THYROID TUMORS

Salma Saud Al-SharhanKing Faisal University – Khobar

Saudi Arabia

NORMAL ANATOMY OF THE THYROID GLAND:

MICROSCOPIC PICTURE OF THE THYROID GLAND:

TYPES OF THYROID CANCER:

Primary: Follicular epithelium – well differentiated papillary follicular Follicular epithelium – undifferentiated Anaplastic Parafollicular cells Medullary Lymphoid cells lymphoma Secondary : metastatic

THE CAUSES:

Radiation exposure to thyroid gland in child hood Schneider AB etal,Radation-induced endocrine tumor Cancer treat res

1997;89:141

Family hx. : a 4 to 10 fold increased risk of well differentiated thyroid cancer in 1st degree relatives with this neoplasia

Galanti MR et al, risk of papillary and follicular thyroid carcinoma , Br J Cancer 1997;75:451

THE CAUSES:

Iodine: Iodine-deficient diets may lead to increase the TSH level and considered goitrogenic

Thyroiditis: (Hashimoto's Disease) may develop into a form of cancer called lymphoma.

TNM STAGING OF THYROID CANCER:

EVALUATION OF THYROID TUMOR:

History:Age and GenderRapid increase in size, dyspnea,

dysphagia and hoarseness of voiceFamily Hx. Of thyroid cancerHx. Of irradiation On Examination:Firmness, Mobility, Size and adherence

to surrounding structuresPresence of lymphadenopathy

INVESTIGATIONS:

FNAC: The accuracy cytological diagnosis

from FNA ranges from 70% to 97% and highly dependent on the skill of the physician and the cytopathologist interpreting it.

Burch HB. Endocrinol Metab Clin North Am 1995;24:663

INVESTIGATIONS:

US: For the presence of malignant assosciations Microcalcification Irregular margins Hypervascularity Extra glandular extension

Frates MC et al, Doppler sonography aid in the predfcation of malignancy of predication of thyroid of nodules J US Med 2003;22:127

INVESTIGATIONS:

US guided FNA : Decrease the nondiagnostic specimen Increase the sensitivity and specificity Avoiding vascular structures

Carmeci C et al, US guided FNA of thyroid masses 1998;8:283

INVESTIGATIONS:Radionuclide Scan:To determine the functional status of the

nodule Hypofunctional “cold nodule”ule”Serum Calcitonin level:Routine measurement of calcitonin level

advocated by some authors to Dx. Medullary cancer is unknown

Ten most common types of Cancer among Adult Saudis by Sex, 2001

EASTERN REGION,2001

PAPILLARY THYROID CANCER:

Cystic or Solid Most common (80-85%)Spread through lymphaticFemale: Male is 3:1

PAPILLARY CANCER

Typical papillary projections and empty (orphan annie-eyed) nuclei

CLINICAL PRESENTATION:Incidental as a small occult tumor <1cm (papillary

microcarcinoma)Mass in the Neck the commonest way papillary cancer presentsGlands in the Side of the NeckThe spread to local glands (sometimes called

erroneously "lateral aberrant thyroid"). Distant Spread Spread to lungs or bone is very rare but when it

occurs unlike most other cancers, cure is possible.

THE FOLLICULAR CANCER:It is unifocal, thickly encapsulated

and shows invasion of both capsule and blood vessels

Spread by the blood stream and rarely

through lymphatic It is unusual tumor (5 -10%)

CLINICAL PRESENTATION:

As a single lump in the thyroid: This is the common mode of presentation. As pain in a bone or a spontaneous

fracture: in case of metastases to bone through the

blood stream 

THE PROGNOSIS IN DIFFERENTIATEDTHYROID CARCINOMA:

The two dominant factors are the age at the diagnosis and the presence of distant metastases.

Mazzafferi El etal, Long term impact of initial surgical and medical therapy on thyroid cancer .Am J Med 1994;97:418

Recent several scoring systems based on multifactorial analysis of risk factors have been advise

Low risk High risk

Patient age < 45 y > 45 y

Tumor size < 4.0 cm

> 4.0 cm

Extrathyoidal extension

absent present

Distant metastases

absent present

High tumor grade

absent present

THE TREATMENT OF WELL DIFFERENTIATED THYROID CANCER:

It Consists of a three- pronged attack :

Thyroid Surgery Radioactive iodine therapy Drug - Thyroxine therapy

SURGERY: Acceptable surgical procedure to remove

thyroid tumor include Ipsilateral lobectomy Near total thyroidectomy Total thyroidectomy The recent American Thyroid Association

Guide lines recommended for more aggressive (total thyroidectomy ) for well differentiated thyroid carcinonoma

Cooper DS et al. Management guidelines for thyroid nodules ,Thyroid2006;19:109

SURGERY : With a 20-year follow up the incidence of

local recurrence with unilateral resection was (14%),whereas, for bilateral resection it was (2%) Brauckhoff M, et al surgery 2006;140:953

For gross involvement of trachea or esophagus resection of these structures with reconstruction

Cooper DS et al. Management guidelines for thyroid nodules , Thyroid2006;19:109

RADIOIODINE THERAPY:

The Indications: 1.After Surgery to destroy any residual

thyroid cancer cells or residual normal thyroid tissue.

2.To treat thyroid cancer that has spread to the lymph nodes, lungs or bones.

3.To treat thyroid cancer recurrence after initial treatment by surgery or previous radioactive iodine or both.

RADIOIODINE THERAPY: Recent American thyroid association

guide lines recommended radioiodine ablation for:

Pt. with stage III or IV disease All Pt. with stage II disease <45 yrs or > 45 yrs Selected Pt. with stage I disease those

with: large tumor ( >1.5 cm ) multifocality residual disease nodal metastasis

Cooper DS et al . Management guide line for patient with thyroid nodules and cancer . Thyroid 2006;16:109

THYROXIN THERAPY :

Recent meta-analysis supported the efficacy of TSH suppression in preventing adverse clinical effect

High risk pt. are maintained at TSH level below 0.1 mU/ L

Low risk pt. TSH level at or below the normal range (0.1- 0.5 mU/ L)

McGriff NJ, et al. effect of thyroid hormone suppression therapy on thyroid cancer. Ann Med 2002;34:557

THYROXIN THERAPY :

The degree of thyroid suppression is dictated by balancing the risk of recurrent thyroid cancer and subclinical thyrotoxicosis particularly the cardiovascular risks

SURVEILLANCE:

CLINICAL IMPACT OF MOLECULAR ANALYSIS ON THYROID MANAGEMENT:

PAILLARY CARCINOMA

FOLLICULAR CARCINOMA

CPTC PDPTC

MIFTC WIFTC PDFTC

Recurrence 10% 50% 10% 40% 60%Deathof disease

5% 40% 10% 40% 60%

RET/PTC 30% 10% 0% 0% 0%

BRAF 40% 70% 0% 0% 0%

P53 <5% <5% <5% <5% 40%

RAS <5% 40% 40% 50% 60%

Looking at BRAF mutation detection of thyroid cancer in FNAB samples demonstrate a 100% specificity and sensitivity in cases of PTC carrying BRAF mutation.

Chung KW,etal. Detection of BRAF in FNA specimen of tyroid nodule.Clin Endocri

2006;65:660-6

MEDULLARY THYROID CANCER:

These are tumors of parafollicular (C cells), which produce a hormone called calcitonin

Types of MTC : Sporadic MTC Familial MTC MEN 2A MEN 2B Familial Non- MEN

CLINCAL PRESENTATION:

Sporadic MTC: asymptomatic thyroid mass Familial MTC : screening stimulation test for

calcitonin or with molecular analysis ( detection of RET gene mutation)

TREATMENT OF SPORADIC MTC:

C cells do not concentrate iodine so radioactive iodine is of no value in the management

Surgery is the only definitive therapy of MTC:

Total thyroidectomy Central node dissection Ipsilateral modified radical neck dissection

A TUMOR ERODING INTO THE CHEST WALL

TREATMENT OF FAMILIAL MTC:

Based on the genetic test for the mutation of RET gene

Since different mutations in the RET gene are associated with variable disease aggressiveness

this leading to individualized treatment of pt. with inherited MTC

MEN2A AND FMTC RX. :

Prophylactic thyroidectomy at age 5 to 6 years

Moley JF. Medullary thyroid carcinoma.

Curr Treat Options Onco 2003;4:339

MEN2B RX.:

Thyroidectomy during infancy

Moley JF. Medullary thyroid carcinoma.

Curr Treat Options Onco 2003;4:339

ANAPLASTIC CANCER OF THE THYROID:

It is a very aggressive tumor with a poor prognosis

A female to male ratio 1.5:1 and a mean age is 67 years

 It is commonest in areas of endemic goiter where there is chronic iodine deficiency.

ATC commonly related to prior diagnosis of well differentiated thyroid cancer

Mclver B et al, Anaplastic Thyroid Carcinoma surgery 2001;130;1028

CLINICAL PRESENTATION:

a long-standing goiter that suddenly increases in size.

Local invasion lead to obstructive symptoms, hemoptysis, dysphagia and hoarseness

At the time of Dx. 25 to 50 % of Pt. have synchronous pulmonary metastases

Mclver B et al, Anaplastic Thyroid Carcinoma .Surgery 2001;130;1028

A CT scan showing anaplastic cancer of the thyroid

A woman with anaplastic cancer of the thyroid

SURGICAL TREATMENT OF ATC:

In the majority of cases surgery is limited to an open biopsy to exclude lymphoma

Mclver B et al, Anaplastic Thyroid Carcinoma .Surgery 2001;130;1028

RADIOTHERAPY AND CHEMOTHERAP:

External beam radiotherapy (EBRR) as been used with limited success to treat locally recurrent ATC

Doxorubicin is the single most effective chemotherapeutic for ATC

Ain KB etal, treatment of anaplastic carcinoma of thyroid. (CATCHIT) Group. Tyroid 2000;10;587

THYROID LYMPHOMA:

Thyroid lymphoma is relatively rare disease constituting <1% of all lymphoma and accounting for 2% of extranodal non- Hodgkin’s lymphoma

Female: Male ratio from 3:1 up to 8:1 Median age is seventh decade of life

Green LD et al, anaplastic thyroid cancer and 1ry thyroid lymphoma. J Surg Oncol 2006;94:725

CLINICAL PRESENTATION:

Local invasion : hoarseness, dyspnea with stridor, or dysphagia

Hypothyroidism in case of Autoimmune thyroiditis or Hashimoto’s thyroiditis

A 70 Y. old lady with diffuse large B cell lymphoma

TREATMENT :

Primary treatment should be EBRT combined with Chemotherapy regimen based on histopathological subtype of lymphoma

Green LD et al, anaplastic thyroid cancer and 1ry thyroid lymphoma. J Surg Oncol 2006;94:725

TREATMENT :

Primary treatment should be EBRT combined with Chemotherapy regimen based on histopathological subtype of lymphoma

Green LD et al, anaplastic thyroid cancer and 1ry thyroid lymphoma. J Surg Oncol 2006;94:725