[PATH] Pituitary Pathology

Question 1

Histologically, typical pituitary adenomas are composed of what type of cells and how are they arranged?

Answer 1

Uniform, polygonal cells arrayed in sheets or cords

Question 2

What 2 morphological features of pituitary adenomas distinguish them from non-neoplastic anterior pituitary parenchyma?

Answer 2

Cellular monomorphism and absence of a reticulin (CT) network

Question 3

Atypical adenomas have a higher propensity for aggressive behavior and are associated with mutations in which gene?

Answer 3

TP53

Question 4

Which genetic mutation is seen in many pituitary adenomas, especially somatotroph cell adenomas; leads to what signaling effects?

Answer 4

GNAS mutations —> α subunit of G_s loses GTPase activity—> ↑↑↑ cAMP

Question 5

Peak age(s) of incidence for pituitary adenomas?

Answer 5

35 to 60 years of age

Question 6

Sometimes rapid enlargement of a pituitary adenoma can lead to acute hemorrhage into an adenoma, a situation known as what?

Answer 6

Pituitary apoplexy

Question 7

Some pituitary adenomas can secrete 2 hormones, what is the most common combination?

Answer 7

GH and prolactin = Bihormonal mammosomatotroph adenoma

Question 8

Large pituitary adenomas, particularly nonfunctioning ones, may cause hypopituitarism how?

Answer 8

By encroaching on and destroying adjacent anterior pituitary parenchyma

Question 9

What is the most common type of lactotroph adenoma based on morphology and what is the major type of cell/characteristics?

Answer 9

• Sparsely granulated lactotroph adenoma
• Comprised of chromophobic cells w/ juxtanuclear localization of the TF PIT-1

Question 10

Lactotroph adenomas have a propensity to undergo what type of morphological change?

Answer 10

Dystrophic calcification, ranging from psammoma bodies to a “pituitary stone.”

Question 11

Serum concentrations of what tend to correlate with the size of a lactotroph adenoma?

Answer 11

Prolactin

Question 12

What are the most common presenting sx’s of lactotroph adenoma in women?

Answer 12

• Amenorrhea
• Galactorrhea
• Diminished libido
• Infertility

Question 13

What are the most common presenting sx’s of lactotroph adenoma in men?

Answer 13

• Decreased libido
• Decreased sperm count
• Mass effect** –> Macroadenomas more common

Question 14

What is another cause of pathologic hyperprolactinemia in the absence of a lactotroph adenoma?

Answer 14

Lactotroph hyperplasia due to loss of dopamine-mediated inhibition of prolactin secretion

Question 15

Hyperprolactinemia in the absence of an adenoma may also be due to what other disease states?

Answer 15

Renal failure or hypothyroidism

Question 16

Lactotroph adenomas can be treated with what drugs?

Answer 16

Dopamine agonists - Bromocriptine or Cabergoline

Question 17

Which 2 serum markers are indicative of a GH-secreting somatotroph adenoma?

Answer 17

↑↑↑↑ GH and IGF-1 levels

Question 18

What is one of the most sensitive tests for acromegaly?

Answer 18

Failure to suppress GH production in response to an oral glucose load

Question 19

What are 2 pharmacological tx options for GH-secreting somatotroph adenomas?

Answer 19

Somatostatin analogs or GH receptor antagonists

Question 20

Majority of corticotroph adenomas are what size at the time of diagnosis?

Answer 20

Microadenomas

Question 21

What is the most commonly seen morphology of corticotroph adenomas?

Answer 21

Basophilic (densely granulated) and occassionally chromophobic (sparsely granulated)

Question 22

Corticotroph adenomas stain positively with what stain due to the presence of POMC?

Answer 22

PAS

Question 23

Explain the mechanism underlying the development of a large destructive pituitary adenoma aka Nelson Syndrome.

Answer 23

Develops folllowing surgical removal of adrenal glands for tx of Cushing Syndrome due to loss of the inhibitory effect of adrenal corticosteroids on a preexisting coritcotroph adenoma

Question 24

How do patients with Nelson Syndrome most commonly present?

Answer 24

With mass effect (i.e., HA’s or bitemporal hemianopia) due to the pituitary tumor and hyperpigmentation due to stimulatory effect of POMC on melanocytes

Question 25

What changes to the skin may be seen with Hypercortisolism?

Answer 25

**Thinning** of skin and **striae**

Question 26

What are the 3 major types of cancer associated with paraneoplastic secretion of ACTH or ACTH-like substance leading to Cushing Syndrome?

Answer 26

- Small-cell carcinoma of lung - Pancreatic carcinoma - Neural tumors

Question 27

How can the high-dose dexamethasone suppression test help to distinguish corticotroph adenomas from ACTH-secreting tumors?

Answer 27

Corticotroph adenomas will show **suppression** of ACTH on **high-dose** dexamethasone suppression test

Question 28

How will corticotroph adenomas respond to CRH stimulation test vs. ACTH-secreting tumors?

Answer 28

Corticotroph adenomas will have ↑↑↑ response to CRH stimulation test

Question 29

Pharmacologic tx of corticotroph adenomas?

Answer 29

**Somatostatin analogs** or **bromocriptine** since some express dopamine receptors and somatostatin receptors

Question 30

The presence of what are essential conditions for the presence of a pituitary carcinoma?

Answer 30

Presence of **craniospinal** or **systemic metastases**

Question 31

Pituitary apoplexy in its most dramatic presentation produces sudden onset of what sx's?

Answer 31

- Excruciating HA - Diplopia - Hypopituitarism

Question 32

Which mutation is associated with familial pituitary adenomas, known as pituitary adenoma predisposition (PAP) syndrome?

Answer 32

Loss-of-function of **AIP**

Question 33

What is the most common form of clinically significant ischemic necrosis of the anterior pituitary?

Answer 33

**Sheehan syndrome** aka postpartum necrosis

Question 34

List some conditions which may be associated with pituitary necrosis

Answer 34

- DIC - Sickle cell anemia - ↑ ICP - Traumatic injury - Shock

Question 35

What are Rathke cleft cysts lined with and how can they lead to hypopituitarism?

Answer 35

- **Ciliated cuboidal epithelium** w/ occasional **goblet cells** and anterior pituitary cells - Can **accumulate** proteinaceous fluid and expand

Question 36

What occurs in primary empty sella syndrome?

Answer 36

Defect in diaphragma sella causes arachnoid mater + CSF to herniate into the sella, expanding the sella and compressing the pituitary

Question 37

Primary empty sella syndrome is most commonly seen in whom?

Answer 37

**Obese women** w/ a hx of **multiple pregnancies**

Question 38

How do individuals with primary empty sella syndrome commonly present?

Answer 38

**Visual field defects** and occasional endocrine abnormalities such as **hyperprolactinemia**

Question 39

What occurs in secondary empty sella syndrome?

Answer 39

**Pituitary adenoma enlarges** the sella and is then either surgically removed or undergoes infarction --\> loss of pituitary function + **empty space**

Question 40

What is an example of an inflammatory disorder and infection which can involve the hypothalamus and cause deficiencies of anterior pituitary hormones and diabetes insipidus?

Answer 40

- Sarcoidosis - Tuberculous meningitis

Question 41

Craniopharyngiomas may be seen in which 2 age groups; what is the most common type and dysfunction caused in each?

Answer 41

- **Kids** (5-15 y/o) = **adamantinomatous craniophryngiomas**; growth retardation from hypopituitarism - **Adults** (\>65 y/o) = **papillary craniopharyngiomas**; signs of ↑ ICP or hypopituitarism

Question 42

What are 4 histological findings of adamantinomatous craniopharyngiomas?

Answer 42

- **Squamous** epithelium embedded in **spongy "reticulum"** w/ **"palisading"** at the periphery - **"Wet"** **keratin** - **Calcified** **cyst** aka **dystrophic calcification** - Cholesterol-rich, thick brownish yellow fluid (**"machine oil"**)

Question 43

Cerebral edema w/ resultant neuro dysfunction is associated with what disorder of ADH?

Answer 43

SIADH

Question 44

What do the papillary type of craniopharyngiomas lack histologically?

Answer 44

Usually lack **keratin, calcification**, and **cysts**