THYROID NEOPLASM.

Dr Shivani.
Dr Keshav Soni.
Dr P. Bhargav Sai.
 CLASSIFICATION
Benign.
¡)Follicular adenoma.
ii)Hurthle cell adenoma
iii Colloid adenoma

Malignant.
1. Differentiated Thyroid Cancer
i) Papillary Carcinoma (80%)
ii) Follicular Carcinoma (10%)
iii) Hurthle cell carcinoma (3%)
2.Anaplastic carcinoma(1-2%)
3. Medullary Carcinoma (5-10%)
4. Malignant Lymphoma (approx1%)
EPIDEMIOLOGY
• Commonest malignant Endocrine tumor, compromise 1% of all
malignancies.

• Annual incidence is 0.5 to 10 per 100,000 persons

• Highest Incidence -> Northern America

• Female to male ratio is 3:1

• Differentiated carcinomas peaks in 3rd and 5th Decade of life

EPIDEMIOLOGY

• Hurthle cell carcinoma peaks in 6th and 7th decade of life

• Anaplastic carcinomas and thyroid lymphomas peaks in 5th and 7th decade.

• In MTC sporadic peaks in 4th to 6 th decade whereas familial peaks in 2nd

and 3rd decade of life

• Papillary thyroid carcinoma - iodine sufficient areas

• Follicular thyroid carcinoma-> iodine deficient areas

Carcinoma according to age
• Children:-
a) Papillary Thyroid carcinoma
b) Medullary thyroid carcinoma associated with MEN type 2.
• Elderly:-
a) Follicular thyroid carcinoma
b) Anaplastic carcinoma
C) Sporadic Medullary thyroid carcinoma
Etiology
• Thyroid cancer arises from two type of cells
Endoderemally derived follicular cells Neuroendrocrine derived calcitonin
producing C cells
• Papillary * Medullary Thyroid carcinomas
• Follicular
• Anaplastic
Etiology
• Radiation -> Papillary thyroid carcinoma
• Single most important factor in differentiated carcinoma is irradiation of
thyroid under 5 years of age.

• Pre-existing multinodular goiter -> Follicular Carcinoma

• Familial
• Increase incidence of thyroid carcinoma among children following exposure
to ionizing radiation after Chernobyl nuclear disaster in Ukraine in 1986.
• Radiotherapy received in adolescents for Hodgkins lymphoma may be
predisposed to PTC
Familial cancer syndromes
Syndrome Thyroid Tumor

Cowdens syndrome(PTEN mutation) FTC and rarely PTC

FAP (APC gene mutation) PTC

Werners syndrome(wrn1 gene) PTC, FTC, Anaplastic cancer

Carney complex (gamma PPAR gene mutation) PTC, FTC

Men 2 syndrome (RET gene mutation)- medullary thyroid cancer.

Genes implicated in thyroid tumorogenesis
Cancer Oncogenes Tumour suppressor genes

Papillary thyroid carcinoma RET, PTC1 , PTC 3, BRAF, GDNF p53

Medullary thyroid carcinoma RET

Follicular carcinoma BAX/PPAR ,mi RNA197, 346 p53, PTEN

Anaplastic BRAF ,Up regulation of miRNA19- p53

72
Clinical Presentation
• Solitary thyroid nodule
- Single most common presentation.
- Up to 99% of nodules are benign.
• Hoarseness of Voice.
• Enlarged Cervical Lymph nodes.
• Difficulty swallowing.
• Dyspnea.
• Persistent cough.
 Carcinoma Clinical features

Papillary Thyroid cancer 1. Slow growing painless thyroid swelling

2. Discrete neck lymph nodes- Lateral aberrant thyroid-> cervical lymph
node invaded by metastatic cancer
3. PTC tends to be multifocal hence total thyroidectomy is done
4. Compression feature > uncommon

Follicular Carcinoma 1. Solitary thyroid nodules with history of rapid size increase and long
standing MNG
2. Tracheal compression stridor
3. +ve Berry’s sign - advanced malignancy
4. Dyspnea, hemoptysis and chest pain when there are lung secondaries
5. Pulsatile secondaries in skull and long bones
6. Cervical lymphadenopathy-> uncommon
 Carcinoma
Anaplastic carcinoma
Medullary thyroid cancer
Clinical Features
1. Long standing neck mass which enlarges rapidly, may be
painful
2. Tracheal obstruction -stridor
3. Hoarseness and dysnea-> common (50%)
4. Vocal cord paralysis(30%)
5. Hard Mass fixed to surrounding structures, may be
ulcerated.
1. Develops in superolateral part of thyroid lobes
2. Neck mass with palpable cervical lymphadenopathy (15 to
20%)
3. Pain -›common
4. Local invasion -> dysphagia, dysnea, dysphonia
5. Sporadic -> unilateral(80%)
6. Familial -> bilateral (90%)
 Pathophysiology
Papillary Thyroid carcinoma
Gross • soft, firm , hard, cystic
• Solitary / multinodular
• Contain brownish black fluid
Microscopy
• Orphan annie eye nuclei ->
characteristic
• Psammoma bodies (50%)
Spread • Slowly progressive and less aggressive
• Spread through lymphatics
• Most commonly to lungs, followed by
bone -> liver -> brain.
• Hematogenous spread less often
• Orphan Annie is strip cartoon character with empty circled eyes.
 Pathophysiology
Follicular Thyroid carcinoma
Types • Invasive -> Hematogenous spread is
common
• Non invasive -> hematogenous spreas
is not common
Typical feature • Capsular invasion
• Angioinvasion
Spread • More aggressive tumour
• Through blood into bones, lungs, liver
• Occasional spread to lymph nodes in
neck (10%)

Bone secondaries typically vascular, warm, pulsatile, localized, commonly seen in skull, long bones, ribs
 Pathophysiology
Hurthle Cell Carcinoma

• Variant of follicular carcinoma according to WHO

• 75-100 percent of tumour is composed of Hurthle cells also known as Oxyphilic
cells- rich in mitochondria (eosinophilic cytoplasm)
• Large, polygonal follicular cells -> abundant granular acidophilic cytoplasm
• Differ from the follicular cancer in :
• Multifocal and bilateral (30 percent)
• Donot take radio iodine (5 percent)
• More likely to metastatize to local nodes (25 percent) and distant metastasis.
 Pathophysiology
Anaplastic Carcinoma

• Arise from de-differentiation of differentiated thyroid carcinoma

Gross • Firm and whitish

Microscopy • Sheaths of cells with marked
heterogenicity
Spread • One of the most aggressive thyroid
malignancy
• Spread through lymphatics commonly
to lungs, brain and bones.
 Pathophysiology
Medullary thyroid carcinoma
Types • Sporadic (75%)
• Familial (25%)
Gross • Well circumscribed
• Not encapsulated
Microscopy • Amyloid stroma wherein malignant
cells are dispersed
• Calcitonin in amyloid on
immunochemistry
Spread • Mainly to lymph nodes (60%)
• MCT associated with MEN type IIB
with pheocrhomocytoma is most
aggressive.
 Pathophysiology
Thyroid Lymphomas

• Most Common -> Non Hodgkins B cell lymphomas- DLBCL

• Commonly arise from chronic lymphocytic thyroiditis(long standing
Hashimoto thyroiditis)
• Chronic antigenic lymphocyte stimulation -> lymphocyte
transformation.
• C/F-Thyoid swelling with B symptoms like fever , night sweats,weight
loss.