Mixed ovarian neoplasms with gastrointestinal-type mucinous and mullerian epithelial components: A rare group of tumors demonstrating the phenotypic plasticity of the mullerian epithelial cell Journal Article
| Authors: | Chui, M. H.; Ellenson, L. H. |
| Article Title: | Mixed ovarian neoplasms with gastrointestinal-type mucinous and mullerian epithelial components: A rare group of tumors demonstrating the phenotypic plasticity of the mullerian epithelial cell |
| Abstract: | Primary mucinous ovarian neoplasms, gastrointestinal-type (GI-type), are composed of mucin-producing tumor cells resembling intestinal goblet cells or gastric foveolar epithelium. In contrast to seromucinous tumors, which exhibit endocervical-type mucinous differentiation and are thought to be derived from endometriosis, the cell/tissue-of-origin of most GI-type mucinous ovarian tumors is unknown. We identified 8 GI-type mucinous ovarian tumors (cystadenomas, n=4; borderline tumor/carcinoma, n=4) with spatially distinct areas that showed morphologic features of Mullerian-type epithelial differentiation (ciliated cells or endometrioid-type glands). Immunohistochemistry for cell lineage markers and Alcian blue (pH 2.5)/Periodic Acid-Schiff staining were performed. Morphologically distinct components were isolated by microdissection, from which extracted DNA was analyzed by targeted next-generation sequencing. In all cases, immunohistochemistry demonstrated mucin-producing cells to be positive for at least one GI marker (CK20 or CDX2), while areas with morphologic features of Mullerian differentiation were positive for PAX8, ER and/or PR, and lacked expression of CK20 and CDX2; CK7 was strongly and diffusely positive in all tumor cells. Tumor cells with a gastric-type phenotype produced neutral mucin, while acidic mucin was present within intestinal-type goblet cells. Targeted sequencing revealed ARID1A mutations in all mixed borderline tumors/carcinomas (n=4); other recurrent genetic alterations included KRAS (n=2) and TP53 mutations (n=2). Shared mutations were present in paired Mullerian and GI-type mucinous tumor components in 4 mixed borderline tumors/carcinomas, with more shared mutations between components than private mutations specific to each component. All mixed borderline tumors/carcinomas were associated with endometriosis (n=3) or Mullerian inclusion cysts (n=1); mutation or loss of ARID1A expression was seen in these putative precursor lesions in 2 cases. Hence, ovarian neoplasms composed of clonally related GI-type mucinous and Mullerian-type epithelial components harbor ARID1A mutations and are frequently associated with endometriosis. The existence of a Mullerian stem/progenitor cell with the capacity to differentiate toward cell lineages within the GI-tract may be involved in the pathogenesis of at least a subset of GI-type mucinous ovarian neoplasms. © 2023 Lippincott Williams and Wilkins. All rights reserved. |
| Keywords: | immunohistochemistry; adult; clinical article; human tissue; protein expression; aged; middle aged; gene mutation; human cell; single nucleotide polymorphism; frameshift mutation; genetics; histopathology; cancer recurrence; follow up; endometrioid carcinoma; ovarian neoplasms; metabolism; cystadenoma; ph; genetic association; pathology; protein p53; tumor marker; cell lineage; stem cell; gastrointestinal neoplasms; genetic susceptibility; ovary tumor; carcinoma in situ; tumor cell; carcinoma; histochemistry; epithelium cell; epithelial cells; heterozygosity loss; cell transdifferentiation; gastrointestinal tract; oncogenesis and malignant transformation; endometriosis; goblet cell; microdissection; mucin; mucins; mucin 6; gastrointestinal tumor; columnar epithelium; phenotypic plasticity; transcription factor pax8; epidermoid cyst; transdifferentiation; periodic acid schiff stain; high throughput sequencing; alcian blue; humans; human; female; article; adaptation, physiological; biomarkers, tumor; gastrointestinal type mucinous ovarian neoplasm; mixed ovarian tumor; mullerian carcinoma; stomach mucin; ciliated epithelium cell; ovarian mucinous cystadenoma; ovarian stroma; physiological adaptation |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 47 |
| Issue: | 7 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2023-07-01 |
| Start Page: | 756 |
| End Page: | 765 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000002045 |
| PUBMED: | 37125505 |
| PROVIDER: | scopus |
| PMCID: | PMC10959257 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Corresponding author is MSK author: Michael Herman Chui -- Source: Scopus |
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