Pituitary neuroendocrine tumors (PitNET) are neuroendocrine tumors originating from adenohypophyseal cells. Although benign, PitNETs sometimes exhibit aggressive biological behavior that was the inspiration for the change of old and traditional name "pituitary adenomas". Current standard in PitNET diagnostics, according to WHO criteria, is immunohistochemistry, with application of antibodies to adenohypophysis hormones and transcription factors TPIT (T-box family member TBX19), PIT1 (pituitary transcription factor 1) and SF-1 (steroidogenic factor-1) according to which, the line of differentiation is assessed. In the PIT1 line of differentiation there are somatotroph, lactotroph and thyrotroph tumors. Somatotroph tumors are from PIT1 lineage that produce growth hormone (GH). The WHO defines the following subtypes of somatotroph tumors: densely granulated and sparsely granulated somatotroph tumor. Lactotroph tumors are the most common neuroendocrine tumors of the pituitary gland. The transcription factors PIT1 and the estrogen receptor a (ERa) play a key role in their genesis. There are two subtypes of lactotroph tumors, densely and sparsely granulated that are differentiated by the type of prolactine (PRL) staining pattern. Thyrotroph tumors expess both PIT1 and GATA binding protein 3 (GATA3), and can show variable positivity for thyroid-stimulating hormone (TSH). Beside these three main tumor types of PIT1 lineage, there are mixed lactotroph and somatotroph tumors, mamosomatotroph tumor, acifophilic "stem cell" tumor, mature and immature plurihormonal tumor. Corticotroph tumors express transcription factor TPIT, and produce adrenocorticotrophic hormone (ACTH). They can be densely granulated and sparsely granulated. Rare subtype of corticotroph tumors, that can show aggressive biological behavior, is Crooke cell tumor. Gonadotroph tumors are of SF1 lineage of differentiation, and they produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Null-cell tumors show no distinct cell lineage, and do not express any of the transcription factors. With the use of transcription factors, these tumors are diagnosed through elimination, and their number tented to decrease.

Introduction. Plurihormonal pituitary neuroendocrine tumours (PitNET)/adenomas are pituitary neuroendocrine tumours composed of monomorphous cell populations expressing anterior pituitary transcription factors and/or hormones belonging to more than one cell lineage. Studies dedicated to plurihormonal tumours are rare and quite heterogenous with their results, bearing in mind changes in diagnostic criteria and inconsistent use of antibodies for anterior pituitary transcription factors in the diagnostic immunohistochemical panel. Material and Methods. We retrospectively analysed all patients surgically treated for PitNETs from 2016 to July 2022 in a tertiary healthcare institution. All tumours previously diagnosed PitNETs with the word “plurihormonal” were re-examined and potentially re-classified, according to 2022 WHO classification of endocrine tumours. Results. Among 721 patients surgically treated for PitNET in 5.5 years period, the diagnosis of plurihormonal PitNET was established in 11 tumours (1.3%). All tumours showed diffuse and intensive positivity for anterior pituitary transcription factors PIT1 and SF1. Clinically, all patients presented with acromegaly. Conclusions. Retrospective studies related to newly defined plurihormonal PitNETs with a reassessment of diagnoses are necessary due to their rarity and ambition to investigate their origin and biological behaviour. The fact that the majority of plurihormonal PitNETs are clinically presented with acromegaly and show simultaneous positivity to PIT1 and SF1 transcription factors deserve special attention and need for further research in larger cohorts of these exceptional tumours.