Departments of Pathology and Laboratory Medicine.
Urology, University of North Carolina, Chapel Hill, NC.
Am J Surg Pathol. 2019 Sep;43(9):1157-1169. doi: 10.1097/PAS.0000000000001240.
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.
后肾腺瘤（MA）在历史上被认为是分化型上皮性 Wilms 瘤（WT）的一种形式，部分基于形态上与这两种肿瘤重叠的病例。最近，大多数 MA 中都发现了 BRAF V600E 突变，但在非选择或甚至上皮为主的 WT 中却没有发现，这表明这是两种具有不同遗传特征的实体。然而，之前没有研究检查过具有上皮性 WT 和 MA 重叠组织学特征的肿瘤中的 BRAF 状态。我们研究了一组 11 个具有重叠组织学特征的病变，其中 2 个我们认为在形态上是其他典型的 MA，具有异常突出的有丝分裂活性，9 个我们归类为上皮 WT，其中有类似于 MA 的区域。这两个有丝分裂活性的 MA 均显示 BRAF V600E 突变。虽然大多数（5/9）具有类似于 MA 区域的上皮 WT 为 BRAF V600E 突变阴性，但有 4 例为阳性。2 例 BRAF V600E 突变阳性 WT 发生在儿童中。一例 6 岁男性病例在形态上与 BRAF V600E 突变阳性的成人病例相似，随后转移到肺部；值得注意的是，转移灶随后在 Braf 靶向治疗后完全消退。另一个发生在一个 3 岁女孩身上，她的术后肾切除术标本的肿瘤有包膜，有丝分裂活性类似于典型的 WT，但也有更多分化的区域类似于 MA。Braf V600E 的免疫组织化学与分子发现相平行，在这 4 例肿瘤的 WT 和 MA 样区域均显示免疫反应性。总之，我们证明 BRAF V600E 突变并非完全局限于典型的 MA，因为它们可能出现在具有有丝分裂活性的 MA 中，以及在成年人和儿童中具有与 MA 形态上重叠的焦点的一部分上皮为主的 WT 中。
