5. Typical Presentation of
Thyroid Cancer (Clinical Symptoms)
Pain in the neck and sometimes in your ears.
Difficulty swallowing, Difficulty breathing or constant
wheezing. Hoarseness that is not related to a cold, A cough
that continues and is not related to a cold.
Slow growth or no growth over several months
Most thyroid cancers present in clinically euthyroid patients
who have normal thyroid function tests.
These tests, including those measuring thyroid stimulating
hormone (TSH), thyroxine (T4), and triiodothyronine (T3),
8. Types of Thyroid Cancer
• Papillary (80%-85%): develops from thyroid follicle cells in 1 or
both lobes; grows slowly but can spread
• Follicular (5%-10%): common in countries with insufficient
iodine consumption; lymph node metastases are uncommon
• Medullary: develops from C-cells, can spread quickly; sporadic
and familial types
• Anaplastic: develops from existing papillary or follicular
cancers; aggressive, usually fatal
• Lymphoma: develops from lymphocytes; uncommon
9. Follicular Adenoma
• Benign, encapsulated tumor showing
evidence of follicular differentiation
• Common
• Predominantly young to middle women
• Presents as solitary thyroid nodule
• Painless nodular mass, cold on isotopic scan
10. Follicular Adenoma
Solitary, Variably
sized,
encapsulated, well-
circumscribed with
homogenous gray-
white to red-brown
cut-surface
+/- degenerative
changes
12. Toxic Single Adenoma (TSA)
• TSA is a single hyper functioning follicular thyroid
adenoma.
• Benign monoclonal tumor that usually is larger than
2.5 cm
• It is the cause in 5% of patients who are thyrotoxic
• Nuclear Scintigraphy scan shows only a single hot
nodule
• TSH is suppressed by excess of thyroxines
• So the rest of the thyroid gland is suppressed
13. Common Symptoms
• Nervousness
• Anxiety
• Increased perspiration
• Heat intolerance
• Tremor
• Hyperactivity
• Palpitations
• Weight loss despite increased appetite
• Reduction in menstrual flow or oligo-
menorrhea
14. Common Signs
• Hyperactivity, Hyper kinesis
• Sinus tachycardia or atrial arrhythmia, AF, CHF
• Systolic hypertension, wide pulse pressure
• Warm, moist, soft and smooth skin- warm handshake
• Excessive perspiration, palmar erythema, Onycholysis
• Lid lag and stare (sympathetic over activity)
• Fine tremor of out stretched hands – format's sign
• Large muscle weakness, Diarrhea, Gynecomastia
15. Follicular Carcinoma
• Second most common form, 10-20%
• Females > Males, average age ~ 45 - 55 yr
• Rare in children
• Solitary nodule, painless, cold on isotopic scan
• Widely invasive Vs. minimally invasive
• 50% 10 yrs. survival Vs. 90%10 yrs. survival
• Haematogenous route is preferred mode of spread
16. Follicular Carcinoma
• Solitary round or oval
nodule
• Encapsulated by Thick
capsule
• Capsular invasion or
vascular invasion
within our outside
capsular wall
17. • Composed of follicles;
• Well-formed follicles
• Poorly-formed follicles
• Cribiform area or Trabecular
formations
• Mitotic activity & nuclear
atypia
18. Follicular Thyroid Cancer
Usually stays in the thyroid
gland, but can spread to the
bones, lungs, and central
nervous system
Usually does not spread to
the lymph nodes
Follicular Thyroid
Cancer
19. Follicular Thyroid Carcinoma
Follicular Adenoma
• No Capsular invasion
• Compressed normal thyroid usu.
present external to capsule
Follicular Carcinoma
• Capsular invasion present
• May have vascular invasion
20. Follicular Thyroid Cancer
Diagnosis and Prognosis
• Most FTCs present as an asymptomatic neck
mass
• If caught early, this type of thyroid cancer is
often curable
Tumors >3 cm have a much higher mortality rate
21. Papillary Carcinoma
• Commonest thyroid malignancy, 75-85%
• Female: Male = 2.5:1
• Mean age at onset = 20 - 40 yrs.
• May affect children
• Prior head & neck radiation exposure
• Indolent, slow-growing painless mass
• Cervical lymphadenopathy may be presenting
feature
22. Papillary Carcinoma
• Morphological Lesion
• Variable size (microscopic
to several cm)
• Solid or cystic
• Infiltrative or encapsulated
• Solitary or multicentric
(20%)
24. Papillary Thyroid Cancer
Characteristics
Unencapsulated tumor nodule with ill-defined margins
Tumor typically firm and solid
May present as nodal enlargement
Commonly metastasizes to neck and mediastinal lymph
nodes
40% to 60% in adults and 90% in children
<5% of patients have distant metastases at time of
diagnosis
Lung is most common site
27. This illustrative cell group shows cardinal features of papillary
carcinoma: nuclear grooves and pseudoinclusion
28. Lymph node with metastasis of papillary thyroid carcinoma
(middle/bottom of image)
29. Anaplastic Carcinoma
• Rare; < 5% of thyroid carcinomas
• Highly malignant and generally fatal < 1yr.
• Elderly ≈ 65 yrs; females slightly > males
• Rapidly enlarging bulky neck mass
• Dysphagia, dyspnoea, hoarseness
30. Anaplastic Carcinoma
Large, firm, necrotic mass
Frequently replaces entire thyroid gland
Extends into adjacent soft tissue, trachea
and oesophagus
Highly anaplastic cell on histology with:
Giant, spindle,small or mix cell population
Foci of papillary or follicular differentiation
34. Medullary Thyroid Carcinoma
(MTC)
Malignant tumour of thyroid C cells
Middle-aged adults
Female :male = 1.3:1
Unilateral involvement of gland
+/- cervical lymph node metastases
5 % of all thyroid malignancies
• Sporadic (80%)
• Rest in the setting of MEN IIA or B or as familial without
associated MEN syndrome
35. Medullary Thyroid Carcinoma
(MTC)
Germ-line mutation in Ret protooncogene on
chromosome 10q11.2
Associated with MEN IIA
Younger patients in twenties
Multicentric and bilateral
Slow growing
Associated with MEN IIB
Even younger patients in teens
Aggressive with early metastasis
Poor prognosis
36. Medullary Thyroid Cancer
Metastases
• Cervical lymph node metastases occur early
• Tumors >1.5 cm are likely to metastasize, often to
bone, lungs, liver, and the central nervous system
• Metastases usually contain calcitonin and stain for
amyloid
37. Gross:(MTC)
• Solid, firm & non-encapsulated
but well circumscribed
• Continuous fibrous capsule (rare)
• Located in the midportion of upper half of
the gland
38. Medullary carcinoma of the thyroid
(MTC) is a distinct thyroid carcinoma
that originates in the parafollicular C
cells of the thyroid gland.
These C cells produce calcitonin.
MTC has a genetic association with
multiple endocrine neoplasia (MEN)
type 2A an
39. Medullary Thyroid Carcinoma
(MTC)
• Corresponding to a
greater concentration of
C-cells
• Solid, lobular or insular
growth patterns
• Tumour cells round,
polygonal or spindle-
shaped
40. Medullary Thyroid Carcinoma
(MTC)
• Medium sized nucleus
• Highly vascular stroma
• Hyalinized collagen
Coarse calcification
• Amyloid deposits stain
orange-red with Congo
Red stain
• Amyloid deposits in
many cases
42. Hürthle Cell Cancer
• A variant of follicular cancer
that tends to be aggressive
• Represents about 3% to 5%
of all types of thyroid cancer
High power magnification
43. Hürthle Cell Cancer
Prognosis
• May be benign or malignant, based on
demonstration of vascular or capsular
invasion
• Malignancies tend to have a worse
prognosis than other follicular tumors and
rarely respond to therapy
• Tend to be locally invasive
44. Hürthle cell carcinoma expanding right IJV lumen, with adjacent smaller
tumour mass. Note cells with uniform round nuclei and abundant granular
cytoplasm (haematoxylin and eosin × 200).
45. Primary Thyroid Lymphoma
• A rare type of thyroid cancer
Affects fewer than 1 in 2
million people
• Constitutes 5% of thyroid
malignancies
Large Cell Lymphoma of the
Thyroid
• Patients may have a history of diffuse goiter (probably the
result of an autoimmune thyroiditis) that suddenly increases in
size, and often diagnosed because of symptoms of airway
obstruction.
• pain, hoarseness, dysphagia, dyspnea,
46. Primary Thyroid Lymphoma
Characteristics and Diagnosis
• Develops in the setting of pre-existing
lymphocytic thyroiditis
• Often diagnosed because of airway obstruction
symptoms
• Tumors are firm, fleshy, and usually pale
• The tumors usually appear as rapidly enlarging masses
that develop over a period of time ranging from several
days to a few weeks.
47. Gross
Cut surface
Solid white with fish flesh appearance
Microscopic
Mostly diffuse large cell type
Sclerosis (focally prominent)
Immunoblastic lymphoma
Low grade lymphomas
small/intermediate cells
Diffuse / follicular pattern
Packing of follicular lumina of
lymphoma
48. Thyroid Carcinoma
Prognosis
Excellent but following factors play important
role:
Age and sex
Size
Multicentricity
Extra-thyroid extension
Distant metastasis
Total encapsulation, pushing margin of growth
& cystic change
50. Secondary Tumours
• Direct extensions from: larynx, pharynx,
oesophagus etc.
• Metastasis from:
renal cell carcinoma, large intestinal
carcinoma, malignant melanoma, lung
carcinoma, breast carcinoma etc.
51. Treatment of Thyroid Cancer
Summary
• Papillary and follicular thyroid cancer
Generally excellent prognosis
Risk for recurrence for as long as 30 years
• Initial management
Surgery and radioactive iodine
LT4 suppressive therapy
• Follow-up
Physical examination
Radioactive iodine scans
Serum Tg
TSH and T4
52.
53. Q-1-A 39-year-old woman presented with a large solid, firm nodules,
painless swelling in her neck. The enlargement had been a gradual
process over 2 years. She had no other symptoms and felt generally
well. On examination, her thyroid was diffusively enlarged and had a
rubbery consistency. There were no signs of thyrotoxicosis or of thyroid
failure.
Thyroid function tests showed that she was euthyroid; T3 was 1.2nmol/l
(NR 0.8-2.4), T4 was 12nmol/l (NR 9-23) and TSH was 6.3mU/l (NR
0.4-5mU/l). However, her serum contained high titre antibodies to
thyroid peroxidase (1/64000; 4000iu/ml).
A biopsy revealed thyroid tissue within the mediastinal lymph node.
A. What is the most likely diagnosis is?
B. Describe the histological lesion.
C. Mention the most common factor related to the development of
the disease.
Editor's Notes
Typical Presentation of Thyroid Cancer.
1
A mass in the thyroid may be found during a routine examination by a health care provider or may be noted by the patient.1 Often thyroid cancer is present in a nodule for months or years with only minimal growth.2 Thus, lack of consistent nodule size over long periods of time does not rule out the presence of thyroid cancer.3
References
1. Kim N, et al. Otolaryngol Clin North Am. 2003;36:17-33.
2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.
3. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.
Types of Thyroid Cancer.
Thyroid cancer is more common in women than in men, and occurs most frequently in individuals between 35 and 45 years of age. There are several types of thyroid cancer.1 Papillary thyroid cancer (PTC) is the most common form, comprising 80% to 85% of thyroid cancers. Papillary thyroid cancer and follicular thyroid cancer (FTC) arise from thyroid follicle cells. Papillary thyroid cancer is frequently a multifocal and bilateral disease while follicular thyroid cancer tends to present as a single focus within the thyroid gland.2 Papillary cancers grow slowly, but often spread to regional cervical lymph nodes.
Follicular thyroid cancer accounts for approximately 5% to 10% of thyroid cancers.1 It is more common in countries where the population does not have sufficient iodine intake.1 Follicular cancer infrequently spreads to regional cervical nodes, but can spread to the lungs and bones.1
Medullary thyroid cancer (MTC) develops from the C-cells and can spread quickly to the lymph nodes, lungs, or liver before a thyroid nodule is detected.1 Medullary cancer can either be sporadic or can arise as a part of a number of genetic syndromes associated with endocrine abnormalities, including hyperparathyroidism and pheochromocytoma (such as multiple endocrine neoplasia [MEN] 2 syndrome).1
Anaplastic thyroid cancer (ATC) is uncommon, and is believed to develop from existing papillary or follicular carcinomas.1 Anaplastic thyroid cancer is one of the most aggressive and lethal of all solid malignancies. In most series, 3-year survival rates were less than 10%.3
Thyroid lymphoma is a rare disease that usually arises in the setting of pre-existing chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis).2
References
1. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.
2. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
3. Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at: http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.
Follicular Thyroid Cancer.
Follicular thyroid cancer is the second most common type of thyroid cancer, accounting for approximately 15% of all thyroid cancers.1 Its peak incidence is in the fifth decade of life in patients living in the United States and it occurs more frequently in women.1
Follicular thyroid cancer usually presents as a fleshy, solid, encapsulated mass that is sometimes focally fibrotic and calcified.2 These tend to be slow-growing tumors and are usually recognized prior to metastasis as a nodule in the thyroid gland.2
Follicular thyroid cancers with only minimal capsular invasion (minimally invasive FTCs) rarely spread to distant sites and are often cured with surgical resection. However, follicular cancers with widespread capsular invasion and/or vascular invasion are more likely to spread to the skeleton, lungs, brain, and other tissues.2 These neoplasms rarely spread to cervical lymph nodes.3
References
1. Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information – Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
2. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
3. Detailed guide: thyroid cancer. American Cancer Society Web site. Available at: http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?dt=43. Accessed December 10, 2003.
Figure 24-20 Capsular integrity in follicular neoplasms. Evaluating the integrity of the capsule is critical in distinguishing follicular adenomas from follicular carcinomas. In adenomas (A), a fibrous capsule, usually thin but occasionally more prominent, circumferentially surrounds the neoplastic follicles and no capsular invasion is seen (arrowheads); compressed normal thyroid parenchyma is usually present external to the capsule (top of the panel). In contrast, follicular carcinomas demonstrate capsular invasion (B, arrow-heads) that may be minimal, as in this case, or widespread with extension into local structures of the neck. The presence of vascular invasion is another feature of follicular carcinomas.
Follicular Thyroid Cancer. Diagnosis and Prognosis.
Most FTCs present as an asymptomatic neck mass.1 Treatment requires surgically removing as much of the thyroid gland as possible and destroying any remaining thyroid tissue, including the metastases, with radioactive iodine (RAI).2 Follicular thyroid cancer is usually curable, but is less so than papillary cancer, and patients with tumors larger than 3 cm have a higher mortality rate as compared with patients who have smaller tumors.3,4 Of the patients who die from FTC, three fourths do so because of distant metastases while only one fourth die from locally invasive disease.3
References
1. Hebra A, et al. Solitary thyroid nodule. eMedicine Web site. Available at: http://www.emedicine.com/ped/topic2120.htm. Accessed December 10, 2003.
2. Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information – Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
3. DeGroot LJ, et al. J Clin Endocrinol Metab. 1990;71:414-424.
4. Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of Thyroid Disease. Monticello, NY:Marcel Dekker, Inc.; 2001:239-241.
Papillary Thyroid Cancer. Characteristics.
Approximately 80% to 90% of PTC cases are comprised of unencapsulated or partially encapsulated tumor nodules with poorly defined margins.1
Papillary thyroid tumors are typically firm and solid. They may be associated with a loss of differentiation that suggests an aggressive neoplasm in middle-aged or elderly patients.1
The tall cell variant is a more aggressive form of PTC compared with the standard PTC variety.1,2 It comprises approximately 10% of total cases2 and some of the tumors are composed of cells with oncocytic cytoplasm.1
Papillary thyroid cancer may present as a nodal enlargement and usually metastasizes in the neck and mediastinal lymph nodes.2 Fewer than 5% of patients have distant metastases at the time of diagnosis, and metastases most often appear in the lungs.2
References
1. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
2. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.
Medullary Thyroid Cancer. Metastases.
In MTC, cervical lymph node metastases occur early and tumors larger than 1.5 cm are likely to metastasize and spread.1,2 Medullary thyroid cancer can also spread to the skeleton, lungs, liver, and the central nervous system.1
The metastases that occur with MTC usually contain calcitonin, which is found in the C-cell, or carcinoembryonic antigen (CEA).3 Both calcitonin and CEA are released into the blood and can be detected with a blood test.3
References
1. Types of thyroid cancer. Virginia Masen Medical Center Web site. Available at: http://www.vmmc.org/dbCancer/sec180604.htm. Accessed December 10, 2003.
2. Thyroid gland disorders. Beers MH, Fletcher AJ, Jones TV, et al, eds. Merck Manual of Medical Information – Home Edition. 2nd ed. Whitehouse Station, NJ: Merck & Co., Inc.; 2003.
3. Thyroid Cancer Detailed Guide. American Cancer Society Web site. Available at: http://documents.cancer.org/196.00/196.00.pdf. Accessed December 10, 2003.
amyloid, visible here as homogeneous extracellular material, derived from calcitonin molecules secreted by the neoplastic cells
Hürthle Cell Cancer.
Hürthle cell cancer is a rare type of thyroid cancer that accounts for 3% to 10% of all thyroid cancers.1 It is an aggressive cancer that tends to poorly concentrate RAI.1,2
Scattered benign Hürthle cells are frequently seen in chronic lymphocytic thyroiditis, multinodular goiter, and subacute thyroiditis.1 However, Hürthle cell neoplasms are hypercellular nodules, with a predominance of Hürthle cells (greater than 75%), few or no lymphocytes, and scanty or absent colloid.1 The presence of an invasion of blood vessels or of the tumor capsule differentiates a malignant Hürthle carcinoma from a benign Hürthle cell adenoma.1
References
1. Aytug S, et al. Hürthle cell carcinoma. eMedicine Web site. Available at: http://www.emedicine.com/med/topic1045.htm. Accessed December 10, 2003.
2. Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of Thyroid Disease. Monticello, NY:Marcel Dekker, Inc.; 2001:239-241.
Hürthle Cell Cancer. Prognosis.
Hürthle cell carcinomas can metastasize to regional lymph nodes as well as spread hematogenously.1 In addition, they are invasive and the capsule and blood vessels should be assessed for invasion.1,2
Patients with malignant Hürthle cell carcinomas have a decreased survival prognosis compared with patients who have other follicular tumors.2 Hürthle cell carcinomas rarely respond to RAI therapy, so the discovery of a Hürthle cell cytology should lead to surgical resection of the lesion; however, there is a strong likelihood of recurrence following surgery.1,2
Caplan et al3 found that 4.4% of Hürthle cell cancers were hot on scan and 8.9% were warm.
References
1. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
2. Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri, EL, Samaan N, eds. Endocrine Tumors. Cambridge, MA: Blackwell; 1993:278-333.
3. Caplan RH, et al. Thyroid. 1994;4:243-248.
Primary Thyroid Lymphoma.
Primary thyroid lymphoma (PTL) is a rare form of thyroid cancer that usually arises in the setting of chronic lymphocytic thyroiditis. The tumors usually appear as rapidly enlarging masses that develop over a period of time ranging from several days to a few weeks.1
Primary thyroid lymphoma affects fewer than 1 in 2 million people, constitutes approximately 5% of thyroid cancers, and is 2 to 3 times more common in women than in men.2
References
1. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
2. Cabanillas F. Thyroid lymphoma. eMedicine Web site. Available at: http://www.emedicine.com/med/topic2271.htm. Accessed December 10, 2003.
Primary Thyroid Lymphoma. Characteristics and Diagnosis.
Patients may have a history of diffuse goiter (probably the result of an autoimmune thyroiditis) that suddenly increases in size,1 and PTL is often diagnosed because of symptoms of airway obstruction.1
Examination reveals PTL tumors to be firm, fleshy tissues that are usually pale,2 and many patients who have PTL present with pain, hoarseness, dysphagia, dyspnea, or stridor. In rare cases, patients have superior vena cava syndrome.1
The mainstay of treatment for PTL is chemotherapy.3 Thyroidectomy is rarely indicated for thyroid lymphoma.3
References
1. Thyroid Disease Manager Web site. Available at: http://www.thyroidmanager.org. Accessed December 10, 2003.
2. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.
3. Ansell SM, et al. Semin Oncol. 1999;26:316-323.
Treatment of Thyroid Cancer. Summary.
In summary, PTC and FTC generally have a good prognosis with 20-year disease-specific mortality rates of less than 2% to 3%, even if cervical lymph node metastases are present at the initial diagnosis. Despite this low mortality rate, clinically significant recurrences can develop 30 years after initial therapy, making lifelong surveillance for recurrent disease mandatory.
Initial management usually begins with surgical removal of the thyroid gland and RAI ablation in all but the most low-risk thyroid cancer patients. Patients are then placed on LT4 therapy, which is carefully titrated to achieve a TSH level that is detectable but below the normal reference range.
Long-term follow-up requires an annual physical examination to detect recurrent thyroid cancer in the neck, measurement of the serum Tg level to detect recurrent thyroid cancer anywhere in the body, and TSH and thyroid hormone level measurements to adjust LT4 suppressive therapy.
Depending on the individual estimate of the risk of recurrence or persistent disease, RAI scanning and stimulated serum Tg level measurements may also be a necessary part of long-term follow-up.
