Incidence, hormonal distribution and postoperative follow up of atypical pituitary adenomas

Yıldırım, Ali Erdem; Divanlıoğlu, Denizhan; Nacar, Osman Arikan; Dursun, Engin; Şahinoğlu, Mert; Ünal, Tuba; Belen, Ahmet Deniz

doi:10.5137/1019-5149.jtn.6828-12.1

Cited by 16 publications

(16 citation statements)

References 15 publications

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“…Scheithauer et al [6] reported 6 atypical cases out of 78 total pituitary adenomas, an incidence of 14.7% similar to the one reported by Zada et al [20]. In a more recent single-center study, 8.9% (13 out of 146) of pituitary adenomas were atypical, and 38.4% of them developed recurrence [21]. Apart from these reports, there are no further studies describing similar epidemiological data on ‘aggressive' pituitary tumors.…”

Section: Epidemiologysupporting

confidence: 55%

Aggressive Pituitary Tumors

et al. 2015

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Pituitary adenomas are common intracranial tumors that are mainly considered as benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by gross invasion of the surrounding tissues, resistance to conventional treatment leading to early and frequent recurrences. Even more rarely, pituitary tumors can give rise to cerebrospinal or systemic metastases qualifying as pituitary carcinomas according to the latest WHO definition. In the same classification, a subset of tumors with relatively distinct histopathological features was identified and defined as atypical adenomas designated to follow a more aggressive clinical course. This classification, although clinically useful, does not provide an accurate correlation between histopathological findings and the clinical behavior of these tumors, neither is it adequate to convey the precise features of ‘aggressive' tumors. Thus, ‘aggressive' pituitary adenomas need to be properly defined with clinical, radiological, histological and molecular markers in order to identify patients at increased risk of early recurrence or subsequent tumor progression. At present, no single marker or classification system of pituitary tumor aggressiveness exists, and clinically useful information in the literature is insufficient to guide diagnostic and therapeutic decisions. Treatment of patients with aggressive pituitary tumors is challenging since conventional treatments often fail, necessitating multiple surgical procedures with additional radiotherapy. Although traditional chemotherapy applied in other neuroendocrine tumors has not been shown to be efficacious, newer agents, particularly temozolomide, have shown promising results and are currently used despite the lack of data from a randomized prospective trial. Molecular targeted therapies such as mTOR and epidermal growth factor inhibitors have also been applied and might prove to be useful in the management of these patients. In the present review, we provide information regarding the epidemiology and clinical, histopathological and molecular features of aggressive pituitary tumors using recent employed definitions. In addition, we review currently employed therapeutic means providing a therapeutic algorithm and highlight the need to identify more specific disease-related and prognostic markers and the necessity for central registration of these tumors.

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Section: Epidemiologysupporting

confidence: 55%

Aggressive Pituitary Tumors

et al. 2015

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“…Zada et al [9] failed to find a significant difference in the recurrence rate between typical and atypical adenomas. Similarly, in a series of 16 recurrent pituitary adenomas, Yildirim et al [3] demonstrated a higher, though not statistically significant, recurrence frequency in atypical pituitary adenomas as compared to typical ones [5/13 (38.4%) and 11/133 (8.2%), respectively], though this might have been due to the relatively small sample size. …”

Section: Introductionmentioning

confidence: 99%

“…The diagnostic criteria for atypical adenomas include high mitotic activity, excessive p53 immunoreactivity and a Ki-67 proliferative index >3% [2]. Pituitary carcinomas are defined by craniospinal or systemic metastases, and the overall prognosis appears poor with a mean survival of 4 years following the development of metastases [3]. According to previous studies, atypical adenomas occurred in about 2.7-15% [4] and pituitary carcinomas in about 0.1-0.2% of reported cases [5,6,7,8].…”

Section: Introductionmentioning

confidence: 99%

Typical and Atypical Pituitary Adenomas: A Single-Center Analysis of Outcome and Prognosis

et al. 2015

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Background and Objective: In 2004, the World Health Organization defined atypical pituitary adenomas as those with a Ki-67 expression >3%, an excessive p53 expression and increased mitotic activity. As the usefulness of this classification is controversial, we reviewed typical and atypical pituitary adenomas to compare the clinical and prognostic features. Patients and Methods: We retrospectively reviewed 343 consecutive pituitary adenomas. Atypical pituitary adenomas represented 18.7% of cases. All patients were operated on at the Department of Neurosurgery of our institution and were followed up at the Hypothalamic-Pituitary Disease Unit of the same institution. The median follow-up time was 75 months (range 7-345). Results: Younger age at diagnosis as well as immunohistochemical positivity for adrenocorticotropic hormone and prolactin correlated with a higher risk of atypical pituitary adenomas, whereas typical and atypical pituitary adenomas did not differ with regard to gender, tumor size, recurrence risk and disease-free survival time (DFST). Among the 219 patients who underwent radical surgery, a Ki-67 expression ≥1.5% was associated with a higher risk of recurrence and a worse DFST, even after correction for age at diagnosis, gender, immunohistochemical classification, tumor size, invasiveness and Knosp classification [p = 0.01; hazard ratio (HR) 2.572; 95% confidence interval (CI) 1.251-5.285). Pituitary adenomas with a Ki-67 expression ≥1.5% showed a worse DFST as compared to pituitary adenomas with a Ki-67 expression <1.5% (HR 2.166; 95% CI 1.154-4.064). Conclusion: In this series, atypical and typical pituitary adenomas did not differ with regard to recurrence and DFST. Pituitary adenomas with a Ki-67 expression ≥1.5% showed a higher recurrence risk and a worse DFST as compared to those with a Ki-67 expression <1.5%. We suggest that a Ki-67 expression ≥1.5% may be useful as a prognostic marker, though this will need to be confirmed by prospective, multicenter data.

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“…According to the WHO, aPA is a PA with aggressive features, such as invasion, and the diagnostic criteria include increased mitotic activity, Ki-67 labeling index (LI) >3%, and extensive p53 immunoreactivity [1]. Pituitary carcinomas (PC) with poor prognosis (4-year mean survival) can be diagnosed when craniospinal or systemic metastasis is confirmed [8]. The aggressive features, however, are not well-defined and can have different interpretations, depending on the individual investigators [5,9].…”

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confidence: 99%

“…In daily practice, the aPAs that correspond to all four features are actually very rare; therefore, the predictive value of these criteria for recurrence is questionable. Moreover, a recurrence has been reported in up to 36% of typical PAs [8-14]. Aside from Ki-67 LI, definite cut-offs for increased mitotic activity and extensive p53 immunoreactivity have not been described in detail [1].…”

mentioning

confidence: 99%

The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence

Kim

Lee

Jung

et al. 2016

J Pathol Transl Med

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BackgroundThe 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.MethodsOne hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.ResultsAnalysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).ConclusionsBased on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

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Incidence, hormonal distribution and postoperative follow up of atypical pituitary adenomas

Cited by 16 publications

References 15 publications

Aggressive Pituitary Tumors

Aggressive Pituitary Tumors

Typical and Atypical Pituitary Adenomas: A Single-Center Analysis of Outcome and Prognosis

The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence

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