Predictive value of NLR, TILs (CD4+/CD8+) and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer.

The combination of perioperative chemotherapy plus complete surgical resection is currently accounted as the first-choice strategy in patients with locally advanced Gastric Cancer (LAGC). Nevertheless, the partial response rate makes it necessary to search biological parameters useful to select patients who would benefit most from neoadjuvant chemotherapy (NAD-CT). We performed a retrospective analysis on a cohort of 65 LAGC cases, EBV negative and without MMR defect, submitted to perioperative chemotherapy plus surgical resection. We evaluated the neutrophil-lymphocytes ratio (NLR) in peripheral blood, the TILs density (reported as CD4/CD8 tissue ratio) and PD-L1 expression by immunohistochemistry on bioptic tissues before the treatment. Results were correlated with the biological features, histological response (TRG) and clinical outcome (PFS and OS). We found that NLR, TILs and PD-L1 expression showed a significant correlation with TNM stage, lymphovascular invasion and response to NAD-CT (TRG). Correlating the NLR, TILs and PD-L1 expression with PFS and OS, we found that patients with lower NLR levels (< 2.5 ratio), lower TILs (< 0.2 ratio) and higher PD-L1 level (CPS ≥ 1) had a significantly better PFS and OS than those with higher NLR, higher TILs and lower PD-L1 expression (p < 0.0001). Multivariate and multiple regression analyses confirmed the predictive and prognostic role of all three parameters, especially when all three parameters are combined. Our study demonstrated that pre-treatment NLR, TILs and PD-L1 expression are predictive and prognostic parameters in NAD-CT-treated LAGC suggesting a pivotal role of the systemic and tumor microenvironment immunological profile in the response to chemotherapy.

Bone marrow megakaryocytic activation predicts fibrotic evolution of Philadelphia-negative myeloproliferative neoplasms.

Philadelphia-negative chronic myeloproliferative neoplasms (MPN) have been traditionally considered as indistinctly slowly progressing conditions; recent evidence proves that a subset of cases have a rapid evolution, so that MPN prognosis needs to be personalized. We identified a new morphological parameter, defined as megakaryocytic activation (M-ACT) based on the coexistence of megakaryocytic emperipolesis, megakaryocytes (MK) cluster formation and evidence of arrangement of collagen fibers around the perimeter of MK. We retrospectively analyzed the bone marrow biopsy of two MPN cohorts of patients with polycythemia (PV) (n=64) and non-PV patients (including essential thrombocythemia, and early/prefibrotic primary myelofibrosis [PMF]) (n=222). M-ACT showed a significant correlation with splenomegaly, white blood cell count, and lactate dehydrogenase serum levels in both groups, with JAK2 V617F allele burden in PV patients, and with CALR mutations, and platelet count in non-PV patients. Progression-free survival, defined as PV-to-secondary MF progression and non-PV-to-overt PMF, was worse in both PV and early/prefibrotic PMF patients with M-ACT in comparison to those without M-ACT (P<0.0001). Interestingly, M-ACT was not found in the subgroup of essential thrombocythemia patients. In conclusion, M-ACT can be helpful in the differential diagnosis of MPN and can represent a new morphologic parameter with a predictive value for progression of MPN.

Metanephric adenoma with BRAF V600K mutation and a doubtful radiological imaging: pitfalls in the diagnostic process.

Metanephric adenoma (MA) is an uncommon benign renal tumor whose histomorphological aspect resembles that of Wilms' tumor and papillary renal cell carcinoma. From a diagnostic and therapeutic perspective, recognition of this entity is important as it has a more favorable clinical outcome compared with Wilms' tumor and papillary renal cell carcinoma. MA should not be treated with nephrectomy if the tumor size is small, opting for a conservative treatment. However, the preoperative diagnosis of this disease is extremely challenging. The present study describes a case of this rare disease, showing an ambiguous radiological imaging and that only after a percutaneous biopsy, was defined as a MA and treated with partial nephrectomy. Moreover, the histological diagnosis of this case was partially complicated by the equivocal immunohistochemical analysis showing negativity for BRAF VE1 staining. Only the mutational analysis demonstrated the presence of the BRAF V600K mutation (for the first time described in a case of metanephric adenoma), highlighting the necessity of sequencing in case of MA with negativity for BRAF VE1 clone.