Original ArticleRecurrences of Pituitary Adenomas or Second De Novo Tumors: Comparisons with First Tumors
Introduction
Recurrent adenomas of the pituitary usually develop after surgery from residual tumor tissue (Possibility 1). Theoretically, especially in Cushing's disease, recurrences also may regrow after complete resection by persistent hyperstimulation of the specific pituitary cell type by releasing hormones1 (Possibility 2). Also, a second independent adenoma may develop de novo (Possibility 3). Lastly, a second adenoma may be found that had not been discovered during surgery of the first adenoma2 (Possibility 4). The Ki-67 index3, 4, 5, 6, 7 and p536, 8, 9 expression are known to be indicators for proliferation that also can be used for evaluating the risk for recurrence.
From the files of our large collection of the German Registry of Pituitary Tumors10 of more than 12,000 cases, we looked for recurrences (Figure 1). These have been defined as regrowth of tumor after complete resection. We compared the structures and the immunostainings of primary and recurrent tumor to find answers to the following questions:
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comparison of proliferation indices between primary and recurrent tumors;
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changes in adenoma types between primary and recurrent adenomas;
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incidence of de novo adenomas; and
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changes in hormone content.
Section snippets
Materials and Methods
This article does not contain any studies with human participants performed by any of the authors. A collection of 12,253 specimens from the German Registry of Pituitary Tumors formed the basis of our studies (Figure 1). This collection contained 312 cases of recurrent pituitary adenomas that could be compared with the primary tumors and at least one recurrence. From these 312 patients, original and recurrent tumors comprised altogether 646 specimens (see Figure 1): 13 densely granulated
Results
Comparing the Ki-67 index (Figure 1 and Table 1), we found that 26.5% of the recurrent adenomas had no significant difference in the data from the primary and the second tumor. An increase of Ki-67 index developed in 42.6% and a decrease of Ki-67 index was seen in 30.9% (Table 1). Significant differences (P > 0.05) could not be measured.
The nuclear expression of p53 (Table 2)—more than 2% distinctly positive nuclei were accepted as significant expression—did not show any significant differences
Discussion
Recurrences after surgical resection develop from residual tumor tissue or from de novo tumor growth. Residual tumor tissue in hormonally inactive adenomas cannot be identified by hormone measurements but only by magnetic resonance imaging when there is measurable regrowth from residual tissue. This was reported in 19%14 and 14.7%15 of cases. Invasive adenomas more often develop recurrences, and if they invade the clivus, the recurrence rate is as high as 57%.16
Recent postoperative magnetic
Acknowledgments
We thank all colleagues for sending tumor material to the German Pituitary Tumor Registry.
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Conflict of interest statement: This study was funded by Novartis Pharma GmbH (Nuremberg, Germany), Novo Nordisk Pharma GmbH (Mainz, Germany), Pfizer Pharma GmbH (Berlin, Germany), and Ipsen Pharma GmbH (Berlin, Germany).