PitNETs are usually restricted in their cytodifferentiation to only one of 3 lineages dictated by expression of the pituitary
transcription factors (TFs) PIT1, TPIT, or SF1.
Tumors that show lineage infidelity and express multiple TFs are rare. We searched the pathology files of 4 institutions for PitNETs with coexpression of PIT1 and SF1. We identified 38
tumors in 21 women and 17 men, average age 53 (range 21-79) years. They represented 1.3 to 2.5% of PitNETs at each center.
Acromegaly was the presentation in 26 patients; 2 had central
hyperthyroidism associated with
growth hormone (GH) excess and one had significantly elevated
prolactin (PRL). The remainder had mass lesions with visual deficits,
hypopituitarism, and/or
headaches.
Tumor size ranged from 0.9 to 5 cm; all 7 lesions smaller than 1 cm were associated with
acromegaly. Larger lesions frequently invaded the cavernous sinuses. Four cases represented a second attempt at surgical resection. PIT1 was usually diffusely positive but 5 cases had variable (patchy or focal) staining. SF1 reactivity was variable in intensity but diffuse in all but 2 cases. GATA3 data, available in 14 cases, identified diffuse positivity in 5 and focal staining in 1. GH was expressed in all but 5
tumors, PRL and
thyrotropin (TSH) were expressed in 14 and 13, respectively,
follicle-stimulating hormone (FSH) in 11 of 18, and
luteinizing hormone (LH) in 4 of 17.
Keratin staining patterns were diffuse perinuclear/membranous in 27, variable perinuclear in 4, and negative in 3; scattered fibrous bodies were seen in 5 and diffuse fibrous bodies in 1. Ki67 labeling index ranged from < 1 to 7.9%. In 3 cases, these
tumors represented one of multiple synchronous PitNETs; a separate corticotroph
tumor was seen in 2 patients and one patient had 2 additional discrete lesions, a sparsely granulated lactotroph, and a pure gonadotroph
tumor comprising a triple
tumor. PitNETs expressing PIT1 and SF1 represent multilineage PitNETs. These rare
tumors have variable clinical and morphological features, most often presenting as large
tumors with GH excess and occasionally as one of multiple synchronous PitNETs of distinct lineages.