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Thyroid cancer hegazy
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- 3. 1. 52 yowoman in good health; presented with back pain of a musculoskeletal nature. Exam of neck: palpable right sided thyroid nodule approx 2x3 cm; gland otherwise not enlarged and no other nodules or lymphadenopathy. Ultrasound: solid nodule; uptake scan: no excess uptake in nodule TFTs: normal A FNA was performed. DX: Hurthle cell neoplasia
- 4. 2. 64 yowoman with hyperlipidemia; presented for a preventive health exam with no complaints. Neck exam: 4x2 cm right sided thyroid nodule, gland otherwise normal, no lymphadenopathy. Ultrasound-solid nodule, uptake scan no excess uptake in nodule. TFTs A FNA was performed. DX: Hurthle cell neoplasia
- 5. 3. 28 yowoman presented after having a thyroid nodule found incidentally on a carotid ultrasound being performed as a normal control for a study. Exam: 2x2 cm right sided thyroid nodule, gland otherwise normal, no lymphadenopathy. TFTs normal Dedicated ultrasound: solid nodule; FNA performed that day because of availability of pathology support DX: Papillary thyroid carcinoma
- 6. Epidemiology • Thyroid nodules:very common • Clinically detectable thyroid carcinoma: rare: <1% of all cancers • Female to male ratio- 2.5:1 • Median age at dx: 45-50
- 7. • Overall incidenceis rising: • In 1935: 1.3/100,000 women, .2/100,000 men • By 1991: 5.8/100,000 women, 2.5/100,000 men • Incidence has continued to rise in past 10 years: most rapid rate of increase in all tracked cancers
- 8. Reason for rise? •Neck irradiation: used between 1910 and 1960 • Better diagnosis? BUT: only rise is in papillary type; if better diagnosis was reason, would expect rise in all types
- 9. Hegedus, L. NEngl J Med 2004;351:1764-1771 Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule
- 10. Classification 1.Benign -Follicular adenoma. 2. Malignant A-Primary -Follicularepithelium: differentiated .Follicular .Papillary -Follicular epithelium: undifferentiated .Anaplastic -Parafollicular cells .Medullary -Lymphoid cells .lymphoma B-Secondary .Metastatic .Local infiltration
- 11. Benign Tumour • Follicularadenoma : - It is present clinically as solitary nodule. -The differentiation between the follicular carcinoma and adenoma can only made by histological examination ,that in adenoma there is no invasion of the capsule or of pericapsular blood vessels . -Treatment ___ wide excision ( preferably a lobectomy ) .
- 12. Malignant tumours 60 17 13 6 4 0 10 20 30 40 50 60 papillary ca follicularca anaplastic ca medullary ca malignant lymphoma
- 13. Thyroid cancer: epithelialtypes Differentiated: Papillary: 70-75 % of all thyroid cancers Follicular: 15-25% Undifferentiated: Anaplastic: 2-5%
- 14. Thyroid cancer: nonepithelial Medullary thyroid cancer • Sporadic • Familial • MEN-2A and B Others: lymphoma, mets from breast, colon, renal and melanoma
- 15. Clinical characteristics thatsuggest Malignancy 1.Gender ___ male gender(F:M__3:1 ??) 2.Age <15,>60 years 3.Hx of head & neck radiation 4.Family hx of thyroid cancer 5.Rapidly enlarging nodule 6.Hard single nodule & nodules fixed to surrounding structures 7.Hx of thyroiditis 8.Hoarseness 9.Cervical lymphadenopathy
- 16. Isolated swelling inthe upper pole of the right thyroid lobe
- 17. Papillary carcinoma - Slowgrowing ,60% multicentric . - M:F--- 1:3 . - Common 20-30 yrs old. - Painless lump in the thyroid gland with enlarged lymph gland. - 80-90% of postradiation ca of the thyroid. - Spread by lymphatics (50% have +ve node at diagnosis) ,with good prognosis ,the presence of nodes does not affect prognosis. - Type of surgery __Lobectomy with isthmusectomy .
- 18. • If thetumor is >3 cm ,male >40 , female >50 , distant metastasis or angioinvasion then _____ Total thyroidectomy is indicated because of poor prognosis. • 85% 10 yr survival.
- 19. • Occult carcinoma: -Papillary carcinoma may present as an enlarged lymph node in Jugular chain with no palpable abnormality of the thyroid .The primary tumour may be about few millimeter in size & termed occult. -The term occult is now applied to all papillary carcinoma < 1.5 cm - These tumor have an excellent prognosis.
- 20. Papillary thyroid carcinoma Pathogenesis: 1.Activation of tyrosine kinase receptors by rearrangement or gene amplification • Results in a chimeric gene • Occurs either by radiation or sporadic 2. Point mutations in BRAF gene • 10X increased risk of thyroid cancer in relatives of thyroid cancer patients: suggests a genetic link
- 21. PTC Presentation: • Solitary nodulemost common • Pathology: typically unencapsulated; may be cystic Papillae: 1 or 2 layers of tumor surrounding fibrovascular core Follicles and colloid are typically absent
- 22. PTC • Psommoma bodies:scarred remnants of tumor papillae that have infarcted • Present in half of papillary thyroid carcinomas
- 23. Histology of papillarythyroid carcinoma showing typical papillary projections and empty (Orphan Annie-eyed) nuclei
- 24. PTC Growth and behavior:minor to major • Microcarcinoma: occult papillary carcinoma, with tumor <1cm • Found in up to 50% of glands at autopsy (rarer in children) • Incidental finding of no clinical importance
- 25. PTC • Other endof spectrum: aggressive metastasis through interthyroidal lymphatic channels to form multifocal tumors • Involves regional lymph nodes • At diagnosis: clinically detectable nodes more common in children (50%) than adults • 2-10% distant mets at dx: 2/3 pulmonary, 1/4 skeletal; also brain, kidneys, liver, adrenals
- 26. PTC Prognosis • Most patientsdo not die of their disease • 80-95% 10 year survival rates • Patients between 20-45: best long term survival • Patients older than 45 with lymph node recurrences are most likely to die from PTC
- 27. PTC • Prognosis ispoorer in patients with large tumors: one large series showed cancer related mortality of 6%/2-3.9cm, 16%/4- 6.9cm and 50%7 cm and above • Several variants have a worse prognosis: tall cell variant=1% of PTC; more aggressive and invasive
- 28. Magnetic resonance imagingscan of papillary cancer with multiple node metastases.
- 29. Schlumberger, M. J.N Engl J Med 1998;338:297-306 Survival Rate among 1701 Patients with Papillary or Follicular Carcinoma and No Distant Metastases at the Time of Diagnosis
- 30. Follicular carcinoma • Unifocal, more aggressive. • M:F___1:3 • 30_40 yrs old. • Common presentation __ lump in the neck. • If tumor spread beyond the thyroid__ pt may complain of breathlessness , chest pain , pain or swelling in the bone.
- 31. • Capsular &vascular invasion are prominent feature. • Blood-borne metastases. • Metastasis to lung &bone • Total thyroidectomy is indicated . • 40% 10 yr survival.
- 32. Follicular thyroid carcinoma •Characterized by follicular differentiation and encapsulation • Invasion of the capsule and blood vessels is the main determinant between adenomas and carcinoma • 2 main forms: minimally invasive and widely invasive • Multicentricity and lymph node involvement are less frequent than in PTC
- 33. Follicular neoplasm ofthe thyroid presenting as an isolated swelling.
- 34. Histology of follicularthyroid carcinoma showing vascular (red arrow) and capsular (black arrow) invasion
- 35. Metastasis in thehumerus from a carcinoma of the thyroid Metastasis in the left parietal bone from a carcinoma of the thyroid
- 36. Follicular carcinoma ofthe thyroid with skull secondaries
- 37. FTC • Minimally invasiveFTC behaves more like PTC • Widely invasive behaves more like anaplastic thyroid carcinoma • Hurthle Cell variant:more aggressive • FTC is more likely than PTC to be nonresponsive to I 131.
- 38. Anaplastic carcinoma • Veryaggressive tumor. • It is the worst variety of thyroid tumor due its rapid spread. • Local infiltration is an early feature. • The common complaint is a swelling in the neck rather than lump ( because the tumor is diffuse & infiltrating) • A dull aching neck pain is quit common. • Hoarseness or change in voice quality is a diagnostic symptom because it implies infiltration of recurrent laryngeal nerve.
- 39. • Many ofthese aggressive lesion present in an advanced stage with tracheal obstruction &required urgent tracheal decompression. • Spread by lymphatic & blood stream. • Chemotherapy & radiation may improve 5 %. • Mean survival 2-4 months.( poor prognosis)
- 40. Anaplastic thyroid carcinoma •Undifferentiated tumor of thyroid follicular epithelium • Very aggressive, with a disease specific mortality approaching 100% • 2/1,000,000 annual incidence • Typical patient is older than differentiated carcinoma, mean age 65 • <10% under 50 • 60-70% women
- 41. ATC • 20% ofATC: history of differentiated thyroid carcinoma, most papillary • 10% of Hurthle cell carcinoma: has anaplastic tumor within • Up to 1/2 of ATC: history of multinodular goiter
- 42. ATC • Presentation: • Nearlyall present with a thyroid mass • Regional or distant spread is present 90% of the time at dx • Lungs, bones, brain most common mets • Rapidly enlarging tumor; often causes compression symptoms like dyspnea, dysphagia, hoarseness • Constitutional symptoms like fatigue, anorexia, wt loss
- 43. ATC • 50% havepalpable nodes at dx • Dx: made by FNA, then CT neck and mediastinum, CXR • Prognostic factors: tumor size <6 cm=25% 2 yr survival >6cm=3-15% 2 yr survival Others: older age, male sex, dyspnea at presentation • No effective treatment for advanced or metastatic ATC: uniformly fatal, with median survival 3-7 mo
- 44. Treatment of differentiated thyroidcarcinoma • Surgery: goal is to remove all tumor tissue from neck • Total or near total thyroidectomy because of risk of multicentricity • Removal of local nodes in PTC, only palpable nodes in FTC because of lower rate of lymph node involvement
- 45. Treatment • I 131:given post op: destroys any remaining normal thyroid tissue, and may destroy occult microcarcinomas • Increases sensitivity of subsequent 1 131 total body scans • 4-6 wks after surgery a total body scan off thyroid replacement with low dose 1 131; if any uptake, a treatment dose is given (2 mCi vs. 30-100 mCi) • Radiation: only if surgical excision is impossible and tissue doesn’t take up I 131
- 46. Followup Goals of followup: •Maintain adequate thyroxine treatment • Detect persistent or recurrent cancer • Recurrences usually occur early but may occur later so follow up for life
- 47. • Thyroxine treatmentgoals: initial serum thyrotropin level 0.1 or less, serum free T3 normal • Check U/S of thyroid area and nodal areas • Serum thyroglobulin levels: TG produced by follicular cells-should not be detectable after total ablation; presence signifies persistent or recurrent disease • 80% of patients with TG >40 have detectable foci or I 131 uptake
- 48. • I 131scanning: needs to be done after withdrawal of thyroxine tx, with TSH >30 needed • Scanning is done 3 days after I 131 given • Low risk patients with no I 131 uptake after 1 year: TSH maintained at low but detectable level (0.1-0.5)
- 49. • Local orregional mets: occur in 5-20% • Excision/I 131 tx/ Radiation tx if no I 131 uptake • Distant mets: If I 131 uptake, high dose I 131 given + RT
- 50. Complications of treatment: •I 131: nausea, sialadenitis common but mild and short duration • Genetic defects: can’t be given to pregnant women • Increased risk of miscarriage in pregnancies within 1 year of tx • Overall relative risk of a second type of cancer only if high cumulative dose of I 131 and/or radiation
- 51. Medullary carcinoma • Aggressivetumors. • It is a neoplasm of parafollicular ( c ) cell. • C-cell calcitonin producing tumor. • High level of serum calcitonin >0.08 ng/ml • Sporadic form is unifocal with worse prognosis , familial form is multifocal with a better prognosis. • Involvement of lymph node occurs in 50_60%.
- 52. • May occurin combination with adrenal phaeochromocytoma & hyperparathyroidism in syndrome known as multiple endocrine neoplasia type IIa (MEN IIa) -Blood-born metastases are common. -Treatment__ Total thyroidectomy with resection of involved lymph node.
- 53. Medullary thyroid cancer •Much less common than epithelial thyroid cancers • Involves abnormalities of parafollicular C- cells • Most cases are sporadic
- 54. Hyperplasia of parafollicularC cells in a child from a family with medullary cancer Histology of medullary carcinoma showing characteristic ‘cell balls’ and amyloid
- 55. MTC • MEN 2A: autosomal dominant disorder characterized by MTC, pheochromocytoma, and primary parathyroid hyperplasia • MEN 2 B: same inheritance; MTC + pheochromocytoma. Occurs at a younger age; more aggressive. • Familial MTC: like MEN 2 A but no other associated abnormalities
- 56. Total thyroidectomy specimenfrom a young girl undergoing surgery following genetic screening, showing a small medullary cancer in the right lobe.
- 57. MTC • Female tomale ratio=1:1 • MEN 2 A and familiar MTC: peak in index cases in 3rd decade • MEN 2 B: children and teens most common age of presentation. • Basal serum calcitonin: usually correlates with tumor mass and is almost always high with palpable tumor
- 58. MTC • MTC inMEN 2 B: more aggressive • Early onset • Surgery often not curative • Death from MTC: 50% of MEN 2 B, 10 % MEN 2 A
- 59. Lymphoma • Usually affectfemale( may have hx of hashimoto’s) • There is a rapid enlargement. • Compressive symptoms are common. • Sensitive for chemotherapy & radiotherapy • Surgery for diagnosis & compressive symptom • Good prognosis if there is no involvement of cervical LN.
- 60.