pituitary pathology Flashcards
Function of T-pit
Trxn factor which promotes differentiation of rathe pouch stem cells into corticotrophs which will secrete ACTH. Also involved in ACTH secreting pituitary adenoma.
Function of Pit-1
Trxn factor which promotes differentiation of Rathke pouch stem cells into somatotroph stem cells. Can also be involved in mixed GH/TSH secreting adenomas
What do somatotroph stem cells differentiate into
- Somatotrophs (secrete GH). 2. Thyrotrophs (secrete TSH)- can also convert back into somatotroph stem cells. 3. mammosomatotroph- further differentiates into somatotroph (GH) or latotroph (PRL)
distribution of cell types in anterior pituitary
Corticotrophs (ACTH) and thyrotrophs (TSH) in middle. Lactotrophs (PRL) and somatotrophs (GH) towards the sides
Staining of somatotrophs
Acidophilic (orangish) on PAS-orange G staining
normal anterior vs posterior pituitary histology
anterior: glandular with acidophilic, basophilic and chromophobic staining cells. Posterior: eosinophilic, fibrillar appearance with occasional swollen axonal processes (herring bodies)
Infundibulum histology
Congested, thin walled closely juxtaposed hypothalamic-hypophyseal portal system
Causes of pituitary adenomas
<5% are familial, the rest are sporadic with an unknown cause.
Genes associated with familial pituitary tumor syndromes
MEN1, CDKN1B, PRKAR1A and AIP (GH secreting adenomas)
Features suggesting an inherited pituitary tumor syndrome
parathyroid tumors, pancreatic endocrine tumors, atrial myxomas, lentigines, Schwann-cell tumors (Carney complex), family history and young age at onset
Pituitary tumor clinical presentation
- hormone hypersecretion: acromegaly, Cushings, amenorrhea/galactorrhea. 2. Sx from mass effect: headaches, vision loss, piuitary gland dysfunction
pituitary adenoma grade
Almost all are WHO grade 1
Microadenoma vs macroadenoma of anterior pituitary
Micro: 10mm, distorts adjacent tissues such as the dura of the sellar floor or diaphragma sella causing headaches
pituitary adenomas and diabetes insipidus
DI is quite uncommon with pituitary adenomas of any size
Macroadenomas most common growth patterns
Most commonly grows directly upwards, compressing the optic chiasm and resulting in bitemporal hemianopsia (loss of lateral visual fields due to compression of medial retinal fields).
Less common growth patterns of macroadenomas of pituitary
- compression of hypothalamus- hypothalamic dysfunction is rare. 2. Lateral growth outside the sella may compress the medial temporal lobe causing seizures. 3. May compress brain parenchyma but lack ability to infiltrate into brain parenchyma as single cells. 4. May extend laterally and compress the wall of the cavernous sinus, enwrapping the carotid artery (but not compromising) and distorting cranial nerves III, IV, and VI (cranial nerve palsies). 5. May extend into sphenoid sinus
Giant adenomas
Invasive adenomas >4cm
Imaging of macroadenomas and giant adenomas
Often show cysts and hemosiderin pigment in neuroimaging or in tumor specimen
Which pituitary tumors are responsive to medical therapy
Prolactinomas and GH secreting tumors (after surgical debulking)
Piuitary adenoma histology
intraoperative touch preparation shows abundant exfoliation of cytologically monotonous cells. Nuclear pleomorphism is uncommon. Mitoses are rare in microadenomas but occasionally seen in macro.
Histochemical stain for adenomas
Reticulin- normal pituitary has a nested pattern whereas adenoma has a disrupted reticulin pattern
Most frequency pituitary adenomas found incidentally at autopsy
prolactinoma, followed by null cell/gonadotroph
clinical signs of prolactinoma
galactorrhea, amenorrhea, infertility, hypogonadism
prolactinoma histology and immunoreactivity
Diffuse growth pattern, monotonous cell population with increased nuclear chromatin content and conspicuous vasculature. Diffuse immunoreactivity for PRL only.
How does the size of a prolactinoma correlate with PRl levels
In premenopausal women, size of adenoma parallels serum levels closely. NOT true for men or post menopausal women.
Treatment of prolactinomas
Medical management with dopamine agonist usually prevents the need for surgery. Surgery is used when pts have low tolerance for meds, tumor doesn’t shrink appropriately with meds, or limited preoperative testing available
Histology of prolactinoma after treatment with dopamine agonist
If recent and long term treatment, severe cytoplasmic shrinkage with near-naked nuclei that should not be mistaken for lymphocytes. Also often shows fibrosis
Clinical signs of gonadotroph cell adenoma/non secretor
headaches, visual field defects, cranial nerve palsies (ptosis, diplopia), pituitary hormone deficits, and rarely-seizzures, stroke or CSF leak.Also hypogonadism or clinically silent
gonadotroph cell adenoma histology
Sheet like architecture, perivascular arrangement of tumor cells, clear cell appearance, can have regions with more abundant oncocytic cytoplasm and regions with more scant cytoplasm.
gonadotroph cell adenoma immunohistochem
Immunoreactivity with alpha subunit and FSH/LH. Patchy distribution
Growth and treatment of non-secretory adenomas including gonadotroph adenomas
Slow growing- usually don’t require post operative radiotherapy
clinical signs of GH secretion tumor
acromegaly- acral enlargement, soft tissu swelling, cardiac hypertrophy, HTN, hyperglycemia, sleep apnea
clinical signs of TSH-cell adenoma
thyroid goiter, hyperthyroxinemia
Clinical signs of corticotroph adenoma
Cushings- hypercortisolism, central obesity, striae, hyperglycemia, osteroporosis, hirsutism
histology of ACTH adenoma
densely granulated ACTH cells growing as sheets of monotonous round cells. Immunoreactivity with ACTH only
How do serum levels of ACTH correlate with size of corticotroph cell adenoma
They do not correlate at all! A small adenoma may cause profound cushings
What is ACTH hyperplasia and how is it diagnosed
An uncommon cause of pituitary ACTH excess. Diagnosed by histology showing expansion, rather than destruction, of acini by reticulin stain. Will show larger acini containing relatively homogenous populations of ACTH reactive cells. Look for ectopic source of CRF
what is pituitary apoplexy
Sudden headache, acute visual changes, ophthalmoplegia (Acute visual loss or inability to move eyes) and altered mental status (confusion) caused by the sudden hemorrhage or infarction of the pituitary gland
What cuases pituitary apoplexy
Occurs in 10-15% of pituitary adenomas, but of varying degree of severity.Not clearly cell type or size dependent. 65% occur in patients with undiagnosed pituitary tumors. Anterior pituitary dysfunction is common.
Pituitary apoplexy treatment
ICU care, steroids, surgery sometimes
pituitary apoplexy histology
necrosis with areas of discernible adenoma
Histology of Rathke cleft cyst
Ciliated columnar cyst lining, abundant amorphous eosinophilic nucin cyst contents in which are embedded small strips of pseudostratified ciliated columnar epithelium. Also squamous metaplasia (associated with cyst recurrence)
What is lymphocytic hypophysitis
Inflammatory process involving the pituitary (usually anterior but posterior can be involved). Primary hypophysitis is an autoimmune disorder involving classically affecting young women during late pregnancy or in the early postpartum period. Secondary type is caused by other factors
Lymphocytic hyophysitis histology
sheets of cytologically bland pure lymphocytic infiltrates
testing for lymphocytic hypophysitis
anti-pituitary autoantibodies is not reliable test.
Primary lymphocytic hypophysitis presentation, diagnosis, treatment
Usually presents as a mass lesion of the pituitary gland simulating pituitary adenoma on neuroimaging studies. Diagnosis: histological. Treatment: corticosteroids usually the only treatment needed. Sometimes surgery
Causes of secondary lymphocytic hypophysitis
TB, sarcoidosis, Wegeners granulomatosis, Sjogren syndrome, Langerhands cell histiocytosis, germ cell tumors, lymphoma, and rarely- pituitary adenoma, craniopharyngioma, or rathke cleft cysts with secondary tissue damage
Craniopharyngioma gross anatomy
Cystic and solid components.
craniopharyngioma histology
ghost cells
What is a hypothalamic hamartoma
Mass of neurons and glial cells. NOT a true neoplasm. fully differentiated neuroglial tissue that closely resembles normal hypothalamus but is jumbled
hypothalamic hamartoma presentation
Clinical manifestations, if any, are those of endocrine hyperfunction due to overproduction of hypothalamic gonadotropin-releasing hormone that can cause precocious puberty. Also can see convulsive laughter known as gelastic seizures
hypothalamic hamartoma treatment
surigcal resection alone IF symptomatic
most common sellar region mass
pituitary adenoma
Who usually gets pituitary adenomas
young to middle age adults
Who usually gets crainpharyngiomas
children and adults- often calcified
GH tumors recurrence
sparsely granulated GH tumors are more aggressive and have increased recurrence
complications of GH tumors
mortality (increases with increasing levels of GH), DI, CSF leak, meningitis.
GH cell adenoma histology
monotonous cells, slightly pleomorphic medium sized cells often wth angular profile. Densely granulated with diffuse, strong staining for GH and keratin reactivity. OR sparsely granulated with cells that lack acidophilia and may show more eccentrically place nuclei and perinuclear clearing in cytoplasm.
Feature of sparsely granulated GH adenomas
often invade bone- will see entrapped bony spicules surrounded by tumor
GH cell adenoma treatment
Somatostatin analog, radiotherapy- convential, stereotactic (less radiation to surrounding structures), and lmited experience wit gamma knife, LINAC and proton beam
