Parathyroid Pathology Flashcards
In early infancy and childhood, the parathyroid glands are composed almost entirely what type of cell?
Chief cells
What are the 3 histological characteristics of the Chief Cells of the parathyroid glands?
- Central round, uniform nuclei
- Light pink or white cytoplasm (water-clear appearance)
- Secretory granules
Which cells of the parathyroid gland have an acidophilic cytoplasm and are tightly packed with mitochondria?
Oxyphil cells
Which cells of the parathyroid hormone contain large amounts of cytoplasmic glycogen and secretory granules containing PTH?
Chief cells
What are 4 specific ways PTH acts to maintain calcium homeostasis?
- ↑ renal tubular reabsorption of Ca2+
- ↑ conversion of Vit D —> active 1,25(OH)2D form in kidneys
- ↑ urinary phosphate excretion
- Augments GI calcium absorption
Secondary hyperparathyroidism is a compensatory hypersecretion of PTH in response to prolonged hypocalcemia, most commonly in the setting of what?
Chronic renal failure
What are 3 causes of primary hyperparathyroidism; which is most common?
- Adenoma = most common
- Primary hyperplasia
- Parathyroid carcinoma
Which 2 molecular defects/mutations have an established role in the development of sporadic parathyroid adenomas?
- Cyclin D1 gene inversion –> overexpression of cyclin D1
- MEN1 mutations
In what 2 ways can MEN1 mutations be associated with parathyroid adenomas and which is more common?
- Germline mutations causing familial MEN1 and can manifest w/ parathyroid adenomas
- MORE common is sporadic parathyroid adenomas, with somatic MEN1 mutations
Which 2 genetic syndromes are associated with familial parathyroid adenoma; what is the associated gene mutated in each?
- MEN type 1 associated w/ MEN1
- MEN type 2 associated w/ RET
Familial hypocalciuric hypercalcemia is a rare disorder due to what mutation and how is it inherited?
- Loss-of-function mutation in parathyroid calcium-sensing receptor gene (CASR)
- Autosomal dominant
What is the typically seen microscopically in parathyroid adenomas; what is the dominant cell type?
- Uniform, polygonal CHIEF cells w/ small, centrally placed nuclei
- A few nests of larger oxyphil cells are present as well
What is “endocrine atypia” in relation to the morphology of some parathyroid adenomas?
Not uncommon to find bizarre and pleomorphic nuclei; this is not a criterion for malignancy
What type of parathyroid adenoma may resemble a Hurthle cell tumor in the thyroid?
Oxyphil adenoma (uncommon)
Which morphological feature of the normal parathyroid glands becomes inconspicous in adenomas and hyperplasia?
Adipose tissue
How does parathyoid adenoma differ from hyperplasia in terms of glands involved?
- Adenoma are almost always solitary, affecting one lobe
- Hyperplasia almost always present in multiple glands
What is often seen morphologically surrounding parathyroid adenomas and how does this differ from parathyroid hyperplasia?
- Adenomas have a rim of compressed, normal parathyroid tissue, generally separated by a fibrous capsule
- Hyperplasia does NOT have a normal rim of parathyroid tissue
What are the only reliable criteria for diagnosis of a parathyroid carcinoma?
- Metastasis = most telltale sign!
- Invasion of surrounding tissues or vasculature
Parathyroid carcinomas are often hard to distinguish from what?
- Adenomas
- Both are solitary and enclosed by fibrous capsule
What 3 interrelated skeletal abnormalities can manifest as a result of symptomatic, untreated hyperparathyroidism?
- Osteoporosis
- Brown tumors
- Osteitis fibrosa cystica
The osteoporosis associated with symptomatic, untreated hyperparathyroidism preferentially involves which bones?
Phalanges + vertebrae + prox. femur
The osteoclast activity associated with hyperparathyroidism affects what type of bone more severly?
Cortical bone (i.e., subperiosteal and endosteal surfaces)
In untreated hyperparathyroidism, what do the osteoclasts due in medullary bone; create what appearance?
- Tunnel into and dissect centrally along the length of the trabeculae
- Create appearance of rail-road tracks aka dissecting osteitis
What are the 3 hallmarks of severe hyperparathyroidism and is known as generalized osteitis fibrosa cystica (von Recklinghausen disease of bone)?
- Osteoclast-driven bone destruction –> microfractures + hemorrhage
- Peritrabecular fibrosis
- Cystic brown tumors (STARTS as a brown tumor)