THYROID CANCER MANAGAMENT DIFFERENT TYPES AND MANAGAMENT

CA THYROID
ONCOLOGY

1. THYROID CANCER Dr Ema Chacko

2. EPIDEMIOLOGY Thyroid malignancy accounts for only about 2% of human malignancies. F:M ratio -3:1 DTC accounted for about 90% of total thyroid cancer cases with 90% of these being papillary carcinoma.

3. CLASSIFICATION OF THYROID CANCER

4. DIFFERENTIATED (FOLLICULAR-DERIVED) THYROID CARCINOMA(DTC) The two major subgroups constituting DTC are PTC and FC. They are distinguished mainly by cytologic features: in PTC, cytology is diagnostic of malignancy whereas in FC, the diagnosis of malignancy requires evidence of tumor invasion through the tumor (not the thyroid) capsule. It is for this reason that PTC is usually diagnosed by fine needle aspiration but diagnosis of FC usually requires at least biopsy

5. Papillary Thyroid Carcinoma Most common histologic type. The distinguishing features of PTC include nuclear enlargement, hypochromasia , intranuclear cytoplasmic inclusions (nuclear pseudoinclusions ), nuclear grooves, and distinct nucleoli. After formalin fixation, nuclei may appear pale and optically clear & resemble “Orphan Annie eyes.” All PTC stain strongly for Tg . In its classic variant, PTC has a tumor architecture comprising branching papillae with fibrovascular cores.

6. Papillary Thyroid Carcinoma PTC most often occurs in pts 30-50yrs old, mean age at diagnosis is 45yrs. Most primary tumours are 1-4cm in diameter, average is about 2cm to 3 cm in greasest dimension. Primary disease confined to the neck in93% to 99% of the patients with PTC at diagnosis. Distant metatasis are diagnosed in only 1% to 7% of the patients with PTC before or within 30 days of primary treatment.

7. The follicular variant of PTC differs from the classic variant by its follicular growth pattern; however, it retains the nuclear features diagnostic of PTC. The oncocytic variant of PTC has the morphology of oncocytomas elsewhere in the body with abundant pink cytoplasm.

8. Follicular carcinoma Follicular Carcinoma FC, like PTC, is a DTC of follicular cell origin. This malignant thyroid neoplasm lacks the cytologic features of PTC. These carcinomas show evidence of thyroid follicle formation and are usually well circumscribed with a defined tumor capsule.

9. Follicular carcinoma FTC occurs in older patients and the mean age is more than 50yrs, about 10 years older than for typical PTC. In most cases average tumor size in FTC is larger than in PTC . Of patients with FTC, 5-20% may have distant metastases at presentation, and the most common sites being lung and bone.

10. Follicular carcinoma The diagnosis of FC is dependent on the presence of one of two histologic features: (a) tumor invasion through the entire tumor capsule or (b) tumor invasion into a blood vessel located in the tumor capsule or immediately outside the tumor capsule.

11. Hurthle Cell Carcinoma Hurthle cells are large and contain abundant granular eosinophilic cytoplasm. Hurthle cells may be seen in both benign and other non– Hurthle cell malignant neoplastic lesions; At least 75% of the tumor must be composed of Hurthle cells to designate it Hurthle cell carcinoma. Similar to FC, Hurthle cell carcinoma requires the presence of capsular or vascular invasion to classify it as a malignant neoplasm.

12. POORLY DIFFERENTIATED THYROID CARCINOMA(PDTC) Are intermediate between DTC and undifferentiated, or anaplastic , thyroid cancers. Histologic appearance and biologic behavior are more aggressive than those of DTC. Widely invasive, and extend beyond the gland. Insular carcinoma is characterized by tumor cells that are arranged in discrete nests separated by a fibrous stroma . Mitoses and necrosis are often present.

13. UNDIFFERENTIATED THYROID CARCINOMA ANAPLASTIC CARCINOMA Most aggressive form of thyroid carcinoma. Most patients are diagnosed at the age of 65 years or older. ATC originates from the thyroid follicular epithelium but shows little to no evidence of histologic differentiation. This tumor is defined as much by its clinical behavior as its histologic appearance. Most ATCs are widely invasive, and freely infiltrate the perithyroidal tissues.

14. Usually accompanied by bulky metastatic lymphadenopathy and distant metastatic spread. Grossly characterized by widely infiltrative disease with areas of necrosis and hemorrhage. Various microscopic patterns: small cell, spindle cell, giant cell, squamoid cell, and pleomorphic cell. They are hypothesized to be lesions that have dedifferentiated from more benign differentiated follicular neoplasms

15. Medullary Thyroid Carcinoma (MTC) Originate from the parafollicular C cells, which are neural crest–derived cells whose function is to produce calcitonin . Cases are seen sporadically (80%) or in association with familial multiple endocrine neoplasia (MEN IIa , MEN IIb , and pure familial MTC) syndromes. Multifocal and bilateral MTCs are usually seen in patients with MEN, but, otherwise, familial and sporadic MTCs are indistinguishable.

16. MTC Grossly, are well circumscribed and nonencapsulated . Microscopically, tumors can have different appearances- solid growth or nests similar to insular carcinoma. Amyloid , is present in approximately 80% of cases, is a characteristic feature of MTC. Calcitonin stains are usually positive and specific for MTC, but up to 20% of cases may not stain for calcitonin ; therefore, other neuroendocrine markers such as chromogranin may be useful.

17. RADIATION-INDUCED THYROID CANCER Exposure to ionizing radiation is an established risk factor for thyroid nodules and cancer. Well-recognized data come from survivors of atomic bombs in Hiroshima and Nagasaki and the nuclear reactor accident in Chernobyl. Women and young children appeared to be most susceptible. An increased risk of thyroid cancer has also been attributed to exposure to therapeutic radiation in children treated for Hodgkin lymphoma, tinea capitis , enlarged tonsils, and enlarged thymus . Radiation-induced thyroid cancer is pathologically indistinguishable from spontaneous forms of the disease and is not associated with more aggressive biology or poorer prognosis.

18. FAMILIAL MEDULLARY THYROID CARCINOMA 25% of cases of MTCs are hereditary. Inherited in an autosomal -dominant fashion because of a germline point mutation in the RET gene on chromosome 10q11.2. Men and women are affected equally. Present with bilateral and multifocal tumors compared to sporadic forms of MTC. The aggressiveness and age of onset of familial MTC differ depending on the specific genetic mutation. Prophylactic thyroidectomies are increasingly being performed on patients at risk for developing MTC.

19. CLINICAL MANIFESTATIONS OF THYROID CANCER Asymptomatic thyroid nodule found incidentally Locally advanced thyroid cancer presents hoarseness from tumor compression of the recurrent laryngeal nerve Airway compromise Dysphagia or respiratory symptoms, Cervical lymphadenopathy Pain and weight loss resulting from metastatic dissemination.

20. DIAGNOSTIC EVALUATION OF THYROID CANCER Fine needle aspiration cytology Laboratory investigation Imaging studies

21. Fine Needle Aspiration Cytology Most imp. Diagnostic tool. Safe and minimally invasive Ultrasound guidance increase the accuracy Gharib and Goellner (1993) found that 69% of FNAC result benign 4% were malignant 10% were intermediate 17% nondiagnostic Sensitivity 83% Specificity 92% False positive rate was 2.9% and false negative rate 5.2 %

22. Laboratory Studies Serum TSH in addition to basic metabolic, renal, and liver function tests and a complete blood count. Other lab tests, such as Tg , T3 , and T4 Serum calcitonin can be measured during the initial evaluation of patients with MTC and is essential during follow up for these patients.

23. Ultrasound and Ultrasound-Guided Fine Needle Aspirate Neck US with Doppler and US-FNA are the standard diagnostic approaches for evaluating thyroid nodules, both palpable and incidentally detected on imaging

24. US-FNA has several benefits: (a) the technique is minimally invasive and is usually performed as an outpatient procedure; (b) the operator can visually verify that the biopsy needle is in the nodule(s) of suspicion; and (c) it allows for evaluation of nonpalpable nodules and, (d) in the setting of cystic lesions, lowers the rate of inadequate specimens

25. Cervical US is effective in identifying lymph node metastases. Cervical lymph node size, presence of calcification, and irregular diffuse intranodular blood flow are important features suggestive of lymph node metastases.

26. Computed Tomography and Magnetic Resonance Imaging CT and MRI commonly detect otherwise clinically occult thyroid nodules. Malignancy is likely with either imaging technique when there are findings of a mass with extrathyroidal extension, lymph node metastases, or both.

27. A major downside to CT is that useful imaging of the neck requires contrast enhancement, which can interfere with subsequent I-131 therapy. Because of their high concentration of iodine, CT contrast agents can seriously compromise the effectiveness of therapeutic I-131. When patients receiving iodinated contrast agents require I-131, therapy should be delayed in order to achieve adequate efficacy. In selected cases, a noncontrasted CT of the chest may be indicated to evaluate the presence of mediastinal and lung metastases.

28. MRI is superior to CT for establishing the local extent of a known cancer, because it will more clearly show esophageal or tracheal invasion. MRI is indicated in the presence of hoarseness, stridor , dysphagia , or other clinical signs of locally extensive thyroid cancer that cannot be adequately assessed by US

29. Nuclear Medicine Studies The four major nuclear medicine studies related to thyroid cancer evaluation with iodine isotopes are : Radioactive iodine uptake (RAIU) Thyroid scan Diagnostic whole-body scan ( DxWBS ), and Post treatment whole-body scan ( RxWBS ).

30. PROGNOSTIC FACTORS

31. STAGING

32. MANAGEMENT OF THYROID CANCER SURGICAL MANAGEMENT MANAGEMENT RADIOACTIVE IODINE EXTERNAL BEAM RADIOTHERAPY THYROID-STIMULATING HORMONE SUPPRESSION CHEMOTHERAPY AND TARGETED AGENTS

33. SURGICAL MANAGEMENT Surgery is the primary treatment of localized thyroid cancer of all histologies . A total thyroidectomy is the preferred oncologic procedure, but the consensus guidelines describe scenarios where lobectomy is acceptable. Complications- Recurrent laryngeal nerve injury (temporary 30% and permanent 2%) Hypothyroidism (temporary 5% and permanent 0.5% )

34. NECK DISSECTION IN DIFFERENTIATED THYROID CANCER A modified radical neck dissection is done for thyroid cancer when there is a visible or palpably positive node. Elective neck dissection -generally not performed for DTC.

35. Complications from thyroidectomy : Recurrent laryngeal nerve injury (temporary 30% and permanent 2%) Hypoparathyroidism (temporary 5% and permanent 0.5%).

36. MANAGEMENT OF DIFFERENTIATED THYROID CANCER WITH RADIOACTIVE IODINE I-131 is taken up by thyroid tissue, including DTC of follicular epithelial origin, at a rate 6.6 times more than most tissues in the body.

37. Goals of Radioactive Iodine Therapy for Differentiated Thyroid Cancer Two basic purposes of adjuvant I-131 are (a) thyroid remnant ablation and (b) adjuvant therapy for residual microscopic disease

38. I-131 provides potent cytotoxicity by targeting thyroid cancer cells remaining in the operative bed, occult lymph node metastases, and distant metastases. Second, RxWBS provides critical information including staging, prognosis, and determining which patients are likely to require additional treatments. Ablation of the remaining thyroid tissue facilitates the use of serum Tg as a very sensitive and specific marker for disease persistence after primary therapy.

39. Indications and dose of I-131

40. EXTERNAL BEAM RADIOTHERAPY FOR THYROID CANCER

41. THYROID-STIMULATING HORMONE SUPPRESSION FOR DIFFERENTIATED THYROID CANCER Supratherapeutic administration of T4 in an effort to drive the TSH below detectable limits thereby decreasing stimulation of residual benign and malignant follicular derived thyroid cells. There is in vitro evidence that TSH receptor stimulation is sufficient to initiate thyroid tumorigenesis .

42. Major limitation to TSH suppression is the associated toxicity as these patients experience subclinical and even overt thyrotoxicosis . As such, these patients are prone to bone demineralization and cardiac abnormalities, including tachyarrhythmia, conduction abnormalities, increased contractility, ventricular hypertrophy, systolic and diastolic dysfunction, and even cardiac death.

43. CHEMOTHERAPY AND TARGETED AGENTS FOR DIFFERENTIATED THYROID CARCINOMA Chemotherapy or targeted systemic therapy is indicated in: adjuvant treatment or treatment for recurrent or metastatic disease for which surgery, EBRT, or I-131 treatment is not a reasonable option

44. Most of the agents currently under investigation target specific pathways involved in cellular proliferation through inhibition of tyrosine kinase (TKI) receptors and angiogenesis through inhibition of vascular endothelial growth factor receptors (VEGFRs).

45. MANAGEMENT OF MEDULLARY THYROID CARCINOMA All patients with MTC should be tested for RET mutations, including sporadic cases. Genetic screening and testing is also indicated. Initial primary management of localized MTC is total thyroidectomy , which is the only completely effective therapy. Central neck dissection should be performed in all cases, and compartment-oriented lateral neck dissection is indicated when clinically involved. There is no role for adjuvant I-131 therapy. All patients should be followed with serum calcitonin levels as this presents a sensitive and specific marker for extent of residual disease.

46. MTC is uncommon and most of the time it behaves as an indolent disease where long survival with uncontrolled tumor is common. For these reasons, there are few studies on the role of EBRT. Traditional cytotoxic systemic therapies have been ineffective in the management of metastatic or recurrent MTC; however, recent advances in therapies targeting the RET–tyrosine kinase receptors have shown promising preclinical and early clinical results.

47. MANAGEMENT OF ANAPLASTIC THYROID CARCINOMA Complete surgical excision should be the goal of initial therapy, when feasible. Surgery should be avoided when complete excision is not possible as debulking does not improve outcomes. There is no therapeutic role for I-131. The great majority of patients with ATC present with poor performance status and locally advanced disease such that gross total resection is not possible. For this reason, the goal of treatment in most ATC cases is palliation.

48. Patients with a good performance status and no evidence of distant metastases should be offered aggressive treatment with maximum safe resection and EBRT, with or without concurrent chemotherapy. There is no consensus on the EBRT fractionation program, but a recent study of the National Cancer Database showed that survival was better when the EBRT total dose was 60 to 75 Gy as compared to lower doses The most aggressive approach is to combine EBRT with chemotherapy involving a taxane , anthracycline , platin , or a combination.

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