Pathology of parathyroids and bone

Question 1

Embryogenesis of parathyroids

Answer 1

• Upper pair (pharyngeal arch 4) and lower pain (pharyngeal arch 3)
• Lower pair migrate w/ thymus (also arch 3)
• Main cell types: chief cells (functional, small, lighter), oxyphil cells (larger, pinker, more granular cytoplasm due to numerous mitos), adipocytes
• Other cells: transitional cells and water-clear cells

Question 2

Anomalies of the parathyroids

Answer 2

• Agenesis: damage to chrom 22 leads to improper formation fo arches 3 and 4
• There is absence of parathyroids, thymus and causes digeorge syndrome
• Manifests as hypoCa, post natal convulsions, deficiency of cellular immunity, associated w/ cleft palate
• CATCH22: Cleft palate, Appearance, Thymus deficiency, Ca low, Heart defects
• Ectopic parathyroids: can be w/in thyroid, near carotid bifurcation, mediastinum, pericardial cavity
• Cysts of parathyroid: rare and usually present as a mass in the neck full of clear fluid

Question 3

Hyperplasia of the parathyroid glands

Answer 3

• All four glands are enlarged, causes 10% of 1o hyperpara
• Characterized by proliferation of chief cells and loss of fat, very lobulated glands
• Usually caused by renal disease (secondary hyperplasia), which leads to hypoCa/hyperPO4-> hyperplasia of parathyroids
• Can only be 1o hyperplasia if systemic d/os are ruled out that could cause 2o hyperplasia: renal disease, mets, etc
• Hyperplasia of parathyroids can be seen in MEN 1 and 2a

Question 4

Tertiary hyperparathyroidism

Answer 4

• Due to development of autonomous parathyroid hyper function in a pt w/ secondary hyperplasia
• The hyper function continues even after the underlying cause of the parathyroid hyperplasia is treated (usual cause is renal failure)
• Thus, there will hyperCa after Rx of the renal failure and vit D is restored b/c the parathyroids are overactive (either hyperplasia or adenoma) and secreting large amounts of PTH
• The Ca levels return to nl when the parathyroids are removed

Question 5

Hyperparathyroidism in MEN syndromes

Answer 5

• MEN 1 (PPP): hyperparathyroidism (usually due to hyperplasia), pituitary adenoma, pancreatic islet cell tumor
• MEN 2a (TAP): Thyroid medullary CA, pheochromocytoma of adrenals, hyperparathyroidism (usually hyperplasia)

Question 6

Parathyroid adenoma

Answer 6

• Most common cause of 1o hyperparathyroidism (90%); single enlarged gland
• Adenomas are generally not palpable
• Under LM they look like a fatless dense nodule surrounded by normal glandular tissue (lots of fat compared to nodule)
• Predominant cells in the nodule are chief cells and water clear cells
• Can use sestamibi scan before surgery to track the remaining over functioning parathyroid tissue (only hyper functioning tissue takes up the dye)

Question 7

Parathyroid carcinoma

Answer 7

• Rare, usually is a palpable mass in the neck
• May be functional or nonfunctional
• Palpable mass in neck and very high serum Ca (>15mg/dl) is parathyroid CA UPO
• Usually have a thick capsule and thick fibrous septae, w/ infiltration of the capsule or capillaries
• There is a high mitotic rate
• Local invasion and mets to lymph nodes are common

Question 8

1o vs 2o hyperpara

Answer 8

• 1o is caused by: single adenoma (usually), primary hyperplasia, multiple adenomas, CA
• Will have high serum Ca
• 2o hyperpara is due to low 1,25OHD levels (b/c of renal failure)
• Will have low serum Ca

Question 9

Presentation of hyperpara

Answer 9

• Many are ASx
• Renal lithiasis, calcinosis
• Emotional instability
• Peptic ulcer disease
• Pancreatitis
• Metastatic calcification
• Bone changes
• Think: bones, stones, abdominal groans and psychic moans

Question 10

Osteitis fibrosa cystica (browns tumor) 1

Answer 10

• Main kind of bone disease in hyperpara
• Characterized by increased osteoclast activity, replacement of marrow and bone w/ fibrous issue, and attempts at repair by osteoblasts
• Mostly affects vertebrae, long bones, head, and hands
• There are thin cortices (subperiosteal resorption), osteopenia, and fibrotic cyst formation

Question 11

Osteitis fibrosa cystica (browns tumor) 2

Answer 11

• Micro: bone is replaced by fibrous tissue, capillaries/hemorrhage, giant cells, and hemosiderophages/foamy macs
• Closely resembles giant cell tumor of bone
• Skull has classic salt and pepper appearance
• Demineralization of vertebrae (fish mouthing)
• Subperiosteal erosion of the digits

Question 12

Hyperparathyroidism of malignancy

Answer 12

• Squamous cell CA-> PTHrP
• Renal cell CA (met to bone)
• Ovarian tumors (met to bone)
• Bladder tumors (met to bone)

Question 13

Hypoparathyroidism

Answer 13

• Causes: injury to gland/surgery, absence of gland (digeorge syndrome, chrom 22)
• Manifestations: neuromuscular, cataracts, calcification of basal ganglia
• Decreased serum Ca, decreased PTH level