Pituitary Pathology Flashcards
Overview of sellar region masses
*Know this for tests
a. 85%+ of sellar region masses are pituitary adenomas, which although not formally graded, are equivalent to WHO grade I; almost all the other non‐pituitary
adenoma sellar region masses are also WHO grade I and treated by surgical
resection except in instances where medical therapies are available
i. These Pituitary adenomas are the most common, and they are usually benign (WHO Grade 1 equivalent)
ii. TX with surgery
b. Some pituitary adenomas are hyperfunctioning and produce physiologically‐ unregulated excess of endocrine hormone(s); many are clinically non functioning and produce mass effect or visual disturbances due to compression of critical nearby anatomical structures
i. usually benign (may have mass effect), sometimes will produce high amount of hormone
c. Most uncommon (Rathke cleft cyst), or rare, sellar region masses (pituicytoma,
spindle cell oncocytoma, hypophysitis) closely mimic pituitary adenomas on
neuroimaging and clinically mimic clinically non functioning pituitary adenomas in
that they present with mass effects or visual disturbance
d. All except craniopharyngioma predominantly affect middle age adults;
craniopharyngioma has two age peaks, pediatric (5‐15 yrs) and middle age (45‐60
yrs) adults
Development of the pituitary gland
a. The hypophysis is an amalgam of two tissues.
b. Early in gestation a finger of ectoderm grows upward from the roof of the mouth.
i. This protrusion is called Rathke’s pouch and will develop into the anterior pituitary or adenohypophysis.
c. At the same time that Rathke’s pouch is developing, another finger of ectodermal tissue evaginates ventrally from the diencephalon of the developing brain.
i. This extension of the ventral brain will become the posterior pituitary or neurohypophysis.
d. Ultimately, the two tissues grow into one another and become tightly apposed, but their structure remains distinctly different, reflecting their differing embryological origins.
Anterior and posterior pituitary gland
12 weeks (left)
Adult posterior gland (right)
a. TTF-1 is a transcription factor that is found in the posterior pituitary
i. use antibody for this transcription factor after 12 weeks
Pituitary gland at 22 weeks gestation
a. The pituitary hormones will begin secreting at 8 weeks of gestation
b. Every few weeks, new types of hormones are secreted
Microadenoma
a. By definition, a microadenoma (seen in the image below) is a tumor less than 10 mm in diameter.
b. Pituitary adenomas may secrete hormones, but most are clinically inactive.
c. Many pituitary lesions are discovered while investigating other neurologic problems; these lesions are called incidentalomas.
d. With the use of MRI increasing, the discovery of such incidental microadenomas will become more of a clinical problem
macroadenoma
The sellar region is a site of various types of tumors. Pituitary adenomas are the most common. They arise from epithelial pituitary cells and account for 10-15% of all intracranial tumors. Tumors exceeding 10 mm are defined as macroadenomas, and those smaller than 10 mm are termed microadenomas. Most pituitary adenomas are microadenomas.
Invasive
macroadenoma
a. May not invade blood vessels… But it can invade:
bone,
sphenoid sinus,
dura
b. Can compress against nerves in cavernous sinus
i. Can compress CN 4,5 and 6
Key Points
a. Less than 5% of pituitary tumors are familial; the rest are sporadic
b. Identifications of inherited pituitary syndromes is important because of the associated pathologies; pituitary tumors might be the presenting feature in these syndromes and important implications exist for family members
c. Four genes have so far been identified as associated with familial pituitary tumors syndromes: MEN1, CDK1B, PRKAR1A, and AIP
d. Up to 20% of patients with clinical features of multiple endocrine neoplasia type 1 do not have a mutation in MEN1; these patients might have mutation CDK1B or other genes not yet identified
e. AIP has been identified as a mutated gene in patients with familial isolated pituitary adenomas, particularly thosewho have adenomas that secrete growth hormone
f. Features that suggest an inherited pituitary tumor syndrome include parathyroid tumors, pancreatic endocrine tumotrs, atrial myxomas, lentigines Schwann-cell tumors (Carney complex), family history and young age at onset
tuitary blastoma related to DICER1 mutation, almost always ACTH IHC(+)
a. Pediatric/young adults occasionally get pituitary adenomas and this population is enriched for syndromic examples; very rare infantile pituitary masses are a different entity: pituitary blastoma
b. Almost all other pituitary adenomas SPORADIC
i. Incidental pituitary adenomas very
common at autopsy— and on neuroimaging
Work up of pituitary adenoma
Find subtypes of pituitary adenoma
*all sorts of staining, don’t need to know
H&E Reticulin CAM5.2 Synaptophysin Prolactin (PRL) Growth hormone (GH) Adrenocorticotrophic hormone (ACTH)
Follicle stimulating hormone (FSH)
(alpha subunit, luteinizing hormone (LH), ER (estrogen receptor)
Also helpful: neurofilament protein (NFP), TTF‐1 for identifying posterior gland or pituicytomas,
anti‐mitochondrial antibody
Transcription factors delineate lineage
Different Adenoma by transcription factor family
- Pit-1
- SF-1
- Tpit
- Transcription Factor negative/unknown
- Plurihormonal adenoma
*85% of usual ACTH adenomas are microadenomas, most prolactinomas in premenopausal women are microadenomas
Pituitary adenoma type by transcription factor family
a. Pit‐1 (pituitary transcription factor)
i. Densely granulated somatotroph (growth hormone) adenoma
ii. Intermediate/mixed/transitional growth hormone adenoma (behaves like densely granulated growth hormone adenoma
iii. Sparsely granulated growth hormone adenoma
iv. Mixed growth hormone‐prolactinoma
v. Mammosomatotroph adenoma
vi. Sparsely granulated prolactin secreting (lactotroph) adenoma
viii. Densely granulated prolactin secreting (lactotroph) adenoma
viii. Acidophil stem cell adenoma
ix. Thyrotroph (TSH) adenoma
x. Silent subtype 3 adenoma (all with Pit‐1, variable GH/PRL/TSH)
b. SF‐1 (steroidogenic factor)
i. Gonadotroph adenoma, with or without IHC(+) for FSH, LH*
(*presence of SF‐1 defines gonadotroph adenoma even if hormone negative)
c. Tpit
i. Densely granulated ACTH (corticotroph) adenoma
ii. Sparsely granulated ACTH (corticotroph) adenoma
iii. Crooke cell adenoma
iv. Clinically silent ACTH adenoma (either densely granulated, i.e. subtype I, or sparsely granulated, i.e., subtype II)
d. Transcription factor negative/unknown
i. Null cell adenoma*
(*increasingly defined as SF‐1, Pit‐1, ACTH IHC negative [Tpit IHC not as widely available])
e. Plurihormonal adenomas
i. Uncertain lineage
7.
Subtyping by hormonal status does matter
85% of usual ACTH adenomas are microadenomas,
most prolactinomas in premenopausal women are microadenomas
Pituitary Adenomas
Non Secretors/weak secretors - Generally present with symptoms of mass effects
a. Headaches
b. Visual Field Deficits
c. Cranial Nerve Palsies
– Ptosis (eyelid droop)
– Diplopia (double vision)
d. Pituitary Hormone Deficits
(Panhypopituitarism)
e. Rarely
– Seizures
– Stroke
– CSF Leak
Classic visual deficit for Pituitary Adenoma
a. Bilateral temporal hemianopsia is classic visual deficit
b. Will lose sight of the lateral visual fields that hit the nasal portion of the eye
i. Crossing fibers at optic chiasm are compressed