Pituitary gland

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The pituitary gland is known as the master gland.

Divisions:[1]

  • Anterior pituitary (AKA adenohypophysis, pars distalis).
  • Posterior pituitary (AKA neurohypophysis, neural pituitary, pars nervosa).

Function

Anterior

Hormones:[2]

  • Growth hormone (GH).
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
  • Thyroid stimulating hormone (TSH)
  • Adrenocorticotropic hormone (ACTH)
  • Prolactin (PRL)

Mnemonic: "Go Look For The Adenoma Please" = GH, LH, FSH, TSH, ACTH, PRL.

Intermedia

  • Originates from the posterior wall of the Rathke’s pouch.
  • Hormones: MSH, ACTH precursor.
  • Contains colloid cysts.

Posterior

Hormones:[2]

  • Oxytocin.
  • Antidiuretic hormone (ADH).

Anatomy and histology

Anatomy

Basic anatomy (simplified):[3]

  • Anterior:
    • Pars distalis.
    • Pars intermedia.
  • Posterior:
    • Pars nervosa.

Embryological origin:[3]

  • Anterior - Rathke's pouch (roof of mouth).
  • Posterior - diencephalon (ventral aspect).

Images:

Histology

Anterior

  • Acidophils (40% of cells) = red or orange.
    • GH, PRL.
  • Basophils (10% of cells) = basophilic (light blue).
    • TSH, LH, FSH, ACTH.
  • Chromophobes (50% of cells) = amphophilic (purplish/grey).

Notes:

  • The cellular product (i.e. hormone produced) is not strictly correlated with the cell type.[4]
  • The cells can be typed using IHC; somatotrophs (GH), lactotrophs (PRL), corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH, LH).[5]

Posterior

Features:[4]

  • Herring bodies - key feature.
    • Eosinophilic axonal dilations filled with lysosomes and neurosecretory granules.
  • Less cellular.
    • Usually more cellular in perivascular location.

Image: Herring bodies (ouhsc.edu).

  • Pituitary gland, low magnification (WC/Athikhun.suw)

DDx for sella turcica lesions

Pituitary necrosis

  • Rare.

Causes of pituitary necrosis

  • Sheehan syndrome - secondary to blood loss in childbirth.[6]
  • Syphilis (fetal-maternal transmission).[7]
  • Mollaret's meningitis - very rare.[8] (???)
  • Spontaneous necrosis of pituitary tumours - case reports.[9]

Images:

Specific entities

Pituitary neuroendocrine tumor (PitNET)

Old terminology Pituitary adenoma is depreceated

General

  • Clinical:[10]
    • Classically: visual field defects (bitemporal hemianopsia).
    • Others (increased intracranial pressure): headache, nausea, vomiting.
    • Tumor of adults.

Morphologic Classification:

  1. Microadenoma <= 1 cm.
  2. Macroadenoma 1-4 cm.
  3. Giant adenoma > 4cm.

May be classified by what they secrete.

  1. Functional (endocrine hyperfunction).
    • Acromegaly/giantism.
    • Hyperprolactinemia.
    • Cushing disease.
    • Hyperthyroidism.
    • Significant elevation of FSH/LH.
  2. Clinically nonfunctioning.

Notes: 

Cushing disease is due to pituitary gland hypersecretion of ACTH (due to a pituitary adenoma or CRH hypersecretion from the hypothalamus).[11]  Cushing syndrome is hypercortisolism not due to pituitary gland pathology.

Imaging:

  • Sellar enlargement.
  • Bone erosion, invasive growth esp. cavernous sinus (35-45%).
  • Inhomogenous signal in T1w MRI.

Familial pituitary adenomas

A pituitary adenoma may be part of a familial syndrome:[12][13]

Syndrome Gene Notes
Multiple endocrine neoplasia I MEN1 characterized by the 3 Ps: pituitary adenoma, parathyroid adenoma, pancreatic neuroendocrine tumour
MEN-1-like syndrome CDKN1B[14] also known as Multiple endocrine neoplasia IV [14]
Carney syndrome PRKAR1A other findings (mnemonic NAME): nevi, atrial myxoma, myxoid neurofibroma, ephelides (freckles)
Isolated pituitary adenoma[15] AIP classically GH-producing adenoma - leads to acromegaly

Microscopic

Features:[16]

  • Loss of fibrous stroma.
    • The cells of a normal (anterior) pituitary are nested.
  • Basophilic cells (corticotrophs).
  • Eosinophilic cells(somatotrophs).

Notes:

  • Smears very well.[17]

The WHO 2022 Classification of tumours of endocrine organs recoginizes following tumours:[18]


PitNET lineage PitNET type subtypes Hormone secretion Transcription factor
PIT1 Somatotroph tumor Densely and sparsely granulated tumor GH, a-subunit+/-, CK+ PIT1
PIT1 Lactotroph tumor Densely and sparsely granulated tumor PRL, CK-ve or weak PIT1, ER
PIT1 Mammosomatotroph tumor GH, PRL (usu. less), CK perinuclear +ve PIT1, ER
PIT1 Thyrotroph tumor TSH, CK-ve or weak PIT1, GATA3
PIT1 Mature plurihormonal PIT1 lineage tumor GH, PRL, TSH, a-subunit +/-ve PIT1, ER, GATA3
Corticotroph adenoma Densely and sparsely granulated adenoma, Crooke cell adenoma ACTH,CAM 5.2 TPIT
Gonadotroph adenoma Sparsely granulated adenoma FSH, LH or a-Subunit SF1, ER, GATA2
Null cell adenoma None None

Other tumours may be classified as plurhormonal or double adenomas or as adenomas with unusual IHC combination.


Images

  • Pituitary adenoma - non-functioning. (WC/KGH)

  • Extensive interstitial and perivascular fibrosis in a pituitary adenoma (WC/jensflorian)

  • Pituitary adenoma - PRL producing, HE. Note the basophilic appearance of the cells (WC/jensflorian)

  • Pituitary adenoma - PRL producing, HE. Extensive regressive changes after after dopamine agonist treatment (WC/jensflorian)

  • Pituitary adenoma - PRL producing, Prolactin IHC (WC/jensflorian)

  • Pituitary adenoma - HGH producing, HE. The cells have a slightly eosinophilic appearance (WC/jensflorian)

  • Sparsely granulated adenoma - HGH producing. Note the numerous fibrous bodies in HE stain (WC/jensflorian)

  • Sparsely granulated adenoma - HGH producing. CK8 IHC highlighting fibrous bodies (WC/jensflorian)

  • Pituitary adenoma - TSH producing. HE stain showing pleomorphism (WC/jensflorian)

  • Pituitary adenoma - TSH producing. TSH IHC can be heterogeneous (WC/jensflorian)

  • Pituitary adenoma - GH producing. (WC/KGH)

  • Pituitary adenoma , HE. This gonadotropin producing adenoma has a papillary architecture (WC/jensflorian)

  • Pituitary adenoma, IHC for FSH (WC/jensflorian)

  • Pituitary adenoma, IHC for LH (WC/jensflorian)

  • Pituitary adenoma , ACTH producing. PAS-O-G stain showing basophilic adenoma cells (WC/jensflorian)

  • Pituitary adenoma , ACTH producing. Strong ACTH IHC in this basophilic adenoma (WC/jensflorian)

  • Pituitary adenoma with vascular pseudorosettes, nonfunctioning (WC/jensflorian)

  • Crooke cell adenoma, HE (WC/Marvin101)

  • Crooke cell adenoma, panCK (WC/Marvin101)

  • Fibrosis in pituitary adenoma.

Stains

  • Reticulin - loss of reticulin between tumour cells.

IHC

  • LH.
  • FSH.
  • TSH - Hyperthyroidism
  • GH - Acromegaly.
  • Prolactin -Galactorrhea, Amenorrhea, Gynecomastia. Golgi staining pattern in sparsely granulated cases.
  • ACTH - Cushing syndrome.
  • PIT-1: stains somatotrophs, lactotrophs and thyrothrops.
  • TPIT: stains corticotrophs.
  • SF1: stains gonadotrophs.
  • Chromogranin A +ve
  • Synaptophysin strongly +ve (except lactotrophs)
  • CAM5.2: fibrous bodies in sparsely granulated somatotroph adenoma, Ring-like staining in Crooke cell adenoma.
  • MIB-1: Usu less than 3%.

Note: Null-cell adenoma must be hormone immunonegative and negative for transcription factors.

Variants

  • Corticotroph adenomas exhibiting Crooke's hyaline change: agressive course.[19]
  • Acidophilic stem cell adenomas: large, locally invasive adenoma with low GH activity. [20]
  • Sparsely granulated somatotroph adenomas are more invasive than other variants and respond less to medical treatment. [21]
  • Lactotroph adenomas in men may show aggressive clinical behavior. [22]
  • Poorly differentiated PIT-1 positive adenomas may show aggresive growth. [23]

Pituitary blastoma

  • New entity introduced in 2017[24]
  • Epithelial glands with rosette-like formations resembling immature Rathke epithelium.
  • Synaptophysin +ve, usu. ACTH+ve
  • DICER1 mutations[25]

Pituitary carcinoma

  • ICD-O: 8272/3
  • Requires presence of cerebrospinal or systemic metastasis.
  • Very rare.
  • 75% are hormonally active (mostly PRL or ACTH).
  • IHC: Synaptophysin, Chromogranin +ve

Rathke cleft cyst

General

  • Benign counterpart of craniopharyngioma.
  • Arises from intermediate lobe of pituitary gland (pars intermedia of pituitary gland).

Radiology:

  • Typically no calcifications.[26]

Radiologic DDx:[26]

Microscopic

Features:

  • Lined by a layer of cuboidal or columnar epithelial with cilia.
  • +/-Goblet cells.[27]
  • +/-Squamous metaplasia ~ may be several layers thick.
  • Cholesterol clefts may be seen in association with rupture.[29]

DDx:

Images:

Craniopharyngioma

Main article: Craniopharyngioma

Gangliocytoma

  • Neuronal cells in abundant neuropil.
  • S-100, Synaptophysin +ve.
  • Isolated sellar cases are very rare.

Image: [[1]]

Mixed Gangliocytoma-adenoma

AKA: ganglioneuroma, pituitary adenoma with neuronal choristoma (PANCH)

  • Neuronal cells mixed with pituitary adenoma cells.
  • Approx. 0.25% of all pituitary adenomas.
  • Association with somatotroph adenomas (acromegaly).

Pituicytoma

Main article: Pituicytoma

Spindle cell oncocytoma

  • Origin: Neurohypophysis or infundibulum.
  • Benign clinical course - WHO grade I.
  • Elongated bipolar, spindle cells.
  • Fascicular or storiform growth patterns.
  • EMA: patchy, S-100+/-ve, GFAP+/-ve, TTF1+ve.
  • It is thought that Spindle cell oncocytomas and Granular cell tumors of the neurohypophysis are variants of Pituicyoma.[30]

Granular cell tumor of the sellar region

Main article: Granular_cell_tumour
  • Origin: Neurohypophysis or infundibulum.
  • Benign clinical course - WHO grade I.
  • Well circumscribed.
  • Polygonal cells with abundant granular cytoplasm.
  • CD68+ve, S-100+/-ve, GFAP+/-ve, TTF1+ve.

  • Granular cell tumor of the sellar region (HE).

Autoimmune hypophysitis

General

Features:[31]

  • Rare.
  • Autoantigens are unknown.
  • May occur in pregnancy.
  • May be misdiagnosed as a nonsecreting adenoma.

Microscopic

Features:[31]

  • Lymphocytic infiltration.

  • Lymphocytic hypophysitis, CD3 IHC. (WC/jensflorian)

See also

References

  1. ↑ http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo.html
  2. ↑ 2.0 2.1 http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Pituitary.html
  3. ↑ 3.0 3.1 URL: http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/histo_pit.html. Accessed on: 31 October 2010.
  4. ↑ 4.0 4.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 26. ISBN 978-0443069826.
  5. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1098-9. ISBN 978-1416031215.
  6. ↑ URL: http://www.mayoclinic.com/health/sheehans-syndrome/DS00889. Accessed on: 16 November 2010.
  7. ↑ URL: http://pediatrics.aappublications.org/cgi/content/full/104/1/e4. Accessed on: 16 November 2010.
  8. ↑ Dancer CM, Woods ML, Henderson RD, Robertson T, Mungomery M, Allworth A (July 2008). "Mollaret's meningitis and pituitary failure associated with a Rathke's cleft cyst". Intern Med J 38 (7): 609–11. doi:10.1111/j.1445-5994.2008.01709.x. PMID 18715308.
  9. ↑ Sachdev Y, Evered DC, Hall R (April 1976). "Spontaneous pituitary necrosis". Br Med J 1 (6015): 942. PMC 1639254. PMID 1268492. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1639254/pdf/brmedj00512-0028a.pdf.
  10. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1100. ISBN 978-1416031215.
  11. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1148. ISBN 978-1416031215.
  12. ↑ Elston, MS.; McDonald, KL.; Clifton-Bligh, RJ.; Robinson, BG. (Aug 2009). "Familial pituitary tumor syndromes.". Nat Rev Endocrinol 5 (8): 453-61. doi:10.1038/nrendo.2009.126. PMID 19564887.
  13. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 554. ISBN 978-1416054542.
  14. ↑ 14.0 14.1 Online 'Mendelian Inheritance in Man' (OMIM) 600778
  15. ↑ Korbonits, M.; Storr, H.; Kumar, AV. (May 2012). "Familial pituitary adenomas - Who should be tested for AIP mutations?". Clin Endocrinol (Oxf). doi:10.1111/j.1365-2265.2012.04445.x. PMID 22612670.
  16. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 36. ISBN 978-0443069826.
  17. ↑ MUN. 24 November 2010.
  18. ↑ "Overview of the 2022 WHO Classification of Pituitary Tumors". Endocr Pathol 33 (1): 6–26. March 2022. doi:10.1007/s12022-022-09703-7. PMID 35291028.
  19. ↑ George, DH.; Scheithauer, BW.; Kovacs, K.; Horvath, E.; Young, WF.; Lloyd, RV.; Meyer, FB. (Oct 2003). "Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma.". Am J Surg Pathol 27 (10): 1330-6. PMID 14508394.
  20. ↑ Horvath, E.; Kovacs, K.; Singer, W.; Smyth, HS.; Killinger, DW.; Erzin, C.; Weiss, MH. (Feb 1981). "Acidophil stem cell adenoma of the human pituitary: clinicopathologic analysis of 15 cases.". Cancer 47 (4): 761-71. PMID 6261917.
  21. ↑ Kato, M.; Inoshita, N.; Sugiyama, T.; Tani, Y.; Shichiri, M.; Sano, T.; Yamada, S.; Hirata, Y. (2012). "Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas.". Endocr J 59 (3): 221-8. PMID 22200580.
  22. ↑ Delgrange, E.; Vasiljevic, A.; Wierinckx, A.; François, P.; Jouanneau, E.; Raverot, G.; Trouillas, J. (Jun 2015). "Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth.". Eur J Endocrinol 172 (6): 791-801. doi:10.1530/EJE-14-0990. PMID 25792376.
  23. ↑ Mete, O.; Gomez-Hernandez, K.; Kucharczyk, W.; Ridout, R.; Zadeh, G.; Gentili, F.; Ezzat, S.; Asa, SL. (Feb 2016). "Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas.". Mod Pathol 29 (2): 131-42. doi:10.1038/modpathol.2015.151. PMID 26743473.
  24. ↑ Lopes, MBS. (Oct 2017). "The 2017 World Health Organization classification of tumors of the pituitary gland: a summary.". Acta Neuropathol 134 (4): 521-535. doi:10.1007/s00401-017-1769-8. PMID 28821944.
  25. ↑ de Kock, L.; Sabbaghian, N.; Plourde, F.; Srivastava, A.; Weber, E.; Bouron-Dal Soglio, D.; Hamel, N.; Choi, JH. et al. (Jul 2014). "Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations.". Acta Neuropathol 128 (1): 111-22. doi:10.1007/s00401-014-1285-z. PMID 24839956.
  26. ↑ 26.0 26.1 URL: http://emedicine.medscape.com/article/343629-overview. Accessed on: 14 November 2010.
  27. ↑ URL: http://www.endotext.org/neuroendo/neuroendo3/neuroendo3.html. Accessed on: 27 May 2010.
  28. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 408. ISBN 978-0443069826.
  29. ↑ URL: http://path.upmc.edu/cases/case177/dx.html. Accessed on: 8 January 2012.
  30. ↑ Mete, O.; Lopes, MB.; Asa, SL. (Nov 2013). "Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma.". Am J Surg Pathol 37 (11): 1694-9. doi:10.1097/PAS.0b013e31829723e7. PMID 23887161.
  31. ↑ 31.0 31.1 Tzou SC, Lupi I, Landek M, et al. (July 2008). "Autoimmune hypophysitis of SJL mice: clinical insights from a new animal model". Endocrinology 149 (7): 3461–9. doi:10.1210/en.2007-1692. PMC 2453094. PMID 18388197. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453094/.

External links

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