(12.16) A Rare Case of a Gonadotroph Plurihormonal Pituitary Neuroendocrine Tumor

Pituitary neuroendocrine tumor (PitNET)/adenoma classification is controversial as the majority of pituitary tumors follow an indolent course. The use of immunohistochemistry (IHC) allows for classification according to lineage-specific transcription factors (TF), cytoplasmic granule density and proliferation index to help identify more aggressive tumors and characterize their hormone expression. We present a rare case of a patient with a plurihormonal PitNET.

Case(s) Description :

A 59-year old male presented to clinic with a complaint of syncope, headache, vision blurriness, fatigue, and 50-pound weight loss over the prior 6 months. Laboratory evaluation was significant for panhypopituitarism with morning cortisol ranging 0.8-1.5 ug/dl on 3 collections, IGF-1 45 ng/ml, total testosterone < 3 ng/dl, FSH 4.5 mIU/mL, LH 1.4 mIU/mL, TSH 0.24 mIU/L, Free T4 1.42 ng/dL, and mildly elevated prolactin (PRL) 34.3 ng/ml. MRI pituitary with and without contrast revealed a 2.5 x 1.8 x 2.4 cm pituitary macroadenoma with superior displacement of the optic chiasm and invasion of the right cavernous sinus. Humphrey visual field testing showed early bilateral superior nasal defects. The patient underwent endoscopic endonasal surgery. On surgical pathology, IHC staining was positive for SF-1 lineage: FSH, LH (focal), GATA3, CAM5.2 and Pit-1 lineage: FSH-a (rare cells). Synaptophysin stained positive with patchy expression of chromogranin A and Ki-67 proliferation index was < 1%. There was no significant expression of estrogen receptor, ACTH, growth hormone, PRL, or TSH. Thus, the tumor was classified as p</span>lurihormonal adenoma/PitNET of SF-1 and Pit-1 lineages. Post-operatively, the patient had a residual 1.2 cm mass with persistent 50% encasement of the right ICA. His vision improved to baseline. He was started on hormone replacement with hydrocortisone, levothyroxine and testosterone.

Discussion :

PitNETs are classified into seven morphofunctional patterns according to hormonal secretion and three lineages according to TF expression: lactotroph (Pit1), somatotroph (Pit1), thyrotroph (Pit1); corticotroph (Tpit); and gonadotroph (SF1). Tumors with SF-1 lineage tend to be nonfunctional and patients present with symptoms of mass effect as well as hypogonadism. While the majority of PitNETs belong to one discrete lineage, there are plurihormonal tumors that express TFs in multiple lineages which suggests they are derived from stem cells. These tumors can have a high risk for recurrence as well as resistance to dopamine and somatostatin agonist therapy. Overall, classification of tumor lineage and hormonal secretion pattern can help identify invasive, aggressive pituitary tumors and aid in their management.