria, elastography, thyroid nodule incidentally detected in 18 FDG-PET CT Page 5 of 79

6 In spite of the extensive investigation performed so far and the advances in medical imaging, namely in ultrasound, no single US feature or guideline can be used to accurately diagnose thyroid cancer as of yet. In the following tables we compare some of the currently used recommendations and guidelines for selection of thyroid nodules for FNAC. Please note these were elaborated in different time periods, through different methods, based on different levels of evidence and some include several grades of recommendation. The discussion of these subjects is beyond the scope of this work. We will also not analyse particular cases such as thyroid nodules in children or in pregnant women. An important issue, transversal to all the guidelines, is the fact that they are flexible. As such, thinking of Medicine as both a Science and an Art, the clinical judgment should be applied to each individual patient. The concept of a high risk clinical history only varies subtly between the guidelines, and includes thyroid cancer or thyroid cancer conditions (MEN2 or MTC) in one or more first degree relatives, exposure to radiation in childhood or adolescence, previous hemithyroidectomy for thyroid cancer, personal history of thyroid cancer conditions (such as Cowden's disease, familial polyposis coli, Carney complex, McCune-Albright syndrome), FDG- avid nodule at PET, age (<14-20 or >45-70), male gender, (3; 4, 5, 6) Endemic goiter and obesity (7). Another relevant issue, also transversal to all guidelines, is the presence of adenopathies suspicious of metastatic thyroid cancer Fig. 2 on page 30 Fig. 3 on page 31 (=thyroid like or cystic or with microcalcifications). They should be submitted to FNAC, together with ipsilateral thyroid nodule, regardless of its ultrasound appearance. In the presence of multiple nodules, each one should be evaluated by itself, submit to FNAC up to 4 nodules (6), rarely more than 2 (4). If the nodules are all similar, submit the dominant one to FNAC (5). The exception to this rule is the absence of intervening thyroid parenchyma between multiple nodules of similar appearance. These represent nodular hyperplasia which, without a high risk history, shouldn't require FNAC. In the last rows of the tables are the criteria used in our department. Page 6 of 79

7 Fig. 48: Table 1 - cystic nodules References: Department of Radiology, HFF Comments: 1 Kim criteria (8) were made based only on non-palpable solid nodules (incidentalomas). Page 7 of 79

8 2 KJR (Korean Society of Thyroid Radiology Guidelines) (9) considers cystic a nodule that is >90% cystic; predominantly cystic, if it is>50% and <90% cystic; predominantly solid if it is>10% e <50%cystic and solid if it is #10% cystic. 3 SRU (Society of Radiologists in Ultrasound)(10) used size criteria for sampling nodules for FNAC. When measuring, the maximal diameter of the nodule should be considered. If any visible halo is present, callipers should be placed outside it. Recent guidelines consider size isn't a useful criterion, since it does not help in distinguishing benign nodules from malignant ones. However, size does influences the prognosis if the nodule proves to be malignant. It is also important to document size in order to assess possible growth in future followup evaluations. Most guidelines classify significant growth as an increase of at least 2mm in two or more diameters or 20% increase in diameter or 50% increase in volume. 4 A spongiform Fig. 8 on page 35 nodule is defined as an aggregation of multiple microcystic components in more than 50% of the nodule, separated by thin septa. They may contain hyperechoic punctiform images, conditioning posterior reverberation artifacts and should be avascular or isovascular compared to the rest of the gland (11). 5 ATA's (American Thyroid Association) (3) suspicious US features are: microcalcifications, hypoechogenicity, increased nodular vascularity, infiltrative margins and taller-than-wide shape on transverse view. 6 ( FSEMTN The French Society of Endocrinology) (5) differentiates the concept of high risk context from that of high risk nodule (at least 2 suspicious US criteria: solid and hypoechoic; microcalcifications; indefinite margins, taller-than-wide shape, type IV vascularization or 20% increase in volume, PET+, clinical characteristics). 7 TIRADS score (Thyroid Imaging Report and Data System) was first developed in 2009 (Park and Horvath) (12,13), with the aim of building a practical score to categorize thyroid nodules and stratify their malignancy risk, similar to the one used in breast imaging. The TIRADS score we present was created by the French group of Gilles Russ in 2011 and subsequently simplified in 2013 (14,15,16). Page 8 of 79

9 The TIRADS suspicious signs are: taller-than-wide shape; irregular borders, microcalcifications, marked hypoechogenicity and high stiffness with elastography. The scores are: TIRADS1 - normal gland TIRADS2 - constantly benign - include the simple cyst, the spongiform nodule, the "White Knight", the isolated macrocalcification and nodular hyperplasia (risk of malignancy 0%). TIRADS3 -very probably benign; no signs of high suspicion and isoechoic or hyperechoic nodule. (Risk of malignancy 0,25%). TIRADS4A - mildly suspect - no sign of high suspicion and mildly hypoechoic (risk of malignancy 6%). TIRADS4B - one or two signs of suspicion; no metastatic lymph nodes (risk of malignancy 69%). TIRADS5 - three to five signs and/or metastatic lymph node (risk of malignancy 100%). What is a White Knight? Fig. 9 on page 36 - It is a well-defined hyperechoic pseudo nodule in the context of thyroiditis, with no halo and no central vascularization. (11) What is an isolate macrocalcification? Fig. 10 on page 36 It is a "scar of a previous colloid cyst", not a true nodule. What is nodular hyperplasia? Confluent posterior and inferior isoechoic nodules, usually non-vascularized. 8 For Nachiappan et al (6), suspicious US features are microcalcifications, marked hypoechogenicity, taller-than wide shape on the transverse plane, cervical lymph node metastasis and extension beyond the thyroid margin. Some less suspicious yet still suspicious features include absence of halo, ill defined or irregular margin, being solid and with increased central vascularity. Page 9 of 79

10 Fig. 49: Table 2- solid nodules References: Department of Radiology, HFF Comments: 9 Kim paper (8) introduced the concepts of markedly hypoechoic Fig. 13 on page 38 nodule (more hypoechoic than the adjacent strap muscles) as opposed to hypoechoic nodule (more hypoechoic than the normal thyroid parenchyma). 10 KJR (9) defines the halo as a hypoechoic rim surrounding a nodule, comprised of a pseudo-capsule, formed by compressed thyroid tissue, fibrous tissue and inflammatory changes. Page 10 of 79

11 11 BTA (British Thyroid Association) (7) differentiates mildly hyperechoic (usually benign) from markedly hyperechoic (indeterminate), possibly a follicular tumour. Fig. 50: Table 3 - shape and calcifications References: Department of Radiology, HFF Comments: 12 Coarse calcifications Fig. 15 on page 39are > 1-2mm, usually with posterior acoustic shadow. They are associated with a 2 fold increased risk of malignity (10). 13 Egg shell calcifications Fig. 16 on page 40 Fig. 17 on page 41 are rim calcifications. If the rim is complete, the nodule is usually benign but if the rim is disrupted Page 11 of 79

12 and there is an extension of hypoechoic mass through the rim, the nodule is suspicious (7). 14 microcalcifications Fig. 18 on page 42 are tiny hiperechoic foci, without posterior acoustic shadow (except if coalescent) and without posterior reverberation artefact or comet tail artefact, are suspicious of papillary thyroid carcinoma. They should be distinguished from colloid granulations, typical of benign nodules. It is important to refer that they can coexist in the same nodule. When in doubt, it is better to perform FNAC. 15 Taller-than-wide shape was first described by Kim, and is considered a suspicious feature on the basis of the different growth pattern of benign tumours (along tissue planes) as opposed to that of malignant ones (across tissue planes). It was defined as a greater AP than T diameter in a transverse Fig. 19 on page 43 section. However, the Korean and French groups (Gilles Russ) also consider a nodule taller-than-wide if there is a greater AP than T diameter in the longitudinal plan Fig. 20 on page 44. Page 12 of 79

13 Fig. 51: Table 4 - margins, elastography, Doppler PET References: Department of Radiology, HFF Comments: 16 Irregular margins, either micro-lobulated, Fig. 21 on page 45 spiculated or angulated are considered a suspicious sign for malignancy (14) FDG-PET is not used to characterize thyroid nodules but if an incidentally FDG avid nodule is detected, 4 of the above analysed recent guidelines consider it should be further evaluated with US and US guided FNAC. The exception being, of course, a disseminated disease whose prognosis would prevent further investigation. 18 The role of Doppler Fig. 24 on page 48 Fig. 25 on page is 49still controversial. Most guidelines consider that marked internal flow, defined as greater flow in the Page 13 of 79

14 centre of the nodule than at the periphery and more flow compared to the normal thyroid parenchyma is a suspicious feature. AACE/AME/ETA (American Association of Clinical Endocrinologists, in collaboration with the Associazione Medici Endocrinologi and the European Thyroid Association) (4) adds the concept of chaotic intra-nodular vascular spots as suspicious. There are several colours or power Doppler pattern classifications. The French Society of Endocrinology (5) uses 4 patterns: I - no vascularity; II- almost exclusive perinodular; III - high peri and intranodular; IV -exclusive or predominant intranodular; Using pulsed Doppler, a resistive index >0,78 is considered suspicious of follicular nodule. Chammas (17), defined 5 vascular patterns with power Doppler (I - absence of signal; II exclusively perinodular; III - perinodular #central; IV -central> peripheral; V - only central). The results associate vascular patterns IV or V (independent of RI) and pattern II or III and RI >0,77 with higher risk of malignancy. 19 Elastography is a new ultrasound technique that evaluates the tissue stiffness. On a clinical basis, a hard nodule is considered more suspicious than a soft one. The French group guidelines include high stiffness of the nodule on elastographic evaluation, if available, as a suspicious criterion. Nevertheless, it should not be used as a single criterion. It is limited by motion artifacts, if the nodules are cystic or calcified and in large goiters with deeply located nodules. It is also operator-dependent and requires a learning curve. There are two kinds of elastography techniques: I-strain, or static elastography Requires an external pressure for tissue deformation. Can be presented as a visual scoring (qualitative) or as a strain-ratio (quantitative). II-shear wave elastography Fig. 26 on page 50 Fig. 27 on page 51 Fig. 28 on page 52 The deformation of the tissue is caused by the US probe's acoustic pulse. It is less operator-dependent and more quantitative than strain elastography. The method can be either a supersonic shear wave (displayed as colour map and/or quantitatively) or acoustic radiation force impulse (ARFI), displayed only quantitatively. Page 14 of 79

15 Some elastography scores have been developed, but their value has yet to be proven. The point of the TIRADS group is that, if elastography is available, a high stiffness of the nodule should be considered suspicious and, as such, used to classify the nodule as TIRADS 4B or 5, which means it should be submitted to FNAC. 20 The authors (18) consider that if the incidentally found nodule doesn't fill the cited criteria, you should not even mention it in your report. 3. FNAC technique Guidelines are consensual about the fact that FNAC of thyroid nodules should be performed under ultrasound guidance, in order to improve diagnostic accuracy. Bellow we describe FNAC techniques used in our department The procedure is explained to the patient and an informed consent form is signed. The nodule(s) to be punctioned are identified by ultrasound. Page 15 of 79

16 Fig. 29: US and US guided FNAC room References: Department of Radiology, HFF Usually no local anaesthesia is necessary. In special cases we use either subcutaneous lidocaine or a topic anaesthetic. A cytotechnologist is present in the room throughout the procedure. Page 16 of 79

17 Fig. 30: Material necessary to perform a quick coloration and to assess the sample's adequateness References: Department of Pathology, HFF The equipment consists in a GE Logic E9 ultrasound display and an ML linear probe with a range of 6 to 15 MHz. The following parameters were present in the pre-set: frequency - 11MHz; dynamic range - 66; cross x beam - low; cross x beam type - near; SRI - HD2; grey map - F; suppression - 2; line density - 2; focus width - 2. We used the colour Doppler and pulsed Doppler functions. For the punctures we use 25 Gauge needles connected to a 25 cm extension and attached to a 10 ml syringe mounted on a metal handle. The reasoning behind the use of this needle size (25 Gauge =0,241µ) is related to the size of the follicle (200µ). We don t use larger needles (22G=0,394µ; 23G=0,318µ) because the aspiration product tends to have more blood and could eventually yield more non diagnostic results. (19). Page 17 of 79

18 Fig. 31: Material used for FNAC. References: Department of Pathology, HFF Page 18 of 79

19 Fig. 32: 25 Gauge needle connected to a 25 cm extension and attached to a 10 ml syringe mounted on a metal handle. References: Department of Pathology, HFF The aspiration technique is used, with the help of the cytotechnologist, who holds the metal handle while the radiologist holds the needle in one hand and the US probe in the other. The needle is continuously visualised by ultrasound during the procedure. Page 19 of 79

20 Fig. 33: The aspiration technique is used, with the help of the cytotechnologist, who holds the metal handle while the radiologist holds the needle in one hand and the US probe in the other. References: Department of Pathology, HFF With the obtained product we make smears on slides, which are either left to dry for DiffQuick stain or preserved in 95% alcohol for Papanicolaou stain. Page 20 of 79

21 Fig. 34: smears References: Department of Pathology, HFF A cytotechnologist is present in all cases and makes use of a quick coloration so as to assess the sample's adequateness (minimum 6 groups of at least 10 well preserved follicular cells). When the sample is inadequate, the procedure is repeated a maximum of 3 or 4 times per nodule. There is not enough data available to decide on the ideal amount of passes for an individual patient/nodule. The needle rinses are also preserved in a liquid preservative (we use cytolyt solution) whenever necessary. When a suspicious lymph node is to be punctured, either pre or post-thyroidectomy, we also rinse the needle in 1cc of saline solution for thyroglobulin dosage. Page 21 of 79

22 Page 22 of 79

23 Fig. 35: rinse of the needle in 1cc of saline solution for thyroglobulin dosage. References: Department of Radiology, HFF 4. Bethesda report In our institution the Bethesda classification is used to report cytology and we follow the proposed recommendations. The Bethesda system for report of thyroid cytopathology was published by the NCI in 2008 (20). It consists of 6 categories, each with an attributed malignancy risk and a follow-up recommendation associated. Bethesda category Risk(%) Recommendation I Non diagnostic Fig. 36 on page 61 Repeat FNAC II Benign Fig. 37 on page Follow-up III Atipia of undetermined 5-15 significance or follicular lesion of undetermined significance (FLUS) Fig. 38 on page 62 Repeat FNAC IV Follicular tumour Fig on page 63 Fig. 40 on page 64 surgery V Suspicious Fig. 41 on page 71 surgery VI Malignant Fig. 42 on page 65 surgery Table 5 -Bethesda categories Regarding the diagnosis of follicular tumour, it is important to remember that the distinction between a (benign) follicular adenoma and a (malignant) follicular carcinoma Page 23 of 79

24 cannot be accomplished by cytology since malignancy is determined by the presence of capsular or vascular invasion, which is only recognizable in histology. Fig. 40: Histology (HE 4x) - thyroid follicular carcinoma with capsular invasion "fish tail" (arrows). References: Department of Pathology, HFF 5. The crucial information the surgeon needs The thyroid surgeon needs precise anatomical information regarding the size and location of the thyroid nodule, presence or absence of nodules in the contralateral lobe, existence of possible anatomical variants (namely arteria lusoria; when present, changes the usual course of the recurrent nerve) and accurate mapping of suspicious cervical lymph nodes. If there is a single nodule, particularly with a cytological undetermined significance, a hemi-thyroidectomy might be considered. Page 24 of 79

25 When a thyroidectomy is planned in a patient with a cytological diagnosis of thyroid carcinoma, a central group compartment dissection is usually performed. The lateral groups and superior mediastinal groups, however, are only dissected if suspicious or positive adenopathies are present. 6. Acknowledge nuclear medicine's role in pre and post-op thyroid evaluation 99m Scintigraphy with either Tc pertechnetate or functional evaluation of the thyroid. 123 I is the only technique that allows Pre-operatively it is used mainly in patients with low TSH to assess whether the nodules are hot, cold or indeterminate. Hot nodules are rarely malignant, not needing FNAC characterization. Cold or indeterminate nodules need US /US guided FNAC characterization. (3,5). Fig. 43 on page 66 Fig. 44 on page 67 Fig. 45 on page 68 Thyroid nodules can be incidentally detected in F18-FDG-PET CT. When present, FNAC is indicated. Fig. 46 on page 69 After total thyroidectomy, in appropriate situations post operative treatment with radioactive iodine is indicated. A whole body scintigraphy post iodine therapy is then performed to evaluate efficacy of treatment and possible residual disease. Fig. 47 on page 70 Page 25 of 79

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30 Images for this section: Page 30 of 79

31 Fig. 2: adenopathy suspicious of metastatic thyroid cancer "cystic" Page 31 of 79

32 Fig. 3: adenopathies suspicious of metastatic thyroid cancer "thyroid like"(arrow) and with"microcalcifications"(curved arrow) Fig. 4: Cyst Page 32 of 79

33 Fig. 5: mixed solid and cystic nodule of the thyroid isthmus Page 33 of 79

34 Fig. 6: cyst with a mixed solid and cystic mural nodule (arrow). Page 34 of 79

35 Fig. 7: cyst with solid mural nodule (arrow). Fig. 8: spongiform nodule (arrow). Page 35 of 79

36 Fig. 9: White Knight (arrow) Fig. 10: isolated macrocalcification (arrow). Page 36 of 79

37 Fig. 11: predominantly isoechoic nodule (arrow) Fig. 12: mildly hypoechoic nodule with a thin peripheral halo (arrow). Page 37 of 79

38 Fig. 13: marked hypoechoic, lobulated margins, "taller than wide" shaped nodule. Page 38 of 79

39 Fig. 14: mildly hyperechoic nodule with a peripheral halo Page 39 of 79

40 Fig. 15: nodule with coarse calcifications (arrow). Page 40 of 79

41 Fig. 16: peripheral complete "egg-shell" calcification Page 41 of 79

42 Fig. 17: incomplete peripheral egg-shell" (arrow), disrupted, with extension of hypoechoic mass beyond the rim (curved arrow). Page 42 of 79

43 Fig. 18: nodule with multiple microcalcifications Page 43 of 79

44 Fig. 19: "taller-than-wide" nodule, transverse view Page 44 of 79

45 Fig. 20: taller-than-wide" nodule, longitudinal view Page 45 of 79

46 Fig. 21: nodule with microlobulated contours (and also with microcalcifications and coarse calcifications). Page 46 of 79

47 Fig. 22: Nodule incidentally detected by 18FDG PET Page 47 of 79

48 Fig. 23: markedly hypoechoic nodule (arrow) with increased, chaotic, internal nodular vascularity (curved arrow, fig 24). Page 48 of 79

49 Fig. 24: markedly hypoechoic nodule (arrow) with increased, chaotic, internal nodular vascularity (curved arrow, fig 24). Page 49 of 79

50 Fig. 25: mixed solid and cystic nodule with peripheral vascularization. Page 50 of 79

51 Fig. 26: shear wave elastography. Shear velocity (cm/s) display mode. Stiffer (red) and softer (blue) areas of the nodule Page 51 of 79

52 Fig. 27: Shear wave elastography display in elasticity mode (KPa). Stiffer (red) and softer (blue) areas of the nodule Page 52 of 79

53 Fig. 28: shear wave elastography display in propagation mode. The interval between the propagation lines are wider in the stiff nodule (arrow) and narrower in the softer normal thyroid parenchyma (curved arrow). Also note the loose of parallelism between the lines in the calcified area (showing that the shear waves aren't propagating properly in this area)(double arrow). Page 53 of 79

54 Fig. 29: US and US guided FNAC room Page 54 of 79

55 Fig. 30: Material necessary to perform a quick coloration and to assess the sample's adequateness Page 55 of 79

56 Fig. 31: Material used for FNAC. Page 56 of 79

57 Fig. 32: 25 Gauge needle connected to a 25 cm extension and attached to a 10 ml syringe mounted on a metal handle. Page 57 of 79

58 Fig. 33: The aspiration technique is used, with the help of the cytotechnologist, who holds the metal handle while the radiologist holds the needle in one hand and the US probe in the other. Page 58 of 79

59 Fig. 34: smears Page 59 of 79

60 Page 60 of 79

61 Fig. 35: rinse of the needle in 1cc of saline solution for thyroglobulin dosage. Fig. 36: Bethesda I - Ampl. Obj 10x - Non-diagnostic: Absence of follicular cells (criteria for adequacy). Page 61 of 79

62 Fig. 37: Bethesda II- Ampl. Obj 10x - Benign: monolayer sheets of follicular cells and abundant thick colloid. Page 62 of 79

63 Fig. 38: Bethesda III - Ampl obj 20x - Follicular Lesion of Undetermined Significance: cluster with microfollicular pattern with some nuclear moulding and absence colloid in a sparsely cellular smear. Page 63 of 79

64 Fig. 39: Bethesda IV - Ampl. Obj 10x - Follicular neoplasm: Monotonous population of follicular cells with a microfollicular arrangement and absence colloid. Page 64 of 79

65 Fig. 40: Histology (HE 4x) - thyroid follicular carcinoma with capsular invasion "fish tail" (arrows). Page 65 of 79

66 Fig. 42: Bethesda VI - Ampl obj 40x - Malignant (Papillary thyroid carcinoma): Enlarged cells with ovoid nuclei, irregular nuclear contours, crowding/overlapping, nuclear grooves, intranuclear pseudoinclusions and dense cytoplasm. Page 66 of 79

67 Fig. 43: Scintigraphy: thyroid, with regular contours and homogeneous uptake - diffuse goiter/hyperthyroidism. Page 67 of 79

68 Fig. 44: Scintigraphy: Hot nodule in the right lobe - toxic adenoma Page 68 of 79

69 Fig. 45: Scintigraphy: Multinodular goiter with nodule showing elective uptake in the right lobe and irregularity of the remaining parenchyma, with cold nodules. Page 69 of 79

70 Fig. 46: Right thyroid nodule in a retrosternal goitre in an axial slice. The PET CT was performed to assess and confirm a breast cancer recurrence. Page 70 of 79

71 Fig. 47: Whole bode scintigraphy 72 hours after iodine therapy for differentiated thyroid cancer. Cervical uptake. Page 71 of 79

72 Fig. 41: Bethesda V - Ampl obj 40x - Suspicious for Malignancy - Cluster of cells with nuclei ovoid shape, moulding and occasional grooves. Page 72 of 79

73 Fig. 48: Table 1 - cystic nodules Page 73 of 79

74 Fig. 49: Table 2- solid nodules Page 74 of 79

75 Fig. 50: Table 3 - shape and calcifications Page 75 of 79

76 Fig. 51: Table 4 - margins, elastography, Doppler PET Page 76 of 79

77 Conclusion Understanding thyroid pathology, regular practice and multidisciplinary team effort are crucial for thyroid imaging evaluation. Personal information References ie 1. Quicherat L, Daveluy A. Dictionnaire Latin-Français. Paris, Libr. Hachette et C, Kumar V, Abbas A et al. Robbins Basic Pathology 8th edition. Saunders Elsevier, Cooper DS, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid: official journal of the American Thyroid Association 2009; 19: Gharib H, Papini E, Paschke R, et al. AACE/AME/ ETA thyroid nodule guidelines. Endocr Pract 2010; 16(Supp1): Wémeau JL, Sadoul JL et al. Guidelines of the French Society of Endocrinology for the management of thyroid nodules. Annales d'endocrinologie 72 (2011) Nachiappan AC, Metwalli ZA, Hailey BS et al. The Thyroid: Review of Imaging Features and Biopsy Techniques with Radiologic-Pathologic Correlation. Radiographics 2014; 34: Perros P, Colley S et al. British Thyroid Association Guidelines for the Management of Thyroid Cancer. Clinical Endocrinology volume 81 supplement 1 july Page 77 of 79

78 8. Kim, E-K, Park, CS et al. New Sonographic Criteria for Recommending Fine-Needle Aspiration Biopsy of Nonpalpable Solid Nodules of the Thyroid. Am J Roentgenol. 2002; 178: Moon J-W, Baek JH, Jung SL et al. Ultrasonography and the Ultrasound-based Management of Thyroid Nodules: Consensus Statement and Recommendations. Korean J Radiol 2011; 12(1): Frates MC, Benson CB, Charboneau JW, et al. Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Radiology 2005;237: Bonavita JA, Mayo J, Babb J et al. Pattern recognition of benign nodules at ultrasound of the thyroid: which nodules can be left alone? AJR Am J Roentgenol. 2009; 193: Park J-I, Lee HJ et al. A proposal for a Thyroid Imaging Report and Data System for Ultrasound Features of Thyroid Carcinoma. Thyroid 2009; 19(11): Horvath E, Majlis S et al. An Ultrasonogram Reporting System for Thyroid Nodules Stratifying Cancer Risk and Clinical Management. J Clin Endocrinol Metab. 2009; 90 (5): Russ G, Bigorgne C et al. Le systemme TIRADS en échographie thyroidienne. Journal de Radiologie 2011; 92: Russ G; Royer B et al. Prospective evaluation of thyroid imaging reporting and data system on 4550 nodules with and without elastography. European Journal of Endocrinology 2013; 166: Monpeyssen H, Tramalloni J et al. Elastography of the thyroid. Diagnostic and interventional imaging 2013; 94: Chammas MC, Gerhard R, et al. Thyroid nodules: evaluation with power Doppler and duplex Doppler ultrasound. Otolaryngol Head Neck Surg Jun;132(6): of 79

79 20. Update_on_Thyroid_FNA,_The_Bethesda_System.pdfAli SZ, Cibas ES. The Bethesda System for Reporting Thyroid Cytopathology. Definitions, Criteria and Explanatory notes. Springer Page 79 of 79

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