NEOPLASMS OF THYROID

Question 1

Most common benign thyroid neoplasia

Answer 1

follicular adenoma

Question 2

list Most common malignant thyroid neoplasia in order:

Answer 2

• Papillary Carcinoma:>85%
• Follicular carcinoma: 5%-15%
• Medullary carcinoma:5%
• Anaplastic carcinoma:< 5%

Question 3

history of radiation of the head and neck, especially first two decades of life.
* Usually presents as a distinct solitary nodule.

Answer 3

thyroid neoplasms

Question 4

features suggessting malignancy in hyroid neoplasms

Answer 4

✓young age, Male, cold nodule
✓Pain, rapid rate of growth and change in voice

Question 5

Radio Iodine uptake studies used to further categorize nodules:
* Hot nodule( increased uptake)

Answer 5

• graves / nodular goiter

Question 6

Radio Iodine uptake studies used to further categorize nodules:
* COLD nodule( dec. uptake)

Answer 6

Adenoma / carcinoma

Question 7

Clinical features of follicular adenoma

Answer 7

• Usually painless solitary
  nodules
• May be functional &
  cause hyperthyroidism
  (toxic adenoma)

Question 8

microscopy of follicular adenoma

Answer 8

• Solitary nodules; Well capsulated tumor;
  Compressed normal gland.
  1 nodule + capsule
• No capsular and vascular invasion & papillary carcinoma nuclear features
• Occasional atypia ( Endocrine atypia)
• Variant- Hurthle cell adenoma

Question 9

Follicular Adenomas is a benign neoplasm derived from ___________

Answer 9

follicular epithelium

Question 10

pathogenesis of follicular adenoma

Answer 10

Most adenomas are Cold nodules ( Toxic- hot).
* Toxic adenomas:
TSH receptor pathway mutations —> autonomy
* Non Functional Adenoma: <20% express RAS gene mutations

Question 11

genetic pathogenesis of papillary carcinoma

Answer 11

Activation of MAP kinase pathway either by
* Rearrangement of tyrosine kinase RET gene
* Point mutation in BRAF gene

**FOLLICULAR CELL DERIVED

Question 12

genetic pathogenesis of Follicular carcinoma

Answer 12

• RAS gene – frequent ( HRAS, N RAS, KRAS)
• P13K/AKT signaling pathway components including its negative
  regulator PTEN
• PAX8 gene

Question 13

list 3 FOLLICULAR CELL DERIVED carcinomas

Answer 13

papillary
follicular
anaplastic

Question 14

genetic pathogenesis of anaplastic carcinoma

Answer 14

• De novo / progression from Papillary/ Follicular carcinoma
• TP53 mutation in additions

Question 15

genetic pathogenesis of medullary carcinoma

Answer 15

Parafollicular C cells derivation

• Familial ( MEN-2) – RET gene ( Chr 10) – tyrosine kinase receptor activation
• Non Familial

Question 16

diagnosis:
* 5% -15% of malignant thyroid tumors
* F > M; 40-60yrs
* Hematogenous spread to bones or lungs is common
* Genetic basis
* ~50% cases harbor mutations in RAS family
of oncogenes
* HRAS, NRAS, and KRAS
* NRAS mutations are most common

Answer 16

follicular carcinoma

Question 17

Gross morphology of follicular carcinoma

Answer 17

Single well circumscribed
nodules or widely infiltrative

Question 18

Microscopic morphology of follicular carcinoma

Answer 18

• Uniform cells forming small
  follicles containing inspissated
  colloid
• Rule out capsular and/or vascular invasion to distinguish follicular adenomas from minimally invasive follicular carcinomas
• Hematogenous spread

Question 19

Gross morphology of papillary carcinoma

Answer 19

• Solitary / Multifocal
• Circumscribed – encapsulated / infiltrating surrounding
  parenchyma
• Papillary excrescences

Question 20

microscopic morphology of papillary carcinoma

Answer 20

• Branching papillae with fibrovascular core covered with uniform cuboidal epithelial cells
• Psammoma bodies - Concentrically calcified structures
  termed within the cores of papillae
• Cells: Nucleus - optically clear (ground-glass or Orphan Annie eye nuclei)
• intranuclear inclusions (“pseudo-inclusions”)
• intranuclear grooves

Question 21

determine diagnosis:
* 80% of malignant thyroid tumors
* F > M
* Age 20-50
* Risk factor
-Radiation exposure

Answer 21

PAPILLARY CARCINOMA

Question 22

pathogenesis of PAPILLARY CARCINOMA

Answer 22

Activation of MAP kinase pathway is
feature of all papillary carcinomas.
-RET protooncogene on chr.10
-Point mutations in BRAF(MAP-Kinase pathway)

Question 23

papillary carcinoma is commonly spread via

Answer 23

cervical lymphnodes

Question 24

RX: for papillary carcinoma

Answer 24

• Resection is curative in most cases
• Radiotherapy with iodine 131 is effective for metastasis

Question 25

prognosis for papillary carcinoma

Answer 25

• Excellent
• 10-year survival 98%

Question 26

origin of medullary carcinoma

Answer 26

Thyroid C cells (parafollicular cells)
secrete calcitonin & follow up + CEA

Question 27

Familial medullary thyroid carcinomas occur in
_____________- & associated with germline
______________ mutations.

Answer 27

MEN-2( 2A and 2B) & RET proto-oncogene

Question 28

____________ are affected in MEN-2 syndrome

Answer 28

younger pts

Question 29

determine the malignancy : GROSS MORPHOLOGY

-solitary nodule or may manifest as multiple lesions involving both lobes areas of necrosis and hemorrhage

Answer 29

medullary carcinoma

Question 30

describe the microscopic morphology of Medullary Carcinoma

Answer 30

-polygonal to spindle-shaped cells
-nests, trabeculae, and even follicles.
-Amyloid deposits - altered calcitonin in the stroma ( Congo red stain/ IHC)
F-amilial cases - Multicentric C cell hyperplasia in the surrounding thyroid

Question 31

clinical presentation of Medullary Carcinoma

Answer 31

mass in the neck, compression effects such as dysphagia or hoarseness, diarrhea (Vaso active intestinal peptide secretion)

Question 32

determine the malignancy:
* Associated with p53 mutations
* F > M; Age > 60yrs
* Firm, enlarging, bulky mass
* Dyspnea & dysphagia
* Tendency for early widespread metastasis & invasion of trachea & esophagus

Answer 32

ANAPLASTIC CARCINOMA

Question 33

describe the microscopic morphology of anaplastic carcinoma:

prognosis:

Answer 33

Undifferentiated anaplastic & pleomorphic cells

Prognosis
* Very aggressive; rapidly fatal