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.
Poorly differentiated pit-1 lineage tumour
(aka Silent subtype III adenoma)
Crooke cell tumour
Null cell tumour
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).
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
Densely granulated somatotroph adenoma (DGSA)
Usually responsive to somatostatin analogues.
Sparsely granulated somatotroph adenoma (SGSA)
Less responsive to somatostatin analogues.
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.
Sparsely granulated lactotroph adenoma (SGLA)
Most common type of prlactin producing adenoma.
Very responsive to dopamine agonists.
Densely granulated lactotroph adenoma (DGLA)
Acidophil stem cell adenoma (ASCA)
More aggressive, favors downward invasion.
Very rare (< 1%)
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”)
Possibly cyclic Cushing’s.
Exhibit the same features, but is not the same thing, as Crooke’s hyaline change.
Most common clinically “non-functioning” tumours (~ 30% of all adenomas).
Silent subtype III adenoma
Aggressive tumour, favors downward invasion.
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.
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