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Paraganglioma is a tumor developed from paraganglia, which are groups of neuroendocrine cells located along the vascular and nerve axes of the head and neck and along the spine. These tumors are benign and still localized in more than 80% of cases. Middle mediastinal paragangliomas represent less than 1% of mediastinal tumors and grow from the superior or middle mediastinal autonomic ganglion; they mostly are non-functional and are found in older patients. The often large volume and complex location of these tumors make their surgical resection challenging forcing the surgical team to resort to cardiopulmonary bypass and practice transfection of the aortic artery. We successfully operated an 80-year-old patient by clamshell incision without bypass or arterial procedure.

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA -rearranged lung adenocarcinoma who developed a A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK-rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers., SCOPUS: ar.j, info:eu-repo/semantics/published

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease in terms of morphological characteristics, protein expression profiles, genetic abnormalities, and potential for progression. Molecular heterogeneity has been extensively studied in DCIS. Yet morphological heterogeneity remains relatively undefined. This study investigated morphological intratumor heterogeneity in a series of 51 large DCIS. Nuclear atypia, DCIS architecture, necrosis, calcifications, stromal architecture, and stromal inflammation were assessed in one biopsy slide and three representative slides from each corresponding resection. For each histopathological feature, a histo-score was determined per slide and compared between the biopsy and the resection, as well as within a single resection. Statistical analysis comprised of Friedman tests, post hoc Wilcoxon tests with Bonferroni corrections, Mann-Whitney U tests, and chi-square tests. Despite substantial morphological heterogeneity in around 50% of DCIS, the histopathological assessment of the biopsy did not statistically significantly differ from the resection. Morphological heterogeneity was not significantly associated with patient age, DCIS size, or type of surgery, except for a weak association between heterogeneous stromal inflammation and smaller DCIS size. At the group level, the degree of heterogeneity did not significantly affect the representativity of a biopsy. At the individual patient level, however, the presence of necrosis, intraductal calcifications, myxoid stromal changes, and high-grade nuclear atypia was underestimated in a minority of DCIS patients. This study confirms the presence of morphological heterogeneity in DCIS for all six evaluated histopathological features. This should be kept in mind when taking biopsy-based treatment decisions for DCIS patients.

Introduction : Lung cancer is the most frequent and the deadliest cancer in the world. In non-small cell lung cancer (NSCLC), which represents 85% of all lung cancers, up to 55% patients relapse following surgery alone or in combination with chemotherapy or radiotherapy. Tumor-infiltrating lymphocytes play a key role in the control of the malignancy and display different phenotypes whilst interacting with cancer cells. Hence, immunoglobulin-A (IgA)-producing cells have been described to have an immunosuppressive function, promoting tumor development and growth in hepatocarcinoma and prostate cancer. Due to the important role of IgA in the lung, we aimed to study the prognostic significance of IgA+ cell infiltration in the epithelial and stromal compartments of resected NSCLCs. [...]

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there

Treatment with pembrolizumab, an anti-programmed cell death-1 (PDCD-1) monoclonal antibody for the treatment of non-small cell lung cancers (NSCLCs) requires prior immunohistochemical (IHC) analysis of the expression of the programmed death-ligand 1 (PD-L1) (also known as CD274 molecule) which is a heterogeneous and complex marker. The present study aimed to investigate how pathological and technical factors (such as tumor location and sampling type, respectively) may affect the PD-L1 evaluation in patients with NSCLC in the daily practice of pathology laboratories. The current study was retrospective, and included 454 patients with NSCLC, for whom PD-L1 expression analysis by IHC was prospectively performed between November 2016 and January 2018. The association between PD-L1 expression and the clinicopathological characteristics of patients was statistically investigated using either the χ2 and Fisher exact tests or the Mann-Whitney and Kruskal-Wallis tests, depending on whether PD-L1 expression was assessed in three large categories (<1, 1-49, ≥50%) or in more precise percentages. Furthermore, the same statistical methodology was used to analyze the heterogeneity of PD-L1 expression according to its sampling type (cytology, biopsy or surgical specimen) and its location (primary tumor, lymph node or distant metastasis). Intra- and inter-observer discrepancies were also studied using double-blind evaluation and concordance analyses based on the weighted κ coefficient. The results demonstrated a significant association between PD-L1 expression and sample location (P=0.005), histological type (P=0.026), total number of mutations (P=0.004) and KRAS proto-oncogene, GTPase mutations (P=0.024). In addition, sampling type did not influence PD-L1 expression. The inter- and intra-observer discrepancies were 15% and between 16 and 17.5%, respectively. The present study confirmed that evaluation of PD-L1 expression by IHC can be performed on all types of samples. In addition, info:eu-repo/semantics/published

The size and focality of the primary tumor in breast cancer (BC) influence therapeutic decision making. The purpose of this study was to evaluate whether preoperative breast magnetic resonance imaging (MRI) is helpful for the assessment of tumor size and surgical planning in early BC. We performed a retrospective review of a prospectively collected database of 174 patients treated at a single institution for invasive BC who had complete documentation of the tumor size from mammography (MMG), ultrasonography (US), and MRI. A total of 186 breast tumors were analyzed. Mean tumor size varied by imaging method: 14.7 mm by MMG, 13.8 mm by US, and 17.9 mm by MRI. The concordance between breast imaging techniques (BIT) and final pathology with a cutoff ≤ 2 mm was 34.8% for MRI, 32.1% for US, and 27.2% for MMG. US and MMG underestimated while MRI and MMG overestimated the real tumor size. Concordance was the same in premenopausal women for MRI and US at 35%, while concordance was higher in postmenopausal women for MRI. Correlations between size determined by BIT and histopathological size were best with MRI (0.59), compared to US (0.56) or MMG (0.42). Intrinsic subtypes of BC had different concordances according to imaging method, but no significant associations were found. MRI examination revealed additional lesions in 13.8% of patients, 69% of these lesions were malignant. MRI changed the surgical plan in 15 patients (8.6%), and the rate of mastectomy increased by 6.9%. MRI estimates BC tumor size more accurately than US or MMG, but a significant overestimation exists. Complementary MRI examination improved the concordance for tumor size between BIT and final pathology in 16.7%. MRI did not alter surgical planning for most patients and allowed more appropriate treatment for 8% of them.