Thyroid and Parathyroid Pathology

Question 1

parathyroid cells types (3)

Answer 1

-Chief cells
-Oxyphillic cells
-Adipose cells

Question 2

Chief Cells (3)

Answer 2

-Functional cells
-Parathyroid hormone synthesis and release
-Contain calcium sensing receptors

Question 3

Parathyroid hormone (4)

Answer 3

Regulates serum calcium
- promoting release of calcium (and phosphate) from bone
- increases production of vitamin D to enhance intestinal calcium absorption
- Deceases calcium loss in urine, increases phosphate excretion

Question 4

Parathyroid Adenoma (3)

Answer 4

> 85% of primary hyperparathyroidism
-10% hereditary
MEN1, MEN2, MEN4, HPT-JT

Question 5

Parathyroid Adenoma vs Hyperplasia (4)

Answer 5

-Can look identical
-Conventional wisdom used to limit adenoma diagnosis to single entity “assuming normality/suppression of remaining glands”
-multiple adenomas in hereditary hyperparathyroidism (ie MEN etc)
-These are now recognised as adenomas, not hyperplasia

Question 6

Hyperplasia (2)

Answer 6

-Primary hyperplasia thought to be v.rare
-Secondary / compensatory hyperplasia associated with physiological stimulus (ie low serum calcium, high serum phosphate, vit D deficiency)

Question 7

Parathyroid Carcinoma (4)

Answer 7

<1% of primary hyperthyroidism cases

Can be familial - 15% of HPT-JT patients will develop

Can be sporadic

CDC73 (usually deletion / inactivation)
-Codes for parafibromin tumour suppressor protein

Question 8

Diagnostic criteria for parathyroid carcinoma (5)

Answer 8

showing at least one of the following:
-Angioinvasion
-Lymphatic invasion
-Perineural invasion
-Invasion of adjacent structures/organs
-Regional/distant metastasis

Question 9

Atypical Parathyroid Tumour (4)

Answer 9

looks weird but doesn’t meet the diagnostic criteria for parathyroid carcinoma

-Atypial cytological and architectural features, extension into capsule (but not through and into surrounding tissue)

-But not to be overused

-Parathyroid adenomas can have variation in appearance / occasional mitoses

Question 10

Thyroid histology (3)

Answer 10

Follicular cells
Parafollicular Cells

Colloid

Question 11

Thyroid physiology (4)

Answer 11

1. hypothalamus releases hormone TRH which stims pituitary gland

2.pituitary gland releases hormone TSH which stims thyroid gland

3.thyroid gland makes the thyroid hormone T3 +T4

3. As T3 + T4 are made they signal hypothalamus + pituitary to stop stimulating e.g. when T3 + 4 are adequate no more needs to be made

Question 12

Thyroid Pathology (4)

Answer 12

Non-neoplastic=
-Inflammatory / Autoimmune

Neoplasia= Benign + Malignant

Question 13

Non Neoplastic (3)

Answer 13

Multinodular goitre

Hashimotos thyroiditis

Graves disease

Question 14

Multinodular goitre (5)

Answer 14

Also called nodular / multinodular hyperplasia
-Colloid goitre, hyperplastic nodule etc
-All represent the same process

Diffuse or nodular enlargement of the gland

Often very distorted

Question 15

Hashimoto Thyroiditis (4)

Answer 15

Autoimmune process
-Elevated circulating antiperoxidase + antithyroglobulin antibodies
-Female predominance

Hyperplastic gland, usually 2-3X normal size, usually diffuse and symmetrical enlargement.

Question 16

Hashimoto Thyroiditis path (3)

Answer 16

lymphatic infiltrate with germinal centre

-follicular trophy
-hurthle cell

Question 17

Graves’ Disease (5)

Answer 17

Also known as diffuse hyperplasia

Autoimmune process
-Diffuse goitre, thyrotoxicosis, infiltrative opthalmopathy

From pathology perspective, important to know if patient has been treated
-Carbimazole can affect the way the cells look microscopically

Question 18

Neoplasms- Benign (2)

Answer 18

Follicular adenoma
-Oncocytic adenoma

Question 19

Neoplasms- Benignish (3)

Answer 19

NIFT-P
Thyroid Tumour of Uncertain Malignant Potential
Hyalising Trabecular Tumour

Question 20

Neoplasms- Malignant (7)

Answer 20

Papillary carcinoma

Medullary carcinoma

Follicular carcinoma
-Oncocytic carcinoma

High grade follicular cell derived non-anaplastic thyroid carcinoma
-Poorly differentiated thyroid carcinoma
-Differentiated high grade thyroid carcinoma

Question 21

Follicular adenoma (2)

Answer 21

Encapsulated neoplasm of thyroid follicular cells

Lacks capsular or vascular invasion

Question 22

Oncocytic adenoma (4)

Answer 22

Previously known as Hurthle cell adenoma

Used to be a subtype of follicular adenoma, now has its own category

Oncocytic cells = swollen and pink

Encapsulated, non invasive

Question 23

Follicular Carcinoma (4)

Answer 23

Looks like a follicular adenoma, but can have capsular invasion or vascular invasion

Or both

Can be widely invasive or minimally invasive, with or without vascular invasion

Additional variant “encapsulated with angioinvasion”

Question 24

Oncocytic Carcinoma (3)

Answer 24

Used to be a variant of follicular carcinoma

Now has its own category

Criteria for malignancy same as follicular adenoma, but lesion must have dominant oncocytic cell component

Question 25

Thyroid Tumours of Uncertain Malignant Potential (3)

Answer 25

Essentially used in situations where invasion is equivocal Or incomplete For example, invasion into capsule, but not all the way through Or tumour bulging into vessels but not fully into endothelial lined space

Question 26

Papillary Thyroid Carcinoma (PTC) (2)

Answer 26

Most common thyroid malignancy Multiple subtypes based on architecture, many have prognostic implications

Question 27

PTC subtypes (11)

Answer 27

-Classic PTC -Encapsulated PTC -Diffuse sclerosing PTC -Sold/trabecular PTC -Warthin-like PTC -Oncocytic PTC -Spindle cell PTC -PTC with fibromatosis/fasciitis-like/desmoid type stroma -Tall cell PTC -Hobnail PTC -Columnar Cell PTC

Question 28

PTC Molecular (3)

Answer 28

BRAF p.V600E mutations most common -Have treatment implications -Other genes which may be involved include RET, TERT promoter mutations, NTRK

Question 29

Medullary Carcinoma (7)

Answer 29

C-cell derived neoplasm Up to a quarter are associated with MEN2a or MEN2b -Germline gain of function mutation in RET proto-oncogene Often associated with increased serum calcitonon and or carcinoembryonic antigen (CEA) Variable histological appearance -Can show amyloid deposition IHC often helpful – calcitonin positive along with neuroendocrine markers

Question 30

Anaplastic Carcinoma (3)

Answer 30

Undifferentiated thyroid carcinoma Characterised by aggressive progression and extremely poor prognosis- Usually fatal outcome Usually thyroid IHC markers are lost, sometimes PAX8 is retained