thyroid cancer. thyroid cancer type and incidence papillary ~ 60-75% follicular ~20-30% medullary...

THYROID CANCERTHYROID CANCER

Thyroid Cancer Type and Thyroid Cancer Type and IncidenceIncidence

Papillary ~ 60-75% Papillary ~ 60-75% Follicular ~20-30%Follicular ~20-30% Medullary ~ 5-10%Medullary ~ 5-10%

Anaplastic ~ 3%Anaplastic ~ 3%

KEY POINTSKEY POINTS

Thyroid cancer is the most common Thyroid cancer is the most common

malignancy of the endocrine glands.malignancy of the endocrine glands.

The great majority of cancers of the The great majority of cancers of the

follicular thyroid epithelium are well-follicular thyroid epithelium are well-

differentiated differentiated (papillary and (papillary and

follicular)follicular) and have a good and have a good

prognosis, particularly in young prognosis, particularly in young

patients.patients.

KEY POINTSKEY POINTS

Thyroid Ca is one of the most Thyroid Ca is one of the most

curable cancers.curable cancers.

The incidence of thyroid Ca in The incidence of thyroid Ca in

thyroid nodules ranges from thyroid nodules ranges from

0.5% to 10%.0.5% to 10%.

ETIOPATHOGENESISETIOPATHOGENESIS ONCOGENES:ONCOGENES:

– gene rearrangements RET/PTC gene rearrangements RET/PTC (papillary Ca)(papillary Ca)

– mutations of the ras gene family mutations of the ras gene family (an early event in thyroid (an early event in thyroid

tumorigenesis)tumorigenesis)

– inactivating mutations of the p53 inactivating mutations of the p53 tumor-suppressor gene tumor-suppressor gene

(undiffereniated thyroid Ca)(undiffereniated thyroid Ca)

ETIOPATHOGENESISETIOPATHOGENESIS

External irradiation of the neck External irradiation of the neck

(the latency period is at least 5 (the latency period is at least 5

years)years)

Iodine deficiency (Iodine deficiency (Follicular CaFollicular Ca))

PAPILLARY CANCERPAPILLARY CANCER

The Most Common Thyroid The Most Common Thyroid

CancerCancer Peak onset ages 30 through 50Peak onset ages 30 through 50

Females more common than males by 3 Females more common than males by 3 to 1 ratioto 1 ratio

Prognosis directly related to tumor size Prognosis directly related to tumor size [less than 1.0 cm - good prognosis[less than 1.0 cm - good prognosis]]

Accounts for 85% of thyroid cancers Accounts for 85% of thyroid cancers due to radiation exposuredue to radiation exposure

PAPILLARY CANCERPAPILLARY CANCER

Spread to lymph nodes of the neck Spread to lymph nodes of the neck

present in more than 50% of casespresent in more than 50% of cases

Distant spread Distant spread (to lungs or bones)(to lungs or bones)

is very uncommonis very uncommon

Overall cure rate very high Overall cure rate very high

(near 100% for small lesions in (near 100% for small lesions in

young patients)young patients)

MANAGEMENT OF MANAGEMENT OF PAPILLARY THYROID PAPILLARY THYROID

CANCERCANCERPapillary carcinomas that are Papillary carcinomas that are

well circumscribed, isolated, and well circumscribed, isolated, and

less than 1cm in a young patient less than 1cm in a young patient

(20-40) without a history of (20-40) without a history of

radiation exposure may be radiation exposure may be

treated with hemithyroidectomy treated with hemithyroidectomy

and isthmusthectomy. and isthmusthectomy.


CANCERCANCERAll others should be treated All others should be treated

with total thyroidectomy and with total thyroidectomy and

removal of any enlarged removal of any enlarged

lymph nodes in the central or lymph nodes in the central or

lateral neck areas.lateral neck areas.


CANCER AFTER SURGERYCANCER AFTER SURGERY

Since papillary cancer may Since papillary cancer may

respond to respond to TSHTSH, thyroid , thyroid

hormone is hormone is givengiven in doses in doses

large enough to suppress large enough to suppress

secretion of secretion of TSHTSH and help and help

prevent a recurrence.prevent a recurrence.



Serum FTSerum FT33 i FT i FT44 should be in the should be in the

normal range to avoid iatrogenic normal range to avoid iatrogenic thyrotoxicosisthyrotoxicosis

Serum Tg, a marker of cell Serum Tg, a marker of cell function, increases dramatically function, increases dramatically during hypothyroidism, while it during hypothyroidism, while it

returns to low levels during returns to low levels during hormone therapyhormone therapy



Papillary cancer cells absorb Papillary cancer cells absorb

iodine and therefore they iodine and therefore they

can be targeted for death can be targeted for death

by giving the toxic isotope by giving the toxic isotope

(I-131).(I-131).


CANCER AFTER SURGERYCANCER AFTER SURGERY In patients with larger tumors, In patients with larger tumors,

spread to lymph nodes or other spread to lymph nodes or other areas, tumors which appear areas, tumors which appear aggressive microscopically, aggressive microscopically,

radioactive iodine is often given in radioactive iodine is often given in expectation that any remaining expectation that any remaining thyroid tissue or cancer that has thyroid tissue or cancer that has spread away from the thyroid will spread away from the thyroid will

take it up and be destroyed.take it up and be destroyed.

PAPILLARY THYROID PAPILLARY THYROID CANCER LONG-TERM CANCER LONG-TERM

FOLLOW UPFOLLOW UP A yearly chest X-ray A yearly chest X-ray Thyroglobulin levelsThyroglobulin levels

a high serum thyroglobulin level that a high serum thyroglobulin level that had previously been low following total had previously been low following total thyroidectomy especially if gradually thyroidectomy especially if gradually

increased with TSH stimulation is increased with TSH stimulation is virtually indicative of recurrence. virtually indicative of recurrence.

A value of greater than 10 ng/ml is often A value of greater than 10 ng/ml is often associated with recurrence even if an associated with recurrence even if an

iodine scan is negative.iodine scan is negative.

FOLLICULAR CANCERFOLLICULAR CANCER

THE SECOND MOST COMMON THYROID THE SECOND MOST COMMON THYROID CANCERCANCER

Peak onset ages 40 through 60Peak onset ages 40 through 60 Females more common than males by 3 Females more common than males by 3

to 1 ratioto 1 ratio Prognosis directly related to tumor size Prognosis directly related to tumor size

[less than 1.0 cm - good prognosis][less than 1.0 cm - good prognosis] Rarely associated with radiation Rarely associated with radiation

exposureexposure Spread to lymph nodes is uncommon Spread to lymph nodes is uncommon

(~10%)(~10%)

FOLLICULAR CANCERFOLLICULAR CANCER

Invasion into vascular structures Invasion into vascular structures (veins and arteries)(veins and arteries) within the within the

thyroid gland is common.thyroid gland is common. Distant spread Distant spread (to lungs or bones)(to lungs or bones) is is

uncommon, but more common than uncommon, but more common than with papillary cancer.with papillary cancer.

Overall cure rate highOverall cure rate high (near 95% for (near 95% for small lesions in young patients),small lesions in young patients), decreases with advanced age.decreases with advanced age.

FOLLICULAR THYROID FOLLICULAR THYROID CANCERCANCER

Many cases of follicular thyroid cancer Many cases of follicular thyroid cancer are subclinical.are subclinical.

Most common presentation of thyroid Most common presentation of thyroid cancer is an asymptomatic thyroid mass, cancer is an asymptomatic thyroid mass, or a nodule, that can be felt in the neck.or a nodule, that can be felt in the neck.

Some patients have persistent cough, Some patients have persistent cough, difficulty breathing, or difficulty difficulty breathing, or difficulty

swallowing.swallowing. Pain seldom is an early warning sign of Pain seldom is an early warning sign of

thyroid cancer.thyroid cancer.


Other symptoms Other symptoms (rare):(rare): pain, pain,

stridor, stridor, vocal cord paralysis, vocal cord paralysis,

hemoptysis, hemoptysis, rapid enlargement.rapid enlargement.

These symptoms can be caused by These symptoms can be caused by

less serious problems.less serious problems.


At diagnosis, 10-15% of At diagnosis, 10-15% of

patients have distant patients have distant

metastases to bone and lung metastases to bone and lung

and initially are evaluated for and initially are evaluated for

pulmonary or osteoarticular pulmonary or osteoarticular

symptoms symptoms (eg, pathologic (eg, pathologic

fracture, spontaneous fracture).fracture, spontaneous fracture).

MANAGEMENT OF MANAGEMENT OF FOLLICULAR THYROID FOLLICULAR THYROID

CANCERCANCER Follicular carcinoma should always Follicular carcinoma should always

be treated with total be treated with total thyreoidectomy.thyreoidectomy.

A completion thyreoidectomy A completion thyreoidectomy should always be performed in should always be performed in patients who have undergone a patients who have undergone a

lobectomy for a presumed benign lobectomy for a presumed benign tumor that proved to be follicular tumor that proved to be follicular carcinoma at definitive histology.carcinoma at definitive histology.

MANAGEMENT OF FOLLICULAR MANAGEMENT OF FOLLICULAR THYROID CANCER AFTER THYROID CANCER AFTER

SURGERYSURGERY

Perform Perform postoperative postoperative scintiscanscintiscan of the neck after 4-6 of the neck after 4-6

weeks. weeks.

If thyroid tissue is present, a If thyroid tissue is present, a dose of radioactive iodine is dose of radioactive iodine is

administrated to destroy administrated to destroy residual tissue. residual tissue.


SURGERYSURGERY

Repeat scintiscan 6-12 Repeat scintiscan 6-12 months after ablation and, months after ablation and, thereafter, every 2 years. thereafter, every 2 years. Radioactive iodineRadioactive iodine may may

ablate the metastatic tissue ablate the metastatic tissue in the lungs and bone.in the lungs and bone.


SURGERYSURGERY

Perform Perform thyroid hormone thyroid hormone

suppressionsuppression in all patients in all patients

with total thyroidectomies with total thyroidectomies

and in all patients who have and in all patients who have

had radioactive ablation of had radioactive ablation of

any remaining thyroid tissue. any remaining thyroid tissue.


SURGERYSURGERY A patient who has had a A patient who has had a

thyroidectomy without parathyroid thyroidectomy without parathyroid

preservation will require preservation will require vitamin D vitamin D

and calciumand calcium for the rest of their for the rest of their

life.life.

Evaluate Evaluate thyroglobulin serum thyroglobulin serum

levelslevels every 6-12 months for at every 6-12 months for at

least 5 years. least 5 years.

FOLLICULAR ADENOMAFOLLICULAR ADENOMA

It is benign neoplasm.It is benign neoplasm.No differentiation is possible No differentiation is possible

between adenoma and carcinoma between adenoma and carcinoma by cytology or in most cases even by cytology or in most cases even

by frozen section.by frozen section.Capsular and vascular invasion Capsular and vascular invasion are key features that distinguish are key features that distinguish between benign and malignant between benign and malignant

follicular proliferation.follicular proliferation.

HÜRTHLE CELL HÜRTHLE CELL CARCINOMACARCINOMA

WHO 1988:WHO 1988: oxyphilic variant oxyphilic variant

of follicular carcinoma.of follicular carcinoma.

It may be also Hürthle cell It may be also Hürthle cell

variant of papillary thyroid Ca. variant of papillary thyroid Ca.

Some authors classify it Some authors classify it

separately as Hürthle cell separately as Hürthle cell

carcinomas.carcinomas.

HÜRTHLE CELL HÜRTHLE CELL CARCINOMACARCINOMA

Although preferentially classified Although preferentially classified among follicular tumors, Hüthle among follicular tumors, Hüthle cell carcinomas are usually more cell carcinomas are usually more

aggresive and metastasizing, aggresive and metastasizing, and they are less prone to take and they are less prone to take

up radioiodine and produce up radioiodine and produce thyroglobulin than well-thyroglobulin than well-differentiated thyroid differentiated thyroid

carcinomas.carcinomas.

ANAPLASTIC CANCER ANAPLASTIC CANCER

Peak onset age 65 and older.Peak onset age 65 and older.Very rare in young patients.Very rare in young patients.

Males more common than Males more common than females by 2 to 1 ratio.females by 2 to 1 ratio.

Can occur many years after Can occur many years after radiation exposure.radiation exposure.

Typically presents as rapidly Typically presents as rapidly growing neck mass.growing neck mass.

ANAPLASTIC CANCERANAPLASTIC CANCER Spread to lymph nodes of the neck Spread to lymph nodes of the neck

present in more than 90% of cases.present in more than 90% of cases. Distant spread Distant spread (to lungs or bones)(to lungs or bones)

is very common even when first is very common even when first diagnosed.diagnosed.

Overall 5-year survival rate is Overall 5-year survival rate is reportedly less than 10%, and reportedly less than 10%, and

most patients do not live longer most patients do not live longer than a few months after diagnosis.than a few months after diagnosis.

ANAPLASTIC CANCER ANAPLASTIC CANCER SYMPTOMSSYMPTOMS

A rapidly growing neck mass A rapidly growing neck mass DysphagiaDysphagia

CoughCoughNeck painNeck painDyspnea Dyspnea

Patients with metastases also may Patients with metastases also may note bone pain, weakness, and coughnote bone pain, weakness, and cough

Neurologic deficits may be observed Neurologic deficits may be observed with brain metastases.with brain metastases.

ANAPLASTIC CANCER ANAPLASTIC CANCER SURGICAL CARESURGICAL CARE

Perform surgery in Perform surgery in

conjunction with radiation conjunction with radiation

and chemotherapy.and chemotherapy.

Use surgery to obtain a Use surgery to obtain a

definitive diagnosis when fine definitive diagnosis when fine

needle aspiration is needle aspiration is

unsuccessful.unsuccessful.

ANAPLASTIC CANCERANAPLASTIC CANCER

Despite the typically large Despite the typically large

size of these tumors, size of these tumors,

extent of resection is extent of resection is

limited when diagnosis is limited when diagnosis is

made.made.


Rather than performing complete Rather than performing complete

thyroidectomy, resect as much thyroidectomy, resect as much

thyroid tissue as possible without thyroid tissue as possible without

attempting resection of all attempting resection of all

adjacent structures because of adjacent structures because of

the high incidence of the high incidence of

postoperative morbidity postoperative morbidity (eg, (eg,

vocal cord paralysis, esophageal vocal cord paralysis, esophageal

fistula).fistula).

ANAPLASTIC CANCERANAPLASTIC CANCERFURTHER INPATIENT CAREFURTHER INPATIENT CARE

Radiotherapy:Radiotherapy:

Despite the fact that ATC is Despite the fact that ATC is

largely radioresistant, use largely radioresistant, use

external beam radiotherapy external beam radiotherapy

for local control.for local control.


Chemotherapy:Chemotherapy: Currently, no available Currently, no available

chemotherapeutic agent or combination chemotherapeutic agent or combination of chemotherapeutic agents shows of chemotherapeutic agents shows sufficient antineoplastic activity to sufficient antineoplastic activity to

prevent death; prevent death;

yet in rare instances, chemotherapy may yet in rare instances, chemotherapy may prolong life by a few weeks or perhaps prolong life by a few weeks or perhaps

months. months.

DoxorubicinDoxorubicin and and cisplatincisplatin are the two most are the two most common agents used.common agents used.

MEDULLARY THYROID MEDULLARY THYROID CANCER CANCER

A distinct thyroid carcinoma A distinct thyroid carcinoma that originates in the that originates in the

parafollicular C cellsparafollicular C cells of the of the thyroid gland. thyroid gland.

These C cells produce calcitonin.These C cells produce calcitonin.Females more common than Females more common than

males males

(except for inherited cancers).(except for inherited cancers).

MEDULLARY THYROID MEDULLARY THYROID CANCER CANCER

Regional metastases Regional metastases (spread (spread to neck lymph nodes)to neck lymph nodes) occurs occurs

earlyearly in the course of the in the course of the disease.disease.

Spread to distant organs Spread to distant organs (metastasis)(metastasis) occurs lateoccurs late and and

can be to the can be to the liver, bone, liver, bone, brain, and adrenal medullabrain, and adrenal medulla..

MEDULLARY THYROID MEDULLARY THYROID CANCERCANCER

Not associated with radiation Not associated with radiation

exposure.exposure.

Usually originates in the Usually originates in the

upper central lobe of the upper central lobe of the

thyroid.thyroid.


Poor prognostic factorsPoor prognostic factors include age >50, male, distant include age >50, male, distant spread spread (metastases),(metastases), and and MEN MEN

II-B.II-B.Residual disease Residual disease (following (following surgery)surgery) or recurrence can be or recurrence can be

detected by measuring detected by measuring calcitonin.calcitonin.


FOUR CLINICAL SETTINGSFOUR CLINICAL SETTINGS

SPORADICSPORADIC Accounts for 80% of all cases of Accounts for 80% of all cases of

medullary thyroid cancermedullary thyroid cancer

MEN II-A MEN II-A (SIPPLE SYNDROME)(SIPPLE SYNDROME) bilateral medullary carcinoma or bilateral medullary carcinoma or

C cell hyperplasia, C cell hyperplasia, pheochromocytomapheochromocytoma

hyperparathyroidism hyperparathyroidism

MEN II-BMEN II-B medullary carcinomamedullary carcinoma pheochromocytomapheochromocytoma

an unusual appearance which is an unusual appearance which is characterized by mucosal characterized by mucosal

ganglioneuromas ganglioneuromas (tumors in the (tumors in the mouth)mouth) and a Marfanoid habitus. and a Marfanoid habitus.

hyperparathyroidism hyperparathyroidism (uncommon)(uncommon) INHERITED MEDULLARY CARCINOMA INHERITED MEDULLARY CARCINOMA

WITHOUT ASSOCIATED WITHOUT ASSOCIATED ENDOCRINOPATHIES.ENDOCRINOPATHIES.

MEDULLARY THYROID CANCER MEDULLARY THYROID CANCER

FOUR CLINICAL SETTINGSFOUR CLINICAL SETTINGS

Endocrine diseases occuring Endocrine diseases occuring together in different endocrine together in different endocrine

glands are due to multiple, mostly glands are due to multiple, mostly hereditary benign and malignant hereditary benign and malignant neoplasms or hyperplasia with neoplasms or hyperplasia with

excessive function excessive function (MEN=MEA),(MEN=MEA), or develop in response to an or develop in response to an

autoimmune reaction affecting autoimmune reaction affecting different endocrine and perhaps different endocrine and perhaps

other glands other glands (autoimmune polyglandular (autoimmune polyglandular

syndromes =APS)syndromes =APS)

AUTOIMMUNE POLYGLANDULAR AUTOIMMUNE POLYGLANDULAR SYNDROMESSYNDROMES

TYPE 1 = Blizzard’s TYPE 1 = Blizzard’s syndromesyndrome

Major components:Major components: Chronic Chronic

mucocutaneous mucocutaneous candidiasiscandidiasis

HypoparathyroidisHypoparathyroidismm

Addison’s diseaseAddison’s disease

+ other + other endocrinopathies endocrinopathies

and featuresand features

TYPE 2 = Schmidt’s TYPE 2 = Schmidt’s syndromesyndrome

Major components:Major components: Autoimmune thyroid Autoimmune thyroid

disease disease Type 1 diabetes Type 1 diabetes

melltusmelltus Addison’s diseaseAddison’s disease Premature ovarian Premature ovarian

failure failure

+ other endocrinopathies + other endocrinopathies and featuresand features


SYMPTOMSSYMPTOMS

a lump at the base of the a lump at the base of the

neck, especially during neck, especially during

swallowing;swallowing;

hoarseness, dysphagia, and hoarseness, dysphagia, and

respiratory difficulty;respiratory difficulty;


SYMPTOMSSYMPTOMSvarious paraneoplastic various paraneoplastic

syndromes, including Cushing or syndromes, including Cushing or

carcinoid syndrome carcinoid syndrome

(uncommon).(uncommon).

Diarrhea secondary to high Diarrhea secondary to high

plasma calcitonin levels.plasma calcitonin levels.

Distant metastases.Distant metastases.

MEDULLARY THYROID MEDULLARY THYROID CANCERCANCERWORKUPWORKUP

Serum calcitonin levels.Serum calcitonin levels.Pentagastrin-stimulated calcitonin Pentagastrin-stimulated calcitonin

levels.levels.DNA testing for DNA testing for RETRET (it may (it may replace the diagnostic method replace the diagnostic method

mentioned above).mentioned above).24-hour urinalysis for 24-hour urinalysis for

catecholamine metabolites. catecholamine metabolites.


Screening for the development of Screening for the development of

familial MCT in family members of familial MCT in family members of

patients with patients with history of MCT or MEN history of MCT or MEN

2A or 2B2A or 2B..

Screen all family members for Screen all family members for

missense mutation in missense mutation in RET in RET in

leukocytes.leukocytes.


A cervical ultrasound A cervical ultrasound

(to detect LN metastases).(to detect LN metastases).

CT scan, MRI, and bone scans.CT scan, MRI, and bone scans.

Fine needle aspiration.Fine needle aspiration.


MANAGEMENTMANAGEMENT All patients should receive All patients should receive total total

thyroidectomythyroidectomy, , a complete central neck a complete central neck dissectiondissection ( (removal of all lymph nodes removal of all lymph nodes

and fatty tissues in the central area of the and fatty tissues in the central area of the neck),neck), and and removal of all lymph nodes and removal of all lymph nodes and surrounding fatty tissuessurrounding fatty tissues within the side within the side of the neck which harbored the tumor.of the neck which harbored the tumor.

Radioactive iodine therapy is not useful.Radioactive iodine therapy is not useful.


MANAGEMENTMANAGEMENT

Long-Term FollowLong-Term Follow

A yearly A yearly chest x-raychest x-ray as well as as well as calcitonin levels.calcitonin levels.

thyroid cancer. thyroid cancer type and incidence papillary ~ 60-75% follicular ~20-30% medullary...

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