Highly infiltrative brain metastasis of RET mutant lung primary: Morphometric assessment and molecular review

Histologic differentiation between primary brain tumors and metastases is an important aspect of intraoperative consultation. We present a case of metastatic carcinoma with microscopic features overlapping with that of an infiltrative glioma.

We present a case of a 51-year-old female with a history of recurrent metastatic non-small cell lung carcinoma (NSCLC). We developed a morphometric approach to contrast the pattern of brain invasion of our index case to that of CNS WHO grade 4, IDH1 R132H mutant astrocytoma, diffuse large B-cell lymphoma (DLBCL), melanoma, and other adenocarcinomas of the lung primary. We designed two novel parameters: number of tumor cells per cluster and percentage of mutual overlap by tumor cells, to quantitatively assess the degree of brain infiltration and invasion of each malignancy. Next, we analyzed our Institutional Database of the molecular findings for all primary lung metastasis to the brain with in-house next-generation sequencing (NGS) panel.

Carcinoma and melanoma showed the largest cluster sizes of cells with an average cluster size of 238 ± 32 and 41 ± 5 cells, and DLBCL had an average of 3.2 ± 0.3 cells per cluster. When we compared extent of cell-to-cell coverage, DLBCL had the largest coverage with an average of 90 ± 8%, adenocarcinoma of the lung had 85 ± 7%, and melanoma had 55 ± 5%. The infiltrative features in this case are commonly seen in diffuse gliomas and are not characteristic of metastases. The molecular findings of co-mutation of RET and TP53 suggest these could emerge as possible drivers of a more infiltrative growth pattern.