Disseminated tumor cells are not associated with established risk factors, L1CAM immunoreactivity and outcome in endometrial carcinoma.

PURPOSE: The presence of disseminated tumor cells (DTC) in the bone marrow of endometrial carcinoma patients has been demonstrated previously. In contrast to breast cancer, no prognostic significance or association with clinicopathological features was revealed for endometrial carcinoma so far. The aim of this study was to investigate DTC in a large patient cohort with in-depth pathology review data available and to study DTC occurrence in the context of L1CAM and long-term disease specific follow-up. METHODS: Patients treated for endometrial carcinoma at the Tuebingen University Women's hospital between 2003 and 2013 were identified. Cases with previous expert central pathology review including L1CAM immunohistochemistry and bone marrow aspirates available were selected. The presence of DTC and L1CAM expression was studied immunohistochemically. RESULTS: In 395 cases with a confirmed diagnosis of endometrial carcinoma, bone marrow aspirates were available. DTC were detected in 17.2%. The presence of DTC was independent from tumor histology, grade, lymphovascular space involvement (LVSI), FIGO stage, myoinvasion, L1CAM immunoreactivity, and nodal metastasis. DTC occurred less frequently in cases with a microcystic elongated and fragmented (MELF) pattern of invasion (2.2 vs. 21.8%, p = 0.0003). Disease progression was distributed equally among patients with and without DTC present. CONCLUSIONS: We were able to confirm previous findings of DTC presence in a large well-characterized cohort of endometrial carcinoma patients. DTC are detectable in almost one-fifth of endometrial carcinoma and occur less frequently with a MELF pattern of invasion. Further studies investigating the role of DTC in endometrial carcinoma are warranted.

Second Opinion Expert Pathology in Endometrial Cancer: Potential Clinical Implications.

OBJECTIVE: In cancer patients, the pathology report serves as an important basis for treatment. Therefore, a correct cancer diagnosis is crucial, and diagnostic discrepancies may be of clinical relevance. It was the aim of this study to perform a specialized histopathology review and to investigate potential clinical implications of expert second opinion pathology in endometrial cancer. METHODS: Patients treated for endometrial carcinoma at the Tübingen University Women's hospital between 2003 and 2013 were identified. Original pathology reports were reviewed, and contributing pathologists were asked to submit original slides and paraffin blocks. Case review was subsequently performed by 3 pathologists specialized in gynecological pathology who were blinded for clinical information. For histological typing, the World Health Organization 2014 classification was used, grading and staging were performed according to International Federation of Gynecology and Obstetrics 2009. Risk assignment was performed based on the 2013 European Society for Medical Oncology clinical practice guidelines. RESULTS: In 565 of 745 cases, which had originally been diagnosed as endometrial carcinoma, archival histological slides and blocks were available. In 55 (9.7%) of 565 cases, a major diagnostic discrepancy of potential clinical relevance was found after expert review. In 38 of these 55 cases, the diagnostic discrepancy was related to tumor type (n = 24), grade (n = 10) or myoinvasion (n = 4). In 17 cases, the diagnosis of endometrial carcinoma could not be confirmed (atypical hyperplasia, n = 10; endometrial carcinosarcoma, n = 4; neuroendocrine carcinoma, n = 1; leiomyosarcoma, n = 1; atypical polypoid adenomyoma, n = 1). Minor discrepancies not changing risk classification were also noted in 214 (37.9%) of 565, most frequently for grade within the low-grade (G1/G2) category (n = 184). CONCLUSIONS: A retrospective gynecopathological case review was shown to reveal limited but significant discrepancies in histological diagnoses as well as typing and grading of endometrial carcinomas, some directly impacting clinical management. Second opinion pathology therefore not only helps to improve the quality of translational research study cohorts but might also help to optimize patient care in difficult cases.

L1CAM: amending the "low-risk" category in endometrial carcinoma.

PURPOSE: Low- and intermediate-risk endometrial carcinomas have an excellent prognosis. Nonetheless, a small subgroup of such patients will experience unexpected relapse. Recently L1CAM was suggested to be a strong prognosticator in endometrial carcinoma. The focus of our study was on low- and intermediate-risk disease, where no or only limited adjuvant treatment is recommended according to current guidelines. METHODS: Endometrial carcinomas of low, intermediate and high-intermediate risk according to published 2016 consensus guidelines were identified. The study was limited to cases with previous central pathology review focusing on histotype, depth of myometrial invasion, presence of lymphovascular space invasion (LVSI) and MELF pattern of invasion. Standard L1CAM immunohistochemistry was performed. Disease-specific uni- and multivariate survival analyses were calculated. RESULTS: A total of 344 cases were available for immunohistochemistry (low-risk: n = 250; intermediate-risk: n = 67; high-intermediate-risk: n = 27). L1CAM positivity rates were: 29/344 (8.4 %; all cases), 18/250 (7.2 %; low-risk), 6/67 (9.0 %; intermediate-risk) and 5/27 (18.5 %; high-intermediate-risk). Expression of L1CAM was independent of LVSI and MELF. L1CAM was a significant independent prognosticator for disease-specific survival with a hazard ratio of 5.98 [CI 1.50-22.14, p = 0.012]. Adverse prognostic significance of L1CAM positivity was maintained after low-risk subgroup analysis (5-year disease-specific survival rates 71.8 vs. 100 %, p < 0.0001). All four tumour-related deaths in the subgroup of low-risk disease occurred in patients with L1CAM-positive tumours. CONCLUSION: The current definition of "low-risk" in endometrial carcinoma should be amended. "Low-risk carcinomas" should be limited to L1CAM-negative tumours. L1CAM status will play a key role in future algorithms to tailor adjuvant treatment and patient follow-up strategies.