Pituitary Tumors Onc26 Pituitary Tumors

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Pituitary Tumors

Last updated: April 4, 2016

Differential Diagnosis of Sellar and Parasellar Tumors 1


Pathophysiology, Pathology 1

Classification 1

Size 1

Hormonal secretion 1

Histology 2

Epidemiology 3

Clinical Features 3

1. Hormonal function control 3

2. Mass effect 3

Diagnosis 4

Skull X-ray 4

Contrast CT 5

Contrast MRI 5

Radionuclide studies 9

Angiography 9

Neuro-ophthalmological evaluation 9

Evaluation of pituitary function 9

Complications 9

Treatment 9

Different Strategies 9

Medical therapy 10

Surgery 10

Postoperatively 10

Radiotherapy 10

Algorithms according to Hormone 11

Prognosis 12

Treatment of recurrence 12



Etiology 12

Clinical Features 12

Diagnosis 12

Treatment 12


Clinical Features 13

Diagnosis 13

Treatment 13


Epidemiology 13

Pathology 13

Grossly 13

Histology 13

Clinical Presentation 15

Diagnosis 15

Treatment 17

Surgery 17

Radiotherapy 18

Chemotherapy 18

Prognosis 18

Neurohypophysis is rare site of neoplasia:

    1. infundibulomas are rare variants of pilocytic astrocytomas.

    2. granular cell tumors (myoblastomas, choristomas) are rare tumors with uncertain cell origin.

Most pituitary tumors are adenomas!

Differential Diagnosis of Sellar and Parasellar Tumors

  1. tumors: pituitary adenoma, pituitary carcinoma, craniopharyngioma, meningioma, metastatic tumors*, optic glioma, chordoma, chondrosarcoma, CN5 schwannoma, dermoid, epidermoid, teratoma, germ cell tumors

*most commonly involve pituitary stalk

H: surgery with histological diagnosis.

  1. not tumors: compression of sella due to hemorrhage, carotid aneurysm, empty sella, Rathke’s cleft cyst, tuber cinereum hamartoma, granulomas (e.g. tuberculosis, sarcoid), lymphocytic hypophysitis?

H: neuroradiological imaging.

  • most common differential for nonsecreting adenoma is craniopharyngioma and empty sella.

  • majority of (para)sellar tumors are benign.

benign ≠ innocent (optic apparatus, hypothalamus, hypophysis)


- neuroepithelial tumors of adenohypophysis.

hormonal syndromes → see p. 2738 >>

Pathophysiology, Pathology

  • putative tumor suppressor gene alterations:

  1. retinoblastoma gene

  2. multiple endocrine neoplasia type I (MEN-I) gene 11q13 (found in 3-4 %) – inherited pituitary adenoma!

  3. p53 deletions correlates with aggressive behavior.

  • pituitary adenomas are not under hypothalamic control.

  • alternative hypothesis: overstimulation (or deranged signaling) from hypothalamus → inappropriate pituitary growth.

  • adenomas grow slowly; initially confined to sella turcica → may grow out of sella and compress / encase / destroy:

    1. optic chiasm

    2. cavernous sinus and internal carotids (lateral extension)

    3. hypothalamus

    4. surrounding bony structures (e.g. sphenoid sinus)

N.B. locally invasive adenomas nearly always are histologically benign! CNS metastases and, rarely, distant metastases can occur!

  • often have small foci of hemorrhage or necrosis, but no mitotic activity.

N.B. pituitary adenomas never have calcifications! (look at CT – if calcium is present, it is craniopharyngioma)

  • adenomas lack discrete capsule, but presence of pseudocapsule facilitates surgical separation.




< 1 cm in diameter – microadenomas

> 1 cm – macroadenomas.

Hormonal secretion

  1. nonsecretors (15-20%) – manifest when reach size of macroadenomamass effect (normal pituitary tissue destruction, pressure on optic chiasm, etc).

  • some nonsecretors secrete α subunit of glycoprotein hormones (FSH, LH, TSH) – suggests origin as gonadotrophs.

  • null cell adenomas demonstrate no evidence (clinical or immunohistochemical) of hormone secretion.

  1. hormone secretors (frequency: prolactin > GH > ACTH > gonadotropins > TSH) – manifest with specific endocrine syndromes. see p. 2738 >>

      • nonsecreting, prolactin-secreting in men*, gonadotropin-secreting, GH-secreting adenomas manifest late (as macroadenomas)!

*main symptom – impotence – men tend to present late for this symptom

      • other adenomas manifest early (still as microadenomas).

      • some tumors secrete multiple hormones (termed null tumors).

      • normally five pituitary cell types are regionally distributed:

lactotrophs and gonadotrophs – widely distributed;

somatotrophs – peripherally (two lateral wings of gland);

thyrotrophs – anteromedially;

corticotrophs – central median wedge.

- on routine staining:

  1. chromophilic cells (acidophilic or basophilic)

  2. chromophobic cells.

N.B. routine staining is meaningless - tumor can be difficult to differentiate from normal tissue or metastatic disease - immunohistochemical staining and electromicroscopy are essential!

  • typical normal acinar structure is lost – adenomas may contain follicular, trabecular, or cystic portions growing as diffuse sheet; cells are arranged in syncytial or sinusoidal pattern; monotonous appearance.

  • nuclei with “salt and pepper” chromatin (s. endocrine chromatin).

  • differentiation of hyperplasia from adenoma may be difficult.

  • types of undifferentiated cell adenomas:

  1. nononcocytic (null)

  2. oncocytoma (s. oxyphil adenoma) - tumor contains buildup of mitochondria.

Adenoma - packeted arrangement of cells resembles that of anterior pituitary, together with prominent vascular network:

d:\viktoro\neuroscience\onc. oncology\00. pictures\pituitary adenoma (micro).jpg

d:\viktoro\neuroscience\onc. oncology\00. pictures\pituitary microadenoma (micro).jpg

Source of picture: “WebPath - The Internet Pathology Laboratory for Medical Education” (by Edward C. Klatt, MD) >>

Photograph of microadenoma (0.9 cm in largest diameter) - incidental null cell adenoma found postmortem; tumor is well delineated and has compressed residual still functional adenohypophysis to crescent shape:

d:\viktoro\neuroscience\onc. oncology\00. pictures\12-4 (allen 1995).jpg

d:\viktoro\neuroscience\onc. oncology\00. pictures\26-2 (macroscopic pituitary adenoma).jpg
d:\viktoro\neuroscience\onc. oncology\00. pictures\26-3 (pituitary adenoma, microscopic).jpg


d:\viktoro\neuroscience\onc. oncology\00. pictures\pituitary macroadenoma (macro).jpg

Source of picture: “WebPath - The Internet Pathology Laboratory for Medical Education” (by Edward C. Klatt, MD) >>


The most common tumor in sella region (except craniopharyngiomas in childhood)

  • 4-20 % of all CNS tumors.

  • most occur in young adults (peak - 3rd-4th decades); children make 10% of all patients.

  • men = women (clinically evident more often in young women); symptomatic prolactinomas and Cushing disease are found more frequently in women.

  • 10% of asymptomatic individuals have focally abnormal pituitary areas on contrast MRI!

  • asymptomatic microadenomas are found in 6-23% of unselected autopsies.

Clinical Features

Most pituitary adenomas can be detected while relatively small (microadenomas) - located in exquisitely sensitive area:

N.B. nonsecreting microadenomas are asymptomatic!

1. Hormonal function control

A) hormonal hypersecretion (most commonly prolactin!)

B) destruction of normal gland → hypopituitarism

N.B. all macroadenomas eventually cause hypopituitarism.

  • if hypopituitarism occurs, hormone loss is sequential: GH → gonadotropins → TSH → ACTH.

  • primary pituitary tumors rarely cause ADH deficiency (except when induced by hypophysectomy); diabetes insipidus is more common in craniopharyngiomas.

2. Mass effect

  1. headache occurs in 20% (can be diffuse and nonpulsatile and may be mistaken for daily headaches; more often in females) – due to stretching of diaphragma sellae and adjacent dural structures; ICP is normal!

N.B. nonspecific headaches may be the only early symptoms, esp. in nonsecreting adenomas!

  • it is still debatable if pituitary tumors can cause / exacerbate headaches, but pituitary surgery is associated with headache improvement or resolution in majority of patients (plus, pituitary surgery was not found to cause or worsen headaches)

Rizzoli P. et al “Headache in Patients With Pituitary Lesions: A Longitudinal Cohort Study” Neurosurgery: March 2016 - Volume 78 - Issue 3 - p 316–323

  1. crossing fibers in optic chiasm (superior bitemporal quadrantanopia → full bitemporal hemianopia - chief and earliest finding in most patients!)

  • relationship of pituitary and optic chiasm:

      1. chiasm directly above pituitary (80%).

      2. chiasm anteriorly to pituitary (9%)

      3. chiasm behind pituitary (11%).

d:\viktoro\neuroscience\onc. oncology\00. pictures\relationship of pituitary and optic chiasm.jpg

  • further expansion compromises noncrossing fibers - affects lower and finally upper nasal quadrants.

  • any pattern of visual loss is possible, e.g.:

  • asymmetrical loss results from chiasm ischemia produced by vessel occlusion.

  • unilateral mass located anterior to postfixed chiasm may produce central scotoma in one eye + upper outer quadrantanopia in contralateral eye (due to von Willebrand's knee - looping of crossing fibers in proximal segment of optic nerve opposite side of their retinal origin) – so called junctional scotoma

Any form of temporal field defect, even if monocular, can result from chiasmal compression

  • some tumors affect only macular fibers → central hemianopic scotomas - may be missed on routine screening (so formal quantitive visual field testing is important in all cases!!!).

  • other findings: optic disc atrophy (generally horizontal-oriented, i.e. bow-tie), dropout of nerve fiber layer in nasal retina, loss of central visual acuity, loss of color vision, visual field defects.

N.B. papilledema is exceptional (seen only in pituitary apoplexy).

  1. lateral extension into cavernous sinus → diplopia, ophthalmoplegias, postganglionic Horner syndrome.

  1. hypothalamic compression (e.g. hyperprolactinemia*, diabetes insipidus, alterations in consciousness, memory, intake of food and water).

*if serum prolactin > 200 μg/L – prolactinoma is more likely!

  1. extension into sphenoid sinusCSF rhinorrhea (≈ 0.5% cases) - cortical bone separating sella from sphenoid sinus is quite thin in normal individuals!

  1. compression of 3rd ventricle → obstructive hydrocephalus.

  1. basal forebrain abnormalities (personality changes, dementia, anosmia).

  1. temporal lobe seizures.

  • pituitary adenomas may enlarge during pregnancy (esp. prolactinomas).


N.B. pituitary adenomas never have calcifications!
Skull X-ray

- limited use.

  • macroadenomas balloon pituitary fossa → asymmetrical floor of pituitary fossa:

frontal projection - one side of fossa is deeper than other;

lateral projection - two more or less parallel lines that create impression of “double floor”.
d:\viktoro\neuroscience\onc. oncology\00. pictures\2-10 (pituitary adenoma, x-ray diagram).jpg
d:\viktoro\neuroscience\onc. oncology\00. pictures\25-1,2.jpg

Contrast CT

(thin-section, direct coronal plane, with bone windows) is usually selected first!

  • macroadenomas are easily detected - hyperdense mass within enlarged pituitary fossa.

  • may miss very small microadenoma (appear as hypodense structures, vs. macroadenomas).

d:\viktoro\neuroscience\onc. oncology\00. pictures\26-1 (pituitary adenoma - ct).jpg

Contrast MRI

- more sensitive method for tumor identification (esp. 1-mm cuts and magnified views through sella – pituitary protocol) - investigation of choice for microadenoma detection!!!

Normal neurohypophysis on T1-MRI shows increased signal (representing neurosecretory granules in ADH-containing axons).
Normal adenohypophysis:

  • T1-MRI - isointense with grey matter.

  • enhances homogeneously (punctate areas of heterogeneity - local variations in vascularity, microcyst formation, or granularity), strongly and rapidly (because it lacks BBB!).

Normal pituitary gland size and configuration are highly variable (esp. in women of childbearing age or pubertal girls – normal hypertrophy of gonadotrophs).

N.B. great care must be exercised in diagnosis of microadenomas on MRI basis without associated evidence of hormonal abnormality.

  • in neonatal period both anterior and posterior lobes are hyperintense and pituitary gland is bulbous in shape.

  • during adolescence and puberty there is significant physiological hypertrophy (in girls upper surface is convex, giving gland almost spherical shape on sagittal views - do not mistake for mass).

Schematic diagram of MRI of normal pituitary fossa: pituitary is bordered laterally by cavernous sinus, which contains internal carotid artery and cranial nerves III, IV, V1 , V2 , and VI; optic chiasm lies immediately above pituitary gland.

d:\viktoro\neuroscience\onc. oncology\00. pictures\25-1 (sabiston 1997).jpg
Source of picture: David C. Sabiston “Sabiston Textbook of Surgery: the Biological Basis of Modern Surgical Practice”, 15th ed. (1997); W.B. Saunders Company; ISBN-13: 978-0721658872 >>


  • unenhanced MRI is not helpful - only some microadenomas have different signal intensity to normal gland.

  • standard MRI protocol for investigation of microadenomas - 1-mm thick coronal T1 spin-echo sequences through pituitary gland before and after IV gadolinium;

  • additional images in sagittal plane are performed in many centers;

  • desirable to perform fat-saturated T1 sequence (fat-suppressed imaging) - eliminates high signal from fat in clivus and clinoid processes (could be mistaken for enhancement).

  • adenomas always enhance less than normal pituitary gland (hypodense area also can represent ischemic stroke in tumor)

  • accuracy can be increased by dynamic pituitary scans (series of rapid images with 10–15 s time intervals for about 3 min following gadolinium IV bolus) - differences in time course of enhancement between adenoma and adjacent normal gland.

N.B. microadenomas enhance later and/or lesser than normal pituitary tissue!

  • other indirect MRI signs:

  1. gland height↑ (normally < 10 mm)

  2. gland upper margin contour alteration from concave or straight to convex

  3. erosion of sella turcica floor adjacent to hypointensity area

  4. displacement of pituitary stalk (normally midline) away from hypointensity area.

Most macroadenomas enhance strongly and uniformly.

  • low-density areas within mass may represent cysts/necrosis/stroke; tumor which enhances only peripherally or not at all may be necrotic.

  • if entire sellar contents are of low density, search for infundibulum - empty sella is much more likely diagnosis than completely cystic pituitary macroadenoma!

  • hemorrhages appear as high-intensity areas.

  • suprasellar extension is easily demonstrated in both coronal and sagittal images.

  • it is more difficult to be sure about lateral extension:

  • displacement of cavernous segments of internal carotid arteries may occur without tumor invasion into cavernous sinus.

  • abnormal signal intensity lateral to this segment of artery, indicates invasion into cavernous sinus.

T2-MRI (left) shows microadenoma; contrast (right) normally enhances pituitary; adenoma appears lighter:

d:\viktoro\neuroscience\onc. oncology\00. pictures\pituitary microadenoma (mri).jpg
Contrast T1-MRI – macroadenoma: adenoma (A) enhances; tumor displaces carotid arteries laterally (black arrows); A1 segments of anterior cerebral arteries (white arrows) and chiasm (arrowheads) drape over mass.

d:\viktoro\neuroscience\onc. oncology\00. pictures\25-8 (sabiston 1997).jpg
Contrast MRI - microadenoma (arrow):

d:\viktoro\neuroscience\onc. oncology\00. pictures\f052028 (abeloff 2000).jpg

Source of picture: Martin D. Abeloff “Clinical Oncology”, 2nd ed. (2000); Churchill Livingstone, Inc.; ISBN-13: 9780443075452 >>

Contrast MRI - macroadenoma (tumor extends out of sella into hypothalamus):

d:\viktoro\neuroscience\onc. oncology\00. pictures\f052029 (abeloff 2000).jpg

Source of picture: Martin D. Abeloff “Clinical Oncology”, 2nd ed. (2000); Churchill Livingstone, Inc.; ISBN-13: 9780443075452 >>

microadenoma - hypodense (arrows) 9 mm in diameter involving right side of pituitary fossa displacing gland and stalk to left:

d:\viktoro\neuroscience\onc. oncology\00. pictures\f420203 (devita 1997).jpg

Source of picture: Vincent T. DeVita Jr. “Cancer: Principles and Practice of Oncology”, 5th ed. (1997); Lippincott Williams & Wilkins; ISBN-13: 978-0397584246 >>

microadenoma (prolactinoma) - hypodense lesion (arrowhead); slight depression of sella floor under tumour:

d:\viktoro\neuroscience\onc. oncology\00. pictures\f098033 (grainger 2001).jpg

Source of picture: Ronald G. Grainger, David J. Allison “Grainger & Allison’s Diagnostic Radiology: A Textbook of Medical Imaging”, 4th ed. (2001); Churchill Livingstone, Inc.; ISBN-13: 978-0443064326 >>

Dynamic coronal T1-MRI;

  1. scan at 90 s following injection of gadolinium reveals microadenoma (arrowhead), which has enhanced to lesser degree than surrounding normal pituitary tissue.

  2. after 4 min enhancement is similar to rest of gland.

d:\viktoro\neuroscience\onc. oncology\00. pictures\f098034 (grainger 2001).jpg

Source of picture: Ronald G. Grainger, David J. Allison “Grainger & Allison’s Diagnostic Radiology: A Textbook of Medical Imaging”, 4th ed. (2001); Churchill Livingstone, Inc.; ISBN-13: 978-0443064326 >>

Contrast T1-MRI: > 1 cm intrasellar mass; note tumor expansion into sphenoid sinus, extension into suprasellar cistern with partial compression of optic chiasm (arrows):

d:\viktoro\neuroscience\onc. oncology\00. pictures\f0110180 (paul and juhl 1998).jpg

Source of picture: John H. Juhl “Paul and Juhl’s Essentials of Radiologic Imaging”, 7th ed. (1998); Lippincott Williams & Wilkins; ISBN-10: 0-397-58421-0 >>

Prolactin-secreting microadenoma: T1-MRI with contrast - hypodense lesion in left pituitary; upward convex margin of left lobe of gland, indicating focal expansion (arrow):

d:\viktoro\neuroscience\onc. oncology\00. pictures\f0110170 (paul and juhl 1998).jpg

Source of picture: John H. Juhl “Paul and Juhl’s Essentials of Radiologic Imaging”, 7th ed. (1998); Lippincott Williams & Wilkins; ISBN-10: 0-397-58421-0 >>

macroadenoma (contrast T1-MRI) - invasion of left cavernous sinus - tumor (white arrow) surrounds left internal carotid artery and sinus appears expanded; normal enhancement of uninvolved right cavernous sinus although tumour encroaches under supraclinoid portion of right internal carotid artery (black arrowhead):

d:\viktoro\neuroscience\onc. oncology\00. pictures\f098035 (grainger 2001).jpg

Source of picture: Ronald G. Grainger, David J. Allison “Grainger & Allison’s Diagnostic Radiology: A Textbook of Medical Imaging”, 4th ed. (2001); Churchill Livingstone, Inc.; ISBN-13: 978-0443064326 >>

Hemorrhagic macroadenoma (T1-MRI without contrast) - hyperintense intrasellar mass; fluid level within this lesion (arrow); pituitary fossa has been expanded; surgery revealed hemorrhagic fluid within macroadenoma:

d:\viktoro\neuroscience\onc. oncology\00. pictures\f0110190 (paul and juhl 1998).jpg

Source of picture: John H. Juhl “Paul and Juhl’s Essentials of Radiologic Imaging”, 7th ed. (1998); Lippincott Williams & Wilkins; ISBN-10: 0-397-58421-0 >>

GH-secreting macroadenoma with left cavernous sinus invasion (T1-MRI without contrast) - convex outward margin of left cavernous sinus (arrow); left internal carotid is elevated:

d:\viktoro\neuroscience\onc. oncology\00. pictures\f0110200 (paul and juhl 1998).jpg

Source of picture: John H. Juhl “Paul and Juhl’s Essentials of Radiologic Imaging”, 7th ed. (1998); Lippincott Williams & Wilkins; ISBN-10: 0-397-58421-0 >>

MRI - hemorrhage into tumor (apoplexy):

d:\viktoro\neuroscience\onc. oncology\00. pictures\f054002a (rowland; merritt\'s 1995).jpgd:\viktoro\neuroscience\onc. oncology\00. pictures\f054002b (rowland; merritt\'s 1995).jpg

  1. CT with contrast - macroadenoma with suprasellar and parasellar extension.

  2. MRI with contrast following bromocriptine therapy shows marked decrease in tumor size such that infundibulum and optic chiasm are decompressed (arrow).

d:\viktoro\neuroscience\onc. oncology\00. pictures\f054006a (rowland; merritt\'s 1995).jpgd:\viktoro\neuroscience\onc. oncology\00. pictures\f054006b (rowland; merritt\'s 1995).jpg

  1. MRI - macroadenoma filling sphenoid sinus and extending into 3rd ventricle floor.

  2. suprasellar component compressing optic chiasm (arrow).

  3. following gross total resection through extended frontal craniotomy - infundibulum is well decompressed (arrow).

  4. no residual tumor, optic chiasm and portion of infundibulum can be clearly seen (arrow).

d:\viktoro\neuroscience\onc. oncology\00. pictures\f054007a (rowland; merritt\'s 1995).jpgd:\viktoro\neuroscience\onc. oncology\00. pictures\f054007b (rowland; merritt\'s 1995).jpg

d:\viktoro\neuroscience\onc. oncology\00. pictures\f054007c (rowland; merritt\'s 1995).jpgd:\viktoro\neuroscience\onc. oncology\00. pictures\f054007d (rowland; merritt\'s 1995).jpg
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