173. Hypothalamus-Pituitary Histo-Path

Question 1

Which nuclei of hypothalamus secrete AVP? Oxytocin?

How does the Ant Pit look on histo? Which cells are acidophilic (red)? Which are basophilic (blue)?

What does the Post Pit look like on histo?

What is the pars intermedia

Answer 1

AVP = supraoptic nuclei
Oxytocin = PVN

Ant pit - epithelial cells compartmentalized into small nest-like acini by reticulin network
Red: somatotrophic (GH), lactotrophic (PRL)
Blue: corticotrophic (ACTH), thyrotrophic (TSH), gonadotrophic (FSH, LH)

Post pit: axons and terminals: axonal expansions visible as HERING BODIES (finely granular, round-to-ellipsoidal structures, pink, contains AVP/Oxytocin), axons supported by specialized glial cells (PITUICYTES)

Pars Intermedia: vestigial structure in humans at interface b/w ant and post pit, cystic change is frequent, likely site of origin of Rathke’s Cleft Cysts

Question 2

Which part of pituitary most susceptible to infarction? Why?

What does infarction look like on histo?

Answer 2

ANT PIT - supplied by low pressure portal venous circulation from hypothalamus

Post pit - supplied by direct branches of inferior hypophyseal arteries

Infarction: central necrosis, loss of nested acinar structure

Question 3

Pituitary Adenoma

• what are they?
• what is CP related to?
• how is it classified on path?
• what are morphological features?

Answer 3

MOST COMMON CAUSE OF HYPERPIT
Present in 14% gen pop (common)
CP due to: secretion of excess hormone, hypopituitarism (local destruction), mass effect
Path: classified by immunohistochemical profile and other features (what hormone it produces)
Morph: monomorphic constituent cells (proliferation of one cell type), paucity (loss) of reticulin network (no sheaths on reticulin stain), low mitotic activity
Types: prolactinoma, GH adenoma, ACTH adenoma, gonadotroph adenoma, thyrotroph cell adenoma, nonfx adenoma

Question 4

Prolactinoma

• epi
• sx
• histo
• ddx
• tx

Answer 4

Epi: most common pit adenoma, micro or macro
Sx: females (amenorrhea, galactorrhea) males (impotence, loss of libido)
Histo: sparsely granulated or densely granulated, many secretory vesicles; dystrophic calcification (pituitary stone)
DDx: must distinguish from STALK EFFECT (tumor in stalk, PRL < 150 - high but not adenoma high)
tx: bromocriptine, cabergoline

Question 5

GH-producing (somatotroph cell) adenoma

• epi
• sx
• histo

Answer 5

epi: 2nd most common, most are macro (long time for sx to appear)
sx: high IGF = acromegaly, gigantism
histo: sparsely granulated, look for Fibrous bodies (solid round perinuclear inclusions)
PRL often present with GH (both have same precursor and are acidophilic)

Question 6

ACTH-producing adenoma

• epi
• histo
• sx/disease types

Answer 6

Epi: usually micro ad dx due to sx
Histo: basophilic, densely granulated, PAS+ ACTH reactive
Sx: hypercortisolism
Cushing Sydrome - hypercortisolism regardless of cause
Cushing Disease - hypercortisolism due to ACTH adenoma
Nelson Syndrome - enlargement of ACTH adenoma after removal of both adrenal glands (loss of negative feedback)

Question 7

Gonadotroph (FSH-LH) cell adenoma
- epi, sx

Thyrotroph (TSH) cell adenoma
- epi, sx

Nonfunctioning pituitary adenoma

• epi
• sx

Answer 7

FSH-LH

• almost always macro
• sx: hypogonadism, sx due to mass effect

TSH

• usually macro
• rare cause of hyperthyroidism

Nonfx

• null cell variant, 25-30% all pit adenomas
• negative hormone stain, diffuse positive neuroendocrine markers
• most often macroadenoma
• sx: mass effect +/- hypopituitarism

Question 8

Pituitary Carcinoma

• Dx
• signs

Answer 8

Defined by presence of metastases and/or craniospinal dissemination (clinical dx)
Poor correlation with cytological atypia (cannot tell if ca on histo!)

Most are hormonally active, extremely rare

Question 9

Rathke’s Cleft Cyst (what is it, histo)

Lymphocytic Hypophysitis (who, what, signs, histo)

CNS Sarcoidosis (what it is, histo)

Tuberculosis Meningitis (histo)

Answer 9

RCC: originate from remnants of Rathke’s pouch (in pars intermedia)
Histo: ciliated cuboidal epithelium (like sino-nasal mucosa - from oral ectoderm)

LH: most common during pregnancy/post-partum
autoimmune disorder
Signs: symmetrical enlargement of pit with ant pit insufficiency (destruction)
Histo: pit gland evenly infiltrated by lymphocytes

CNSS: assoc w/ systemic sarcoid, affects structures in suprasellar region, histo: non-caseating granulomatous inflammation w/ multinucleated giant cells (Langhan’s Giant Cell)

TB Meningitis: caseating granuloma

Question 10

Sheehan’s Syndrome vs. Pituitary Apoplexy (what are they?)

Answer 10

Sheehans: ischemic necrosis usually post-partum bleeding causing ant pit ischemia/infarct

Apoplexy: sudden hemorrhage into pit gland, often occuring into pit adenoma (neurosurgical emergency)!

Question 11

Diabetes insipidus vs. Inappropriate ADH secretion

- variants/causes of each

Answer 11

DI: central and nephrogenic variants
Central: due to primary DI (idiopathic/hereditary), trauma (SURGERY MOST COMMON CAUSE), vascular disease, neoplasms, infections, inflammatory diseases

SIADH: caused by extra-CNS disorders (MOST COMMON) and some CNS diseases
extra-CNS: neoplasia (small cell carcinoma of lung), adrenal insufficiency, myxedema, cirrhosis, cardiac disease, drugs (blood volume loss)
CNS: trauma, CNS infections, neoplasms (local destruction)

Question 12

Hypothalamic Suprasellar Tumors
- give pt population and histo findings for the following:
Adamantinomatous Craniopharyngioma
Papillarycraniopharyngioma
Germinoma

Answer 12

AC: kids + adults, suprasellar w/ intrasellar extension, surgically curable
Histo: “wet keratin” (not flaky), peripheral palisading nuclei (bunched in periphery), squamous cells (proliferate)

PC: exclusively adults (40-55yo)
histo: well-differentiated squamous epithelium w/o keratin, less palisading, papillary structure of squamous epithelium

G: children + young adults, most common CNS germ cell tumor, usually pineal/suprasellar
histo: tumor cells w/ clear cytoplasm, lymphocytes