Pathology of invasive pituitary tumors with special reference to functional classification

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✓ Pituitary adenomas may remain intrasellar or infiltrate dura and bone. Invasive adenomas are not considered to be malignant; in biological behavior they are between non-infiltrative adenomas and pituitary carcinomas. The latter are defined as tumors with subarachnoid, brain, or systemic metastasis. Invasion may be defined radiologically, operatively, or histologically. On the basis of operatively assessed tumor size and gross invasion of dura and bone as well as immunocytochemical and ultrastructural analysis of 365 pituitary adenomas, the following data were obtained. There were 23 growth hormone (GH)-cell adenomas: 14% microadenomas and 86% macroadenomas; their overall frequency of invasion was 50%. There were 24 prolactin (PRL)-cell adenomas: 33% microadenomas and 67% macroadenomas, with an overall frequency of invasion of 52%. Mixed GH-cell and PRL-cell adenomas were found in 35 cases; 26% were microadenomas and 74% were macroadenomas, and the overall frequency of invasion was 31%. Sixty patients had adrenocorticotropic hormone (ACTH)-cell adenomas (Cushing's disease): 87% microadenomas and 13% macroadenomas; the overall frequency of invasion was 25% (in 8% of microadenomas and 62% of macroadenomas). Twenty patients had ACTH-cell adenomas (Nelson's syndrome): 30% microadenomas and 70% macroadenomas; the overall frequency of invasion in these cases was 50% (in 17% of microadenomas and 64% of macroadenomas). Silent ACTH-cell adenomas, 100% macroadenomas, were found in 11 patients, with an 82% frequency of invasion. There were 32 follicle-stimulating and luteinizing hormone adenomas, all macroadenomas, with a frequency of invasion of 21%. Four patients had thyroid-stimulating hormone adenomas, all macroadenomas, with a 75% frequency of invasion. Null-cell adenomas were found in 93 cases: 2% microadenomas and 98% macroadenomas, with a frequency of invasion of 42%. There were 63 plurihormonal adenomas (GH, PRL, glycoprotein): 25% microadenomas and 75% macroadenomas, with a 50% overall frequency of invasion.

Based on this study, and on their usual frequency of occurrence, the estimated rate of gross invasion by pituitary adenomas of all types is approximately 35%. It is concluded that immunocytochemical and ultrastructural characteristics of pituitary adenomas reflect the tendency of these tumors to infiltrate and hence may be of prognostic significance.

Article Information

Address reprint requests to: Bernd W. Scheithauer, M.D., Section of Surgical Pathology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.

© AANS, except where prohibited by US copyright law.

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Figures

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    Horizontal section of the pituitary gland demonstrating two circumscribed macroadenomas (Ad) within the substance of the adenohypophysis. N = neurohypophysis; S = pituitary stalk.

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    Whole-mount microsection of pituitary microadenoma (Ad) which, although grossly circumscribed, shows microscopic infiltration (asterisks) of the anterior capsule. N = neurohypophysis. Gomori's reticulin, × 5. (Reproduced from Scheithauer BW: Surgical pathology of the pituitary and sellar region, in Laws ER Jr, Randall RV, Kern EB, et al (eds): Management of Pituitary Adenomas and Related Lesions With Emphasis on Transsphenoidal Microsurgery. New York: Appleton-Century-Crofts, 1982, pp 129–218, by permission of the publisher.)

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    Photomicrograph of a typical pituitary adenoma demonstrating the characteristic smooth, noninvasive interface of the tumor with the dural pituitary capsule. H & E, × 100. (Reproduced from Selman WR, Laws ER, Scheithauer BW, et al: The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64:402–401, 1986, by permission of the publisher.)

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    Photomicrograph showing cellular pleomorphism in clinically typical pituitary adenoma. Such cytological atypia is of no prognostic significance and should not prompt a diagnosis of malignancy. H & E, × 265. (Reproduced from Scheithauer BW: Surgical pathology of the pituitary and sellar region, in Laws ER Jr, Randall RV, Kern EB, et al (eds): Management of Pituitary Adenomas and Related Lesions with Emphasis on Trans sphenoidal Microsurgery. New York: Appleton-Century-Crofts, 1982, pp 129–218, by permission of the publisher.)

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    Metastatic lesions of corticotropic pituitary carcinoma in the spinal cord (upper) and in caudal nerve roots (lower). (Reproduced from Scheithauer BW: Surgical pathology of the pituitary and sellar region, in Laws ER Jr, Randall RV, Kern EB, et al (eds): Management of Pituitary Adenomas and Related Lesions with Emphasis on Transsphenoidal Microsurgery. New York: Appleton-Century-Crofts, 1982, pp 129–218, by permission of the publisher.)

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    Left: Photomicrograph showing lymph node metastasis of a corticotropic pituitary carcinoma. H & E, × 250. Right: Immunocytochemistry confirmed the presence of adrenocorticotropic hormone within the tumor cells. Immunoperoxidase technique, × 250.

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    Photomicrographs of invasive pituitary adenoma. Left: Individual cells and clusters of adenoma are seen within the substance of the dura. H & E, × 112. (Reproduced from Selman WR, Laws ER, Scheithauer BW, et al: The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64:402–401, 1986, by permission of the publisher.) Right: Invasive pituitary adenoma (Ad) involving the walls of the cavernous sinus. Tongue-like extensions of adenoma dissect between the sinus wall (S) and a cranial nerve (N). H & E, × 45. (Reproduced from Scheithauer BW: Surgical pathology of the pituitary: the adenomas. Part II. Pathol Annu 19 (Part 2):269–329, 1984, by permission of the publisher.)

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    Gross photograph of a macroadenoma (Ad) of the pituitary. Note total replacement of the adenohypophysis as well as encroachment upon the neurohypophysis (N).

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    Pituitary adenoma with suprasellar extension (A) and posterior displacement and marked attenuation of the overlying optic chiasm (C).

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    Left: Pituitary adenoma with marked suprasellar extension and deep indentation of the third ventricle by the tumor. Right: Invasive pituitary adenoma demonstrating growth on the brain surface and within the leptomeninges. Parenchymal invasion is uncommon and is more often observed in association with frank pituitary carcinoma.

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    Sagittal section of the sella and sphenoid sinus showing an adenoma with suprasellar extension and erosion of the sellar floor (arrow). (Reproduced from Scheithauer BW: Surgical pathology of the pituitary and sellar region, in Laws ER Jr, Randall RV, Kern EB, et al (eds): Management of Pituitary Adenomas and Related Lesions With Emphasis on Transsphenoidal Microsurgery. New York: Appleton-Century-Crofts, 1982, pp 129–218, by permission of the publisher.)

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    Photomicrograph of an invasive pituitary adenoma showing infiltration of the sphenoid sinus submucosa by the adenoma cells. H & E,× 43.

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    Coronal section of a cavernous sinus filled with invasive pituitary adenoma showing entrapment of the left third cranial nerve (arrow). (Reproduced from Scheithauer BW: Surgical pathology of the pituitary and sellar region, in Laws ER Jr, Randall RV, Kern EB, et al (eds): Management of Pituitary Adenomas and Related Lesions With Emphasis on Transsphenoidal Microsurgery. New York: Appleton-Century-Crofts, 1982, pp 129–218, by permission of the publisher.)

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    Perineurial invasion of a cranial nerve within the cavernous sinus. Although a frequent accompaniment of large invasive pituitary adenomas, cranial neuropathy is most often due to stretching or compression of nerves. H & E, × 50. (Reproduced from Scheithauer BW: Surgical pathology of the pituitary and sellar region, in Laws ER Jr, Randall RV, Kern EB, et al (eds): Management of Pituitary Adenomas and Related Lesions With Emphasis on Transsphenoidal Microsurgery. New York: Appleton-Century-Crofts, 1982, pp 129–218, by permission of the publisher.)

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