Anatomic Abstracts

June 2006

Editor:
Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD

Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas
Synchronous endometrial and ovarian carcinomas
Reproducibility of the diagnosis of atypical endometrial hyperplasia

Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas

The results of attempts to identify histopathologic parameters that contribute to the clinical outcome of patients with ependymomas have aroused controversy. This may be due to the relative rareness of ependymomas. Furthermore, myxopapillary ependymomas and subependymomas were included in many investigations and may have confounded results because those tumors should be considered clinicopathologic entities distinct from other ependymomas. In this retrospective study, the authors investigated the influence of the histologic subtype of ependymomas and individual histologic features on the outcome of 69 patients with ependymomas. They excluded from the analysis myxopapillary ependymomas, subependymomas, and ependymomas with spinal localizations. The ependymomas were subdivided into cellular, papillary, clear cell, and tanycytic subtypes. The study spanned 30 years. The authors found no differences in clinical outcome between the four histologic subtypes of ependymomas. Neither tumor localization (either infratentorial or supratentorial), patient age, nor gender affected survival. The survival of patients who underwent complete tumor resection differed significantly from that of patients who underwent partial resection. In univariate analysis, the features of nuclear atypia, mitotic index, and MIB-1 labeling index significantly influenced survival. With regard to survival, the presence of microcysts, blood vessel density, and the feature of vascular hyalinization demonstrated a trend but did not reach significance. In multivariate analysis, only the mitotic index and MIB-1 labeling index were identified as factors with independent prognostic significance (P=0.027 and P=0.023, respectively). The proliferation indices correlated strongly. The authors concluded that the results of the univariate analysis indicated that for patients with intracranial ependymoma, nuclear atypia, mitotic index, and MIB-1 labeling index significantly influenced survival. In the multivariate analysis, mitotic index and MIB-1 labeling index were the only features that had independent prognostic significance. Because both showed strong correlations, only one of them should be included in a grading scheme for intracranial ependymomas.

Kurt E, Zheng PP, Hop WC, et al. Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas, excluding myxopapillary ependymomas and subependymomas. Cancer. 2006;106:388–395.

Reprints: Dr. Johan M. Kros, Dept. of Pathology, Location JN1, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 DR Rotterdam, Netherlands; j.m.kros@erasmusmc.nl

Synchronous endometrial and ovarian carcinomas

Simultaneous carcinomas of the endometrium and ovary may represent a diagnostic dilemma, and clinical management of such cases may be problematic. In surgical pathology practice, the authors classify them as double primary tumors (DP) or a single primary tumor with metastasis (PM), according to the conventional clinicopathologic criteria. The distinction has important therapeutic and prognostic implications, but it can be difficult to make, especially in advanced cases. In this study, the authors assessed tumor cell clonality in 13 cases with synchronous endometrial and ovarian endometrioid adenocarcinomas using PCR-based microsatellite analysis of microdissected archival tissues for loss of heterozygosity (LOH) and microsatellite instability (MSI). All paired endometrial and ovarian tumors demonstrated MSI or LOH, or both, except for one case. Therefore the microsatellite analysis was informative in 92.3 percent of the cases. Nine of 26 tumors (34.6 percent) exhibited MSI-H, and 15 of 26 (57.7 percent) showed LOH. Microsatellite analysis suggested 10 DP and two PM cases, in contrast to the four DP and nine PM cases classified according to clinicopathologic criteria. Molecular analysis was not informative in one case. The authors concluded that analysis of microsatellite abnormality is a helpful adjunct in assessing synchronous tumors, especially to differentiate DP from PM in advanced tumor cases. Moreover, the combination of conventional clinicopathologic evaluation and molecular analysis is important and helpful in distinguishing between the two groups of synchronous tumors.

Nishimura N, Hachisuga T, Nabeshima K, et al. Synchronous endometrial and ovarian carcinomas: analysis of genetic relationship of the tumors. Int J Oncol. 2005;27(6): 1519–1526.

Reprints: Dr. N. Nishimura, Dept. of Pathology, Fukuoka University School of Medicine, Jonan-ku, Fukuoka 814-0180, Japan; guriguranobita@yahoo.co.jp

Reproducibility of the diagnosis of atypical endometrial hyperplasia

Most gynecologists determine therapy based on International Society of Gynecologic Pathologists/ World Health Organization classification of endometrial hyperplasia, the reproducibility of which has been questioned. The Gynecologic Oncology Group initiated a protocol to assess the efficacy of hormonal therapy of atypical endometrial hyperplasia (AEH). Primary goals of the first phase (part A) were to prospectively determine the reproducibility of the referring institution’s pathologist diagnosis of AEH by a panel of three gynecologic pathologists and to determine the reproducibility of diagnoses by panel members. The Gynecologic Oncology Group entered 306 women on this protocol with a referring institution’s pathologist diagnosis of AEH based on biopsy or curettage. Available slides were assessed independently and interpreted by each of the three gynecologic pathologists, who used International Society of Gynecologic Pathologists/World Health Organization criteria. The majority diagnosis was based on diagnostic concordance by at least two of the three panelists. The referring institution’s pathologist diagnosis of AEH was supported by the majority of the panel in only 38 percent of cases. Overall kappa value for the panel diagnosis of AEH was 0.28. The majority diagnosis was adenocarcinoma in 29 percent, cycling endometrium in seven percent, and nonatypical hyperplasia in 18 percent of cases. The three panelists reached unanimous agreement for any diagnosis in 40 percent of cases. For the panel, paired kappa values for any diagnosis ranged from 0.34 to 0.43, with an overall kappa value of 0.40. The authors concluded that reproducibility of the referring institution’s pathologist diagnosis of AEH by a panel of gynecologic pathologists is poor. It is common for pathologists to underestimate and overestimate the severity of the lesion. The level of reproducibility among subspecialist panel members for diagnosis of AEH in these specimens is also poor. Better criteria and better sampling are needed to improve the reproducibility of this diagnosis, particularly if it is to be used in making clinical decisions.

Zaino RJ, Kauderer J, Trimble CL, et al. Reproducibility of the diagnosis of atypical endometrial hyperplasia: a gynecologic oncology group study. Cancer. 2006;106:804–811.

Reprints: Denise Mackey, Gynecologic Oncology Group, Administrative Office, 4 Penn Center, 1600 JFK Blvd., Suite 1020, Philadelphia, PA 19103; rzaino@psu.edu