Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications
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Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications. / Miermeister, Christian P; Petersenn, Stephan; Buchfelder, Michael; Fahlbusch, Rudolf; Lüdecke, Dieter K; Hölsken, Annett; Bergmann, Markus; Knappe, Hans Ulrich; Hans, Volkmar H; Flitsch, Jörg; Saeger, Wolfgang; Buslei, Rolf.
In: ACTA NEUROPATHOL COM, Vol. 3, 2015, p. 50.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Histological criteria for atypical pituitary adenomas - data from the German pituitary adenoma registry suggests modifications
AU - Miermeister, Christian P
AU - Petersenn, Stephan
AU - Buchfelder, Michael
AU - Fahlbusch, Rudolf
AU - Lüdecke, Dieter K
AU - Hölsken, Annett
AU - Bergmann, Markus
AU - Knappe, Hans Ulrich
AU - Hans, Volkmar H
AU - Flitsch, Jörg
AU - Saeger, Wolfgang
AU - Buslei, Rolf
PY - 2015
Y1 - 2015
N2 - INTRODUCTION: The term atypical pituitary adenoma (APA) was revised in the 2004 World Health Organization (WHO) classification of pituitary tumors. However, two of the four parameters required for the diagnosis of APAs were formulated rather vaguely (i.e., "extensive" nuclear staining for p53; "elevated" mitotic index). Based on a case-control study using a representative cohort of typical pituitary adenomas and APAs selected from the German Pituitary Tumor Registry, we aimed to obtain reliable cut-off values for both p53 and the mitotic index. In addition, we analyzed the impact of all four individual parameters (invasiveness, Ki67-index, p53, mitotic index) on the selectivity for differentiating both adenoma subtypes.METHODS: Of the 308 patients included in the study, 98 were diagnosed as APAs (incidence 2.9 %) and 10 patients suffered from a pituitary carcinoma (incidence 0.2 %). As a control group, we selected 200 group matched patients with typical pituitary adenomas (TPAs). Cut-off values were attained using ROC analysis.RESULTS: We determined significant threshold values for p53 (≥2 %; AUC: 0.94) and the mitotic index (≥2 mitosis within 10 high power fields; AUC: 0.89). The most reliable individual marker for differentiating TPAs and APAs was a Ki-67-labeling index ≥ 4 % (AUC: 0.98). Using logistic regression analysis (LRA) we were able to show that all four criteria (Ki-67 (p < 0.001); OR 5.2// p53 (p < 0.001); OR 3.1// mitotic index (p < 0.001); OR 2.1// invasiveness (p < 0.001); OR 8.2)) were significant for the group of APAs. Furthermore, we describe the presence of nucleoli as a new favorable parameter for TPAs (p = 0.008; OR: 0.4; CI95 %: 0.18; 0.77).CONCLUSIONS: Here we present a proposed rectification of the current WHO classification of pituitary tumors describing an additional marker for TPA and specific threshold values for p53 and the mitotic index. This will greatly help in the reliable diagnosis of APAs and facilitate further studies to ascertain the prognostic relevance of this categorization.
AB - INTRODUCTION: The term atypical pituitary adenoma (APA) was revised in the 2004 World Health Organization (WHO) classification of pituitary tumors. However, two of the four parameters required for the diagnosis of APAs were formulated rather vaguely (i.e., "extensive" nuclear staining for p53; "elevated" mitotic index). Based on a case-control study using a representative cohort of typical pituitary adenomas and APAs selected from the German Pituitary Tumor Registry, we aimed to obtain reliable cut-off values for both p53 and the mitotic index. In addition, we analyzed the impact of all four individual parameters (invasiveness, Ki67-index, p53, mitotic index) on the selectivity for differentiating both adenoma subtypes.METHODS: Of the 308 patients included in the study, 98 were diagnosed as APAs (incidence 2.9 %) and 10 patients suffered from a pituitary carcinoma (incidence 0.2 %). As a control group, we selected 200 group matched patients with typical pituitary adenomas (TPAs). Cut-off values were attained using ROC analysis.RESULTS: We determined significant threshold values for p53 (≥2 %; AUC: 0.94) and the mitotic index (≥2 mitosis within 10 high power fields; AUC: 0.89). The most reliable individual marker for differentiating TPAs and APAs was a Ki-67-labeling index ≥ 4 % (AUC: 0.98). Using logistic regression analysis (LRA) we were able to show that all four criteria (Ki-67 (p < 0.001); OR 5.2// p53 (p < 0.001); OR 3.1// mitotic index (p < 0.001); OR 2.1// invasiveness (p < 0.001); OR 8.2)) were significant for the group of APAs. Furthermore, we describe the presence of nucleoli as a new favorable parameter for TPAs (p = 0.008; OR: 0.4; CI95 %: 0.18; 0.77).CONCLUSIONS: Here we present a proposed rectification of the current WHO classification of pituitary tumors describing an additional marker for TPA and specific threshold values for p53 and the mitotic index. This will greatly help in the reliable diagnosis of APAs and facilitate further studies to ascertain the prognostic relevance of this categorization.
U2 - 10.1186/s40478-015-0229-8
DO - 10.1186/s40478-015-0229-8
M3 - SCORING: Journal article
C2 - 26285571
VL - 3
SP - 50
JO - ACTA NEUROPATHOL COM
JF - ACTA NEUROPATHOL COM
SN - 2051-5960
ER -
