Histological features associated with occult lymph node metastasis in FIGO clinical stage I, grade I endometrioid carcinoma.

Lymph node involvement affects prognosis/treatment in endometrial carcinoma patients. We assessed various histological features associated with nodal metastasis in patients with grade I, stage I endometrial endometrioid carcinoma (EEC). Eighteen stage I EECs with occult positive lymph nodes and 36 controls were assessed for depth of myoinvasion; microcystic, elongated and fragmented (MELF) pattern of myometrial invasion; lymphovascular invasion (LVI); and epithelial metaplasia. Nodal metastases were subclassified as isolated tumour cells (ITCs; ≤0.2 mm), micrometastasis (>0.2 mm and <2 mm), or macrometastasis (≥2 mm). Node-positive cases had significantly higher rates of LVI (P < 0.001) and MELF invasion (P = 0.003) on univariate analysis. Only LVI was associated significantly with nodal metastasis on multivariate analysis (P = 0.002). Tumours with MELF invasion demonstrated reduced E-cadherin expression. Macrometastases were identified in seven cases (39%) with or without micrometastasis/ITCs. Eight (44%) contained only ITCs. Eleven (61%) had histiocyte-like nodal metastases. Biopsy material from four of six (67%) and five of 17 (29%) cases with and without nodal metastasis showed detached eosinophilic tumour cell buds. Of the former, three were associated with histiocyte-like nodal metastases - a feature absent in biopsies without tumour budding. Lymph nodes from grade I EEC exhibiting cellular budding or LVI should be examined for occult metastases, especially in the form of histiocyte-like cells.

Han G ，Lim D ，Leitao MM Jr ，Abu-Rustum NR ，Soslow RA ... -  《-》

Endometrioid endometrial carcinomas with microcystic, elongated, and fragmented (MELF) type of myoinvasion: role of immunohistochemistry in the detection of occult lymph node metastases and their clinical significance.

In endometrioid endometrial carcinomas (EECs), microcystic, elongated, and fragmented (MELF) myoinvasion is associated with easily overlooked lymph node metastases; however, the role of immunohistochemistry in their detection and their clinical significance have not been addressed. We identified MELF in 43 of 101 (43%) myoinvasive EECs. Nodes were removed in 49 (49%), 25 with MELF and 24 without MELF. Metastases were initially reported in 3 of the former (12%) and 2 of the latter (8%). All negative nodes were reviewed, and cytokeratin immunohistochemistry was performed. Three metastases were identified in the MELF group but none in the EECs without MELF. By immunohistochemistry, metastatic nodal isolated tumor cells (ITCs) were found in 6 of the remaining 19 MELF-positive cases. In contrast, lymph node metastases were detected in only 2 of the 22 EECs without MELF. MELF-positive cases had more lymph node metastases (P=.03) than myoinvasive EECs without MELF. At follow-up, all 6 patients with grade 1-2 EECs and nodal ITCs/micrometastases were alive (5 no evidence of disease and 1 with perineal disease). In contrast, 3 of 4 patients with grade 3 EECs and nodal ITCs/micrometastases died of disease, and the other patient was alive with tumor. In MELF, the frequency of ITCs/micrometastases in apparently negative lymph nodes is high. In patients with grade 1-2 EEC who had not received chemotherapy, the presence of nodal ITCs/micrometastases did not affect survival. In contrast, in high-grade tumors, ITCs/micrometastases were associated with unfavorable prognosis. Immunohistochemistry should be done in MELF-positive cases to detect occult lymph node metastases, especially in high-grade tumors.

Espinosa I ，Serrat N ，Zannoni GF ，Rovira R ，D'Angelo E ，Prat J ... -  《-》

Lymphovascular space invasion in microcystic elongated and fragmented (MELF)-pattern well-differentiated endometrioid adenocarcinoma is associated with a higher rate of lymph node metastasis.

Hertel JD ，Huettner PC ，Pfeifer JD 《-》

Microcystic, elongated, and fragmented pattern invasion is mainly associated with isolated tumor cell pattern metastases in International Federation of Gynecology and Obstetrics grade I endometrioid endometrial cancer.

Although many studies have evaluated the impact of mismatch repair protein loss of expression (MMR LOE) or microcystic, elongated, and fragmented (MELF) pattern of myometrial invasion as individual factors in endometrial cancer, we analyzed the combined impact of both. We reviewed every case of International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid endometrial cancers (EECs) from our institution, between 2011 and 2015, that had a sentinel lymph node biopsy and/or a lymphadenectomy, and examined the following data: age, myometrial infiltration, MELF infiltration, lymphovascular space invasion, and lymph node status. These cases were then grouped according to the absence of lymph node metastases, the presence of isolated tumor cell (ITC) lymph node metastases, or the presence of non-ITC metastases. Among the 127 cases that were in our study, 105 patients did not have nodal metastases, whereas 22 patients showed metastases, of which 11 were ITC. MMR LOE was only significantly associated with a higher odds ratio (OR) of metastases (OR, 7.44; P < .001). MELF was only associated with a higher OR of ITC-pattern metastases (OR, 32.3; P < .001). This study distinguished the effects of MELF and MMR LOE on the risk of metastases in FIGO grade 1 EEC. Further research on the clinical impact of MELF and ITC-pattern metastases is warranted to better guide clinicians on the management of patients with FIGO grade 1 EEC harboring such characteristics, which are still considered low-risk cancer.

Pelletier MP ，Trinh VQ ，Stephenson P ，Mes-Masson AM ，Samouelian V ，Provencher DM ，Rahimi K ... -  《-》

The association of the microcystic, elongated and fragmented (MELF) invasion pattern in endometrial carcinomas with deep myometrial invasion, lymphovascular space invasion and lymph node metastasis.

Dogan Altunpulluk M ，Kir G ，Topal CS ，Cetiner H ，Gocmen A ... -  《-》