Intratumoral desmoplastic stroma in carcinoma brain metastases harbors stromal cells with a cancer-associated fibroblast (CAF)-like immunophenotype

Abstract Background Research on the tumor microenvironment of brain metastases (BM) has largely focused on immune response, while the intratumoral stromal compartment remains poorly characterized. In primary carcinomas, cancer-associated fibroblast (CAF) are intratumoral stromal cells that enable tumor progression. A subset of carcinoma BM shows intratumoral desmoplastic stroma (IDS) including stromal cells. This raises the question of whether this represents a CAF population in an organ devoid of resident fibroblasts. Methods Whole-slide immunohistochemistry using a CAF marker panel (ASMA, CD90, COL11A1, SPARC) was performed in 19 carcinoma BM with IDS and in 10 glioblastomas. Stroma staining was scored semi-quantitatively (0–3). An independent cohort of 20 primary carcinomas with desmoplastic stroma was analyzed descriptively using the same approach. Results IDS stroma cells in BM exhibited consistent CAF-like immunophenotypes across the panel. Marker expression did not differ by primary tumor site (ASMA p = 0.439; CD90 p = 0.711; COL11A1 p = 0.328; SPARC p = 0.369). Compared with glioblastomas, carcinoma metastases showed markedly higher ASMA and COL11A1 scores ( p < 0.001 each). The summed CAF panel score was substantially higher in carcinoma metastases than in glioblastomas ( p < 0.001). IDS cells lacked immunoreactivity supporting glial or endothelial origin (GFAP/S100/Olig2 negative; CD34 negative) and showed no evidence of entrapped axons. Conclusion A subset of carcinoma BM contains an IDS compartment with a CAF-like immunophenotype that is distinct from glioblastoma and normal brain. These findings provide a histopathological framework supporting the presence of an intratumoral stromal compartment with a CAF-like immunophenotype in BM and motivate mechanistic studies to define cellular origin, subtype composition, and functional roles.