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Atypical pituitary adenomas: incidence, clinical characteristics, and implications

Clinical article

Gabriel Zada Department of Neurosurgery and

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 M.D.
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Whitney W. Woodmansee Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

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 M.D.
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Shakti Ramkissoon Pathology and

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 M.D., Ph.D.
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Jordan Amadio Department of Neurosurgery and

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Vania Nose Pathology and

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Edward R. Laws Jr. Department of Neurosurgery and

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Page Range:
336–344
Volume/Issue:
Volume 114: Issue 2
DOI link:
https://doi.org/10.3171/2010.8.JNS10290
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The 2004 WHO classification of pituitary adenomas now includes an “atypical” variant, defined as follows: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity. The authors review the incidence of this atypical histopathological subtype and its correlation with tumor subtype, invasion, and surgical features.

Methods

The records of 121 consecutive patients who underwent transsphenoidal surgery for pituitary adenomas during an 18-month period were retrospectively reviewed for evidence of atypical adenomas.

Results

Eighteen adenomas (15%) met the criteria for atypical lesions; 17 (94%) of the 18 were macroadenomas. On imaging, 15 (83%) demonstrated imaging evidence of surrounding invasion, compared with 45% of typical adenomas (p = 0.004). Atypical tumors occurred in 12 female (67%) and 6 male (33%) patients. Patient age ranged from 16 to 70 years (mean 48 years). Nine patients (50%) had hormonally active tumors, and 9 had nonfunctional lesions. Four (22%) of the 18 patients presented to us with recurrent tumors. Immunohistochemical analysis demonstrated the following tumor subtypes: GH-secreting adenoma with plurihormonal staining (5 patients [28%]); null-cell adenoma (5 patients [28%]); silent ACTH tumor (3 patients [17%]), ACTH-staining tumor with Cushing's disease (2 patients [11%]), prolactinoma (2 patients [11%]), and silent FSH-staining tumor (1 patient [6%]). The MIB-1 labeling index ranged from 3% to 20% (mean 7%).

Conclusions

Atypical tumors were identified in 15% of resected pituitary adenomas, and they tended to be aggressive, invasive macroadenomas. More longitudinal follow-up is required to determine whether surgical outcomes, potential for recurrence, or metastasis of atypical adenomas vary significantly from their typical counterparts.

Abbreviations used in this paper:

ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; GH = growth hormone; LH = luteinizing hormone; PRL = prolactin; TSH = thyroid-stimulating hormone.
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Contributor Notes

Address correspondence to: Gabriel Zada, M.D., Department of Neurosurgery, Brigham and Women's Hospital, 15 Francis Street, PBB3, Boston, Massachusetts 02115. email: gzada@usc.edu.

Please include this information when citing this paper: published online September 24, 2010; DOI: 10.3171/2010.8.JNS10290.

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