Novel clinicopathological and molecular characterization of metanephric adenoma: a study of 28 cases

Ying Ding,Yangyang Jiang,Ran Hu,Xuejie Li,Hai Li,Zhihong Zhang,Yan Zhu,Cong Wang,Guoxin Song,Xiao He,Guoqiang Ping,Jinsong Wang,Wenbin Huang,Gang Chen,Chen Miao,Ping Mei

doi:10.1186/s13000-018-0732-x

Abstract

BackgroundMetanephric adenoma is a rare, benign renal neoplasm with occasional misdiagnosis. However, its molecular characterization is not fully understood.MethodsIn this study, we use the hybrid capture-based Next-Generation Sequencing to sequence a panel of 295 well-established oncogene or tumor suppressor genes in 28 cases of MA patients in China. Novel clinicopathological markers associated with the mitogen-activated protein kinase (MAPK) pathway in metanephric adenoma were detected by immunohistochemistry.ResultsIt was found that except for BRAF (22/28) mutations (c.1799 T > A, p.V600E), NF1 (6/28), NOTCH1 (5/28), SPEN (5/28), AKT2 (4/28), APC (4/28), ATRX (3/28), and ETV4 (3/28) mutations could also be detected. Meanwhile, a novel and rare gene fusion of STARD9-BRAF, CUX1-BRAF, and LOC100507389-BRAF was detected in one MA patient. In addition, although MEK phosphorylation was normally activated, the phosphorylation level of ERK was low in metanephric adenoma cases. Highly expressed p16 and DUSP6 may have contributed to these results, which maintained MA as a benign renal tumor.ConclusionsThis study provides novel molecular and pathological markers for metanephric adenoma, which could improve its diagnosis and increase the understanding of its pathologic mechanism.

Highlights

Metanephric adenoma is a rare, benign renal neoplasm with occasional misdiagnosis
It was found that eight cases were misdiagnosed: two cases were reclassified as solid variant papillary renal cell carcinoma, one was epithelial-predominant nephroblastoma, one was tubulocystic carcinoma, one was renal mucinous tubular and spindle cell carcinoma (MTSCC), one was juxtaglomerular cell tumor, one was renal oncocytoma, and one was renal solitary fibrous tumor
Tubulocystic carcinoma, MTSCC, reninoma, renal oncocytoma and renal solitary fibrous tumor have different morphological characterizes with Metanephric adenoma (MA), which were excluded after double-blinded review by two expert pathologists from our department

Summary

Introduction

Metanephric adenoma is a rare, benign renal neoplasm with occasional misdiagnosis. Metanephric adenoma (MA) is a rare, benign renal neoplasm, as it exhibits a low proliferation rate and favorable outcome [1]. MA is comprised of primitive metanephric tubular epithelial cells, which are arranged tightly as small acini structures [3, 4]. There is similar morphology between MA and other renal tumors such as epithelial-predominant nephroblastoma (Wilms tumor) and the solid variant of type 1 papillary renal cell carcinoma (PRCC), both of which demonstrate aggressive behavior. These similar morphologies seriously influence clinical diagnosis and therapy [6, 7].

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