Stains & CD markers
Pit1


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PubMed Search: Pit1

William McDonald, M.D.
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Cite this page: McDonald W. Pit1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsPIT1.html. Accessed January 29th, 2023.
Definition / general
  • Pituitary adenoma / pituitary neuroendocrine tumor has traditionally been classified using a combination of immunohistochemical stains for anterior pituitary hormones, including stains for prolactin, growth hormone, thyrotrophs (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenocorticotropic hormone (ACTH) and the alpha subunit (ASU) of the glycoprotein hormones
  • Immunostains for anterior pituitary transcription factors, pituitary transcription factor 1 (Pit1), steroidogenic factor 1 (SF1) and T box transcription factor (Tpit) have been shown to have higher sensitivity and specificity than hormone IHC stains and are often used in conjunction with them to classify pituitary adenomas
    • Transcription factor Pit1 drives lactotroph, somatotroph and thyrotroph differentiation and IHC for Pit1 is useful in identifying pituitary adenomas in this lineage
  • Immunohistochemical stains for Pit1 identify nonneoplastic populations within the anterior pituitary, including lactotroph, somatotroph, mammosomatotroph and thyrotroph cells
    • IHC for Pit1 is principally used for identifying pituitary adenomas of the Pit1 lineage, both silent and functioning
Essential features
  • Pit1 IHC shows strong nuclear staining
  • Pit1 is expressed in the anterior pituitary gland within normal lactotroph, somatotroph, mammosomatotroph and thyrotroph cells as well as within adenomas showing differentiation along these lines
  • As a marker of Pit1 lineage adenomas, Pit1 IHC is more sensitive and specific than IHC stain for prolactin, growth hormone and TSH (Mod Pathol 2018;31:900, Pituitary 2022;25:997)
Terminology
  • Common name: pituitary transcription factor 1 (Pit1)
  • Formal protein name: POU class 1 homeobox 1
  • Gene name (HUGO Gene Nomenclature Committee [HGNC] approved gene symbol): POU1F1
Pathophysiology
  • Pit1 is a pituitary specific transcription factor that drives differentiation of lactotroph, somatotroph, mammosomatotroph and thyrotroph cells
  • Rare cases of pituitary hormone deficiency can be caused by germline mutations in the gene for Pit1 (POU1F1)
Diagrams / tables

Contributed by William McDonald, M.D.
Pit1 drives the lineage containing lactotroph, somatotroph, mammosomatotroph and thyrotroph cells

Pit1 drives lineage between cells

Pituitary adenomas with Pit1 expression

Clinical features
  • Pit1 lineage adenomas may be hormonally functional, whispering (minimally functional) or silent
  • Functional adenomas tend to be smaller; macroadenomas are often hormonally silent
Interpretation
  • Nuclear expression is evaluated (reactivity only in the cytoplasm is regarded as negative)
  • Pit1 immunoreactivity in Pit1 lineage adenomas is typically diffuse, strong and nuclear (score 7 or 8 in the Allred IHC scoring scale) (Mod Pathol 1998;11:155)
  • Immunoreactivity in nonneoplastic anterior pituitary gland shows moderate to strong nuclear staining in many adenohypophysis cells, corresponding to lactotroph, somatotroph, mammosomatotroph and thyrotroph cells, which comprises the majority of adenohypophysis cells
  • Pit1 lineage pituitary adenomas commonly show immunoreactivity patterns that do not neatly fit into current WHO nomenclature (Pituitary 2022;25:997)
Uses by pathologists
  • Useful for diagnosis of Pit1 lineage adenomas
    • More sensitive than antibodies to growth hormone, prolactin or TSH (Mod Pathol 2018;31:900, Pituitary 2022;25:997)
    • Also present within normal anterior pituitary gland, so the presence of pituitary adenoma must be supported by morphology in H&E stains, occasionally with the support of ancillary stains such as reticulin or other transcription factors
  • Often used in conjunction with IHC for SF1 and Tpit to establish the lineage of a pituitary adenoma (Arch Pathol Lab Med 2021;145:592, Endocr Pathol 2015;26:349)
Prognostic factors
  • Pit1 IHC by itself is not prognostic
Microscopic (histologic) images

Contributed by William McDonald, M.D.

Normal adenohypophysis

Pituitary adenoma associated with acromegaly

Lactotroph adenoma

Plurihormonal Pit1 lineage tumor

Positive staining - normal
Positive staining - disease
Negative staining
Sample pathology report
  • Sella turcica, resection:
    • Pituitary adenoma (pituitary neuroendocrine tumor), somatotroph type (see comment)
    • Comment: This tumor shows diffuse nuclear immunoreactivity for Pit1 and no immunoreactivity for SF1, Tpit, prolactin or TSH. Immunoreactivity for growth hormone is strong and a low molecular weight cytokeratin CAM5.2 immunostain shows diffuse cytoplasmic staining without a prominent globular pattern, suggesting that this is a densely granulated subtype of somatotroph adenoma.
    • Clinical information (mandatory to include): The patient presented with enlargement of hands and feet and coarsening of facial features. Magnetic resonance imaging showed a 16 mm hypoenhancing mass within the pituitary gland.
    • Available preoperative endocrine testing (also mandatory):
      • IGF1: 858 (33 - 220 ng/mL)
      • GH: 16 (0.01 - 0.97 ng/mL)
      • PRL: 6.70 (2.64 - 13.13 ng/mL)
      • Cortisol: 9.5 (a.m. draw 5.0 - 25.0 ug/dL)
      • TSH: 1.02 (0.35 - 4.94 uIU/mL)
Board review style question #1

A 61 year old man presents with hypogonadotropic hypogonadism. MRI reveals a 2.5 cm sellar and suprasellar tumor. No signs or symptoms of hormone excess are clinically present. Hormone testing confirms low serum testosterone and minimally elevated serum prolactin, attributed to stalk effect. Transsphenoidal resection confirms pituitary adenoma by H&E stain. The adenoma shows immunohistochemical staining as illustrated above. How is this adenoma best classified?

  1. Corticotroph adenoma
  2. Gonadotroph adenoma
  3. Mature plurihormonal Pit1 lineage adenoma
  4. Null cell adenoma
Board review style answer #1
C. Mature plurihormonal Pit1 lineage adenoma. This otherwise clinically silent adenoma became symptomatic when hypogonadism was detected. Strong, diffuse nuclear immunoreactivity for Pit1, widespread prolactin immunoreactivity and patchy growth hormone and TSH immunoreactivity are present; immunoreactivity for both GATA3 and estrogen receptors is also present. Diffuse, cytoplasmic staining for CAM5.2 is also observed. Corticotroph adenoma (answer A) would have strong, diffuse Tpit immunoreactivity with variable ACTH staining and low molecular weight cytokeratin positivity. Gonadotroph adenoma (answer B) often presents in a similar fashion as a clinically nonfunctioning macroadenoma; therefore, it would have SF1 immunoreactivity and lack staining for Pit1. Null cell adenoma (answer D) by definition lacks hormone or transcription factor immunostaining.

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