Characterisation and impact of intratumoural stroma in melanoma and carcinoma brain metastases

Research on the tumour microenvironment in brain metastases (BM) has predominantly focused on the immune response, while the presence, morphological patterns, and potential clinical relevance of intratumoural stroma remain less intensively investigated. We retrospectively analysed 604 BM (529 carcinomas, 75 melanomas) from 556 patients. Intratumoural stroma was histomorphologically classified into absent/unclear (Group 0), present without desmoplasia (Group 1) or with desmoplasia (Group 2). Associations with histological features, clinical parameters, and survival were evaluated. Intratumoural stroma was absent in 63.2% of tumours (n = 382), was present without desmoplasia in 14.9% (n = 90), and was desmoplastic in 21.9% (n = 132). Desmoplasia was most frequent in metastases from breast carcinomas and pulmonary squamous cell carcinomas. No significant associations were found between stroma groups and age, sex, brain location, PD-L1 expression, oncogenic mutations in lung carcinoma, or breast-cancer molecular subtype. Independent predictors of poorer survival were increasing age (HR = 1.029, 95% CI: 1.018-1.039, p < 0.001), male sex (HR = 1.492, 95% CI: 1.204-1.849, p < 0.001), and infratentorial location (HR = 1.402, 95% CI: 1.125-1.748, p = 0.003). Stroma groups showed no independent prognostic value in the overall cohort. However, subgroup analysis of non-small cell lung cancer revealed a U-shaped relationship, with Group 1 stroma linked to better survival (p = 0.020). In summary, intratumoural stroma in BM is a carcinoma-specific phenomenon, absent in melanoma. Patient outcomes, however, were primarily determined by demographic and anatomical factors rather than stromal morphology in the overall cohort but may have clinical relevance in particular tumour subgroups.

Keywords: brain metastasis; desmoplasia; histomorphology; intratumoural stroma; survival analysis; tumour microenvironment.