Clinical implications of accurate subtyping of pituitary adenomas: perspectives from the treating physician

Abstract

Pituitary adenomas comprise a heterogenous group of adenohypophyseal tumours with distinct clinicopathological features across both the clinically functioning and silent groups. Although, predicting a clinically aggressive course remains challenging, accurate subtyping of pituitary adenomas offers valuable prognostic information that together with other clinical and radiological information serves as a platform for tailored treatment and follow-up. For instance, silent subtype 3 pituitary adenomas, silent corticotroph adenomas, acidophil stem cell adenomas, Crooke cell adenomas, and sparsely granulated somatotroph adenomas show more invasive growth. This review has been formulated as a set of practical questions that address the distinct clinical behaviour of a selected group of pituitary adenoma subtypes.

Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas

“…Similar to a recent case that we reported but did not include in this cohort, 23 our results also highlight that silent subtype 3 adenomas should be added to the list of Pit-1 lineage adenomas that can present with scattered fibrous bodies, similar to acidophil stem cell adenomas, [3][4][5] which also express Pit-1. However, acidophil stem cell adenomas are distinguished from silent subtype 3 adenomas by their oncocytic nature and predominant diffuse cytoplasmic staining pattern for PRL with only focal GH expression to indicate plurihormonality in some cases.…”

“…TSH-producing pituitary adenomas have traditionally been associated with clinically aggressive disease. [3][4][5] Based on our current findings, we propose that detailed histopathological examination of samples from patients with hyperthyroidism should allow prospective elucidation of the clinical, biochemical and radiological features that distinguish thyrotroph adenomas from silent subtype 3 adenomas and further clarification of whether they have differing outcomes and prognosis.…”

“…[3][4] As a consequence, differentiated adenomas usually exhibit diffuse adenohypophysial hormone positivity, with the exception of sparsely granulated somatotroph adenomas where positivity for GH can be focal and weak, however, the presence of fibrous bodies in 475% of tumor cells is identified. [3][4][5]22 In contrast to differentiated Pit-1 cell lineage adenomas, silent subtype 3 adenomas show variable, focal or scattered positivity for one or more adenohypophysial hormones including GH, PRL and beta-TSH. These features are consistent with a monomorphous plurihormonal adenoma of Pit-1 lineage in the vast majority of our cases.…”

“…However, acidophil stem cell adenomas are distinguished from silent subtype 3 adenomas by their oncocytic nature and predominant diffuse cytoplasmic staining pattern for PRL with only focal GH expression to indicate plurihormonality in some cases. [3][4][5] …”

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] The application of pituitary cell lineage-specific transcription factors and other biomarkers has shown that most of these neoplasms are of gonadotroph origin. [3][4][5]8,19 In addition, a distinct subset of aggressive nonfunctioning pituitary adenomas includes silent corticotroph adenomas (Type 1 silent corticotroph adenoma: nonfunctioning densely granulated corticotroph adenoma; Type 2 silent corticotroph adenoma: nonfunctioning sparsely granulated corticotroph adenomas), which are characterized by a propensity to develop apoplexy, have a higher recurrence rate, and exhibit greater invasion. 8,10,[14][15][16][17] Originally classified as the third variant of silent corticotroph adenoma, silent subtype 3 adenomas are considered to be a distinct and aggressive histologic variant of pituitary adenoma.…”