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 .…”

Endocervical Adenocarcinoma Showing Microcystic, Elongated, and Fragmented (MELF) Pattern of Stromal Invasion: A Single-Institutional Analysis of 10 Cases with Comprehensive Clinicopathological Analyses and Ki-67 Immunostaining

“…They speculated that on the invasive tumor front, the elevated expression of NNMT might contribute to the characteristic morphology of MELF through the suppression of H3K9me2 followed by the enhancement of various pathways related to cell migration and invasion [37]. Meanwhile, the molecular features of MELF pattern in EAC have only been investigated in our recent case study [15]. In this single-case report, we conducted targeted sequencing analysis using tissue samples obtained from the MELF and conventional tumor areas of usual-type HPVA EAC.…”

“…It has been reported in EEC that the tumor cells and glands representing MELF pattern are rarely positive for Ki-67, suggesting that MELF pattern is associated with cellular senescence or growth arrest [8,15,34]. Kihara et al [8] suggested that these findings can explain why there is no significant difference in patient survival between MELF-positive and MELF-negative groups, despite more frequent LVSI and LNM in patients with EEC with MELF pattern.…”

“…We recently encountered a case of usual-type HPVA EAC with MELF pattern. In this case, we observed that the MELF area displayed a very low proliferative activity compared to those of a conventional tumor area [15]. In this study, we comprehensively investigated the clinicopathological characteristics of 10 patients with EAC showing MELF pattern.…”