An Endometrioid Carcinoma With an Adenoma Malignum-like Pattern of Invasion: New Insight into Molecular Features

Meng Jia, Shi-Li Yu, Ping-Li Sun
In: International Journal of Gynecological Pathology · 2026 · doi:10.1097/pgp.0000000000001205 · PMID:42456098 · W7168363346
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This study analyzed the molecular features of an endometrioid carcinoma with an adenoma malignum-like invasion pattern, identifying several single nucleotide variations in genes including ARID1A, CTNNB1, PTEN, BCOR, and MAPK4.

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This case study investigates the molecular characteristics of a rare endometrioid carcinoma exhibiting an adenoma malignum-like invasion pattern, which is typically associated with bland morphology but can present at advanced stages. Using next-generation sequencing on 571 genes, the researchers identified specific genetic alterations including mutations in ARID1A, CTNNB1, PTEN, BCOR, and MAPK4, while noting the absence of POLE or TP53 changes and stable microsatellite status. These findings confirm the endometrioid lineage of this distinct histological variant and highlight its unique mutational profile compared to other uterine cancers. This paper is centrally about endometriosis — specifically, it examines endometrioid carcinoma, a malignancy strongly linked to endometriosis, by analyzing the molecular drivers of its rare adenoma malignum-like invasive subtype.

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Abstract

Adenoma malignum-like (AM-L) pattern is the least common invasion type in endometrioid carcinoma of the uterus and is characterized by a bland morphologic appearance in accordance with International Federation of Gynecology and Obstetrics Grade 1 endometrioid carcinoma. However, the biological behavior of the AM-L pattern is not always indolent, and it may present at an advanced tumor stage. Although several studies have described the clinicopathological features of this pattern, the molecular alterations have not yet been explored. Here, we report a case of endometrioid carcinoma with AM-L invasion pattern and analyzed its genetic alterations using a next-generation sequencing panel that included 571 genes. Six single nucleotide variations or insertion/deletion alterations were detected, including ARID1A exon 4 c.1848dup p.(S617Lfs*6), CTNNB1 exon 3 c.101G>A p.(G34E), PTEN exon 5 c.332G>A p.(W111*), PTEN exon 6 c.548dup p.(N184Efs*6), BCOR exon 10 c.4376A>G p.(N1459S), and MAPK4 exon 6 c.1594G>A p.(G532S). Neither POLE nor TP53 alteration was detected. No copy number variations or gene fusions were observed. The microsatellite status was stable, and the tumor mutational burden was low. The molecular features demonstrate the endometrioid nature of the AM-L pattern. Further studies are needed to explore the significance of these genetic alterations in this particular pattern and to clarify their oncogenic mechanism.
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An Endometrioid Carcinoma With an Adenoma Malignum-like Pattern of Invasion: New Insight into Molecular Features - Meng Jia - Shi-Li Yu - Ping-Li Sun Adenoma malignum-like (AM-L) pattern is the least common invasion type in endometrioid carcinoma of the uterus and is characterized by a bland morphologic appearance in accordance with International Federation of Gynecology and Obstetrics Grade 1 endometrioid carcinoma. However, the biological behavior of the AM-L pattern is not always indolent, and it may present at an advanced tumor stage. Although several studies have described the clinicopathological features of this pattern, the molecular alterations have not yet been explored. Here, we report a case of endometrioid carcinoma with AM-L invasion pattern and analyzed its genetic alterations using a next-generation sequencing panel that included 571 genes. Six single nucleotide variations or insertion/deletion alterations were detected, including ARID1A exon 4 c.1848dup p.(S617Lfs*6), CTNNB1 exon 3 c.101G>A p.(G34E), PTEN exon 5 c.332G>A p.(W111*), PTEN exon 6 c.548dup p.(N184Efs*6), BCOR exon 10 c.4376A>G p.(N1459S), and MAPK4 exon 6 c.1594G>A p.(G532S). Neither POLE nor TP53 alteration was detected. No copy number variations or gene fusions were observed. The microsatellite status was stable, and the tumor mutational burden was low. The molecular features demonstrate the endometrioid nature of the AM-L pattern. Further studies are needed to explore the significance of these genetic alterations in this particular pattern and to clarify their oncogenic mechanism.

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