Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Genes Chromosomes Cancer. 2024 Sep;63(9):e23266. doi: 10.1002/gcc.23266.
Classical and mixed congenital mesoblastic nephroma (CMN) are characterized by an internal tandem duplication (ITD) of the EGFR gene, in contrast to cellular CMN that usually harbors an ETV6::NTRK3 gene fusion. This same fusion occurs in infantile fibrosarcoma, and this tumor can be considered as the soft tissue equivalent of cellular CMN. A soft tissue equivalent of classic/mixed CMN remains undefined at the genetic level. Since classical CMN resembles fibromatosis of soft tissue histologically, we asked whether fibromatosis in children might show EGFR ITD. ITD was investigated using the polymerase chain reaction and primers for exons 18 and 25 of the EGFR gene. Seven of the eight cases of classical or mixed CMN were positive by this approach, but none of the five cellular CMNs. Of 11 cases of fibromatosis (six plantar, two digital, and three desmoid), none were positive for EGFR ITD. Within the limits of this small study, we conclude that pediatric fibromatosis is likely not characterized by EGFR ITD. There are isolated reports of pediatric soft tissue tumors that harbor EGFR ITD, but these have the appearance of infantile fibrosarcoma or mixed CMN rather than fibromatosis. We did not find any such cases, since all 14 cases of infantile fibrosarcoma in our study had an ETV6::NTRK3 fusion. The soft tissue tumors with EGFR ITD are not a morphologic match for the low-grade histology of classical CMN. Whether they have a similar favorable biology or behave more like fibrosarcoma with an ETV6::NTRK3 fusion or an alternative fusion involving other kinases remains to be determined.
经典型和混合型先天性中胚层肾瘤（CMN）的特征是 EGFR 基因的内部串联重复（ITD），而细胞型 CMN 通常携带 ETV6::NTRK3 基因融合。这种融合同样发生在婴儿纤维肉瘤中，而这种肿瘤可以被视为细胞型 CMN 的软组织等效物。经典/混合型 CMN 的软组织等效物在遗传水平上仍未定义。由于经典型 CMN 在组织学上类似于软组织纤维瘤，我们想知道儿童的纤维瘤是否会显示 EGFR ITD。使用聚合酶链反应和 EGFR 基因外显子 18 和 25 的引物来研究 ITD。通过这种方法，8 例经典型或混合型 CMN 中有 7 例为阳性，但 5 例细胞型 CMN 均为阴性。11 例纤维瘤（6 例足底、2 例指部和 3 例硬纤维瘤）中，没有 EGFR ITD 阳性。在这项小型研究的范围内，我们得出结论，儿科纤维瘤可能不具有 EGFR ITD 特征。有孤立的儿科软组织肿瘤报告具有 EGFR ITD，但这些肿瘤具有婴儿纤维肉瘤或混合 CMN 的外观，而不是纤维瘤。我们没有发现任何这样的病例，因为我们研究中的 14 例婴儿纤维肉瘤均具有 ETV6::NTRK3 融合。具有 EGFR ITD 的软组织肿瘤与经典型 CMN 的低级别组织学不符。它们是否具有相似的良好生物学特性，或者更像具有 ETV6::NTRK3 融合的纤维肉瘤或涉及其他激酶的替代融合，还有待确定。
