Malignant pleural mesothelioma is a rare tumor with a poor prognosis. The only universally recognized pathological prognostic factor is histopathological subtype with a shorter survival in non-epithelioid subtypes. Recently, a grading of epithelioid mesothelioma on surgical resection has been proposed. The aim of our work is to assess the prognostic role of several histopathological factors on a retrospective cohort of 116 patients diagnosed as a pleural mesothelioma for more than 95% of patients on pleural biopsy. Our work shows that mitotic count <3/10 HPF (p < 0.0001), the lack of necrosis (p = 0.0379), mild nuclear atypia (p = 0.0054), the lack of atypical mitoses (p = 0.0265), a nucleoli size <3 μm (p = 0.0139), and a nucleoli absent or visible at 200× or higher magnification (p = 0.0170) are significantly associated with a better median overall survival in epithelioid mesothelioma. The presence of atypical mitoses was found to be related to a worse median survival in non-epithelioid mesothelioma. Mitotic count, necrosis, nuclear atypia, and nucleoli size are not associated with overall survival in non-epithelioid mesothelioma. Our work highlights that histopathological prognostic factors can be assessed on pleural biopsies and can predict reliably median overall survival. This is of interest in order to define subgroups of patients who could benefit of different therapies and select patients who could benefit of surgical excision.

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Primary lung adenocarcinoma is classified according to predominant histopathologic architecture into lepidic, papillary, acinar, solid, and micropapillary subtypes. These subtypes are related to overall survival in primary lung adenocarcinoma. The main goal of our work was to evaluate the prognostic impact of this classification on surgical resection of brain adenocarcinoma metastases in 97 patients with surgically resected brain metastases of lung adenocarcinoma from 2008 to 2017. Histopathologic subtype is associated with overall survival (P=0.0085): 30.1±5.6 months for papillary-predominant pattern, 26.5±6.3 months for acinar-predominant pattern, 13.8±1.4 months for solid pattern, 11.6±10.1 for micropapillary pattern. A “low grade” group comprising acinar and papillary-predominant pattern tumors showed a longer overall survival (28.5±4.1 mo) when compared with high-grade–predominant pattern (solid and micropapillary patterns) (13.7±1.4 mo), P=0.0011. On multivariate analysis, age below 55 years at the time of resection (hazard ratio, 3.56; 95% confidence interval, 1.12-11.31) and groups of architectural patterns (hazard ratio, 4.25; 95% confidence interval, 1.83-9.9) were related to overall survival (P=0.031 and 0.00078, respectively). Predominant architectural pattern evaluated on the surgical specimen of brain metastasis is a major prognostic factor of overall survival in metastatic lung adenocarcinoma.

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Treatment for lung adenocarcinoma frequently diverges from standard treatment in older patients. Clinical, pathologic, and molecular characteristics of lung cancer in patients over 75 years old have not been fully described. The aim of our work was to describe the rate of EGFR, KRAS, BRAF, and HER2 mutations, and ALK rearrangement and pathologic characteristics in patients with lung adenocarcinoma over 75, compared with patients below 75 years old. This is a retrospective study from 2 cohorts: a histopathologic cohort of all consecutively resected lung adenocarcinoma in our institution for patients over 75 (n=54, from 2006 to 2017) compared with patients below 75 years old (n=148, from 2014 to 2017) and a molecular cohort of all stage IIIb or IV lung adenocarcinoma from 2009 to 2017 (n=1611). Papillary and lepidic components were more frequently found in patients over 75 years old (P=0.046 and 0.0078, respectively). The rate of current smokers was lower in older patients (P<0.0001). EGFR mutations were more frequent in patients over 75 than in younger patients: 17% versus 8.1% (P<0.0001). The mutually exclusive KRAS mutation was more frequent in patients below 75 years old than in older patients: 25.8% versus 12.8% (P<0.0001). There was no difference for the proportion of the 2 most frequent EGFR mutations (exon 19 deletion and L858R mutation) (P=0.85) or KRAS-mutated codon (P=0.22) between tumors in younger or older patients. There was no statistically significant difference for the presence of BRAF, HER2 mutations, and ALK rearrangement (P=0.44, 0.71, and 1, respectively). Our work highlights the fact that EGFR mutations are more frequent in patients over 75 years old in our population. We can hypothesize that this difference might be mainly caused by the less frequent occurrence of tobacco-smoking-related lung cancers in the elderly and the presence of a lepidic or papillary component in this age group.