Metanephric Adenoma-Epithelial Wilms Tumor Overlap Lesions: An Analysis of BRAF Status

Sara E. Wobker, Andres Matoso, Christine Pratilas, Shamlal Mangray, Gang Zheng, Ming-Tseh Lin, Marija Debeljak, Jonathan Ira Epstein, Pedram Argani

Research output: Contribution to journalArticle

Abstract

Metanephric adenoma (MA) has historically been considered to represent a differentiated form of epithelial Wilms tumor (WT), based in part upon cases that morphologically overlap these 2 neoplasms. More recently, BRAF V600E mutations have been demonstrated in the majority of MAs but not in unselected or even epithelial-predominant WTs, suggesting 2 genetically distinct entities. However, no prior study has examined BRAF status in neoplasms with overlapping histologic features of epithelial WT and MA. We studied a cohort of 11 such overlapping lesions, 2 of which we considered morphologically to be otherwise typical MAs with unusually prominent mitotic activity and 9 of which we classified as epithelial WTs with areas resembling MA. Both mitotically active MAs demonstrated the BRAF V600E mutation. While the majority (5/9) of epithelial WTs with areas resembling MA were negative for BRAF V600E mutation, 4 such cases were positive. Two BRAF V600E mutation-positive WTs occurred in children. One case in a 6-year-old male was morphologically similar to the BRAF V600E mutation-positive adult cases and subsequently metastasized to the lungs; remarkably, the metastases then completely resolved on Braf targeted therapy. A second occurred in a 3-year-old girl whose posttherapy nephrectomy specimen's tumor was encapsulated and mitotically active like a typical WT, but also had more differentiated areas resembling MA. Immunohistochemistry for Braf V600E paralleled the molecular findings, demonstrating immunoreactivity in both the WT and MA-like areas of all 4 of these neoplasms. In summary, we demonstrate that BRAF V600E mutations are not entirely restricted to typical MA, as they may be seen in MAs showing mitotic activity along with a subset of epithelial-predominant WTs in adults and children that have foci which overlap morphologically with MA.

Original languageEnglish (US)
JournalAmerican Journal of Surgical Pathology
DOIs
StatePublished - Jan 1 2019

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Wilms Tumor
Adenoma
Mutation
Neoplasms
Nephrectomy
Immunohistochemistry
Neoplasm Metastasis
Lung

Keywords

  • BRAF
  • metanephric
  • renal neoplasm
  • Wilms

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

@article{40bae12ab3594be8af94ce474f99fa9d,
title = "Metanephric Adenoma-Epithelial Wilms Tumor Overlap Lesions: An Analysis of BRAF Status",
abstract = "Metanephric adenoma (MA) has historically been considered to represent a differentiated form of epithelial Wilms tumor (WT), based in part upon cases that morphologically overlap these 2 neoplasms. More recently, BRAF V600E mutations have been demonstrated in the majority of MAs but not in unselected or even epithelial-predominant WTs, suggesting 2 genetically distinct entities. However, no prior study has examined BRAF status in neoplasms with overlapping histologic features of epithelial WT and MA. We studied a cohort of 11 such overlapping lesions, 2 of which we considered morphologically to be otherwise typical MAs with unusually prominent mitotic activity and 9 of which we classified as epithelial WTs with areas resembling MA. Both mitotically active MAs demonstrated the BRAF V600E mutation. While the majority (5/9) of epithelial WTs with areas resembling MA were negative for BRAF V600E mutation, 4 such cases were positive. Two BRAF V600E mutation-positive WTs occurred in children. One case in a 6-year-old male was morphologically similar to the BRAF V600E mutation-positive adult cases and subsequently metastasized to the lungs; remarkably, the metastases then completely resolved on Braf targeted therapy. A second occurred in a 3-year-old girl whose posttherapy nephrectomy specimen's tumor was encapsulated and mitotically active like a typical WT, but also had more differentiated areas resembling MA. Immunohistochemistry for Braf V600E paralleled the molecular findings, demonstrating immunoreactivity in both the WT and MA-like areas of all 4 of these neoplasms. In summary, we demonstrate that BRAF V600E mutations are not entirely restricted to typical MA, as they may be seen in MAs showing mitotic activity along with a subset of epithelial-predominant WTs in adults and children that have foci which overlap morphologically with MA.",
keywords = "BRAF, metanephric, renal neoplasm, Wilms",
author = "Wobker, {Sara E.} and Andres Matoso and Christine Pratilas and Shamlal Mangray and Gang Zheng and Ming-Tseh Lin and Marija Debeljak and Epstein, {Jonathan Ira} and Pedram Argani",
year = "2019",
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day = "1",
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language = "English (US)",
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TY - JOUR

T1 - Metanephric Adenoma-Epithelial Wilms Tumor Overlap Lesions

T2 - An Analysis of BRAF Status

AU - Wobker, Sara E.

AU - Matoso, Andres

AU - Pratilas, Christine

AU - Mangray, Shamlal

AU - Zheng, Gang

AU - Lin, Ming-Tseh

AU - Debeljak, Marija

AU - Epstein, Jonathan Ira

AU - Argani, Pedram

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Metanephric adenoma (MA) has historically been considered to represent a differentiated form of epithelial Wilms tumor (WT), based in part upon cases that morphologically overlap these 2 neoplasms. More recently, BRAF V600E mutations have been demonstrated in the majority of MAs but not in unselected or even epithelial-predominant WTs, suggesting 2 genetically distinct entities. However, no prior study has examined BRAF status in neoplasms with overlapping histologic features of epithelial WT and MA. We studied a cohort of 11 such overlapping lesions, 2 of which we considered morphologically to be otherwise typical MAs with unusually prominent mitotic activity and 9 of which we classified as epithelial WTs with areas resembling MA. Both mitotically active MAs demonstrated the BRAF V600E mutation. While the majority (5/9) of epithelial WTs with areas resembling MA were negative for BRAF V600E mutation, 4 such cases were positive. Two BRAF V600E mutation-positive WTs occurred in children. One case in a 6-year-old male was morphologically similar to the BRAF V600E mutation-positive adult cases and subsequently metastasized to the lungs; remarkably, the metastases then completely resolved on Braf targeted therapy. A second occurred in a 3-year-old girl whose posttherapy nephrectomy specimen's tumor was encapsulated and mitotically active like a typical WT, but also had more differentiated areas resembling MA. Immunohistochemistry for Braf V600E paralleled the molecular findings, demonstrating immunoreactivity in both the WT and MA-like areas of all 4 of these neoplasms. In summary, we demonstrate that BRAF V600E mutations are not entirely restricted to typical MA, as they may be seen in MAs showing mitotic activity along with a subset of epithelial-predominant WTs in adults and children that have foci which overlap morphologically with MA.

AB - Metanephric adenoma (MA) has historically been considered to represent a differentiated form of epithelial Wilms tumor (WT), based in part upon cases that morphologically overlap these 2 neoplasms. More recently, BRAF V600E mutations have been demonstrated in the majority of MAs but not in unselected or even epithelial-predominant WTs, suggesting 2 genetically distinct entities. However, no prior study has examined BRAF status in neoplasms with overlapping histologic features of epithelial WT and MA. We studied a cohort of 11 such overlapping lesions, 2 of which we considered morphologically to be otherwise typical MAs with unusually prominent mitotic activity and 9 of which we classified as epithelial WTs with areas resembling MA. Both mitotically active MAs demonstrated the BRAF V600E mutation. While the majority (5/9) of epithelial WTs with areas resembling MA were negative for BRAF V600E mutation, 4 such cases were positive. Two BRAF V600E mutation-positive WTs occurred in children. One case in a 6-year-old male was morphologically similar to the BRAF V600E mutation-positive adult cases and subsequently metastasized to the lungs; remarkably, the metastases then completely resolved on Braf targeted therapy. A second occurred in a 3-year-old girl whose posttherapy nephrectomy specimen's tumor was encapsulated and mitotically active like a typical WT, but also had more differentiated areas resembling MA. Immunohistochemistry for Braf V600E paralleled the molecular findings, demonstrating immunoreactivity in both the WT and MA-like areas of all 4 of these neoplasms. In summary, we demonstrate that BRAF V600E mutations are not entirely restricted to typical MA, as they may be seen in MAs showing mitotic activity along with a subset of epithelial-predominant WTs in adults and children that have foci which overlap morphologically with MA.

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