Unusual epithelial and stromal changes in myoinvasive endometrioid adenocarcinoma: a study of their frequency, associated diagnostic problems, and prognostic significance

Abstract

The authors have noted that when the myoinvasive glands of endometrioid carcinomas evoke a prominent fibromyxoid stromal reaction, they sometimes undergo distinctive changes. These are characterized by outpouchings from typical neoplastic glands that become detached and often lined by flattened epithelium, sometimes appearing as microcysts. The glands may less often become elongated or undergo fragmentation into small solid clusters or single cells. For this constellation of changes, which in aggregate are distinctive, the authors have coined the acronym MELF (microcystic, elongated, fragmented). The authors evaluated the prognostic significance of these stromal and glandular features and their association with each other and with other histopathologic and clinical prognostic factors by studying 115 unselected myoinvasive endometrial endometrioid carcinomas. The histologic slides and clinical records were reviewed to collect data on age, recurrences or metastases, survival, stromal reaction pattern (fibromyxoid, lymphocytic, or absent), presence of MELF, FIGO grade, depth of myometrial invasion, vascular invasion, squamous differentiation, and presence or absence of necrosis. Factors associated with an unfavorable outcome (recurrence or death) included a fibromyxoid stromal reaction, age older than 70 years, advanced stage, vascular invasion, FIGO grade, depth of myoinvasion, and the presence of tumor necrosis. The presence of a host lymphocytic reaction was associated with a favorable outcome. A multivariate logistic regression model identified stage and age older than 70 years as independent prognostic factors. The MELF changes were associated with the presence of a host stromal reaction (most strongly with a fibromyxoid reaction) and vascular invasion. Within the group associated with a fibromyxoid reaction, patients exhibiting MELF had a better survival. In conclusion, a fibromyxoid reaction in cases of endometrioid carcinoma is associated with a higher frequency of death or recurrence and it is frequently accompanied by distinctive morphologic changes (MELF) in myoinvasive glands as well as lymphatic or blood vessel invasion. MELF is associated with a fibromyxoid reaction but is not independently associated with an adverse effect on prognosis. A lymphocytic stromal reaction is associated with a favorable effect on prognosis and is less often accompanied by the distinctive morphologic changes (MELF) highlighted herein.