Immature PIT1-lineage Pituitary Neuroendocrine Tumors/Adenomas, a Morphologically Unique Pituitary Neuroendocrine Tumors/Adenomas Commonly With Cytologic Atypia Features and a Predilection for Aggressive Clinical Potential.

Abstract

Immature PIT1-lineage pituitary neuroendocrine tumors (PitNETs)/adenomas (Immature PIT1-lineage tumors) are a rare and underrecognized subtype of PitNETs that exhibits distinct cytologic atypia features and aggressive clinical potential. This study characterizes the clinical, radiological, histologic, and immunohistochemical features of 15 immature PIT1-lineage tumors identified from 1084 PitNETs patients over 5 years. Our cohort of 6 males and 9 females had a median age of 37.00 years (range: 23 to 68 y). All patients presented with pituitary macrotumors with an average size of 27.13×22.60×22.13 mm (length×width×height). The invasive growth pattern was identifiable, with 40.00% of tumors presenting with advanced stage (Knosp type 3 and 4) disease, followed by 20.00% Knosp type 2, 26.67% type 1, and 13.33% type 0. Clinical follow-up in 11 patients (median duration: 10.91 mo) revealed local recurrence in 1 case (9.09%). Microscopically, immature PIT1-lineage tumors comprised epithelioid (n=14) or spindle-shaped (n=1) chromophobic or weak basophilic cells with marked cytologic atypia, macronucleoli, and nuclear pseudoinclusions. By immunohistochemistry, most cases showed a consistent stain for PIT1 but limited expression of PIT1 family hormones in conjunction with diffuse or focal expression of CK8/18 (Cam 5.2), whereas none of the mimics showed a similar stain pattern in such a distinct way. We corroborate that immature PIT1-lineage tumors are rare, aggressive, and morphologically unique PitNETs/adenomas with cytologic atypia features. Immunohistochemistry may facilitate diagnosis in the distinction from histologic mimics.