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.

Keywords: adenoma; carcinoma; invasion; metastasis; neuroendocrine tumor; pituitary.

Figure 1

MRI of intrasellar PitNET. The sella shows asymmetry with enlargement of the left side that contains a tumor distorting half of the pituitary.

Figure 2

MRI of large invasive PitNET. There is a large heterogeneous soft tissue tumor mass encasing the optic nerves centered on the clivus, sella and skull base with exophytic suprasellar lobulations. It also encases the internal carotid arteries bilaterally. There is posterior displacement of the cerebral peduncle on the left side with elevation of the basal ganglia. There is also displacement of the left temporal lobe with milder posterior displacement of the left mid brain and pons.

Figure 3

Histology of corticotroph tumor. This well-differentiated tumor with solid architecture is composed of cells with basophilic cytoplasm that stains intensely for ACTH and keratins (CAM 5.2). It presented in a middle-aged woman with Cushing disease, was resected surgically but recurred several times, eventually giving rise to distant metastasis and ultimately causing the patient’s demise. The only unusual morphological finding was a Ki67 proliferation index that reached 10% in hotspots.

Figure 4

Histology of lactotroph tumor. This tumor that caused hyperprolactinemia was treated with dopamine agonist but continued to grow; it was resected surgically and had the typical morphology of a sparsely granulated lactotroph tumor with dopaminergic effects: the small tumor cells are trapped in a fibrovascular stroma, they show nuclear reactivity for PIT1 and ER, and there is scant cytoplasmic PRL. Depsite two surgical sellar resections, she later developed metastases in brain and bone.

Figure 5

Histology of Crooke cell tumor. This tumor is composed of large cells with abundant pale acidophillic hyaline cytoplasm that stains for ACTH with accentuation at the cell periphery and focally in the juxtanuclear area. The cytoplasm contains a striking ring-like intense positivity for keratins (CAM 5.2) corresponding to the hyaline material. This aggressive tumor with a Ki67 labeling index, that did not exceed 6%, invaded bony structures in and around the sella and ultimately caused the demise of the patient but there was no evidence of metastatic spread.