115th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology (USCAP), San-Antonio, Kuzey Mariana Adaları, 21 - 26 Mart 2026, cilt.106, (Özet Bildiri)
Mixed epithelial and stromal tumor (MEST), including the purely cystic subtype, adult cystic nephroma (CN), is an uncommon benign renal neoplasm that occurs mostly in middle-aged women. Prior studies have shown that adult MEST lack the characteristic molecular findings of pediatric CN and congenital mesoblastic nephroma. To date, comprehensive molecular genetic investigation of MEST has not been performed; its pathogenesis and any recurrent genomic alterations remain unknown.
Design
Archival cases of MEST were retrieved. Available clinicopathologic features were recorded. All available hematoxylin and eosin (H&E) and immunohistochemistry (IHC) slides were re-reviewed. Representative formalin fixed paraffin embedded tissue blocks were selected for targeted DNA next generation sequencing (NGS) panel.
Results
Fourteen cases of MEST were identified. All arose in female patients (median 49 y) and showed variable admixtures of bland epithelial glands, tubules, and cysts within an ovarian-type spindle cell stroma (Figure 1). No features of malignancy were identified. Of 13 cases with follow-up, all are without recurrence. Additional clinicopathologic features are listed in Table 1. Relative whole-chromosome gains of chromosome 12 were identified in 5/14 (35.7%) MESTs based on NGS (N=4/13) and cytogenetic analysis (N=1). Additional non-recurrent copy changes were observed in 4 cases, including 1 case without chromosome 12 gain (Figure 2). No clinically actionable alterations were identified, and there were no alterations in renal neoplasia related genes (e.g. VHL, FH, SDHA/B, BAP1, NF2, TCEB1/ELOC, TFEB, TFE3, DICER1, MTOR, TSC1, TSC2).
This is the first evidence of recurrent alterations in MEST. Partial or complete gains involving chromosome 12 is not specific, and is described in a range of human neoplasia, including testicular germ cell tumors associated with germ cell neoplasia in situ (isochromosome 12p), a subset of chronic lymphocytic leukemias (trisomy 12), and multiple sarcoma subtypes (gains/amplifications of 12q12-q15). Perhaps most relevant to MEST, trisomy 12 is the most common alteration seen in ovarian fibromas, and multiple arm and whole-chromosome level gains, including chromosome 12, are characteristic of testicular sex-cord stromal tumors. Lack of significant genomic findings in 6 MESTs may be artifactual, given the relatively low tumor content in these cystic lesions. Nevertheless, copy number variations in MEST is supportive of a neoplastic process.
