Null Cell Adenomas of the Pituitary Gland: an Institutional Review of Their Clinical Imaging and Behavioral Characteristics

Abstract

The aim of the study was to establish if the null cell adenoma (NCA) forms a distinct subgroup with unique clinicopathological characteristics within the nonfunctioning pituitary adenoma group particularly in relation to the silent gonadotroph adenomas (SGAs). We identified 31 patients with the pathological diagnosis of NCA verified by routine histology and immunohistochemistry with distinct differentiation from SGAs by an established negative testing for SF-1 at the Toronto Western Hospital between December 2004 and August 2010. We reviewed their demographic data, clinical features, magnetic resonance imaging, and the histologic variables: MIB-1, FGFR4, and P27. We compared these to 63 SGAs identified within the same period. All the NCAs were macroadenomas with diameter ranging from 15-57 mm and tumor volumes between 1.95-53.5 mm(3). Preoperative cavernous sinus tumor growth was able to predict the presence of a residual after surgery (p = 0.023). Furthermore, preoperative cavernous sinus extension (p = 0.002) and negative P27 expression (p = 0.035) were able to independently predict the subsequent growth of the postoperative tumor residual. Comparing the NCA to SGA, we found that MIB-1 was higher in NCA (mean ± SD = 3.43 ± 2.76 %) compared to SGAs (mean ± SD = 2.49 ± 1.41 %) (p = 0.044). The preoperative and postoperative tumor volume doubling times (TVDTs) displayed a negative correlation in the SGA (r = -0.855, p = 0.002) while in the NCA, a positive correlation was evident (r = 0.718, p = 0.029). Our study suggests that the NCAs are a distinct group with differing behavioral characteristics from the SGAs. It also appears that the finding of cavernous sinus extension on preoperative imaging and a negative P27 expression on immunohistochemistry in NCAs may be valuable tools in predicting residual tumor growth which may impact on postoperative care.

Long non-coding RNA C5orf66-AS1 is downregulated in pituitary null cell adenomas and is associated with their invasiveness

“…Results of electron microscopy show that pituitary null cell adenoma cells have special features such as electron-lucent cytoplasm, with relatively few, poorly developed organelles and small, spherical, and usually sparse secretory granules ( 2 , 3 ). Although pituitary null cell adenomas are presumed to originate from gonadotropic cells ( 3 , 24 ), some studies argue that null cell adenomas are different from gonadotropic adenomas ( 25 , 26 ). However, the actual origin and detailed mechanism underlying the pathogenesis of pituitary null cell adenoma have not been elucidated to date.…”

How to Classify Pituitary Neuroendocrine Tumors (PitNET)s in 2020

“…Such tumors are rare, about 1%-2% [8], but need to be specifically studied. Indeed, it has been recently claimed that "null cell adenoma" are more aggressive than gonadotroph adenoma [51,52]. We emphasize that immunonegative tumors should be diagnosed after ruling out primary non-pituitary neuroendocrine or metastatic sellar tumors (c.f.…”

European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas

“…It is also recognised that lactotroph tumours in men (37,38) and silent corticotroph (ACTH positive) tumours demonstrate a more aggressive course, and may recur earlier than silent gonadotroph tumours (39,40,41). Rarely, initially silent corticotroph tumours may evolve to secrete ACTH after many years of follow-up, and this transformation may also herald more aggressive tumour behaviour (42,43,44,45).…”