Thyroid neoplasms


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Thyroid neoplasms

  1. 1. Thyroid Neoplasms
  2. 2. Solitary Thyroid Nodule • The majority of thyroid nodules are benign and do not require removal. • Therefore, it is of utmost importance to determine which patients with solitary thyroid nodule would benefit from surgery.
  3. 3. History • Details regarding the nodule, such as – time of onset, change in size, • Associated symptoms, such as – pain, dysphagia, dyspnea, or choking, should be elicited. • Pain is an unusual symptom and when present, should raise suspicion for – intrathyroidal hemorrhage in a benign nodule, thyroiditis, or malignancy. • Patients with medullary thyroid cancer may complain of a dull, aching sensation.
  4. 4. History • A hx of hoarseness is worrisome because it may be secondary to malignant involvement of the recurrent laryngeal nerves. • Most importantly, patients should be questioned regarding risk factors for malignancy, – such as exposure to ionizing radiation and family history of thyroid and other malignancies associated with thyroid cancer. • External Beam Radiation- The risk is maximum 20 to 30 years after exposure
  5. 5. • Family History – is a risk factor for the development of both medullary and nonmedullary thyroid cancer – Familial medullary thyroid cancers occur in isolation or in association with other tumors as part of multiple endocrine neoplasia type 2 (MEN2) syndromes. – Nonmedullary thyroid cancers can occur in association with other known familial cancer syndromes such as • Cowden's syndrome, Werner's (adult progeroid) syndrome, and familial adenomatous polyposis. – Nonmedullary thyroid cancers also can occur independently of these syndromes.
  6. 6. Physical Examination • Thyroid masses move with swallowing and failure to observe the patient swallowing may lead one to miss a large substernal goiter. • The thyroid gland is best palpated from behind the patient and with the neck in mild extension. • The cricoid cartilage is an important landmark – because the isthmus is situated just below it. • Nodules that are hard, gritty, or fixed to surrounding structures, such as to the trachea or strap muscles – more likely to be malignant. • The cervical chain of lymph nodes should be assessed as well as the nodes in the posterior triangle. • One should examine the patient for a Delphian node and pyramidal lobe situated just above the thyroid isthmus and cricoid cartilage.
  7. 7. Diagnostic Tests • Fine-Needle Aspiration Biopsy – single most important test in the evaluation of patients with thyroid masses – can be performed with or without ultrasound guidance. – Ultrasound guidance is recommended for • nodules that are difficult to palpate and • for complex, solid cystic nodules that recur after the initial aspiration. • After FNA biopsy, the majority of nodules can be categorized into the following groups: benign (65%), suspicious (20%), malignant (5%), and nondiagnostic (10%). • The incidence of false-positive results is approximately 1% and false-negative results occur in approximately 3% of patients.
  8. 8. • Nondiagnostic, it should usually be repeated. – Bloody FNA biopsy may also be reported as nondiagnostic and often indicates a follicular neoplasm. • Benign lesions include cysts and colloid nodules. The risk of malignancy in this setting is less than 3%. • Suspicious cytology- The risk of malignancy is 10 to 20%. – Most are follicular or Hürthle cell neoplasms. – Diagnosis of malignancy in this situation relies on demonstrating capsular or vascular invasion, • features that cannot be determined via FNA biopsy.
  9. 9. • FNA biopsy is also less reliable in patients who have a history of head and neck irradiation or a family history of thyroid cancer, – because of a higher likelihood of multifocal lesions. • There is little or no value in repeating an FNA biopsy for a follicular or Hürthle cell lesion, • Repeat FNA biopsy can be useful for patients when the cytology has some abnormalities that suggest a papillary thyroid cancer, but not enough to make this diagnosis.
  10. 10. Laboratory Studies • Serum TSH- Most patients with thyroid nodules are euthyroid. – If a patient with a nodule is found to be hyperthyroid, the risk of malignancy is approximately 1%. • Serum Tg levels cannot differentiate benign from malignant thyroid nodules unless the levels are extremely high, – in which case metastatic thyroid cancer should be suspected. – Useful in following patients who have undergone total thyroidectomy for thyroid cancer – For serial evaluation of patients undergoing nonoperative management of thyroid nodules. • Serum calcitonin levels should be obtained in patients with medullary thyroid cancer or a family history of medullary thyroid cancer (MTC) or MEN2.
  11. 11. Imaging • Ultrasound is helpful for detecting nonpalpable thyroid nodules, – for differentiating solid from cystic nodules, and – for identifying adjacent lymphadenopathy. – It also provides a noninvasive and inexpensive method of following the size of suspected benign nodules diagnosed by FNA biopsy. • CT and MRI are unnecessary in the routine evaluation of thyroid tumors, except for large, fixed, or substernal lesions. • Scanning the thyroid with 123I or 99mTc is rarely necessary, unless evaluating patients for "hot" or autonomous thyroid nodules. – currently recommended in the assessment of thyroid nodules only in patients – who have follicular thyroid nodules on FNA biopsy and a suppressed TSH.
  12. 12. Management • Malignant tumors are treated by thyroidectomy • Simple thyroid cysts resolve with aspiration in approximately 75% of cases, although some require a second or third aspiration. – Unilateral thyroid lobectomy is recommended • If the cyst persists after three attempts at aspiration. • for cysts greater than 4 cm in diameter • for complex cysts with solid and cystic components, because of higher incidence of malignancy (15%). • When FNA biopsy is used in complex nodules, the solid portion should be sampled.
  13. 13. • If a colloid nodule is diagnosed by FNA biopsy, patients should still be observed with serial ultrasound and Tg measurements. – If the nodule enlarges, repeat FNA biopsy is often indicated. – l-thyroxine in doses sufficient to maintain a serum TSH level between 0.1 and 1.0 µU/ mL may also be administered. • Most effective for nodules smaller than 3 cm. – Previous irradiation of the thyroid gland or who has a family history of thyroid cancer• total or near-total thyroidectomy – High incidence of thyroid cancer (40%) – and decreased reliability of FNA biopsy in this setting.
  14. 14. Papillary Carcinoma • 80% of all thyroid malignancies in iodine-sufficient areas • The predominant thyroid cancer in children and individuals exposed to external radiation. • Occurs more often in women, with a 2:1 female: male ratio; • The mean age at presentation is 30 to 40 years. • Most patients are euthyroid and present with a slowgrowing painless mass in the neck. • Dysphagia, dyspnea, and dysphonia are usually associated with locally advanced invasive disease. • Lymph node metastases are common, especially in children and young adults, and may be the presenting complaint.
  15. 15. • The so-called "lateral aberrant thyroid" almost always denotes a cervical lymph node that has been invaded by metastatic cancer. • Suspicion of thyroid cancer often originates through physical examination of the patient and a review of the patient's history. • Diagnosis is established by FNA biopsy of the thyroid mass or lymph node. • Distant metastases are uncommon at initial presentation, but may ultimately develop in up to 20% of patients. • The most common sites are the lungs, followed by bone, liver, and brain.
  16. 16. Pathology • Gross - hard and whitish and remain flat on sectioning with a blade, in contrast to normal tissue or benign nodular lesions that tend to bulge. – Macroscopic calcification, necrosis, or cystic change may be apparent. • Histologically- may exhibit papillary projections, a mixed pattern of papillary and follicular structures, or a pure follicular pattern (follicular variant). • The diagnosis is established by characteristic cellular features. – Cells are cuboidal with pale, abundant cytoplasm, – "grooving," crowded nuclei, and intranuclear cytoplasmic inclusions, leading to the designation of Orphan Annie nuclei, which allows diagnosis by FNA biopsy. – Psammoma bodies, which are microscopic, calcified deposits representing clumps of sloughed cells, may be present.
  17. 17. • Mixed papillary–follicular tumors and follicular variant of papillary carcinoma are classified as papillary carcinomas because they act biologically as papillary carcinomas. • Multifocality - in up to 85% of cases. It is associated with an increased risk of cervical nodal metastases • Rarely invade adjacent structures such as the trachea, esophagus, and recurrent laryngeal nerves. • Other variants of papillary carcinoma (approximately 1% of all papillary carcinomas) include – tall cell, insular, columnar, diffuse sclerosing, clear cell, trabecular, and poorly differentiated types. – They are generally associated with a worse prognosis
  18. 18. Prognostic Indicators • In general, patients with PTC have an excellent prognosis with a greater than 95% 10-year survival rate. • AGES scoring system, which incorporates age, histologic grade, extrathyroidal invasion and metastases, and tumor size to predict the risk of dying from papillary cancer. • The MACIS scale- metastases, age at presentation, completeness of original surgical resection, extrathyroidal invasion, and size of original lesion • AMES system
  19. 19. Papillary or Follicular Tumors Stage Younger than age 45 Years I II Age 45 Years and older I II III IVA IVB IVC Medullary Thyroid Cancer Stage I II III IVA IVB IVC Anaplastic Cancer Stage IVA IVB IVC TNM Any T, Any N, M0 Any T, Any N, M1 T1, N0, M0 T2, N0, M0 T3, N0, M0; T1-3, N1a, M0 T4a, N0-1a, M0; T1-4a, N1b, M0 T4b, Any N, M0 Any T, any N, M1 TNM T1, N0, M0 T2-3, N0, M0 T1-3, N1a, M0 T4a, N0-1a, M0; T1-4a, N1b, M0 T4b, any N, M0 Any T, Any N, M1 TNM T4a, Any N, M0 T4b, Any N, M0 Any T, Any M, M1
  20. 20. Definitions • • • • • • Primary tumor (T) TX = Primary tumor cannot be assessed T0 = No evidence of primary tumor T1 = Tumor ≤2 cm in diameter, limited to thyroid T2 = Tumor >2 cm but <4 cm in diameter, limited to thyroid T3 = Tumor >4 cm in diameter, limited to thyroid, or any tumor with minimal extrathyroidal invasion • T4a = Any size tumor extending beyond capsule to invade subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve, or intrathyroidal anaplastic cancer • T4b = Tumor invading prevertebral fascia, or encasing carotid artery or mediastinal vessels; or extrathyroidal anaplastic cancer
  21. 21. • Regional lymph nodes (N)—include central, lateral cervical, and upper mediastinal nodes • NX = Regional lymph nodes cannot be assessed • N0 = No regional lymph node metastasis • N1 = Regional lymph node metastasis • N1a = Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes) • N1b = Metastases to unilateral, bilateral, or contralateral cervical or superior mediastinal LNs
  22. 22. Surgical Treatment • Total or near-total thyroidectomy
  23. 23. Follicular Carcinoma • Follicular carcinomas account for 10% of thyroid cancers • Occur more commonly in iodine-deficient areas. • The overall incidence of this tumor is, probably as a result of iodine supplementation and improved histologic classification. • female: male ratio of 3:1, • a mean age at presentation of 50 years.
  24. 24. • Usually present as solitary thyroid nodules, – Occasionally with a history of rapid size increase, and long-standing goiter. • Pain is uncommon, unless hemorrhage into the nodule has occurred. • Unlike papillary cancers, cervical lymphadenopathy is uncommon at initial presentation (approximately 5%) • Although distant metastases may be present.
  25. 25. • may be hyperfunctioning in less than 1% of cases, – leading patients to present with signs and symptoms of thyrotoxicosis. • FNA biopsy is unable to distinguish benign follicular lesions from follicular carcinomas. • Therefore, preoperative diagnosis of cancer is difficult unless distant metastases are present. • Large follicular tumors (>4 cm) in older men are more likely to be malignant.
  26. 26. Pathology • Usually solitary lesions, the majority of which are surrounded by a capsule. • Histologically, follicles are present, but the lumen may be devoid of colloid. • Malignancy is defined by the presence of capsular and vascular invasion. • Minimally-invasive tumors – appear grossly encapsulated – but have evidence of microscopic invasion through the tumor capsule and/or – invasion into small- to medium-size vessels (venous caliber) in or immediately outside the capsule, but not within the tumor.
  27. 27. • Widely invasive tumors demonstrate evidence of large-vessel invasion and/or broad areas of tumor invasion through the capsule. – They may, in fact, be unencapsulated. • Tumor infiltration and invasion, as well as tumor thrombus within the middle thyroid or jugular veins, may be apparent at operation.
  28. 28. Surgical Treatment and Prognosis • Patients diagnosed by FNA biopsy as having a follicular lesion should undergo thyroid lobectomy because at least 80% of these patients will have benign adenomas. • Some surgeons recommend total thyroidectomy in older patients with follicular lesions larger than 4 cm because of the higher risk of cancer in this setting (50%). • Intraoperative frozen-section examination – usually is not helpful, – but should be performed • when there is evidence of capsular or vascular invasion, or • when adjacent lymphadenopathy is present. • Total thyroidectomy should be performed when thyroid cancer is diagnosed.
  29. 29. Hürthle Cell Carcinoma • 3% of all thyroid malignancies • Subtype of follicular thyroid cancer. • Like follicular cancers, Hürthle cell cancers are characterized by vascular or capsular invasion, and therefore cannot be diagnosed by FNA biopsy. • Tumors contain sheets of eosinophilic cells packed with mitochondria, which are derived from the oxyphilic cells of the thyroid gland. • differ from follicular carcinomas in that they are more often – multifocal and bilateral (approximately 30%), – usually do not take up RAI (approximately 5%), – are more likely to metastasize to local nodes (25%) and distant sites – are associated with a higher mortality rate (20% at 10 yrs).
  30. 30. • Hence, they are considered to be a separate class of tumors by some surgeons. • Management is similar to that of follicular neoplasms, – with lobectomy and isthmusectomy being sufficient surgical treatment for unilateral Hürthle cell adenomas. • When Hürthle cell neoplasms are found to be invasive on intraoperative, frozen-section, or definitive paraffin-section histology, – then total thyroidectomy should be performed.
  31. 31. • Radioiodine Therapy- benefit to patients with differentiated thyroid cancer • External Beam Radiotherapy and Chemotherapy – External beam radiotherapy is occasionally required to control unresectable, locally invasive or recurrent disease – and to treat metastases in support bones to decrease the risk of fractures. • Single and multidrug chemotherapy has been used with little success in disseminated thyroid cancer. – Adriamycin and Taxol are the most frequently used agents.
  32. 32. Medullary Carcinoma • MTCs account for about 5% of thyroid malignancies • arise from the parafollicular or C cells of the thyroid, which, in turn, are derived from the ultimobranchial bodies. • These cells are concentrated superolaterally in the thyroid lobes, which is where MTC usually develops. • C cells secrete calcitonin, a 32-amino-acid polypeptide that functions to lower serum calcium levels. (regulator of calcium metabolism) • Most MTCs occur sporadically. • However, approximately 25% occur within the spectrum of several inherited syndromes such as familial medullary thyroid cancer, MEN2A, and MEN2B. – All these variants are known to result secondary to germline mutations in the RET proto-oncogene.
  33. 33. • Patients with MTC often present with a neck mass that may be associated with palpable cervical lymphadenopathy (15 to 20%). • Local pain or aching is more common in patients with these tumors, and local invasion may produce symptoms of dysphagia, dyspnea, or dysphonia. • Distant blood-borne metastases to the liver, bone (frequently osteoblastic), and lung occur later in the disease. • The female:male ratio is 1.5:1. • Most patients present between 50 and 60 years of age, although patients with familial disease present at a younger age. • Medullary thyroid tumors secrete – not only calcitonin and carcinoembryonic antigen (CEA), – but also other peptides such as calcitonin gene-related peptide (CGRP), histaminadases, prostaglandins E2 and F2, and serotonin.
  34. 34. Pathology • MTCs are typically unilateral (80%) in patients with sporadic disease, • and multicentric in familial cases, with bilateral tumors occurring in up to 90% of familial patients. • Familial cases are also associated with C-cell hyperplasia, which is considered a premalignant lesion
  35. 35. Diagnosis • The diagnosis of MTC is established – by history, physical examination, – raised serum calcitonin or CEA levels, – FNA cytology of the thyroid mass. • Attention to family history is important • because approximately 25% of patients with MTC have familial disease.
  36. 36. • Total thyroidectomy is the treatment of choice for patients with MTC because of – the high incidence of multicentricity, – the more aggressive course, – 131I therapy is not usually effective. • External beam radiotherapy is controversial, but is recommended for patients with unresectable residual or recurrent tumor. • There is no effective chemotherapy regimen.
  37. 37. Anaplastic Carcinoma • approximately 1% of all thyroid malignancies • Women are more commonly affected, and the majority of tumors present in the seventh and eighth decades of life. • The typical patient has a long-standing neck mass, which rapidly enlarges and may be painful. • Associated symptoms, such as dysphonia, dysphagia, and dyspnea, are common. • The tumor is large and may be fixed to surrounding structures or may be ulcerated
  38. 38. • Lymph nodes usually are palpable at presentation. • Evidence of metastatic spread also may be present. • Diagnosis is confirmed by FNA biopsy revealing characteristic giant and multinucleated cells. • Incisional biopsy is occasionally needed to confirm the diagnosis and isthmusectomy is performed to alleviate tracheal compression.
  39. 39. • Pathology – Gross - firm and whitish in appearance. – Microscopically, sheets of cells with marked heterogeneity are seen. • Treatment and Prognosis – This tumor is one of the most aggressive thyroid malignancies, with few patients surviving 6 months beyond diagnosis. – All forms of treatment have been disappointing.
  40. 40. Lymphoma • A ccount for less than 1% of thyroid malignancies • most are of the non-Hodgkin's B-cell type. • Although the disease can arise as part of a generalized lymphomatous condition, most thyroid lymphomas develop in patients with chronic lymphocytic thyroiditis. • Patients usually present with symptoms similar to those of patients with anaplastic carcinoma, although the rapidly enlarging neck mass often is painless. • Patients may present with acute respiratory distress. • The diagnosis usually is suggested by FNA biopsy, although needle-core or open biopsy may be necessary for definitive diagnosis. • Staging studies should be obtained to assess the extent of extrathyroidal spread.
  41. 41. Treatment and Prognosis • Respond rapidly to chemotherapy (CHOP—cyclophosphamide, doxorubicin, vincristine, and prednisone), which is also associated with improved survival. • Combined treatment with radiotherapy and chemotherapy is often recommended. • Thyroidectomy and nodal resection are used to alleviate symptoms of airway obstruction in patients who do not respond quickly to the above regimens, or in patients who have completed the regimen prior to diagnosis. • Prognosis depends on – the histologic grade of the tumor and – whether the lymphoma is confined to the thyroid gland or is disseminated. • The overall 5-year survival rate is about 50%; – patients with extrathyroidal disease have markedly lower survival rates.
  42. 42. Metastatic Carcinoma • The thyroid gland is a rare site of metastases from other cancers, including kidney, breast, lung, and melanoma. • Clinical examination and a review of the patient's history often suggest the source of the metastatic disease, and FNA biopsy usually provides definitive diagnosis. • Resection of the thyroid, usually lobectomy, may be helpful in many patients, depending on the status of their primary tumor