neoplasms of the thyroid
TRANSCRIPT
NEOPLASMS OF THE THYROID GLAND
KWADWO ANING ABU
•Benign 1.Adenoma
a.Follicular i.colloid variantii.embryonaliii.fetaliv.Hurthle cell variant
b.Papillary c.Atypical
MalignantPrimary Follicular epithelium –well differentiated Follicular Papillary Hurthle cell Follicular epithelium – undifferentiated Anaplastic Parafollicular cells Medullary Lymphoid cells LymphomaSecondaryMetastaticLocal infiltration
BENIGN NEOPLASM OF THE THYROID• Adenoma of the thyroid originates from the follicular epithelium
(occasionally Hurthle cell) and is predominantly follicular but may be papillary. • Follicular adenoma histologically has an appearance similar to that of
nodular goitre and the cell types are I. colloid variant (microfollicular). II. Hurthle cellIII. and fetal (macro follicular) .
• It presents a solitary swelling which maybe over 10cm in diameter and is encapsulated by compression of adjacent normal thyroid tissue. Occasionally, micro invasion will be seen suggesting a malignant change.• It is important to distinguish the lesion from a malignant neoplasm by
appropriate investigations.• FNAC cannot be used to distinguish between follicular adenoma and
follicular adenocarcinoma because it is difficult to exclude the presence of vascular and/or capsular invasion which are the features of malignancy.
TREATMENT• Hemithyroidectomy of the affected lobe is done.• Total Thyroidectomy is indicated especially for follicular adenoma and
adenomas due to germline or somatic mutation of the TSH receptor gene.
MALIGNANT NEOPLASM OF THE THYROID• Malignant neoplasm of the thyroid is uncommon and with a uniform
world incidence of 40 per million accounts for less than I % of all malignancies.• It is seen from childhood to old age with a peak incidence in the 6th
decade in Europe and America but in the 4th in Africa and Asia most probably because of the lower life expectancy.• It is 3 times more common in females.
AETIOLOGY• Irradiation, The single most important aetiological factor in thyroid
carcinoma, particularly papillary carcinoma, is irradiation of the thyroid under 5 years of age.• TSH; The incidence of follicular carcinoma is high in goiter endemic
areas, possibly as a result of TSH stimulation.(iodine deficient).• Iodine rich areas have a higher incidence of papillary cell carcinomas.• Nearness to volcanoes People living near volcanoes e.g. Hawaii have a
much higher incidence of thyroid cancer.
• Hashimotots thyroiditis; Patients with the disease have a 70-fold increased risk of lymphoma.• Heredity; About 25 % of cases of medullary carcinoma are familial,
genetically determined and associated with multiple endocrine neoplasia (MEN) or familial medullary carcinoma syndrome. The syndromes are inherited as autosomal dominant traits with complete penetrance. • There is also an association between familial intestinal adenomatous
polyposis and papillary carcinoma.
TYPES OF MALIGNANT THYROID NEOPLASIA1.Papillary adenocarcinoma• It is the commonest accounting for 60-70% in Europe and North
America; but most of them, about75 %, are of the mixed papillary and follicular adenocarcinoma. • In Nigeria, only 20% of malignant thyroids are papillary and in India,
40% .
• It accounts for most cases in children and has the highest incidence in the 3rd and 4th decades. It is slow- growing and remains localized for a long time and metastasizes late to the cervical and upper mediastinal lymph nodes . • There is microscopic intraglandular spread to the contralateral lobe in
nearly 90 % of patients and 7% may grow if the lobe is not resected
• There are several variants of PTC• 1. papillary adenocarcarcinoma which is small and may be a sclerotic
encapsulated nodule.• 2.encapsulated variant with a capsule like an adenoma though there is local
invasion.• 3. folicular variant with predominance of follicles over papillae though the
metastases show mainly papillae.• 4.diffuse sclerosing variant seen mainly in children which is infiltrated with
lymphocytes , very aggressive and with poor prognosis.• 5.tall papillary variant, is seen in the eldely and very aggressive with poor
prognosis.
2.Follicular adenocarcinoma
• It accounts for 20% in Europe and North America, 30% in India and for about 60% in Nigeria . • The highest incidence is in the 5th decade. It is slow- growing and usually
osteolytic and vascular, and metastases can concentrate radio-iodine. • The tumour ,seen mainly in women, contains colloid and may appear
encapsulated . Microscopically; it consists of follicles and looks more like thyroid but microscopically, there is invasion of the capsule and of the vascular spaces in the capsular region.
• Multiple foci are seldom seen and lymph node involvement is much less common than in papillary carcinoma. • Blood-borne metastases are more common and the eventual
mortality rate is twice that of papillary cancer.
• Hurthle Cell Carcinoma (HCC)• Most aggressive type of WDTC• About 5% of WDTC• High incidence of bilateral
thyroid lobe involvement• High incidence of recurrence and
high mortality.
3. Medullary thyroid carcinoma
• It is an APUDoma and arises from the parafollicular C-cells which originate from the neural crest and secrete calcitonin.• It may be sporadic (75 %) when
only one lobe is usually affected or as part of the familial syndrome MEN lla, MEN IIb or NON MEN familial MTC (25%) when the tumour is multicentric and both lobes are usually affected.
• It starts as a generalized C-cell hyperplasia followed by the development of tumour. • It is thus multifocal in the thyroid in 80% of cases and may secrete
serotonin and prostaglandin with resulting watery diarrhoea and flushing in about 30% produce, histamine, calcitonin and calcitonin gene-related peptide. • ACTH, somatostatin, bombesin, CEA and VIP may also be produced
usually with no clinical significance. It presents between 50 and 70 but when familial before 30. It spreads usually by lymphatics but also by blood vessels.
4.Undifferentiated (anaplastic) adenocarcinoma
• It accounts for about 5% of thyroid carcinomas. It is hard, rapidly growing and consists of sheets of undifferentiated small or giant cells.• Although it may arise de novo , it
is often associated with a concurrent differentiated thyroid cancer. It is initiated by mutation in the RAS proto-oncogene. • .
5.Lymphoma.• It accounts for 5%. • The risk is increased 70-fold by Hashimoto's thyroiditis which often
leads to hypothyroidism and so to increased TSH production. • Most are of the diffuse histiocytic type but a few are low grade B-cell
lymphoma. • Staging after total body scanning is essential.
6. Fibrosarcoma and squamous cell carcinoma are rare.
Presentation • The tumour may present as• 1. A swelling of the thyroid which may have been present for some years or
is of recent onset, enlarging rapidly and may be aapainful. It may be solitary or multinodular.• 2. Dyspnoea from pressure on the trachea, hoarseness of voice from
infiltration of the recurrent laryngeal nerve or dysphagia from infiltrative pressure of the oesophagus. Rarely, there may be Horner's syndrome from involvement of the cervical sympathetic chain.
• 3. Swellings of the neck from secondary deposits in the cervical lymph nodes without obvious swelling of the thyroid.• 4. Pathological fracture of a long bone or spine or as a pulsating bone
tumour especially in the skull,.• 5. Hyperthyroidism or hypothyroidism.• 6.There may be a family history of thyroid cancer or exposure of the
head and neck to irradiation.
On Examination
• I. The swelling may be a single nodule which is firm and movable within the thyroid, or hard and fixed.• 2. The whole gland may be irregularly enlarged or multinodular, hard
and craggy with or without some fixity to trachea and surrounding tissues.• 3. The cervical nodes maybe enlarged, firm and mobile or hard and
fixed. The cervical nodes may be enlarged without an obvious swelling of the thyroid.
• 4. There may be hoarseness of the voice and laryngoscopy may reveal abductor paralysis of a cord.• 5. Secondary deposits in bone may be present and are warm, soft and
fluctuant often with a bruit.• A thyroid swelling of recent origin in a child, male or the elderly
should be viewed with suspicion. • Associated dysphonia is ominous. An irregular, firm, tender, painful or
fixed goiter with lymph nodes is very suggestive of maligancy.
INVESTIGATIONS• 1.Laryngoscopy. • All patients suspected of thyroid neoplasm must have their larynx
examined to determine or rule out:• (i) Cord paralysis or paresis due to recurrent laryngeal nerve involvement.• (ii) Laryngeal infiltration.• (iii) Laryngeal pathology. Hoarseness in a goitrous patient may be due to
papilloma of the vocal cord.
• 2. Radiology of the neck, thoracic inlet, lungs and bones suspected of deposits. • There may be fine stippled calcification in the tumour suggestive of
psammoma bodies of papillary adenocarcinoma. • Displacement and narrowing of the trachea and, very rarely,
carcinomatous infiltration of the trachea may be detected. Secondary deposits in the lungs and skeleton may also be detected.
3.Scan: The swelling may be 'cold ' . Fifty percent of 'cold ‘ solitary swellings are in fact part of simple multi-nodular goitre, the other nodules being clinically impalpable. Of the remaining 50%, only about 12 % are malignant. However, a 'cold' nodule is a strong indication for urgent surgery as it may be malignant. 2% of well-differentiated tumours take up the isotope. The liver, bones and lungs are also scanned for metastases. Isotope imaging with pentavalent Technetium -99m dimercaptosuccinic acid (99mTc (V) DMSA) or Iodine -131 meta-iodo benzylguanidine (1)1 IMIBG) is used to determine the extent of local disease and monitor recurrence after surgery.
• 4. Fine needle aspiration cytology (FNAC). • It is useful in diagnosing papillary, medullary and anaplastic carcinoma. • There is a small risk of false-negative results. It is difficult to differentiate between
benign and malignant follicular tumours by FNAC.• Results of FNA biopsy may be broadly grouped in several ways, including the following:• (1) malignant, • (2) indeterminate or suspicious, • (3) benign, and • (4) nondiagnostic.• In cases of nondiagnostic cytology, repeat FNA using ultrasound guidance is indicated
and yields diagnostic cytology in 50% to 75% of cases.
• 5. Serum thyroglobulin/calcitonin. The serum thyroglobulin in papillary or follicular cancer and serum calcitonin (basaI or stimulated) in medullary cancer are elevated. They fall after complete removal of the tumour. • Elevation later indicates recurrence. In suspected MTC in MEN II, basal and
pentagastrin-stimulated serum calcitonin are elevated and DNA analysis for mutation of RET on Cr 10 is diagnostic. • The immediate family of the patient is screened for MTC.• 6. In MTC, investigations for MEN should be done. In particular,
phaechromocytoma should be ruled out to avoid a possible crisis during surgery .• 7. In lymphoma, staging is done after total body scanning.
TNM STAGING OF THYROID NEOPLASMS
Primary tumor (T)TX Primary tumor cannot be assessedT0 No evidence of primary tumor is foundT1 Tumor size ≤ 2 cm in greatest dimension and is limited to the thyroid
T1a Tumor ≤ 1 cm, limited to the thyroidT1b Tumor > 1 cm but ≤ 2 cm in greatest dimension, limited to the
thyroidT2 Tumor size > 2 cm but ≤ 4 cm, limited to the thyroid.T3 Tumor size >4 cm, limited to the thyroid or any tumor with minimal
extrathyroidal extension (eg, extension to sternothyroid muscle or perithyroid soft tissues)
T4a Moderately advanced disease; tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve
T4b Very advanced disease; tumor invades prevertebral fascia or encases carotid artery or mediastinal vessel
All anaplastic carcinomas are considered stage IV:T4a Intrathyroidal anaplastic carcinomaT4b Anaplastic carcinoma with gross extrathyroid extension
Regional lymph nodes (N)
Regional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes:
NX Regional 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 (levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (level VII)
Distant metastasis (M)
M0 No distant metastasis is found
M1 Distant metastasis is present
Stage groupingSeparate stage groupings are recommended for papillary or follicular (differentiated), medullary, and anaplastic (undifferentiated) carcinomaPapillary and follicular thyroid cancer (age < 45y):Stage T N MI Any T Any N M0II Any T Any N M1Papillary and follicular; differentiated (age ≥ 45y):Stage T N MI T1 N0 M0II T2 N0 M0III T3 N0 M0IVA T1-3 N1a M0
T4a N1b M0IVB T4b Any N M0IVC Any T Any N M1
Anaplastic carcinoma (all anaplastic carcinomas are considered stage IV):Stage T N MIVA T4a Any N M0IVB T4b Any N M0IVC Any T Any N M1Medullary carcinoma (all age groups):Stage T N MI T1 N0 M0II T2, T3 N0 M0III T1-T3 N1a M0IVA T4a N0 M0
T4a N1a M0T1 N1b M0T2 N1b M0T3 N1b M0T4a N1b M0T4a N0, N1b M0T1-T4a N1b M0
IVB T4b Any N M0IVC Any T Any N M1
TREATMENT• 1, Surgery• For well-differentiated papillary adenocarcinoma, total or near-total
thyroidectomy leaving a rim of thyroid tissue posteriorly in the contralateral lobe to protect the parathyroids is done . Most intra-glandular micrometastases are thereby removed.• Total lobectomy of the affected lobe with isthmusectomy in low-risk
patients (ie young women with well defined 2cm tumour and no extrathyroidal involvement) is also acceptable, however because of intra-glandular micrometastases in the remaining lobe, there may be a local recurrence of 7%. • If lymph nodes are affected, the regional lymph nodes should be cleared
• Follicular carcinoma is treated by total thyroidectomy as it is resistant to external irradiation. • Total thyroidectomy, with resection of the regional lymph nodes, and
radioiodine treatment significantly improve recurrence- free survival in children and should be the primary treatment of differentiated thyroid carcinoma.• Complete resection of localized distant metastasis of differentiated
thyroid carcinoma may be associated with improved survival. • Palliative resection is indicated to improve quality of life for
symptomatic distant metastasis.
• In MTC, total thyroidectomy with dissection of the central, lateral and upper mediastinal lymph nodes (level VII) is performed. Prophylactic surgery is done for positive screened family members. • In affected children, malignancy occurs before age 10 years and
metastases after 14 years. • It is therefore recommended that for MEN II a, prophylactic total
thyroidectomy should be done at 3 years and for MENllb at I year when lymph node clearance is unlikely to be necessary.
• In anaplastic cancer, total thyroidectomy may be tried if seen early. But most are advanced and if the trachea is obstructed, the central part of the tumour is resected to relieve the obstruction. • This is followed by external beam radiation and chemotherapy with
doxorubicin.
• 2, Radiotherapy• Anaplastic rumours and lymphomas are irradiated with external beam
radiation whether surgery has been possible or not. • Inoperable differentiated rumours and lymph node metastases are also
irradiated.• 3, Chemotherapy• In lymphoma , cyclophosphamide, doxorubicin, vincristine and
prednisolone are given after external beam radiation. • In anaplastic carcinoma doxorubicin may be given.
• 4. Radioactive iodine• It is useful as an adjunct to surgery in papillary and follicular tumours and
also for micrometastases. After total thyroidectomy, radio-iodine uptake and scan are done . If there is uptake locally or in any part of the body from metastases, radio-iodine therapy is given. • Scanning is done at 3-monthly intervals and radio-iodine given if there is
uptake.• 5. Inhibition of TSH• As follicular and papillary rumours are TSH dependant, thyroxine O.3g/day
is given to inhibit TSH release and also as a replacement therapy.
Prognosis
• It depends primarily on the pathological type and to some extent on the age and sex of the patient. It is good in those under 40 and in females. • Papillary adenocarcinoma has the best prognosis, 84 %, 63 % and 60%
being alive at 5, 20 and 30years respectively.• With follicular tumour, nearly 60% and 40% are alive at 5 and 30 years
respectively. • Anaplastic carcinoma has a very poor prognosis, most patients being dead
within a year and very few at 3 years. • In medullary carcinoma, 50% of patients are dead by 10 years. In sporadic
MTC, 55 % are alive at 10 years. In MEN lIb 10% survive 10years. In MEN IIA, 90% are alive at 10 years.
• On the whole, prognosis worsens with 1. increasing age (40-60) especially in men,2. increasing size (> 3cm) or grade of the tumour, 3. extrathyroidal involvement and 4. distant metastases.
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