Solitary thyroid nodule

Seminar on Solitary Thyroid Nodule

1. SOLITARY THYROID NODULE MODERATED BY DR. P. P. DAS DR. A. SARMA DR. M. M. ALAM PRESENTED BY JAYDEEP MALAKAR

2. DEFINITIONS OLD : In an otherwise normal gland, a single palpable nodule in the thyroid on clinical examination. NEW : A DISCRETE lesion /nodule, WITHIN the thyroid, that is PALPABLY and/or RADIOLOGICALLY DISTINCT from the surrounding thyroid parenchyma. *5-15 % of all Solitary Thyroid Nodules = Thyroid Malignancy.

3. The prevalence of thyroid nodules detected on palpation (Broken Line) or by Ultrasonography or Post Mortem examination (Solid Line) * * Mazzaferri EL. Management of a solitary thyroid nodule. New England Journal of Medicine. 1993 Feb 25;328(8):553-9.

4. SOLITARY THYROID NODULE MULTI NODULAR GOITRE COLLOID GOITRE

5. EPIDEMIOLOGY A palpable thyroid nodule is usually > 1 cm. Prevalence varies considerably worldwide, depending on regional iodine sufficiency. Iodine deficient areas: up to 50% of adults. Iodine sufficient areas: ~5% of adults (U.S.A). It is more common in women (6.4%) than men (1.5%). The prevalence is 4% by palpation, 19 to 67% by ultrasound examination, and 50% in autopsy series.

6. CLASSIFICATIONS Benign 90% Cysts Adenomas Papillary Follicular Colloid Fetal Embryonic Hurthle Cell Type Toxic Adenoma Solitary Hyperfunctioning thyroid nodule Non Toxic Adenoma Solitary Nonfunctioning thyroid nodule

7. CLASSIFICATIONS Malignant 10% Primary Follicular Epithelium – Differentiated Papillary 80% Follicular 10% Follicular Epithelium – Poorly Differentiated Anaplastic 5% Parafollicular Cells Medullary 2.5% Lymphoid Cells Lymphoma 2.5% Secondary Metastatic Local infiltration The main aim in the evaluation of STN is to differentiate benign from malignant lesions at a reasonable cost & trauma to the patient.

8. SYMPTOMS AND SIGNS SYMPTOMS A. Nontoxic adenomas: Large adenomas present as a neck mass. Smaller adenomas are typically asymptomatic. B. Toxic adenoma: Symptoms of thyrotoxicosis . C. Association with other Endocrinopathies (MEN) : Multifold Symptoms SIGNS Most palpable nodules are > 1 cm in diameter. Ability to detect a palpable thyroid nodule on physical examination depends on : a. Location within the gland, c. Degree of adiposity and b. Anatomy of patient’s neck d. Experience of examiner.

9. HISTORY The thyroid nodule is often discovered incidentally during a clinical examination performed for another purpose. Size: All nodules larger than 1 cm and nonpalpable nodules with suspicious imaging need further evaluation. >4cm increases incidence of malignancy. Rate of growth: Over hours with pain suggests hemorrhage into an existing nodule. Over weeks is more strongly associated with malignancy , and During levothyroxine therapy is especially suggestive of cancer . Sudden change in the size of a pre-existing nodule may indicate malignancy .

10. HISTORY Age and Gender -Around 20 to 50% of solitary nodules in patients younger than 20 years are malignant. -Pediatric thyroid carcinoma occurs in teenage years (mean 16) and in girls 5.6 times more often than in boys. -Beyond 70 years of age, malignancy is not common, but prognosis is worse when present. -Risk of malignancy in men is twice that of women. Diet -Patients from iodine-sufficient areas have a higher rate of malignancy than those from iodine- deficient areas (5.3% vs 2.7%)*. However, follicular and anaplastic carcinomas are relatively more common in iodine-deficient areas. *Zimmermann MB, Galetti V. Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies. Thyroid research. 2015 Dec;8(1):8.

11. HISTORY WELL DIFFERENTIATED THYROID CANCER GARDNER’S SYNDROME (AD) FAP. Osseous/Soft Tissue Tumours Retinal Epithelium Hypertrophy Supernumerary Teeth. MEDULLARY CARCINOMA THYROID MEN II A&B (AD). COWDEN’S SYNDROME (AD) Multiple hamartomas Fibrocystic Breast Disease. Breast Cancer (PTEN)

12. EXPOSURE TO RADIATION The risk is maximum 20 to 30 years after exposure. Papillary Thyroid Carcinoma is most common. Thyroid nodule + History of radiation = 40% Chance of Thyroid Cancer. Exposure to Radiation for Hodgkin’s Lymphoma / CA Breast 35 years after exposure, in 7- 10% of exposed patients. 100 Rads - Thyroid nodules, Thyroid carcinoma >2000 Rads - Prevent thyroid neoplasm (Thyroid gland destroyed) 10 mSv = 1 Rad A  chest x-ray , delivers 0.1 mSv .

13. PHYSICAL EXAMINATION Consists of local examination of thyroid and systemic examination for features of hypo/hyperthyroidism and other stigmata of malignancy or other etiology. The thyroid gland and nodules within it move with swallowing. The size, site, shape consistency and presence of any other palpable nodules should be noted. Nodule with firm consistency - autoimmune thyroid disease Stony hard consistency favors malignancy . Firm nodule along with fixity suggests invasion and may be a pointer toward malignancy .

14. Positive Pemberton’s Sign To demonstrate the presence of latent pressure in the thoracic inlet. “Cork effect” Retrosternal Goiter.

15. SUMMARY OF MALIGNANT CHARACTERISTICS Young patients (< 20 years) or old (> 70 years), Male sex, H/O external neck radiation during childhood or adolescence, Recent change in voice (RLN Involvement) Past family history of thyroid carcinoma. Enlarging Nodule (Size >4 cms ) Firm consistency of nodule, Irregular shape, Fixation to underlying or overlying tissues, Suspicious regional lymphadenopathy . Family history of PTC, MTC, or MEN2

16. DIFFERENTIAL DIAGNOSIS Primary thyroid cancer Functioning adenoma Nonfunctioning adenoma Cyst Thyroid lymphoma Cancer metastasizing to the thyroid Hashimoto’s Thyroiditis. Simple Goiter Development defects e.g. - ectopic tissue.

17. DIAGNOSTIC APPROACH Evaluation of a STN consists of 2 components. To determine if nodule is autonomously functioning and possibly causing hyperthyroidism Or has high risk of malignancy.

18. WORK UP OF A THYROID NODULE

19. SEROLOGY AND BIOCHEMICAL TESTS Initial screening test FOR ALL PATIENTS with a thyroid nodule is serum TSH level to know if the patient is euthyroid , hypothyroid or hyperthyroid. Most of the patients with a thyroid nodule are euthyroid and if they are not euthyroid , then the underlying pathology is likely to be benign and functional. When hypothyroidism is confirmed, anti thyroid peroxidase antibodies should be assayed to evaluate for Hashimoto’s thyroiditis . A baseline preoperative ionized calcium estimation is helpful, since a parathyroid adenoma may mimic a thyroid nodule. This also gives a clue to MEN I or II and helps decide further plan of management.

20. SEROLOGY AND BIOCHEMICAL TESTS Routine evaluation of thyroglobulin and calcitonin levels is not recommended since this approach is not cost effective. Thyroglobulin levels are useful as a surveillance test in well differentiated thyroid carcinoma after a total thyroidectomy but it has no role in initial evaluation of a thyroid nodule. Patients having positive family history of MTC, a serum calcitonin should be included in the initial test as it is sensitive in detecting even small MTCs. Patients with personal or family history of MTC, mutational screening of the RET protooncogene should be employed. High levels of TPOab suggests an autoimmune etiology – Hashimoto’s Thyroiditis .

21. FINE-NEEDLE ASPIRATION CYTOLOGY Fine-Needle Aspiration Cytology (FNAC) is the most important diagnostic evaluation for a thyroid nodule. It is the safest, most cost-effective, and most reliable technique to differentiate between benign and malignant diseases of the thyroid. FNACs reduces the number of thyroidectomies by half while doubling the surgical confirmation of carcinoma. FNAC can be done with or without USG guidance. USG guided FNAC is more reliable, rapid, accurate and safe. The specimen should be evaluated immediately on-site to judge the adequacy of FNA specimen. For proper reporting, smear should be adequate.

22. FINE-NEEDLE ASPIRATION CYTOLOGY For a thyroid FNA specimen to be satisfactory for evaluation at least 6 groups of benign follicular cells are required and each group should be composed of at least 10 cells. Current sensitivity and specificity generally exceed 90 and 70%, respectively. Since, the size of needle used is very small (21 to 24 gauge), needle-track seeding is unlikely. The false negative rate varies from 1 to 5% and is associated with cysts or nodules smaller than 1 cm or masses greater than 3 cm.

23. THE BETHESDA SYSTEM FOR REPORTING THYROID CYTOPATHOLOGY

24. THE THY CLASSIFICATION ADOPTED BY THE ROYAL COLLEGE OF PHYSICIANS CLASS DESCRIPTION ACTION Thy1 Non-diagnostic ( inadequate/ technical artefact precludes interpretation) FNAC should be repeated with or without ultrasound guidance .. Thy 1 c Non-diagnostic cystic Thy2 Non- neoplastic (features consistent with a nodular goitre or thyroiditis ). Two non neoplastic results 3-6 /12 months apart advised Thy3 ( i ) All follicular lesions. Lobectomy . Complete thyroidectomy will be necessary if histology proves malignant. Thy3 (ii) Worrying feature but cells to scanty to qualify for Thy 4 Discuss with cytopathologist to determine course of action.

25. THE THY CLASSIFICATION ADOPTED BY THE ROYAL COLLEGE OF PHYSICIANS CLASS DESCRIPTION ACTION Thy4 Suspicious of malignancy (but not diagnostic) Surgical intervention indicated for differentiated tumour . Further treatment dependent upon pathology report. For lymphoma, metastatic tumour or undifferentiated i.e. anaplastic thyroid carcinoma, further investigation indicated. Thy5   Diagnostic of malignancy Surgical intervention indicated for differentiated thyroid cancer, depending on tumour size, clinical stage and other risk factors such as gender and extremes of age. Appropriate further investigation indicated alongside radiotherapy/chemotherapy for anaplastic carcinoma, lymphoma or metastatic tumor.

26. FNAC SPECIMENS 70% Benign, 5% Malignant, 10% Suspicious, and 15% Unsatisfactory

27. USG GUIDED FNAC Indicated if: Palpation-guided FNA is non diagnostic Complex (solid/cystic) nodule Palpable small nodule (<1.5 cm) Impalpable nodule Abnormal cervical nodes Nodule with suspicious US features

28. BENIGN (-VE) CYTOLOGY Most common finding Indicative of: Colloid nodule Macrofollicular adenoma Lymphocytic thyroiditis Granulomatous thyroiditis Benign cyst

29. MALIGNANT (+VE) CYTOLOGY Commonest is Papillary Thyroid Cancer: Increased cellularity , Tumor cells arranged in sheets and papillary cell groups. Typical nuclear abnormalities, which include intranuclear holes and grooves. Others include: MTC, anaplastic carcinoma, and high grade metastatic cancers

30. SUSPICIOUS CYTOLOGY Diagnosis cannot be made Includes: Follicular neoplasms (Adenoma vs Carcinoma) Hürthle cell neoplasms . Reidels Thyroiditis Atypical PTC Thyroid Lymphoma. Patients with a family history of Thyroid Malignancy. Patients with history of low dose radiation exposure during childhood.

31. INDICATIONS FOR REPEAT FNA Follow-up of benign nodule Enlarging nodule Recurrent cyst Nodule >4 cm Initial FNA non-diagnostic. No nodule shrinkage after T4 therapy

32. THYROGLOBULIN OF FNA OF CERVICAL L.N. Thyroglobulin ( Tg ) can be measured in lymph node or nodule aspirates. FNA- Tg levels were markedly elevated in metastatic lymph nodes FNA- Tg sensitivity is 84.0% The combination of cytology plus FNA- Tg increased FNA sensitivity from 76% to 92.0%.

33. IMMUNOHISTOCHEMICAL MARKERS HBME-1 ( Hector Battifora mesothelia-1) monoclonal antibody stains papillary cancer positively but does not stain benign follicular tumors Galectin-3 acts as a cell-death suppressor distinguishes benign from malignant thyroid follicular tumors. MoAb 47 ( Monoclonal Antibody 47) Thyroid peroxide (TPO) immunochemistry with a monoclonal antibody termed Moab 47 increases the accuracy of FNAC in patients with follicular carcinoma.

34. Monolayered Sheets Of Follicular Cells In Goiter.

35. Papillary Carcinoma Of Thyroid Increased cellularity , Tumor cells arranged in sheets and papillary cell groups. Typical nuclear abnormalities, which include intranuclear holes and grooves

36. Medullary Carcinoma— Intracytoplasmic Granules With Plasmacytoid Cells

37. Follicular Pattern

38. IMAGING THE THYROID

39. ULTRASONOGRAPHY Most sensitive test to detect lesions in the thyroid. It is recommended that ALL patients who have a nodular thyroid, with a palpable solitary nodule or a multinodular goiter, be evaluated by US. Not indicated as screening test in general population . Indicated in: Palpable nodule - History of radiation to the neck Age<20 & >70 - Family history of MTC, MEN2, or PTC Presence of cervical lymphadenopathy .

40. ULTRASONOGRAPHY FEATURES OF MALIGNANCY Hypoechogenicity in solid nodules, Presence of micro calcifications, Irregular shape, Taller than wider lesion Intra nodular vascular spots, Absence of halo and Cystic elements. Evidence of invasion or regional lymphadenopathy , and Increased blood flow in the center of the nodule seen on a Doppler study suggests high malignancy. *Macroscopic Capsular Breach and Nodal involvement are diagnostic of malignancy.

41. ULTRASONOGRAPHIC FEATURES OF BENIGN AND MALIGNANT NODULE

42. THYROID IMAGING REPORTING AND DATA SYSTEM TIRADS was first used by Horvath et al to standardize the reporting of results of thyroid USG. Helpful in the stratification of nodules in benign and malignant. 10 ultrasound patterns were described. He related the rate of malignancy according to the pattern. Six categories, ranging from a normal thyroid gland to a malignant nodule.

43. TIRADS system of classification

44. The TIRADS classification algorithm

45. Should be limited to patients with a low TSH level to identify autonomously functioning nodules (~5%). Nodules with increased uptake (hot) are toxic adenomas and almost never malignant. (1- 4% chances only). Nodules that accumulate radionuclide equal to surrounding tissue (warm), or nodules with low uptake (cold), are most often benign (~80%) but may be malignant in upto 25% of the cases and therefore require FNA biopsy. THYROID SCINTIGRAPHY (123IODINE OR 99MTECHNETIUM)

46. CT SCAN / MRI CT Scanning & MRI role is limited, except to see the spread and compression of neighboring structures. Both can accurately determine substernal extension and invasion of surrounding structures, such as esophagus, larynx, or trachea, and should be used only if invasion or substernal extension is suspected. The use of contrast dyes delivers an iodine load that can delay postoperative thyroid scanning for 4 to 8 weeks and can also cause a subclinically hyperthyroid patient to enter thyroid storm.

47. PET- SCAN Indicated in follow up to detect recurrence. The phenomenon of the PET identified thyroid incidentallomas is becoming more prevalent.

48. ELASTOGRAPHY Noninvasive ultrasound procedure which gives information about tissue stiffness. Stiffness depends upon the composition and structural organization of the lesion. When pressure is exerted on thyroid tissue with ultrasound probe, strain values of the thyroid nodule and the parenchyma can be obtained. This pressure can be applied by using a probe from outside or using the in vivo compression caused by carotid artery pulsation. Quantitative elastography provides a time elasticity graph, plotted on the region of interest, in compression and relaxation cycle. Thus, two images of thyroid are acquired, before and after compression with the probe. The tissue displacement is noted by analyzing the imaging beam. A software is used for accurate measurement of tissue distortion

49. INCIDENTALLOMAS Clinically non-palpable incidental thyroid swelling < 1 cm are called “ incidentallomas ”. These are not uncommonly noted during surgery or imaging performed for another purpose. In patients with low risk characteristics these nodules are less cancerous. Also, there is no evidence to show that treatment of such sub centimetric micro carcinomas improves outcome. The exception to the above is an incidentalloma identified by FDG-PET scan, which carries a 50% chance of malignancy and therefore should be operated.

50. THYROID SURGERIES TOTAL THYROIDECTOMY HEMI THYROIDECTOMY SUBTOTAL THYROIDECTOMY HARTLEY DUNHILL PROCEDURE Near Total Thyroidectomy = Small Amount of thyroid tissue left in the Trache Oesophageal Groove

51. THYROID SURGERIES Total thyroidectomy = 2 total lobectomy + isthmusectomy Subtotal thyroidectomy = 2 subtotal lobectomy + isthmusectomy (4-6 grams in both lobes are preserved) Near-total thyroidectomy = Total lobectomy + subtotal lobectomy + Isthemusectomy . Lobectomy = Total Lobectomy + Isthmusectomy

52. SURGICAL MANAGEMENT Cyst : Aspirate. Maximum 3 times and if it still recurrs , Hemithyroidectomy . Papillary : Total Thyroidectomy + Removal of Enlarged Central Lymph Nodes. If any LN is positive then MRND on that side. Follicular : Total Thyroidectomy . Lymph Nodes preserved. Medullary : Total Thyroidectomy + Routine Central Lymph Node Dissection + Ipsilateral MRND if size of tumour is >1cm and Bilateral MRND if any LN is positive. Anaplastic : Total Thyroidectomy only in early phases; Tracheostomy . Lymphoma (Intermediate NHL) : CHOP; Radiation.

53. COMPLICATIONS FNA: Local discomfort, Hematomas, Infection. THYROIDECTOMY : Tension Haematoma . Respiratory Obstruction. Nerve Injuries (RLN/SLN/CST- Horner’s Syndrome) PTH Insufficiency Thyroid Insufficiency. Thyroid Crisis.

54. FOLLOWUP Thyroglobulin levels checked every 6 months. Normally undetectable after total thyroidectomy (<2 ng / mL ). Simultaneous Cervical USG every 6-12 months. If TG is raised and Nodule is + on USG = Indicates Recurrence = RAI Ablation. If TG is raised and Nodule is – on USG = Indication for PET Scan = RAI Ablation.

55. PROGNOSIS Benign nodules; usually persist or grow slowly & Malignant transformation is rare. Malignant nodules; Prognosis depends on histology.

56. PREVENTION Avoid exposure to external radiation. Adequate iodine intake may reduce the incidence of thyroid nodular disease.

57. CONCLUSION The goal of the evaluation of the solitary thyroid nodule is to identify whether the patient will require surgical treatment and to identify a malignancy. A majority of the thyroid nodules present with a lump in front of the neck, common in females, 90% of them are benign, adenoma being the commonest amongst benign lesion. FNAC is a very reliable and powerful screening method in the pre- operative diagnoses of Simple Thyroid Nodule. Jointly, FNAC, thyroid imaging, and ultrasonography can detect them with 90% accuracy. Thyroid scan is indispensable for toxic nodular goitre .

58. TNM DEFINITIONS (AJCC 8E) TX – Primary Tumor cannot be assessed. T0 – No evidence of Primary Tumor. T1 – Size ≤ 2 cms ; Intrathyroid . T1a - ≤ 1cm T1b – 1-2 cms . T2 – 2-4 cms . T3 - > 4 cms . T3a - > 4 cms intrathyroid . T3b – Any Size, Extrathyroid extension upto Strap Muscles. T4 – Any size, gross Extrathyroid extension. T4a – Larynx, Trachea, Esophagus, RLN. T4b - Prevertebral Fascia, Carotids. NX – Regional LN Cannot Be Assessed. N0 – No evidence of regional LN metastasis. N0a - ≥1 Confirmed benign lymph node. N0b – No radiological or clinical evidence of LN Metastasis. N1 – Metastasis to regional Nodes. N1a – Level VI or VII Positive, Unilateral or Bilateral. N1b – Levels I-V or retropharyngeal LN Positive, Unilateral or Bilateral . M0 - No Distant Metastasis. M1 - Distant Metastasis Present.

59. CLINICAL APPROACH TO SOLITARY THYROID NODULE WITH AN AIM TO EVALUATE AND TREAT