Plurihormonal PIT-1-Positive Pituitary Adenomas: A Systematic Review and Single-Center Series

Abstract

Objective: The 2017 World Health Organization classification of pituitary adenomas identified the plurihormonal PIT-1-positive (PP1) adenoma as a distinct subtype. The reported data suggest that PP1 adenomas encompass the former class of silent subtype 3 (SS3) adenomas and might have an aggressive phenotype. In the present study, we summarized the current clinical data on PP1 and SS3 adenomas and compared the reported data with the data from a single institutional cohort.

Methods: Medline and Google Scholar were searched from 1990 to 2020 for clinical series of PP1 and SS3 adenomas in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. Studies were included if they had reported pituitary pathology as PP1 or SS3 adenomas and had reported the clinical outcomes after surgical intervention. To better define the PP1 phenotype compared with non-PP1 adenomas, we also reviewed the adenomas treated surgically at our institution from 2012 to 2019.

Results: Of all the tumors reported in the studies as PP1 or SS3, 99% were macroadenomas and 18% were giant adenomas (>4 cm). Of the reported patients, 31.8% had received radiotherapy, and 22.9% had undergone multiple surgeries for their pituitary tumor. In our single-center experience, 20 patients had an adenoma that met the criteria for a PP1 adenoma. Compared with the 1146 non-PP1 tumors, the PP1 tumors did not show statistically significant differences in the extent of resection, size, number of previous surgeries, future reoperations, rate of radiotherapy, p53 staining, or MIB-1 labeling index.

Conclusions: The findings from the present large, single-center study comparing PP1 and non-PP1 adenomas do not suggest that PP1 tumors are more aggressive. Further work is warranted to identify the pathologic subtypes of pituitary adenomas that are consistently more clinically aggressive.

Keywords: Atypical pituitary adenoma; PIT-1; Pituitary adenoma; Plurihormonal; Silent subtype 3 adenoma.

Figure 1.

T1-weighted magnetic resonance imaging (MRI) scans of plurihormonal PIT-1–positive (PP1) pituitary adenomas. T1-weighted, gadolinium-enhanced MRI scans of a (A and B) microadenoma (maximal dimension, 7 mm), (C and D) macroadenoma (maximal dimension, 18 mm), and (E and F) giant pituitary adenoma (maximal dimension, 41 mm), all with >5% staining of growth hormone, β-Subunit of thyroid-stimulating hormone, and prolactin and diffuse PIT-1–positive staining.

Figure 2.

Typical histological and immunohistochemical features of PIT-1–positive plurihormonal adenoma. All tumors included in this category demonstrated monomorphous features with no evidence of the acinar pattern of the normal pituitary gland. (A) Hematoxylin and eosin staining, (B) PIT-1 staining, (C) growth hormone staining, (D) prolactin staining, and (E) β-subunit of thyroid-stimulating hormone staining (original magnification ×200).