SM158 Parathyroid Histology/Pathology

Question 1

Normal number of parathyroid glands, arrangement, color, anatomical location

Answer 1

4 glands normally (can have 5 or 6)

Arranged in 2 pairs (upper and lower)

Color varies from red to tan to yellow depending on fat content

Upper pair: posteriolateral border of the middle third of thyroid, lower pair: posteriolateral border of the lower third

Question 2

Embryology of upper and lower pairs of glands

Answer 2

Upper: arises from 4th branchial cleft, descends with the thyroid gland

Lower: arises from the 3rd branchial cleft, descends with the thymus

Question 3

Chief cell histology

Answer 3

Main cell type. Pink, polygonal, central/round/uniform nuclei, water-clear appearance when glycogen is abundant. Secretory granules with PTH.

Question 4

Oxyphil cell histology

Answer 4

Slightly larger than chief cells, acidic cytoplasm, packed with mitochondria. Glycogen granules present but no secretory granules.

Question 5

What stimulates release of PTH?

Answer 5

Level of free calcium in the blood (hypocalcemia = more release)

Question 6

5 ways that PTH regulates serum calcium levels

Answer 6

1) Increases renal tubular absorption
2) Converts vit. D to active form in kidneys
3) Increases urinary phosphate excretion
4) Increases gut absorption
5) Mobilizes stores from bone

Question 7

Anomalous sites where the parathyroid glands might end up

Answer 7

Carotid sheath, behind the cervical or thoracic esophagus, mediastinum, inside the thyroid, pharynx

Question 8

Most common cause of clinically apparent hypercalcemia

Answer 8

Malignancy

Question 9

Pathophys of hypercalcemia in malignancy

Answer 9

Consequence of bone resorption (either from metastases or PTHrP). With PTHrP, expression of RANKL on osteoblasts is promoted. These osteoblasts bind RANK on osteoclast progenitors, inducing their differentiation into mature osteoclasts.

Question 10

3 most common causes of primary hyperparathyroidism

Answer 10

Adenoma > hyperplasia > carcinoma

Question 11

Genetic syndrome associated with primary hyperparathyroidism

Answer 11

MEN-1
MEN-2A
Familial hypocalcuric hypercalcemia (CASR gene)

Question 12

Parathyroid adenomas: gross and microscopic appearance

Answer 12

Gross: well-circumscribed, soft, tan or red nodule with a delicate capsule. Other glands will be normal in size or shrunken (due to feedback inhibition)

Microscopic: uniform polygonal chief cells with small nuclei. Adipocytes are usually absent

Question 13

How do you differentiate parathyroid adenoma and primary hyperplasia?

Answer 13

Typically, adenomas are singular and the other glands will be normal-sized or shrunken. In hyperplasia they should all be enlarged.

Question 14

Parathyroid carcinoma: gross and microscopic appearance

Answer 14

Gross: it can look like an adenoma or it can clearly have infiltrated surrounding tissue (poorly-circumscribed). Grey-white, more irregular.

Microscopic: looks like normal chief cells. Surrounded by a dense, fibrous capsule. Only reliable criteria is metastasis.

Question 15

What type of bone is most affected by hyperparathyroidism?

Answer 15

Cortical > cancellous

Question 16

Generalized osteitis fibrosa cystica triad

Answer 16

A.K.A. von Recklinghausen disease

1) increased bone cell activity (both -clasts and -blasts), 2) peritrabecular fibrosis, 3) cystic brown tumors

Question 17

Brown tumor pathogenesis

Answer 17

Bone loss causes microfractures and secondary hemorrhages, which leads to an influx of macrophages and ingrowth of reparative fibrous tissue

Question 18

Other condition in DDx for brown tumor hyperparathyroidism?

Answer 18

Central giant cell granuloma of bone
Indistinguishable from brown tumor, also affects jaw
Differentiate because no elevated PTH or hypercalcemia

Question 19

Examples of morphological changes in the bone of individuals with secondary hyperparathyroidism

Answer 19

Dissecting osteitis (“railroad tracks”)
Subperiosteal resorption
Brown tumors
Osteoporosis

Question 20

Hyperparathyroidism symptoms

Answer 20

Mnemonic: painful bones, renal stones (nephrolithiaisis), abdominal groans, and psychic moans (depression, lethargy)

Question 21

Secondary hyperparathyroidism: most common etiology, pathology, symptoms

Answer 21

Chronic renal failure is most common cause
Path: more chief cells, more water-clear cells, less fat cells
Symptoms: dominated by renal failure

Question 22

Tertiary hyperparathyroidism

Answer 22

Parathyroid activity becomes autonomous and excessive, causing hypercalcemia

Question 23

Hypoparathyroidism: main etiology

Answer 23

Inadvertent consequence of surgery (thyroidectomy usually)