MELF Pattern of Invasion: A Frequent Finding in Endometrial Carcinoma with DNA Mismatch Repair Abnormalities
Yaser R Hussein, Karuna Garg, Robert A Soslow, Deborah DeLair. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: MELF is a recently described pattern of myometrial invasion by endometrial carcinoma (EC), characterized by microcystic, elongated, and fragmented glands surrounded by inflamed fibromyxoid stroma, and can be seen in approximately 15% of ECs. MELF is associated with the presence of lymphovascular invasion (LVI) and mucinous differentiation. The aim of this study was to assess the frequency of MELF invasion in ECs that show abnormal immunohistochemical (IHC) staining for the DNA mismatch repair (MMR) proteins.
Design: All ECs with abnormal IHC for MMR with slides available (2006-present) were reviewed. A total of 74 patients were identified. All available slides were reviewed. Clinical history was obtained from electronic medical records.
Results: Of the 74 EC patients with abnormal IHC-MMR, myometrial invasion was found in 62 (84%), of which 45 (73%) had MELF pattern of myometrial invasion. Patients with DNA MMR defects and MELF pattern had a mean age of 55 years (range, 27-76). Of these 45 patients, MSH2/MSH6 loss was found in 16 (36%), while MLH1/PMS2 loss was identified in 29 cases (64%). Among all patients with MLH1/PMS2 abnormalities, 29/42 (83%) showed MELF while 16 of 26 (62%) cases with MSH2/MSH6 abnormalities had MELF. The majority of tumors (33/45) were endometrioid type; 5 were undifferentiated/dedifferentiated; 6 showed mixed histology; and one was a carcinosarcoma (MMMT). Of the endometrioid tumors, 7 (21%) were FIGO grade 1; 19 (58%) were grade 2; and 7 were (21%) grade 3I.Thirty-one cases (69%) had LVI. Mucinous and squamous differentiation was found in 31 (69%) and 27 cases (60%), respectively. The majority had increased tumor infiltrating lymphocyte and peri-tumoral lymphocytes. Clinically, 23 (51%) of the patients presented at FIGO stage I; 5 (11%) at FIGO stage II; while the remaining (38%) were FIGO stages III and IV.
Conclusions: MELF pattern of myometrial invasion is frequently seen in myoinvasive EC with DNA MMR abnormalities. The rates of MELF in EC with abnormal IHC-MMR appear to be much higher than those reported in the literature for unselcetd ECs, suggesting an association between the two. Although previously described as occurring in predominantly low-grade tumors, in our series, MELF occurred in a significant number of tumors with high-grade histology.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 109, Tuesday Morning