Pathology: Pituitary, hypothalamus and pineal gland Flashcards
The anterior lobe of the pituitary is also known as the…
adenohypophysis
The posterior lobe of the pituitary is also known as …
neurohypophysis
What are the three major morphologic cell types found in the anterior pituitary based on staining ?
Acidophils (eosinophilic)
Basophilic
Chromophobe
What hormone producing cells of the anterior pituitary are considered Acidophilic (eosinophilic) ?
Somatotrophs: produce Growth Hormone
Latotrophs: Produce PRL
What hormone producing cells of the anterior pituitary are considered Basophils ?
Corticotrophs: Make ACTH, POMC, MSH and Endorphins
Gonadotrophs : Make FSH and LH
What hormone producing cells of the anterior pituitary comprise half of the hormone cells found in the pituitary ?
Somatotrophs (GH)
What hormone producing cells of the anterior pituitary are considered Chromophobes ?
Thyrotrophs : Make TSH
Technically, these cells are pale blue but are less chromatic then the basophils
What is the hallmark of ‘healthy’ pituitary tissue on microscopy ?
BONUS: what kind of tissue is the Ant. pit comprised of ?
The presence of all three cell types (if there is a portion dominated by a single cell type, then it usually points to some kind of adenoma)
BONUS: Ectoderm
The posterior pituitary is called the neurohypophysis because….
It is derived from neural tissue, it is a direct extension of the hypothalamus
What are the modified glial cells of the posterior pituitary known as ? HITSO BONUS: what would they stain with ?
pituicytes
Bonus: GFAP
What are the two peptides that are secreted by the posterior pituitary (produced in the hypothalamus, just released in post. pit.) ?
Oxytocin Arginine Vasopressin (ADH)
Hyperpituitarism (excessive secretion of trophic hormones) is caused by which 5 pathologies ?
Pituitary Adenoma (Only real lesion seen in pit.) Hyperplasia of Pit. Carcinomas of Ant. Pit Ectopic Production of Pit. hormones Hypothalamic disorders.
Hypopituitarism (decreased secretion of trophic hormones ) is typically caused by …
Destructive proscess: Iscehmia Surgery/Radiation Inflammation Non-Functional adenomas
What are the three basic symptoms seen in patients with an enlarged pituitary (adenoma, hyperplasia etc.) ?
ALL ASSOCIATED WITH MASS EFFECT:
Head Ache
Temporal Field Vision Defects
Pituitary dysfunction: Hyperpituitarism (functional ), Hypopituitarism (non-functional)
Sellar expansion with bony erosion and disruption of the diaphragmatic sell of sella turcica are all signs of what condition ?
Enlarged
Why does enlargement of the pituitary cause bilateral temporal hemianopsia ?
Compresses the desiccating fibers of the optic chiasm (optic chasm is anterior to pituitary) by extending superiorly through the diaphragm sella.
Where do most adenomas arise in the pituitary ?
Anterior lobe
What is the most common cause of hyperpituitarism ?
Pituitary adenoma (anterior lobe)
Functional pituitary adenoma
Functional: Makes hormones (in excess) , shows clinical manifestations
Non-Functional pituitary adenoma
IHC/ultrastructural demonstration of hormone production
Leads to Hypopituitarism
Clinically, more associated with Mass Effect
Show Abrupt enlargement of the tumor secondary to acute hemorrhage (pituitary apoplexy)
What is the most common form of pituitary adenoma leading to Hyperpituitarism?
Prolactin Secreting Adenoma
Second most common is GH Secreting, these two are often seen at the same time. Why ? Both Acidophils ?
What age of person is more likely to get Pituitary Adenoma with hyperpituitarism ?
Adults age 35-60
microadenoma
less than 1cm
Macroadenoma size ?
greater than 1 cm
Which is more invasive, micro or macro adenoma ?
Microadenoma
Micro or Macroadenoma :Silent and hormone-negative, come to clinical attn at a later stage.
Macroadenoma
Are pit. adenomas well circumscribed lesions ?
YES
Are pit. adenomas encapsulated ?
NO
What region of the anatomy is the pituitary confined to ? (may extend beyond this when transformed in adenoma can infiltrate surrounding tissues)
The sella turcica
In large adenomas, why do you see regions of necrosis and hemorrhage in the lesion ?
The tumor is outgrowing its blood supply so portion of it will die or burst.
What surrounding tissues can pit. adenomas infiltrate ?
Cavernous and sphenoid sinuses
Dura, and on occasion, the brain
What kind of supporting connective tissue do you often see in pit. adenoma ?
Sparse Reticulin (Soft, gelatinous consistency )
What cellular morphology pattern do you often see in pit. adenoma ?
Monomorphism (only one type of the three staining cell types are typically present)
What normal connective tissue constituent is often missing or in low concentration with pit.adenoma ?
Reticulin network
How are cells arranged in pit. adenoma ?
Relatively uniform, polygonal cells arrayed in sheets or cords
Eosinophilic monomorphism: what cells are most likely involved in this adenoma ?
LACTOTROPHS (Prolactinomais most common)
Could also be GH Secreting Adenoma
Basophilic monomorphism: what cells are most likely involved in this adenoma ?
Corticotrophs or Gonadotrophs (possibly thyrotrophs but this is VERY RARE, also these are more chrmophobic)
What are the two major morphologies of Prolactinoma ?
Sparsely granulated prolactinoma: more chromophobic, weakly acidophilic
Densely granulated prolactinoma: Strongly acidophilic
What kind of calcification is associated with prolactinoma ?
Dystrophic (due to the propensity of adenomas to have necrosis/hemorrhage after outgrowing their blood source).
May be in the form of:
Isolated psammoma bodies(round lamalated concretion)
OR
Extensive calcification (pituitary stone)
Who is most likely to get a pituitary adenoma ?
Women, aged 20-40
What other etiologies beside prolactinoma may lead to increased prolactin secretion ?
Pregnancy
Elevated by nipple stimulation
Response to stress
Hyperplasia of Lactotrophs
Trauma to: Dopaminergic neurons of the hypothalamus (DA is inhibitory to PRL secretion, low DA = High PRL) Pituitary stalk (head trauma) Drugs that block dopamine receptors on lactotroph cells
Pharmaceutical treatment for Prolactinoma ?
Bromocriptine (DA agonist, leads to activation of DA Receptors on Lactotrophs –> decreased PRL synthesis/release.)
Second most common type of functioning pituitary adenoma ?
Growth Hormone Cell Adenoma(GHCA)
(AKA somatotroph cell adenomas)
What are the two histological subtypes of GHCA ?
Densely granulated: Monomorphic and acidophilic.Strong cytoplasmic GH reactivity on IHC
Sparsely granulated:Chromophobe cells with nuclear and cytologic pleomorphism, Focal, weak staining for GH.
Beside GH, what other hormone will be elevated in GHCA ?
IGF-1 (made in the liver in response to GH binding)
GHCA causes gigantism in which age group ?
Children: before the growth plates close
Disporportionately long arms and legs.
Acromegaly is a disease of which age group ?
Adults. After growth plates close (GHCA will cause growth of the skin, soft tissues, Viscera((thyroid, heart, liver, and adrenals)
) and bones of the hands, face and feet)
Which clinical manifestation is most dangerous to patients with acromegaly ?
Growth of the viscera –> cardiomegaly
What is the best test for GHCA ?
Glcuose Load Test: Give a large bolus of glucose to the patient. Normally this would feedback inhibit the release of GH. If it fails to lower GH levels and there are clinical sign of the disease, you most likely have GHCA.
What is the pharmaceutical treatment for GHCA ?
Ocreotide (somatostatin analog, inhibits production of GH)
If this does not work, surgical resection is often done.
What kind of staining would you see in a biopsy of a patient with an ACTH cell adenoma ?
Two Types:
Dense Granular: Basophilic !
Sparse Granular: Chromophobic, slightly basophilic
Which disease (syndrome) is associated with an ACTH Cell Adenoma ?
Cushings Syndrome (Excessive cortisol) Cushings Disease (directly due to Adenoma of the pituitary --> increased ACTH levels
What is this syndrome: After removal of the Adrenal glands for treatment of Cushings, a large destructive adenoma forms from a preexisting ACTH Cell Adenoma ( micro adenoma)
Nelson Syndrome
Why does Nelson Syndrome occur ?
Removal of the adrenal glands takes away the negative feedback from corticosteroids that was keeping the micoadenoma at bey.
Why does Prolactinoma cause amenorrhea ?
Prolactin is actually inhibitory to GnRH. Thus if there is too much prolactin there will be low GnRH. If GnRH is low, FSH and LH will be too low to elicit menses.
Gonadotroph adenomas will lead to increased production of LH and FSH. What will be the effect of increased LH in pre-menopausal women ?
Amenorrhea
What occurs in men with Gonadotroph Adenomas ?
decreasd libido, due to decreased testosterone !
What are Gonadotroph adenomas associated with in the gonads ?
Secondary gonadal hypofucntion
Are thyrotroph adenomas common ?
no, very rare.
Approximately 1% of all pituitary adenomas
Rare cause of hyperthyroidism
What are the most common functional neoplasms associated with Pituitary Carcinoma ?
Prolactin and ACTH
Where are the usual sites of metastases with Pituitary Carcinoma ?
Craniospinal (can be systemic)
What percentage of the anterior pituitary parenchyma must be lost to see clinical hypopituitarism ?
75%
The loss of parenchyma is due to growing Non-functional adenoma. Leads to the healthy pituitary being squashed against the bony portion of the sella.
What is the main cause of hypopituitarism ?
Subarachnoid hemorrhage
Will surgical resection or radiation lead to hypo or hyperpituitarism ?
hypo
Other causes are usually related to tumor or space occupying lesion.
What is pituitary apoplexy ? what does it cause ?
Sudden hemorrhage into the pituitary gland, mostly associated with pituitary adenoma
What are the signs and symptoms of pituitary apoplexy ?
Causes sudden onset of excruciating headache, diplopia, and hypopituitarism
In severe cases: Cardiovascular collapse, loss of consciousness, and sudden death (neurosurgical emergency)
Who gets Sheehan syndrome ?
Post-partum mothers.
SHEEHAN IS THE MOST COMMON FORM OF ISCHEMIC NECROSIS IN THE ANT. PITUITARY GLAND –> HYPOPITUITARISM
What happens during pregnancy that may set a woman up for Sheehan syndrome ?
Enlargement of the pituitary w/o compensatory angiogenesis to sustain such an increase.
What occurs during birth that causes Sheehan syndrome in the mother ?
Loss of blood via hemorrhage. The pituitary is not as vascularized enough for increased growth,so blood loss induces anoxia –> infarct of the pituitary
CAUSE HYPOPITUITARISM
What occurs to the pituitary post infarct/necrosis ?
Resorbed and replaced by a nubbin of fibrous tissue
What other conditions (besides Sheehans) cause necrosis of the pituitary ?
Disseminated intravascular coagulation Sickle cell anemia Elevated intracranial pressure Traumatic injury Shock of any origin
A Rathke Cleft cyst can lead to hypopituitarism. What kind of cells line this structure ?
Lined by ciliated cuboidal epithelium
Occasional goblet cells
What accumulates in cells of a Rathke Cleft Cyst in the pituitary ?
proteinaceous fluid
pituitary dwarfism is due to ….
growth hormone deficiency
Laron dwarfism is due to ….
insensitivity of cells to GH –> Low IGF-1 !
What may be seen in post partum women with hypopitutarism ?
inability to lactate (no PRL released)
What will you see with decreased MSH release from corticotrophs in hypopituitarism ?
Pasty White, translucent ghost motha fuckas. (Decreased melanin production)
Which hypothalamic suprasellar tumor arises most often in the optic chasm ?
Glioma
This suprasellar tumor is derived from vestigial remnants of Rathke’s pouch
Craniopharyngioma
What is the bimodal age range for developing a Craniopharyngioma ?
One peak in childhood at 5-15 yrs
Second peak is in adulthood (65 yrs old)
What occurs to children’s growth when they have a Craniopharyngioma ?
it is retarded. (due to pituitary hypofunction and GH deficiency associated with it)
Are Craniopharyngioma soft and non-encapsulated ?
NOOOO
They are solid and ENCAPSULATED (unlike adenomas)
What neurologic symptoms might you see due to mass effect with Craniopharyngioma ?
Headache and visual disturbances (pressing on optic chiasm) as well as compression of other cranial nerves. They also compress the third ventricle and base of the brain (never a good thing)
Are Craniopharyngioma usually multiloculated or cystic ?
Cystic
Adamantinomatous craniopharyngioma is most often seen in ….
children
This kind of craniopharyngioma calcifies rarely and is seen in adults ….
Papillary craniopharyngioma (adults) Calcifies only rarely
This kind of craniopharyngioma calcifies often and show radiographically dense areas of calcification….
Adamantinomatous craniopharyngioma
“dystrophic calcification”
“Nests or cords of stratified squamous epithelium” with “Compact, lamellar keratin formation (Wet Keratin)” and “peripheral Palisading of the squamous epithelium” describes the histology of this form of craniopharyngioma….
Adamantinomatous craniopharyngioma
wet keratin looks like “sidewalk chalk” according to stevens.
Adamantinomatous craniopharyngioma is often cystic in nature. Describe the contents of the cyst….
Cysts contain a cholesterol-rich, thick brownish-yellow fluid that is “machine oil’-like in color and consistency.
Solid sheets and papillae lined by well-differentiated squamous epithelium and lack keratin, calcification and cyst is descriptive of this kind of craniopharyngioma….
Papillary craniopharyngioma (adults)
What kind of malignancy are craniopharyngiomas at risk for turning into ?
squamous cell carcinomas (usually occurs after radiation)
Minute, pinecone-shaped organ found between the superior colliculi at the base of the brain…
Pineal gland
pineocytes are cells of the pineal gland which are capable of …
photosensory and neuroendocrine functions
What is the principle role of the pineal gland ?
Integration of light stimuli to produce melatonin which regulates circadian rhythm
What kind of tumors do tumors of the pineal gland (rare) resemble ?
seminoma or ovarian dysgerminoma
What are the two classification of pineal gland tumors
Pineoblastoma
Pineocytoma
Based on their level of differentiation
Correlates with their aggressiveness
