36 Thyroid Malignant conditions

  1. Discuss the management of solitary thyroid nodule. [TU 2060/12] 

    What is thyroid nodule?
    A thyroid nodule is a discrete and radiographically definable lesion within the thyroid.
  2. Importance of discrete thyroid swelling?
    The importance of discrete swellings lies in the risk of neoplasia compared with other thyroid swellings.

    • 15 per cent of isolated swellings prove to be malignant
    • 30–40 per cent are follicular adenomas
    • The remainder are non-neoplastic, largely consisting of areas of colloid degeneration, thyroiditis or cysts.
  3. Classification of thyroid nodule by radioactive scanning?
    Cold nodule: Does not take up any radioactivity—80% is benign and 10–20% is malignant.

    Warm nodule: They take up same radioactivity as the rest of the gland.

    Hot nodule: The nodule takes up all radioactivities and rest of the gland is suppressed. Only 1% is malignant. Some may be toxic adenoma.
  4. Common cause of solitary thyroid nodule?
    • Colloid nodule - most common cause
    • Follicular adenoma
    • Carcinoma thyroid
    • Thyroid cyst.
  5. Indications of thyroid resection?
    • (1) local compressive or inflammatory symptoms,
    • (2) hyperfunction, and
    • (3) malignancy or concern for malignancy
  6. Ultrasonographic Features associated With Thyroid Carcinoma?
    • Microcalcifications
    • Absent halo
    • IntraNodular vascularity
    • Irregular margins or
    • Solid
    • Hypoechogenicity 
    • Shape that is taller than its width on transverse view (Height)  [@ MANISH]
  7. American Thyroid Association Sonographic Patterns and Estimated Risk of Malignancy for Thyroid Nodules?
    • Sonographic pattern // Estimated risk of malignancy // Consider biopsy
    • High suspicion // >70-90 // ≥1 cm
    • Intermediate suspicion // 10-20 // ≥1 cm
    • Low suspicion // 5-10 // ≥1.5 cm
    • Very low suspicion // < 3 //≥2 cm
    • Benign // <1 // No biopsy
  8. Indication of CT and MRI in thyroid nodules?
    • CT and MRI do not add significantly to the workup of uncomplicated thyroid nodules.
    • However, either modality may be helpful in evaluating local extension in more advanced stages of thyroid cancer.
  9. Risk of iodine contrast in hyperthyroid patients?
    • If a patient with uncontrolled hyperthyroidism is given a large iodine load without appropriate medical management, there is the potential to trigger thyroid storm, which may be life-threatening.
    • Another concern related to iodinated contrast agents is that patients must be iodine depleted before therapeutic RAI treatment of thyroid cancer. The large iodine load decreases the target cell avidity for further iodine uptake after iodinated contrast agent administration. In most cases, 4 weeks is adequate time for the clearance of iodine after a CT scan.
  10. Indication of FNAC in nodule <1cm.
    • Nodules associated with suspicious lymphadenopathy based on ultrasound or clinical examination
    • Nodules in patients with family history of PTC
    • History of radiation exposure
    • Prior personal history of thyroid cancer; and
    • Lesions positive on FDG-PET.
  11. Bethesda Criteria for Reporting Thyroid Cytopathology?
    • Catagory // Usual Management
    • 1—Nondiagnostic or unsatisfactory // Repeat FNA with image guidance
    • 2—Benign // Clinical follow-up
    • 3—atypia of undetermined significance/follicular lesion of undetermined significance // Repeat FNA or lobectomy, BRAF mutation testing
    • 4—follicular neoplasm or suspicious for follicular neoplasm (specify if Hürthle cell type) // Repeat FNA or lobectomy, BRAF mutation testing
    • 5—Suspicious for malignancy (specify type) // Lobectomy or total thyroidectomy
    • 6—Malignant (specify type) // Total thyroidectomy

    Image Upload 1
  12. FNAC finding of PTC and FTC?
    • PTC is the most common thyroid cancer and has discrete cellular cytologic characteristics that make FNA extremely accurate in securing this particular diagnosis.
    • In contrast, the diagnosis of FTC is not made based on cellular features and instead is based on demonstration of capsular or vascular invasion by follicular cells. This architectural finding cannot be determined by FNA.
  13. Classify thyroid malignancy. [TU 2061,63,64,65/2]
    Benign -  Follicular adenoma


    • A) Primary
    • i) Follicular epithelium differentiated –
    • -  Follicular, Papillary
    • ii) Follicular epithelium undifferentiated - Anaplastic
    • iii) Parafollicular cells - Medullary
    • iv) Lymphoid cells - Lymphoma

    B) Secondary - Metastatic, Local infiltration
  14. How to differntiate papillary and follicular thyroid carcinoma? [TU 2072] 

    What are the risk factors for thyroid carcinoma? [TU 2073] 

    Features of Papillary Thyroid Carcinoma?
    • Most common thyroid malignancy (70% to 80%) and usually is associated with an excellent prognosis
    • Common in young females
    • Risk factor - Childhood radiation, family history of thyroid carcinoma
    • Associated with presence of a familial syndrome that includes thyroid carcinoma, such as Werner syndrome, Cowden syndrome, Carney complex, and familial polyposis.

    • Werner syndrome - adult progeria
    • Cowden syndrome - multiple hamartoma syndrome
    • Carney complex (its subsets LAMB syndrome and NAME syndrome) - myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity
  15. Pathological finding of PTC?
    • Findings of intranuclear inclusion bodies and nuclear grooving (orphan annie nuclei) on the FNA specimen confirm the diagnosis of PTC
    • Calcified clumps of cells, known as psammoma bodies, which are most likely caused by sloughed
    • papillary projections, is diagnostic of PTC
  16. Varients of PTC?
    • Tall cell carcinomas
    • Columnar,
    • Classic PTC
    • Diffuse Sclerosing
    • Follicular variant
    • Hobnail,
    • Solid

    (Columnar, hobnail, and tall cell carcinomas - more aggressive in their biologic behavior)
  17. Clinical features of PTC?
    • PTC most typically manifests either as a palpable thyroid nodule or as an incidental imaging finding.
    • A metastatic PTC manifests as a painless lateral neck
    • mass that is clinically detected before detecting the primary thyroid lesion.
  18. Enlist high risk criteria for a case of well differentiated carcinoma of thyroid. [TU 2066] 

    Prognostic Risk Classification for Patients With Differentiated Thyroid Carcinoma (AMES or AGES) - Clinical scoring
    Image Upload 2
  19. TNM staging of PTC?
    • Primary Tumor (T)
    • T1a ≤1 cm, intrathyroidal
    • T1b 1-2 cm, intrathyroidal
    • T2 2-4 cm, intrathyroidal
    • T3 >4 cm limited to the thyroid or any size with minimal extrathyroidal extension (muscle, soft tissue)
    • T4a Invades subcutaneous tissue, larynx, trachea, esophagus, or RLN
    • T4b Invades prevertebral fascia or encases carotid or mediastinal vessels

    • Regional Lymph Nodes (N)
    • N1a Positive in level VI
    • N1b Positive beyond level VI

    • Distant Metastasis (M)
    • M1 Distant metastasis

    • TNM classification is different for patients with age >45 years and <45 years. For example - 
    • <45 yrs - M1 - Stage II 
    • >45 yrs - M1 - Stage IVc
  20. Features of FTC?
    • FTC is a disease of an older population compared with PTC, with a peak incidence between ages 40 and 60 years.
    • It occurs more commonly in women, with a ratio of approximately 3 : 1.
    • Increased incidence in geographic distributions associated with iodine deficiency
    • Not associated with radiation exposure
  21. Pathology of FTC?
    • Follicular cells without capsular or vascular invasion - follicular adenoma.
    • Follicular cells occupying abnormal positions, including capsular or vascular invasion - FTC
    • - Minimally invasive
    • - Widely invasive
    • - Hürthle cell carcinoma 
    • Lymph node involvement is unusual in FTC, while high rate of lymph node involvement in PTC. Spread is by hematogenous route.
    • The most common sites for metastatic deposits are lytic bone lesions and lung.

    Types of follicular carcinoma - Follicular, InSular and Hurtle cell [@ FISH]
  22. Describe the hurthele cell carcinoma of thyroid gland. [TU 2063/2]
    • Consists of oxyphilic cells, increased number of mitochondria and tend to occur in older patients.
    • Hürthle cell carcinoma, a variant of follicular thyroid cancer, may be associated with poorer prognosis than follicular cancer, perhaps related to the tumor's poor affinity for taking up radioactive iodine.
    • Hürthle cell has been shown to have an increased recurrence rate in local lymph nodes.

    99mTc labeled sestamibi scan is required to detect metastatic foci from Hurthle cell tumor.

    Hurthle cell neoplasm confined to one lobe: Hemithyroidectomy—if frozen section biopsy shows carcinoma, total thyroidectomy and central lymph node dissection
  23. Clinical features of FTC?
    • Painless thyroid mass
    • Hoarseness and firm fixation of the mass - advanced disease and a poor prognosis
  24. How do you manage a case of papillary carcinoma thyroid in a 52 year old woman who presented with 3 cm nodule in right lobe thyroid. [TU 2066/10] 

    How do you manage a case of 3cm follicular carcinoma right thyroid in a 50 year old male diagnosed after hemi thyroidectomy. TU 2069/1] 

    Outline the management of follicular carcinoma of thyroid. [TU 2063,65,72/3]

    Outline the management of papillary carcinoma of thyroid gland. [TU 2061,  64,73/5] 

    Discuss the controversies in surgical treatment of thyroid cancer. [TU 2062/5] 
    • Extent of Thyroid Resection
    • Lymph Node Dissection
    • Completion Thyroidectomy
    • Radioactive Iodine Therapy
    • Thyroid-Stimulating Hormone Suppression. 

    Targeted therapy with tyrosine kinase inhibitors - to manage advanced cases of metastatic DTC that are refractory to RAI, rapidly progressive, and not amenable to other means of therapy.
  25. Extent of Thyroid Resection?
    • (1) hemithyroidectomy/thyroid lobectomy with or without isthmusectomy;
    • (2) near-total thyroidectomy, defined by leaving less than 1 g of tissue adjacent to the RLN at the ligament of Berry on one side; and
    • (3) Subtotal thyroidectomy, leaving a 4-7-g remnant - not done for thyorid malignancy, can be done on Graves disease 
    • - Bilateral subtotal thyroidectomy
    • - Total lobectomy on one side with a subtotal thyroidectomy on the other side (Hartley-Dunhill procedure)
    • (4) total thyroidectomy - removal of all visible thyroid tissue.
  26. Treatment of DTC?
    • <1 cm -
    • - Surgery is not clearly required for these lesions, if there are no clinically involved cervical lymph nodes, no extrathyroidal extension, and no history of head and neck irradiation.
    • - Similarly, if a DTC less than 1 cm is diagnosed after thyroid lobectomy, completion thyroidectomy is not required if there are no clinically involved cervical lymph nodes, no extrathyroidal extension, and no history of head and neck irradiation.

    • > 1 cm -
    • A) Total thyroidectomy is indicated in situations in which RAI therapy is planned. Indications of RAI are 

    • High risk cases -  
    • - DTCs > 4 cm
    • - Extrathyroidal extension
    • - Regional or distant metastases

    • Other indications:
    • - Patient and physician preference
    • - Age older than 45 years
    • - Contralateral nodules
    • - Prior irradiation
    • - Familial DTC.

    B) If none of the above-mentioned factors are concerns, thyroid lobectomy may be adequate surgical therapy

    C) At the present time, many physicians still prefer to offer RAI for many of these cancers, and many of these patients receive total thyroidectomy
  27. What is the rationale of doing total thyroidectomy in differentiated thyroid cancerconfined to one lobe?
    • „„ This removes all intrathyroidal tumors including occult site of carcinomas in the other lobe and thereby decrease the possibility of recurrent cancer in the other lobe
    • „„ Allows for whole body radioiodine scanning and ablation of metastatic disease with radioiodine
    • „„ Renders serum thyroglobulin level more sensitive for detecting recurrent or metastatic disease.
  28. Lymph node dissection in Thyroid carcinoma?
    • A) Level VI dissection
    • - PTC is the most common thyroid carcinoma and has a high frequency of lymph node metastasis
    • - Central compartment nodes should be assessed at the time of thyroidectomy by visual inspection and palpation, in addition to preoperative ultrasound. If pathologic nodes are encountered, a therapeutic central neck dissection should be performed.
    • - Many surgeons believe that prophylactic level VI dissection should be performed routinely in the setting of thyroid cancer, even in patients with clinically uninvolved nodes. Others argue against routine prophylactic dissection.
    • - In the setting of clinically negative central compartment nodes, a prophylactic dissection is more clearly indicated in higher risk situations, such as tumors that are larger than 4 cm,tumors with gross extrathyroidal extension, and tumors with lateral neck nodal disease.

    • B) Lateral neck lymph node dissection 
    • - Lateral neck should be evaluated for malignancy before thyroidectomy. All patients with a known thyroid carcinoma or a Bethesda System category 5 FNA specimen should have careful physical examination and ultrasound evaluation of the lateral compartment for pathologic lymphadenopathy. If pathologic appearing nodes are found, FNA biopsy should be performed. In the presence of pathologically confirmed lateral neck nodal disease, an ipsilateral therapeutic lateral neck dissection is indicated.
  29. Purpose of RAI therapy?
    • (1) ablation of remnant thyroid tissue to facilitate detection of later disease recurrence by imaging and Tg assay,
    • (2) adjuvant therapy with the intention of targeting occult metastatic disease, and
    • (3) primary treatment of known persistent disease
  30. Preparation before RAI therapy?
    • Several steps must be taken to ensure that the targeted cells have active uptake of the RAI.
    • Making the cells iodine avid by maintaining a low iodine diet for 1 to 2 weeks before RAI administration.
    • Urine iodine may be measured to ensure that the patient is iodine depleted, particularly if there was a recent large iodine exposure such as iodinated contrast agent or amiodarone. 
    • The other consideration is that RAI uptake is stimulated by TSH, and high levels of TSH are needed before administration of RAI. The goal TSH greater than 30 mIU/liter has been generally adopted. This TSH elevation may be achieved either by withdrawal of thyroid hormone or by the administration of exogenous recombinant human thyroid stimulating hormone (rhTSH). If thyroid hormone withdrawal isused, levothyroxine should be held for 3 to 4 weeks before a planned RAI therapy.
    • The advantage of using rhTSH is that hypothyroidism may be avoided completely.
  31. Thyroid-Stimulating Hormone Suppression after thyroidectomy?
    • Because DTCs continue to express the TSH receptor and TSH continues to function as a growth factor for these cancers, suppression of TSH is another element of therapy for DTCs.
    • TSH suppression is accomplished by giving supraphysiologic doses of exogenous thyroid hormone.

    • Target level of TSH - 
    • High-risk DTC - TSH <0.1 mIU/liter.
    • Intermediate-risk lesions - TSH 0.1 - 0.5 mIU/liter
    • Low-risk DTC - TSH 0.5 to 2.0 mIU/liter
  32. Short notes on occult thyroid cancer. [TU 2062]
    DTCs less than 1 cm in diameter are defined as microcarcinomas (Occult carcinoma).
  33. What is Medullary thyroid carcinoma?
    • The malignancy originates in the parafollicular cells, or C cells, which reside in the upper poles of the thyroid lobes and are of neural crest origin.
    • MTC occurs most commonly in a sporadic form (80%); it occurs less commonly as an autosomal dominant inherited disorder such as MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC).
  34. Clinical features of MTC?
    • (1) a palpable mass in the thyroid
    • (2) elevated calcitonin level.

    • Associated with mutations in the RET proto-oncogene.
    • This calcitonin excess is not clinically associated with hypocalcemia but may rarely result in symptoms of diarrhea and flushing in patients with advanced disease.
    • Carcinoembryonic antigen may also be elevated in MTC
  35. Workup of MTC?
    • Serum calcitonin
    • Carcinoembryonic antigen
    • USG of the lateral neck including lateral compartment
    • Genetic testing for germline RET mutation
    • Biochemical evaluation for pheochromocytoma.
  36. Treatment of MTC?
    If patients are found to have a pheochromocytoma, this must be operated on first Operation in a patient with undiagnosed pheochromocytoma may result in hypertensive crisis and death. 

    Total thyroidectomy is the treatment of choice for patients with MTC because of the high incidence of multicentricity, the more aggressive course, and the fact that 131I therapy usually is not effective.

    Central compartment nodes frequently are involved early in the disease process, so that a bilateral prophylactic central neck node dissection should be routinely performed.

    Patients with MTC or a syndromic predisposition to MTC - Total thyroidectomy with prophylactic level VI LN dissection. 

    If MTC is diagnosed postoperatively in a patient undergoing less than total thyroidectomy - completion thyroidectomy and nodal dissection

    • Suppression of serum thyroid-stimulating hormone (TSH) concentrations is not indicated in patients with MTC because C cells are not TSH-responsive.
    • Similarly, adjuvant therapy with radioiodine is not indicated, because the tumor cells do not concentrate iodine.
    • Serum calcitonin and CEA should be measured two to three months after surgery to detect the presence of residual disease.
  37. When will you consider prophylactic thyroidectomy in familial or MEN 2A or MEN 2B associated MTC?
    • If RET proto-oncogene is positive, total thyroidectomy may be considered as early as 5 years of age in family members of MEN 2A and FMTC.
    • In MEN 2B, total thyroidectomy may be considered as early as 1st year of life.

    [@ MEN are to be dangerous - MEN 2B is dangerous, operate early]
  38. MEN I (Wermer's syndrome)
    • o Pituitary,
    • o Parathyroid and
    • o Pancreas.
    • [@0M/3P]

    Image Upload 3
  39. MEN IIa or II (Sipple's disease)
    • o Medullary carcinoma of thyroid 
    • o Pheochromocytoma and
    • o Parathyroid  
    • [@ 1M/2P, Sipple for Second (MEN II)]
    • Image Upload 4
  40. MEN II b or III
    • o Medullary carcinoma of thyroid,
    • o Mucocutaneous neuromas/Marfanoid Habitus and
    • o Pheochromocytoma
    • [@2M/1P]

    Image Upload 5
  41. What is Anaplastic thyroid carcinoma?
    ATC is the most aggressive form of thyroid carcinoma with a disease-specific mortality approaching 100%. A typical manifestation is an older patient with dysphagia, cervical tenderness, and a painful, rapidly enlarging neck mass. Patients frequently have a history of prior or coexistent DTC, and up to 50% have history of goiter. Findings may also include superior vena cava syndrome. The clinical situation  deteriorates rapidly into tracheal obstruction and rapid local invasion of surrounding structures.
  42. Steps of total thyroidectomy?
    • Anesthesia: GA
    • Position of patient: Patient is supine, neck extended (barking dog position)
    • Dressing and draping: painting done from the level of the chin to the upper chest.
    • Incision: 2 cm above the suprasternal
    • notch extending from posterior border of one sternocleidomastoid to the posterior border of opposite sternocleidomastoid, the skin, superficial fascia and platysma are cut.
    • Raising the skin flaps: The upper skin flap, superficial fascia and the platysma is dissected and the upper flap is raised up to the upper border of the thyroid cartilage. The lower flap of skin is raised up to the suprasternal notch. Skin flaps retracted using Jolls retractor. 
    • Incision of deep cervical fascia: The investing layer of the deep cervical fascia is incised in the midline. if the anterior jugular veins come on the way, these may be ligated and divided.
    • The investing layer of the deep cervical fascia along with the strap muscles are lifted up from the thyroid gland to expose the lateral lobes of the gland covered by the pretracheal fascia. The pretracheal fascia is incised and the finger passed around the plane between the pretracheal fascia and the thyroid gland.
    • Division of the middle thyroid vein: Division of middle thyroid vein: This is the first vessel to be tackled in thyroidectomy as it is aslender vessel and is a direct tributary of internal jugular vein. The thyroid lobe is retracted medially and the middle thyroid vein is identified emerging from the middle of the thyroid lobe runing transversely into the internal jugular vein. The thyroid lobe is mobilized medially and the middle thyroid vein is identified passing from the middle of the lateral lobe to the internal jugular vein and ligated.
    • Division of superior thyroid vessels: The muscles are retracted upwards and laterally and the superior pole of lateral lobe of thyroid is exposed. The superior thyroid vessels are dissected close to the upper pole of the lobe. The superior thyroid artery and vein should be ligated separately. Care should be taken to avoid damage to external laryngeal nerve.
    • Division of inferior thyroid artery: The gland is retracted medially and the branches of the inferior thyroid artery are identified entering the lower pole of the thyroid lobe. At this stage the recurrent laryngeal nerve is identified running vertically up along the tracheoesophageal groove. The parathyroid glands are identified and preserved. The individual branches of the inferior thyroid artery are identified and divided in between ligatures.
    • Division of inferior thyroid veins: The inferior thyroid veins emerge from the lower pole of the lateral lobe. These veins are dissected and divided in between ligatures.
    • The dissection on the other side now divides the middle thyroid vein, superior thyroid vessels, inferior thyroid artery branches and the inferior thyroid veins in the same way as done above.
    • Dissection of the thyroid isthmus: The thyroid isthmus is dissected free from the trachea by using a thyroid dissector.
    • Arteria thyroidea ima if present should be dissected,ligated and divided. once these vessels are ligated and divided, thyroid lobes and isthmus are attached to the larynx and trachea by pretracheal fascia and Berry’s ligament.
    • The small vessels from tracheal and esophageal branches are cauterized and divided. The pretracheal fascia and Berry’s ligament is then divided taking care not to injure the recurrent laryngeal nerve.
    • Control of bleeding and placement of drain: All bleeding points are checked and bleedingcontrolled with ligatures or diathermy coagulation. two suction drainage tubes are kept one each at the sites of resected lobe
    • Closure: The investing layer of the deep fascia is apposed with interrupted 3-0 polyglactin sutures.
    • The platysma is apposed with 3-0 polyglactin sutures. The skin is apposed with interrupted monofilament sutures or by subcuticular sutures.
  43. Enumerate the complications of subtotal thyroidectomy performed for primary thyrotoxicosis and how would you treat them? [TU 2056,57] 

    Postoperative complications of thyroidectomy?
    • 1. Haemorrhage - tension haematoma deep to the cervical fascia is usually due to reactionary haemorrhage from one of the thyroid arteries; occasionally, haemorrhage from a thyroid remnant or a thyroid vein. It may require urgent decompression and secure the bleeding vessels.
    • A subcutaneous haematoma or collection of serum may form under the skin flaps and require evacuation in the following 48 hours.

    2. Respiratory obstruction - due to due to laryngeal oedema, tension haematoma.

    3. Recurrent laryngeal nerve paralysis and voice change. Preoperative vocal cord assessment should be done before thyroidectomy. 

    4. Thyroid insufficiency 

    5. Parathyroid insufficiency - If blood supplies to the parathyroid glands are compromised, parathyroid glands appear dusky after 20–30 minutes. Parathyroid glands are removed, cut into fragments and implanted into sternocleidomastoid muscle or on non-dominant forearm muscle.

    6. Thyrotoxic crisis (storm) - acute exacerbation of hyperthyroidism. This requires the administration of intravenous fluids, cooling the patient with ice packs, administration of oxygen, diuretics for cardiac failure, digoxin for uncontrolled atrial fibrillation, sedation and intravenous hydrocortisone. Specific treatment is by propylthiouracil, Lugol’s iodine 10 drops 8-hourly by mouth or sodium iodide 1 g i.v. Propranolol intravenously (1–2 mg) or orally (40 mg 6-hourly) will block alpha-adrenergic effects

    7. Wound infection

    8. Hypertrophic or keloid scar

    9. Stitch granuloma
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36 Thyroid Malignant conditions