Pituitary Carcinoma: A Review of the Literature

Brian T. Ragel, M.D., William T. Couldwell, M.D., Ph.D.


Neurosurg Focus. 2004;16(4) 

In This Article

Histopathology of Pituitary Carcinomas

The histological and cytological characteristics of pituitary carcinomas vary from bland and monotonous to frankly malignant.[79] Fifty percent of primary tumors and the majority of metastases display nuclear pleomorphism and/or hyperchromasia.[79] An increased number of mitotic figures are seen in pituitary carcinomas (Fig. 1);[26,80] however, the mitotic index for all pituitary tumors (such as pituitary adenomas, invasive adenomas, and pituitary carcinomas) is low with a mean mitotic index of only 0.016%.[79] Therefore, mitotic figures do not necessarily provide an indication of a tumor's invasive potential. Histologically, features of frank pituitary malignancy appear suspicious for a metastatic disease from a systemic organ, with breast being the most common.[24] Immunohistochemically these tumors exhibit staining patterns similar to that of the primary intrasellar adenoma. In general, as pituitary tumors become more aggressive they exhibit a trend for increased microvascular density and increased MIB-1 (Ki-67) and p53 staining (Fig. 2).

Comparison of the histological and immunohistochemical features of an ACTH-secreting pituitary tumor and its metastasis to the liver (carcinoma). A: Pituitary tumor composed of uniform cells with abundant cytoplasm. Mitotic figures are not observed. B: Pituitary carcinoma composed of densely packed cells with a high mitotic rate (arrows). C: Tumor showing peripheral cytoplasmic staining for ACTH (arrows). D: The ACTH immunoreactivity in the carcinoma was limited to only a few cells (arrows). H & E (A and B) and immunoperoxidese staining for ACTH (C and D); original magnification, x 350 (bars = 100 µM). Reprinted from Cancer Letters, Volume 126, Hinton DR, Hahn JA, Weiss MH, et al., Loss of Rb expression in an ACTH-secreting pituitary carcinoma, pp 209–214, copyright 1998, with permission from Elsevier.

Expression of p53 in an ACTH-secreting pituitary tumor and a carcinoma. A: Pituitary tumor showing no p53 immunoreactivity. B: Pituitary carcinoma showing strong nuclear p53 immunoreactivity in almost all tumor cells. Immunohistochemical staining for p53, original magnification x 350, (bars = 100 µM). Reprinted from Cancer Letters, Volume 126, Hinton DR, Hahn JA, Weiss MH, et al., Loss of Rb expression in an ACTH-secreting pituitary carcinoma, pp 209–214, copyright 1998, with permission from Elsevier.

Vidal, et al.,[115] evaluated microvascular density in 157 pituitary tumors and seven pituitary carcinomas by using the vascular endothelial marker CD-34 antigen. This study showed a trend toward increased vascularity with more invasive tumors, but the trend did not reach statistical significance. No correlation was found between the MIB-1 LI and microvessel density.

Typical antibodies used to recognize pituitary hormones include those to ACTH, PRL, GH, FSH, LH, TSH, and the α-subunit of the glycoprotein hormones (LH, FSH, and TSH). Other markers aiding in the diagnosis of pituitary origin tumors are cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, and chromogranin A.

An ultrastructural study of 11 pituitary carcinomas showed that metastatic lesions maintain some of their basic ultrastructural markers.[95] Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. In most cases, significant cellular atypia and mitotic activity were observed. A unique feature in two ACTH-producing carcinomas was the variable admixture of a smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In two cases, both involving PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Indeed, the distinction between pituitary adenomas and carcinomas cannot be made on ultrastructural analysis alone.[95]


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