Pituitary carcinoma: reclassification and implications in the NET schema

Abstract

The entity known as pituitary carcinoma has been traditionally defined as a tumor of adenohypophysial cells that metastasizes systemically or craniospinally independent of the histological appearance of the lesion. Reported cases of pituitary carcinoma have clinically and histologically resembled their non-metastatic counterparts that were classified as adenomas; the majority of cases were initially diagnosed as adenomas, and with tumor progression and spread, the diagnosis was changed to carcinoma. This classification has been challenged since the definition of malignancy in most organs is not based only on metastatic spread. The extent of local invasion resulting in an inability to completely resect an adenohypophysial tumor can have serious consequences that can cause harm and are therefore not benign. To address this dilemma, it was proposed that pituitary tumors be classified as neuroendocrine tumors. This change in nomenclature is totally appropriate since these tumors are composed of classical neuroendocrine cells; as with other neuroendocrine tumors, they have variable behavior that can be indolent but can involve metastasis. With the new nomenclature there is no requirement for a distinction between adenomas and carcinomas. Moreover, the WHO/IARC has provided an overarching classification for neuroendocrine neoplasms at all body sites; in this new classification, the term 'neuroendocrine carcinoma' is reserved for poorly-differentiated high-grade malignancies that are clinically, morphologically and genetically distinct from well differentiated neuroendocrine tumors. It remains to be determined if there are true pituitary neuroendocrine carcinomas.

Prolactinoma e hiperprolactinemia. Posicionamiento de la SMNE

“…La definición de un prolactinoma maligno sigue estando en debate debido a que no hay biomarcadores que permitan predecir su posible comportamiento metastásico en comparación con los tumores agresivos que no lo hacen y que los tumores pueden persistir o recurrir aun con un tratamiento óptimo 168 . El criterio habitual es muy estricto y requiere demostrar que hay una metástasis sistémica o craneoespinal que no pueda explicarse por extensión directa 169 . La 5.ª edición de la serie de clasificación de la OMS aceptó la nomenclatura de «tumor neuroendocrino hipofisario» o PitNET desde hace algunos años, la cual no incluye los términos adenoma ni carcinoma, sino que los unifica en un solo término, al igual que las neoplasias neuroendocrinas en otros sitios.…”

Updates in neuroendocrine neoplasms: From mechanisms to the clinic

“…The development of pituitary tumours is strongly dependent on epigenetic mechanisms such as promoter methylation 25,26 , modification of histone tails and of non-coding RNAs 27 .…”

The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis

“…Most PitNETs are slow-growing and benign. A metastatic behavior of PitNETs is exceptionally rare (< 0.5% of PitNETs) ( 187 ). PitNETs are frequently hormone-secreting, which indicates an origin from hormone-secreting cells of the adenohypophysis.…”