HISTOPATHOLOGICAL RESPONSE TO CHEMOTHERAPY IN STAGE M NEUROBLASTOMA: CORRELATION WITH BONE MARROW INFILTRATION PATTERNS AND CLINICAL OUTCOME.

Background. The histopathological response of primary neuroblastoma (NB) to induction chemotherapy remains poorly characterized. We investigated its association with bone marrow (BM) infiltration patterns at diagnosis and outcomes in stage M NB. Materials and Methods. We retrospectively reviewed 36 patients with BM involvement and evaluable post-induction primary tumor specimens, treated in Padua between January 2004 and April 2023. Viable tumor and nonviable tissue (necrosis and fibrosis) were quantified, and BM infiltration was classified as clumps or diffuse. Associations with histopathological response, overall survival (OS), and event-free survival (EFS) were assessed using comparative analyses, linear regression, Kaplan-Meier estimates, and Cox models. Results. Twenty patients (55.6%) had a clumps pattern and 16 (44.4%) a diffuse pattern. Diffuse infiltration was associated with less viable tumor (median 40% vs. 90%) and more nonviable tissue (60% vs. 10%; both p = 0.019). Fibrosis distributions also differed (p = 0.005). The association with greater nonviability remained significant after adjustment for MYCN amplification (adjusted difference, 24.1 percentage points; p = 0.046). Despite this, the diffuse pattern was associated with worse EFS (log-rank p = 0.039), while OS showed a nonsignificant trend (p = 0.093). After adjustment for MYCN amplification and nonviable tissue proportion, diffuse infiltration remained associated with worse EFS (HR = 3.03; p = 0.019) and OS (HR = 2.71; p = 0.038). Nonviable tissue proportion was not significantly associated with OS or EFS in univariable or adjusted analyses. Conclusions. Diffuse BM infiltration was associated with greater primary tumor nonviability after induction chemotherapy but poorer outcomes. Local histopathological response may therefore not reflect systemic disease aggressiveness. BM infiltration patterns may provide prognostic information in metastatic NB.