P- Pituitary and Sellar Region Flashcards
What percent of intracranial neoplasms are pituitary adenomas?
What age people are affected?
What is the most common hormone secreted?
10-15% of intracranial neoplasms are pituitary adenomas.
98% occur in adults.
The most common hormone producing adenoma is one that secretes prolactin.
Patients with pituitary adenomas can present in what 2 ways?
- symptoms of mass effect (headache, visual disturbance, loss of normal pituitary function due to compression of the native gland)
- symptoms of hormone excess
What are the 3 most common “mass effects” caused by pituitary tumors?
Which is most common?
- headache
- visual deficiency due to compression of optic chiasm [more common than LOF]
- LOF due to compression of the pituitary gland [insidious onset]
In addition to compression of the normal gland, what other structures can be invaded by pituitary adenomas?
- upward –> brain
- lateral –> cavernous sinuses
- downward–> paranasal sinuses/nasal cavity
A young woman presents with amenorrhea and galactorrhea. What adenoma are you concerned about?
Lactotroph cell adenoma (secretes prolactin)
*This is the most common hormone producing adenoma
What adenoma are you concerned about if a younger patient presents with gigantism or an older patient presents with acromegaly?
Somatotroph cell adenoma (GH)
What adenoma are you concerned with if the patient has signs/symptoms of Cushing’s disease?
Corticotroph cell adenoma (ACTH)
*small and difficult to find if hormonally active
What is the most common presenting manifestation of thyrotroph cell adenoma?
hyperthyroidism (however this is a rare cause)
What is the most common presenting manifestation of gonadotroph cell adenoma?
Mass effect
What is the most common presenting manifestation of null cell adenoma?
Mass effect [may in fact be FSH/LH tumors]
What are the 2 most common combinations of mixed adenoma (plurihumoral)?
- GH/prolactin
2. GH/prolactin/TSH
What is the difference between microadenoma, macroadenoma and giant?
Micro = less than 10mm diameter Macro = 10mm to 4cm Giant = over 4cm
Describe the histology of a pituitary adenoma.
- small columnar/cuboidal/polygonal cells
- monomorphic [all cells look the same]
- round/oval nuclei [2x size of lymphocyte]
- “salt and pepper” chromatin [neuroendocrine]
**mitotic figures are UNCOMMON
What is the age at which prolactin-producing adenomas are likely to occur?
What determines the degree of hyperprolactinemia?
20-40 years old
Hyperprolactinemia varies with tumor size.
How do prolactin-producing adenomas differ between men and women?
Women:
- get tumors earlier
- microadenomas
- lower serum prolactin [400 ng/ml]
- amenorrhea, galactorrhea
Men
- get tumors later
- macroadenomas
- higher serum prolactin [2000 ng/ml]
- decreased libido, sexual impotence
What is the effect of prolactin-producing adenoma on prepubertal girls and boys? Pubertal?
Prepubertal children have symptoms of mass effect:
- headache
- visual disturbance
- growth failure
Pubertal Girls:
- mass effect
- menstrual abnormalities/pubertal delay
- galactorrhea
Pubertal Boys:
- mass effect
- growth arrest
- pubertal delay
Why does compression of the pituitary stalk lead to elevated serum prolactin? How much does serum prolactin usually increase by?
What is this phenomenon called?
Dopamine is secreted from PVN and arcuate nucleus of the hypothalamus into the pituitary gland to inhibit secretion of prolactin.
If the pituitary stalk is compressed by a neoplastic or non-neoplastic mass, dopamine will not get to the pituitary gland.
Prolactin will be increased but below 100 ng/ml.
This is called “stalk effect”.
In general, a prolactin level over ______ indicates an adenoma.
250 ng/ml
Describe prolactin-producing adenomas:
- on imaging
- grossly
- histologically
Imaging: microadenoma
Grossly: soft, tan-red mass
Histologically:
- monomorphic
- round-to-oval nuclei [sometimes elongated, pleomorphic]
- architecture is “sheet-like”
- densly OR sparsely granulated
- psammoma bodies [lamillated calcific structure]
- interstitial deposits of amyloid
What genetic component is associated with prolactin-producing adenomas?
Most are sporadic, however, there has been a link to MEN-1 [where they are the most common pituitary adenoma type]
What is treatment for prolactin-producing adenomas?
Dopamine agonists because they:
- reduce tumor size
- lower serum prolactin concentration
GH producing adenomas are composed of cells differentiating as ________________________. This excess GH can lead to _________ in children and _________ in adults.
adenohypophyseal somatotrophs
Children –> gigantism
Adults –> acromegaly
What is acromegaly?
- Enlargement of hands, feet due to soft tissue hypertrophy.
- Coarse facial features
- large tongue/uvula [leads to sleep apnea]
What signs/symptoms are associated with:
- mass effect of GH-producing adenoma [3]
- excess GH/IGF-1 effect of adenoma [4]
Mass Effect:
- visual symptoms due to impinging on optic chiasm
- hydrocephalus [3rd ventricle]
- ophthalmoplegia [invaded cavernous sinus]
Excess GH/IGF1:
- gigantism/acromegaly
- obstructive sleep apnea (due to enlarged tongue/uvula)
- peripheral arthropathy (articular cartilage overgrowth)
- LV hypertrophy –> arrhythmia
How is the laboratory diagnosis of GH- producing adenoma made?
What is treatment?
Diagnosis:
demonstrating elevated IGF-1 in the plasma
Treatment:
- surgery
- SST analogs—-I GH secretion
What are the 3 ways GH secreting adenomas are classified?
- Entirely somatotrophs - classify by the density of their secretory granules
- Mammosomatotroph - individual cells produce BOTH GH and prolactin
- Mixed GH-prolactin adenomas
How do densely granulated somatotrophs differ histologically from sparsely granulated?
Dense:
- columnar/cuboidal
- monomorphic
- round-to-oval nuclei
- abundant cytoplasmic granules
Sparse:
- pleomorphic nuclei
- fewer granules
- paranuclear keratin filaments (fibrous bodies)
What genetics are associated with GH secreting adenomas?
Most occur sporadically, howevern some occur as a component of MEN-1.
MEN1 - 0-37%
Carney’s complex - 10-20%
ACTH producing adenomas are neoplasms composed of cells differentiating as ____________________. The neoplastic cells make ________ in excess.
Adenohypophyseal corticotrophs which make excess proopiomelanocortin (POMC).
POMC is a peptide from which ACTH is cleaved.
What age group and sex are ACTH secreting adenomas more common in?
Women (8:1)
30-40 years old
What is the difference between Cushing’s disease and Cushing’s syndrome?
How can you clinically determine the difference?
Disease = the constellation of symptoms due to production of excess ACTH by a pituitary adenoma
Syndrome= constellation of symptoms due to excess cortisol by a NON-PITUITARY SOURCE [such as an adrenal tumor].
The location of the excess can be determined by tested based on the negative feedback control of cortisol.
Pituitary problem will have high serum ACTH
Adrenal problem/anywhere else will have low ACTH because the cortisol will have negatively fed-back on the H-P axis
What are the 6 major symptoms of Cushing’s?
- excess fat in abdomen, neck, supraclavicular
- thinning of skin
- purple stria on chest/abdomen
- insulin resistance
- immunocompromised/susceptible to infection
- neuropsychiatric symptoms [depression, sleeplessness, emotionally labile]
How is the laboratory diagnosis of Cushing’s syndrome established?
- measuring total cortisol in the urine/24hrs
2. demonstrating loss of circadian rhythm of cortisol secretion
What is seen on imaging, grossly, and histologically for ACTH secreting adenomas?
Imaging: 80% microadenoma, 5% macro, 15% below detection of imaging
Gross: soft and red. SO SMALL that they are difficult for surgeons to find.
Histology:
- monomorphic cells
- round-to-oval nuclei
- abundant basophilic cytoplasm
- immunohistochemically stains for ACTH
What is a “silent” ACTH adenoma? How does the clinical course compare to other ACTH adenomas?
It is when a pituitary adenoma has immunohistochemically stained for ACTH but there is no clinical presentation/biological signs of hypercortisolism.
These tumors have a MORE aggressive clinical course.
What are the genetic components of ACTH secreting adenomas?
They are mostly sporadic, but they can occur as a component of MEN-1.
What is the definition of a “null cell adenoma”?
It is a pituitary adenoma with cells differentiating as adenohypophyseal cells with NO immunohistochemical differentiation.
[rarely, they will express FSH or LH]
What gender and age group are null cell adenomas most common in?
There is no gender specificity.
Null cell adenomas are common in OLDER patients and do not occur younger than 40
Null cell adenomas show no signs/symptoms related to excess hormone secretion except for what?
What symptoms are shown will null cell adenomas?
Prolactin could be elevated due to stalk effect [loss of dopamine inhibition of prolactin secreting cells]
Mass effect symptoms:
- headache
- visual disturbances
- loss of normal pituitary function
How do null cell adenomas appear on imaging? Grossly?
Histologically?
Imaging: large and invade cavernous sinuses or extend into hypothalamus or nasal cavity. They may contain CYSTS filled with hemorrhage or clear fluid
Gross: yellow-tan, soft
Histologically:
- columnar, polygonal
- round/oval nuclei
- sheet-like architecture
What is the genetic association of null cell adenoma?
There is none.
[no definite association with MEN-1 or Carney’s complex]
What is pituitary apoplexy?
What kind of tumor does it occur most often with?
Sudden enlargement of an adenoma due to hemorrhage, often with accompanying infarction.
Occurs most frequently with large, non-secreting adenomas [like null cell]
A patient presents with subarachnoid hemorrhage, increased intracranial pressure, headache, visual symptoms, and worsened hypopituitarism. What is the likely cause?
Pituitary apoplexy
What are the 5 symptoms of pituitary apoplexy?
- subarachnoid hemorrhage
- hypopituitarism
- visual disturbance
- increased intracranial pressure
- headache
What is a pituicytoma?
What part of the pituitary gland does it affect?
It is a neoplasm composed of neurohypophyseal pituicytes in the posterior pituitary.
Pituicytes are supporting glial cells of the post. pituitary.
What grade are pituicytomas?
What age patient is mostly affected by them?
WHO 1 = non-infiltrative, expanding mass
Adults 40-60 are most affected
How do pituicytomas look on imaging, grossly, and histologically?
Imaging: well-circumscribed ANYWHERE in the posterior pituitary so can be suprasellar or intrasellar
Gross: tan and rubbery
Histologically:
- elongated, bipolar glial cells
- monomorphic eliptical nuclei
- architecture is intersecting fascicles
What are the 3 pituitary/sellar neoplasms most frequently found in children?
- craniopharyngioma
- pilocytic astrocytoma
- germ cell tumors
What are the 3 most common sellar region neoplasms in adults?
- pituitary adenoma
- meningioma
- craniopharyngioma
What cells make up craniopharyngiomas? How do they develop?
What are the two histologic variants?
Craniopharyngiomas are squamous epithelial tumors of the sellar region that develop due to proliferation of cells in Rathke’s pouch.
- papillary [only 40-55]
- adamantinomatous {more common 5-15 and 45-60}
What is the age distribution for craniopharyngiomas?
What histologic type is present in each age group?
5-15 = adamantinonmatous 45-60 = adamantinomatous
40-55 = papillary
What is the grade of craniopharyngiomas?
WHO 1 = well differentiated, non-invasive, expanding mass
What are the signs and symptoms of craniopharyngioma in adults? Children?
Who is more likely to get diabetes insipitus?
When would elevated intracranial pressure present?
Adults = visual disturbances
Children = endocrine disturbances
Diabetes insipitus in 15% kids, 30% adults
Elevated intracranial pressure if the third ventricle is involved
What is seen on imaging for craniopharyngiomas?
There will be well-circumscribed masses usually in the suprasellar region
What is seen grossly for craniopharyngiomas?
How do adamantinomatous and papillary differ?
Adamantinomatous have variegated with:
- cystic areas - dark greenish-brown fluid
- fibrotic areas
- calcification
- cells clustered near vessels or nerves or brain
Papillary do NOT have cysts or calcifications
Describe the histology of adamantinomatous variant of craniopharyngioma.
How does it differ from papillary?
- basaloid cells at interface with brain
- loose connective tissue
- cords/lobules of well-differentiated squamous epithelial cells
- nodules of keratin
- cysts fill with squamous debris
Papillary does NOT have basaloid layer or nodules of keratin
What mutations are associated with craniopharyngiomas?
Adamantinomatous are associated with B-catenin mutations.
Papillary are not associated with mutations
What is the prognosis of craniopharyngiomas?
What is the key factor for recurrence?
10 year recurrence free and 10 year survival are 60-90%
The key factor for recurrence is the extent of resection [tumors >5cm have worse prognosis]
What is the most common glioma in children? What is the grade of this tumor?
What is the age and sex distribution?
Pilocytic astrocytoma - slow growing astrocytoma
WHO1 = well-circumscribed, non-infiltrative, space expanding
Less than 20years old with no sex preference.
Where are pilocytic astrocytomas located?
Throughout the CNS most frequently in:
- cerebellum
- thalamus, hypothalamus, optic pathways
A child presents with headache, nausea, vomiting and clumsiness. What tumor are you concerned about and in what location?
Pilocytic astrocytoma in the cerebellum
If a child patient presents with hemiparesis, what tumor are you concerned about and what location would it be in?
Pilocytic astroctroma in the thalamic region because the hemiparesis is from impingement on internal capsule
How do pilocytic astrocytomas appear on imaging?
- well-circumscribed
- contrast enhancing
- cystic
How do pilocytic astrocytomas look grossly? Histologically?
Grossly - well demarcated grey, soft, tan, cystic
Histologically:
- astrocytic cells have hair-like cytoplasmic processes
- biphasic architecture with:
- packed, overlapping bipolar astrocytes
- loosely arranged stellate astrocytes - Rosenthal fibers (eosinophilic corkscrew)
- eosinophilic granular bodies
What genetics are associated with pilocytic astrocytomas?
- 15% of patients with NF1 (neurofibromatosis type 1) develop pilocytic astrocytoma in the optic nerves
- Sporadic = loss of 17q (NF1 suppressor gene)
What determines prognosis for pilocytic astrocytomas?
- location
- extent of resection
- presence/absence of NF1
Where are Rathke’s cleft cysts found?
What size must they be to become symptomatic?
It is located between the anterior and posterior pituitary.
If the cyst is >1cm it can extend into the sella and suprasellar region and become symptomatic
Describe the histology of Rathke’s cysts.
- single layer of columnar epithelium on thin layer of collagenous connective tissue
- goblet cells
- ciliated cells
- cells surround watery/mucoid material
[can have squamous metaplasia! the opp. of Barrett’s]
What is lymphocytic hypophysitis?
Inflammatory infiltrate in the anterior pituitiary as a result of an autoimmune disorder.
It leads to pancreatic insufficiency.
Who is usually affected by lymphocytic hypophysitis?
women in late pregnancy and sometimes after delivery.
How does lymphocytic hypophysitis appear grossly and microscopically?
Gross: areas of the gland affected are firm
Histologic:
- B and T lymphocytes
- plasma cells
- histiocytes
- lymphoid follicles with germinal centers
What other endocrine organs are frequently affected in lymphocytic hypophysitis?
- adrenal gland
2. thyroid
What is treatment for lymphocytic hypophysitis?
- corticosteroids
- hormone replacement
- surgical decompression of the pituitary gland
