Atypical pituitary adenomas: incidence, clinical characteristics, and implications.
OBJECTIVE
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.
Zada
Gabriel
G
Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. gzada@usc.edu
Woodmansee
Whitney W
WW
Ramkissoon
Shakti
S
Amadio
Jordan
J
Nose
Vania
V
Laws
Edward R
ER
D000236:Adenoma / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen