Use of mismatch repair immunohistochemistry and microsatellite instability testing: exploring Canadian practices.

BACKGROUND: The mismatch repair (MMR) status of tumors is being increasingly recognized as a prognostic, predictive, and possible germline predisposition/Lynch syndrome (LS) biomarker in colorectal cancer and other cancer types, particularly in endometrial cancer. Current methods (clinical history and tumor morphology) to predict MMR deficiency (dMMR) are suboptimal, and implementation of reflex laboratory testing of appropriate tumors has been recommended, a strategy requiring test standardization and clinical coordination. METHODS: Two web-based questionnaires were administered, a general and a specialist laboratory questionnaire, to establish the availability of such tests, requisite clinical/pathology integration, current mode of test initiation, reporting and recommendation practices, and education and attitudes among pathologists. Technical aspects were reviewed on the basis of specialist laboratory practice. RESULTS: Of 76 respondents, 21.5% were unaware or were uncertain whether they had access to MMR immunohistochemistry. Although 78.9% of respondents had access to such testing, an integrated approach to the identification of patients with LS is lacking, being limited to just 9 centers. The majority (70%) of testing is clinician initiated, with variable implementation of reflex testing and divergent practices in recommendation to test. Standardized reporting is lacking in many centers. Education on MMR in endometrial cancer is poor compared with that in colorectal cancer (P<0.0001). INTERPRETATION: This multicenter questionnaire highlights heterogenous practices in dMMR testing and LS identification, both in clinical terms and with regard to technical aspects of testing. An integrated multidisciplinary approach is lacking, and there is a need to educate physicians and resolve ethical issues. A Canadian consensus statement and national guidelines on dMMR testing are urgently needed, requiring input from pathologists, clinicians, and genetic counselors.

Müllerian adenosarcomas with unusual growth patterns: staging issues.

Uterine adenosarcomas are uncommon mixed Müllerian neoplasms, most commonly arising in the uterine corpus. A new Federation of International Gynecologic Organization staging system for these tumors has recently been implemented. This staging system is an improvement on the earlier generic application of the 1988 Federation of International Gynecologic Organization staging system for endometrial cancer to adenosarcoma. Herein, we report 3 uterine adenosarcomas with unusual features. For 2 of these, no specific staging guidelines are provided by either the earlier or, more importantly, the new staging system. The first case is of an adenosarcoma arising in the eutopic endometrium with involvement of underlying adenomyosis without myometrial invasion; the second originated in a mural adenomyoma in the absence of eutopic endometrial involvement; and the third case encompassed synchronous endometrial and extrauterine (peritoneal) neoplasms. Such cases are rare, and there is insufficient evidence to be definitive about staging. Thus, we suggest a descriptive reporting strategy for adenosarcomas with these unusual features. We also propose a reporting nomenclature for such cases to ensure standardization such that they can be adequately recorded in synoptic reporting protocols. This will facilitate reliable data collection such that an evidence-based staging system for these scenarios may be derived.

Endometrial giant cell carcinoma: a case series and review of the spectrum of endometrial neoplasms containing giant cells.

Poorly differentiated endometrial carcinomas of specific type include the rarely reported endometrial carcinoma with a malignant giant cell component [endometrial giant cell carcinoma (GCC)]. Since the initial description in 1991, there has only been 1 subsequent case report of this entity. We report another 5 cases. The patients ranged in age from 53 to 83 years, presenting with vaginal bleeding, anemia, or a pelvic mass. Four of the 5 tumors contained areas of endometrial adenocarcinoma of usual type, with a variable giant cell component. The conventional cell types present included 1 case with clear cell carcinoma (30% of tumor volume), 2 with high-grade endometrioid carcinoma (50% and 70% of tumor volume, respectively) and 1 with serous histology (10% of tumor volume). One was composed exclusively of giant cell carcinoma. The giant cell component in all cases consisted of poorly cohesive nests of bizarre multinucleated giant cells with mononuclear tumor cells. A striking peritumoral and intratumoral inflammatory cell infiltrate composed of lymphocytes, plasma cells and focal eosinophils, and neutrophils was present and emperipolesis was noted in 4 of the 5 cases. The giant cells showed focal staining for epithelial markers (AE1/AE3 and CAM 5.2). Three of the patients presented with stage 1A disease, 1 with stage 1B disease, and 1 tumor was advanced, presenting as stage IIIC2. One patient in whom the tumor was exclusively of the giant cell type, developed lung metastasis 4 years after diagnosis and 1 patient is disease free after 14 years. The remaining 3 patients showed no evidence of disease with 15 to 32 months of follow-up. As histotype supplemented by staging information is critical in selection of treatment modalities and in prognostication in uterine malignancies, accurate classification is mandated. Here, we present a series of endometrial carcinomas containing a component of GCC and discuss the spectrum of giant cell-containing uterine neoplasms. At this time, however, the cumulative data on endometrial GCC are limited and the prognostic significance of the presence and the extent of a giant cell component in endometrial carcinoma remains uncertain.