Usual-Type Endocervical Adenocarcinoma with a Microcystic, Elongated, and Fragmented Pattern of Stromal Invasion: A Case Report with Emphasis on Ki-67 Immunostaining and Targeted Sequencing Results

Abstract

The microcystic, elongated, and fragmented (MELF) pattern is a unique myometrial invasion pattern occasionally found at the invasive front of endometrial endometrioid carcinoma (EEC). Herein, we report an uncommon case of usual-type endocervical adenocarcinoma (UEA) with a MELF pattern. We comprehensively analyzed its clinicopathological and molecular features, which has not been previously documented. A 67-year-old woman presented with a cervical mass and underwent radical hysterectomy. Histologically, the MELF pattern of UEA was almost identical to that of EEC. Tumor glands exhibited a microcystic appearance or elongated structures with compression forming a slit-like lumen. The tumor glands were irregularly fragmented into small clusters or single cells. Cells lining the tumor glands possessed conspicuous eosinophilic cytoplasm with squamoid or flattened endothelium-like appearance. These glands or cells were accompanied by a prominent fibromyxoid stromal reaction. Lymphovascular invasion was occasionally observed. Immunostaining revealed diffuse and strong cytokeratin 7 expression and block p16 positivity in both conventional and MELF components. However, the MELF component displayed a very low Ki-67 proliferation index compared to that of the conventional component, which showed markedly increased Ki-67 expression. Targeted sequencing analysis revealed that the MELF component harbored pathogenic mutations in <i>ARID1A</i>, <i>KRAS</i>, and <i>PTEN</i>, identical to those detected in the conventional component. In summary, the morphological features of the MELF pattern in UEA were similar to those in EEC. We found significant differences in Ki-67 expression status between conventional and MELF components, but the mutational profiles were identical. Our findings should be confirmed in larger cohorts of patients with UEA showing a MELF pattern.

Comprehensive Immunohistochemical Analysis of Mesonephric Marker Expression in Low-grade Endometrial Endometrioid Carcinoma

“…The latter manifests as variable-sized morules or solid sheets of eosinophilic cells with occasional keratinization, whereas the former is characterized by the presence of columnar or pseudostratified epithelial cells containing intracytoplasmic mucin. Three (6.0%) patients developed tumors that showed a microcystic, elongated, and fragmented pattern of myometrial invasion, which is characterized by loss of conventional glandular architecture, presence of squamoid or histiocyte-like cells with eosinophilic cytoplasm, formation of microcysts, compressed elongated structures, flattened and fragmented glandular epithelium, and an edematous or fibromyxoid stroma associated with an acute inflammatory response 25–29 .…”