Re-biopsy after first line treatment in advanced NSCLC can reveal changes in PD-L1 expression.

OBJECTIVES: Re-biopsy in progressive advanced Non-Small-Cell Lung Cancer (NSCLC) after first line treatment may reveal information about evolving tumor biology during treatment. Our study aims to investigate the feasibility, risk of complications, and clinical relevance of performing re-biopsy systematically. MATERIALS AND METHODS: NSCLC patients with advanced, non-targetable disease, receiving first line systemic treatment, were included in a prospective single-centre study (NCT03512847). A diagnostic biopsy was performed at baseline and repeated at time of progression, preferentially from the progressive lesions as determined by CT or PET/CT. The primary endpoint was feasibility, including complication rate to re-biopsy. Secondary endpoints were clinical relevance, defined as a potential of changing treatment or follow-up, due to new histological evidence, specifically a change in PD-L1 Tumor Proportion Score (TPS). RESULTS: Fifty-one patients with progressive advanced NSCLC had re-biopsy performed. Median time from patients' acceptance to biopsy was seven days (range: 0-31). Complication rate was 6% (n = 3) represented by pneumothorax, hydro-pneumothorax and pneumonia, respectively. No severe or chronic complications occurred. Sufficient material for PD-L1 analyses was obtained in 46 of 51 patients: the remaining five cases had insufficient tissue for analyses, no malignant cells/only suspected malignant cells, questioning whether progression was real. PD-L1 TPS change was observed in 33% of patients (n = 15) and 17% (n = 8) had potentially clinically relevant changes. A significantly higher chance of PD-L1 TPS change was observed in chemotherapy-treated patients. CONCLUSION: Our study showed that re-biopsy is feasible, with low risk of complications, and can be clinically relevant in patients with suspected progression in advanced NSCLC.

Pleural epithelioid hemangioendothelioma mimicking pleural empyema: A case report.

Malignant pleural effusion is an important and difficult differential diagnosis to pleural empyema. Epithelioid hemangioendothelioma is an uncommon vascular tumor, which typically occurs in liver, lung or bone. We present an extremely rare case of primary pleural epithelioid hemangioendothelioma mimicking pleural empyema. We conclude, that pleural epithelioid hemangioendothelioma should be kept in mind as a differential diagnosis in patients suspected of empyema.

The JAK2V617F allele burden and STAT3- and STAT5 phosphorylation in myeloproliferative neoplasms: early prefibrotic myelofibrosis compared with essential thrombocythemia, polycythemia vera and myelofibrosis.

Early prefibrotic myelofibrosis (early PMF) is a diagnosis that clinically and histologically mimic essential thrombocythemia (ET), but is important to distinguish from ET, polycythemia vera (PV) and primary myelofibrosis (PMF) due to its different prognosis and clinical evolution. In this study, we assessed the allele burden of JAK2V617F in bone marrow biopsies from patients with these chronic myeloproliferative neoplasms. We correlated our findings with the amount of phosphorylated STAT3 (P-STAT3) and STAT5 (P-STAT5) in megakaryocyte nuclei in the bone marrow. The JAK2V617F allele burden was significantly higher in patients with PV (median: 50.99, range: 23.08-97.29, p < 0.01 and p < 0.01) and PMF (median: 44.13, range: 33.61-92.17, p < 0.05 and p < 0.01) compared with a low allele burden in ET (median: 23.465, range: 8.67-47.92) and early PMF (median: 25.68, range: 0.61-49.13) respectively. In addition, we found a significantly higher phosphorylation of STAT5 and STAT3 in the JAK2V617F positive group than in the negative group. There was no positive correlation between increasing JAK2V617F allele burden and the amount of P-STAT3 and P-STAT5. However, we found low values of P-STAT5 in bone marrow biopsies from patients with ETJAK2V617F+ as compared with patients with early PMFJAK2V617F+. Although this difference was statistically significant, larger studies are needed to firmly support this conclusion.

Use of commercially available rabbit monoclonal antibodies for immunofluorescence double staining.

Immunohistochemistry, that is, the use of polyclonal and monoclonal antibodies to detect cell and tissue antigens at a microscopical level is a powerful tool for both research and diagnostic purposes. Especially in the field of hematologic disease, there is often a need to detect several antigens synchronously, and we report here a fast and easy technique for demonstrating more than 1 antigen in 1 slide using immunofluorescence. We have used commercially available rabbit monoclonal antibodies (Cyclin D1, CD3, CD5, CD23, etc.) paired with mouse monoclonal antibodies (CD7, CD20, CD79a, Pax-5, etc.) for double immunofluorescence labeling on paraffin-embedded tissue sections. Commercially available rabbit monoclonal antibodies in combination with mouse monoclonal antibodies proved useful in double immunofluorescence labeling on paraffin-embedded tissue, and all combinations used yielded excellent results.