CNS Tumor
Tumors of the sellar region
Pituitary Hyperplasia

Author: Nelli S. Lakis, M.D., M.Sc. (see Authors page)

Revised: 18 October 2016, last major update October 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Pituitary Hyperplasia[title]
Cite this page: Pituitary Hyperplasia . PathologyOutlines.com website. http://pathologyoutlines.com/topic/cnstumorpituitaryhyperplasia.html. Accessed August 20th, 2017.
Definition / general
  • Nonneoplastic increase in adenohypophyseal cell number
Essential features
  • Nodular hyperplasia without compressive features or a diffuse increase in pituitary cells without effacement of gland architecture
Epidemiology
Sites
  • Adenohypophysis
Pathophysiology
  • Physiologic response to end - organ failure
    • Most common: Prolactin cell hyperplasia in pregnancy, lactation or estrogen treatment
    • ACTH cell hyperplasia due to hypocortisolism in Addison disease
    • TSH cell hyperplasia with longstanding primary hypothyroidism
    • Gonadotroph hyperplasia in primary hypogonadism due to Klinefelter or Turner syndrome
  • Pathologic hyperplasia associated with ectopic excess of releasing hormones
    • GH cell hyperplasia due to increased GH releasing hormone secreted by pancreatic islet cell tumor, pheochromocytoma, bronchial and thymic carcinoid tumors
    • ACTH cell hyperplasia due to corticotropin releasing hormone secretion from hypothalamic hamartoma or neuroendocrine tumors
  • Syndromic: mammosomatotroph hyperplasia in McCune - Albright syndrome, Carney complex
  • Idiopathic
  • Hereditary (J Clin Endocrinol Metab 2011;96:E2078)
Clinical features
Hormone related hyperplasia
  • GH cell: gigantism or acromegaly
  • Prolactin cell: hyperprolactinemia
  • ACTH cell: Cushing disease
  • TSH cell:
    • Hyperprolactinemia
    • Long standing primary hypothyroidism results in TSH hyperplasia
    • Lack of negative feedback from thyroxine (T4) leads to elevated levels of TRH that stimulates both pituitary TSH and PRL cells (Endocrinol Diabetes Metab Case Rep 2015;2015:150056)
  • LH-FSH: result of early onset hypogonadism
Diagnosis
  • Biopsy - Excision
  • Rarely removed surgically
  • Most likely identified at autopsy
Laboratory
  • Hormonal levels as indicated
Radiology description
  • Symmetric 2 - 3x enlargement of pituitary gland on CT / MRI
  • Homogeneously enhancing gland with convex superior margin
  • No sellar destruction
Radiology images

Images hosted on other servers:
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Sagittal and coronal magnetic
resonance images

Prognostic factors
  • Excellent with medical treatment
  • Rarely associated with adenoma
Case reports
  • Three family members (ages 1, 2 and 33 years old) with very early onset of gigantism associated with abnormally high serum levels of GH and prolactin, and diffuse mammosomatotroph hyperplasia of pituitary (J Clin Endocrinol Metab 2011;96:E2078)
  • 46 year old woman with typical Cushing syndrome and a rare case of pituicytoma accompanied by corticotroph hyperplasia (Medicine (Baltimore) 2016;95:e3062)
  • Treatment
    • Usually correct underlying endocrinologic disturbance
    • Surgery: for GH and ACTH hyperplasia
    • Adjuvant therapy: medical treatment for hypothyroidism
    Gross description
    • In the rare event the entire gland is removed, it is diffusely enlarged and tan white with no discernible nodules
    • Specimen may be fragmented
    Microscopic (histologic) description
    • Nodular hyperplasia
      • Mild acinar expansion <
      • Relative cellular monomorphism within affected acinus
      • Noncompressive; indistinct demarcation
      • Difficult to diagnose in fragmented specimen
    • Diffuse hyperplasia
      • Numerical increase in pituitary cells without alteration in architecture
    • Rare mitotic activity
    • GH cell hyperplasia: chromophobic to eosinophilic polygonal cells
    • PRL cell hyperplasia: chromophobic with rare microcalcifications
    • ACTH cell hyperplasia: amphophilic with large vacuoles (lysosomes) and Crooke cell change
    • TSH cell hyperplasia: chromophobic, occasional spindle cells and multiple, large PAS+ lysosomes
    • LH - FSH hyperplasia: hypervacuolization (castration cells)
    Microscopic (histologic) images

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    Various images

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    Crooke hyaline change


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    Reticulin staining in normal,
    hyperplastic and neoplastic
    pituitary

    Cytology description
    • Hypercellular smear with heterogeneous cell populations
    Positive stains
    • Cytoplasmic reactivity for respective hormones
    • Reticulin highlights retention of acinar architecture and may show some expanded acini
    • PAS highlights lysosomes in TSH hyperplasia
    • Ki67 labeling may be mildly increased (normal gland is completely negative)
    Electron microscopy description
    • Same as normal pituitary:
      • GH producing somatotrophs: rough endoplasmic reticulum, well formed Golgi complexes and numerous large, dense secretory granules
      • PRL producing lactotrophs: elaborate rough endoplasmic reticulum arranged in parallel arrays, occasionally forming concentric structures known as “Nebenkern” formations, prominent Golgi complexes and extrusion of secretory granules at the lateral cell borders known as “misplaced exocytosis”
      • GH and PRL producing mammosomatotroph: irregular, elongated and pleomorphic large granules and “misplaced exocytosis”
      • TSH producing thyrotrophs: short dilated rough endoplasmic reticulum and small secretory granules that align along the plasma membrane
      • ACTH producing corticotrophs: secretory granules are pleomorphic in shape and electron density with indentations and evaginations of granule membranes, resulting in “heart” and “teardrop” shapes; also small bundles of intermediate (keratin) filaments throughout the cytoplasm
    Differential diagnosis
    • Normal Adenohypophysis
      • Heterogeneous cell populations within normal acini
      • ACTH cells normally aggregate at the lateral wings of anterior pituitary

    • Pituitary adenoma
      • Larger, homogeneous cell populations with splayed and disrupted reticulin network
      • Compresses adjacent normal acini