Previous studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid... Show morePrevious studies in patients with mature B-cell lymphomas (MBCL) have shown that pathogenic TP53 aberrations are associated with inferior chemotherapeutic efficacy and survival outcomes. In solid malignancies, p53 immunohistochemistry is commonly used as a surrogate marker to assess TP53 mutations, but this correlation is not yet well-established in lymphomas. This study evaluated the accuracy of p53 immunohistochemistry as a surrogate marker for TP53 mutational analysis in a large real-world patient cohort of 354 MBCL patients within routine diagnostic practice. For each case, p53 IHC was assigned to one of three categories: wild type (staining 1-50% of tumor cells with variable nuclear staining), abnormal complete absence or abnormal overexpression (strong and diffuse staining > 50% of tumor cells). Pathogenic variants of TP53 were identified with a targeted next generation sequencing (tNGS) panel. Wild type p53 expression was observed in 267 cases (75.4%), complete absence in twenty cases (5.7%) and the overexpression pattern in 67 cases (18.9%). tNGS identified a pathogenic TP53 mutation in 102 patients (29%). The overall accuracy of p53 IHC was 84.5% (95% CI 80.3-88.1), with a robust specificity of 92.1% (95% CI 88.0- 95.1), but a low sensitivity of 65.7% (95% CI 55.7-74.8). These results suggest that the performance of p53 IHC is insufficient as a surrogate marker for TP53 mutations in our real-world routine diagnostic workup of MBCL patients. By using p53 immunohistochemistry alone, there is a significant risk a TP53 mutation will be missed, resulting in misevaluation of a high-risk patient. Therefore, molecular analysis is recommended in all MBCL patients, especially for further development of risk-directed therapies based on TP53 mutation status. Show less
Background: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection ... Show moreBackground: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC Methods: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes. Results: We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0 % (95 % confidence interval [CI] 82.7 %-90.3 %), 85.6 % (95 %CI 81.2 %-89.2 %), and 60.3 % (95 %CI 54.7 %-65.7 %). Curative resection rate was 23.7 % (95 %CI 15.9 %-33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %-70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological surgery was performed in 49/320 (15.3 %), with residual cancer in 11/49 (22.4 %). Endoscopic follow-up was available in 200/242 (82.6 %), with a median of 4 months and residual cancer in 1 (0.5 %) following an incomplete resection. Conclusions: eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes. Show less
Background Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection ... Show moreBackground Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC < 2 cm. We aimed to report clinical outcomes and short-term results.Methods Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes.Results We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0 % (95 % confidence interval [CI] 82.7 %–90.3 %), 85.6 % (95 %CI 81.2 %–89.2 %), and 60.3 % (95 %CI 54.7 %–65.7 %). Curative resection rate was 23.7 % (95 %CI 15.9 %–33.6 %) for primary resection of T1 CRC and 60.8 % (95 %CI 50.4 %–70.4 %) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3 %. The severe adverse event rate was 2.2 %. Additional oncological surgery was performed in 49/320 (15.3 %), with residual cancer in 11/49 (22.4 %). Endoscopic follow-up was available in 200/242 (82.6 %), with a median of 4 months and residual cancer in 1 (0.5 %) following an incomplete resection.Conclusions eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes. Show less
Primary cutaneous large B-cell lymphomas can be divided into primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type. Accurately making the distinction... Show morePrimary cutaneous large B-cell lymphomas can be divided into primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type. Accurately making the distinction between these two lymphomas at the time of diagnosis is essential for the patient, as there are differences in prognosis (5 year overall survival >95% versus <50%) and first choice treatment (radiotherapy versus polychemotherapy). The thesis aimed to better characterize both subtypes genetically and clinicopathologically in search for markers differentiating between the subtypes. Furthermore, genetic studies were performed on primary cutaneous large B-cell lymphoma, leg type, in search for leads for targeted therapy in this aggressive type of primary cutaneous large B-cell lymphoma. Finally, a series of methotrexate-associated B-cell lymphoproliferative disorders presenting in the skin (mimicking primary cutaneous large B-cell lymphomas) were studied, in search of clinicopathologic features characteristic for this disorder. Show less
In the World Health Organization (WHO) 2008 classification 2 main types of primary cutaneous large B-cell lymphomas (PCLBCLs) are distinguished: primary cutaneous follicle center lymphoma (PCFCL)... Show moreIn the World Health Organization (WHO) 2008 classification 2 main types of primary cutaneous large B-cell lymphomas (PCLBCLs) are distinguished: primary cutaneous follicle center lymphoma (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCBCL-LT). PCFCL has a 5-year overall survival rate of 95%, and PCBCL-LT of approximately 50%. Expression profiling studies have shown higher RNA expression of the IgM heavy chain in PCBCL-LT compared with PCFCL. To find out whether this difference could also be demonstrated at the protein level, we performed immunohistochemical staining for B-cell receptor heavy and light chains on skin biopsies from 53 patients with PCFCL and 40 patients with PCBCL-LT. All 40 cases of PCBCL-LT consistently showed cytoplasmic staining for IgM, in 18 of them with coexpression of IgD. In contrast, only 5 of the PCFCL cases showed cytoplasmic staining for IgM and/or IgD, including all 3 PCFCLs presenting on the leg. Hence, staining for IgM on paraffin-embedded sections seems to be an additional tool for differentiating between the 2 entities in clinical pathology practice. Analogous to other nodal and extranodal large B-cell lymphomas, expression of IgM in PCLBCL seems to be related to an activated B cell-like phenotype. Finally, the expression of IgM (and IgD) in this type of lymphoma might imply defective class switch recombination. Show less
