Pathology

Pathology confirms the diagnosis of a pituitary tumour and classifies the tumour into a subtype. Subtype classification helps with prognosis and guides future therapy and follow up. A tumours subtype is determined by immunohistochemical staining for hormones, transcription factors, and other proteins.

Transcription Factor	Subtype	Clinical
Pit-1	Lactotroph tumours	Hyperprolactinemia
Pit-1	Somatotroph tumours	Acromegaly
Pit-1	Thyrotroph tumours	Central Hyperthyroidism
Pit-1	Poorly differentiated pit-1 lineage tumour (aka Silent subtype III adenoma)
Tpit	Corticotroph tumours	Cushing’s
Tpit	Crooke cell tumour	Cushing’s
SF-1	Gonadotroph tumour
None	Null cell tumour
Unusual combination	Plurihormonal pituitary tumour

Silent vs Null Cell

• The name silent pituitary tumour refers to absence of clinical and biochemical evidence of elevation hormone levels, not to immunohistochemical staining. The most common type of silent adenomas are gonadotroph adenomas.
• The name null cell pituitary tumour refers to absence of immunohistochemical staining on pathology. This is much less common and becomes increasingly less common as more transcription factors are identified and better detected.

Atypical, Aggressive and Invasive Pituitary Tumours

Atypical adenomas are defined by the following histopathological criteria:

• Ki67 proliferation index ≥ 3%.
• Invasive growth pattern on pathology.
• Nuclear staining for p53.

Invasiveness is often assessed by radiology and includes:

• Sphenoid sinus invasion (Hardy classification).
• Cavernous sinus invasion (Knosp classification).
• Size
  • Microadenoma < 10 mm in largest dimension
  • Macroadenoma ≥ 10 mm
  • Giant adenoma > 30 mm or ≥ 40 mm or > 10 mm3 by volume in (varying definitions)

Aggressive pituitary tumours describe the tumours risk of recurrence and need for multiple surgeries and/or radiation. There are currently no agreed upon criteria for aggressive pituitary tumours. Predictors of aggressiveness include local invasion on radiology, tumour subtype, and past behaviour of the tumour.

Pituitary carcinoma is defined by the presence of cerebrospinal and/or systemic metastasis but there are no histopathological criteria.

Clinical Correlations Quick Reference

Somatotrophs

Densely granulated somatotroph adenoma (DGSA)

• Usually responsive to somatostatin analogues.

Sparsely granulated somatotroph adenoma (SGSA)

• Less responsive to somatostatin analogues.
• More aggressive.

Mammosomatotroph adenoma

• Similar to DGSA’s, but also stain for prolactin.

Mixed somatotroph and lactotroph adenoma

• Most commonly a mix of DGSAs and SGLAs

Plurihormonal GH secreting adenoma

• Mostly DGSAs with variable mammosomatotroph and thyrotroph differentiation.

Lactotrophs

Sparsely granulated lactotroph adenoma (SGLA)

• Most common type of prlactin producing adenoma.
• Very responsive to dopamine agonists.

Densely granulated lactotroph adenoma (DGLA)

• More aggressive.

Acidophil stem cell adenoma (ASCA)

• More aggressive, favors downward invasion.

Thyrotrophs

Thyrotroph adenoma

• Very rare (< 1%)
• More aggressive.

Corticotrophs

Densely granulated corticotroph adenoma

• Usually microadenomas, presenting with Cushing’s (“Small tumour, big Cushing”)

Sparsely granulated corticotroph adenoma

• Aggressive and large, but less florid Cushing’s (“Big tumour, small Cushing”)

Crooke-cell adenoma

• Unusual, aggressive.
• Possibly cyclic Cushing’s.
• Exhibit the same features, but is not the same thing, as Crooke’s hyaline change.

Gonadotrophs

Gonadotroph adenoma

• Most common clinically “non-functioning” tumours (~ 30% of all adenomas).

Other

Silent subtype III adenoma

• Aggressive tumour, favors downward invasion.
• Plurihormonal staining.
• Typically clinically silent, but may have hyperprolactinemia or acromegaly.

Null cell adenoma

• No specific cell type differentiation.

Crooke’s hyaline change

• Changes seen in nontumourous corticotroph’s that have been exposed to high cortisol levels.
• Typical finding in biopsies of normal pituitary taken during resection of an ACTH-producing corticotroph adenoma associated with Cushing’s disease.

References

• Asa SL, Mete O. What’s new in pituitary pathology? Histopathology. 2018 Jan;72(1):133-141.
• Mete O, Asa SL. Clinicopathological correlations in pituitary adenomas. Brain Pathol. 2012 Jul;22(4):443-53.
• Mete O, Lopes MB. Overview of the 2017 WHO Classification of Pituitary Tumors. Endocr Pathol. 2017 Sep;28(3):228-243.
• Di Ieva A, Rotondo F, Syro LV, Cusimano MD, Kovacs K. Aggressive pituitary adenomas–diagnosis and emerging treatments. Nat Rev Endocrinol. 2014 Jul;10(7):423-35.