Diagnostic performance of immunohistochemistry markers for malignant pleural mesothelioma diagnosis and subtypes. A systematic review and meta-analysis.

BACKGROUND: Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis. METHODS: The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model. RESULTS: 103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2-40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis. CONCLUSION: Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.

Multiple mutations in the EGFR gene in lung cancer: a systematic review.

Background: Lung cancer is a public health problem worldwide. Currently, identifying genetic mutations in the epidermal growth factor receptor (EGFR) has brought significant changes in diagnosing and managing patients with lung cancer. The presence of multiple mutations, defined as the presence of more than one EGFR mutation, has been reported in a few studies. Therefore, we carried out this systematic review to describe the most common multiple mutations in the EGFR gene. Methods: We conduct a systematic review of descriptive studies, cohorts, and clinical trials published in Scopus, PubMed, Scielo, and Virtual Health Library literature. The inclusion criteria for the systematic review were descriptive studies, cohorts, and clinical trials with the presence of multiple mutations in the EGFR gene. It was followed the Preferred Reporting Items for Systematic Meta-Analyses (PRISMA) guidelines. Results: In the systematic review, 41 articles were included. Four hundred and forty-six cases with multiple mutations in the EGFR gene were found (0.95% of the patients included in the studies). The most prevalent dual mutations observed were T790M + L858R and deletions in exon 19 + T790M. Triple mutations were found in 9 cases (2.017%). According to reports, the presence of T790M mutation in the multiple mutations has been associated with poor clinical outcomes. Discussion: The presence of multiple mutations in the EGFR gene is rare. It is of great importance to consider the T790M mutation since it generates resistance to pharmacological management and has worse outcomes. The most important limitation was that clinical information data and follow-up could not be collected in a large percentage of patients. Therefore, future work should be focused on clinical characteristics, follow-up and repercussions in the treatment of patients with multiple mutations.

Synchronous or collision solid neoplasms and lymphomas: A systematic review of 308 case reports.

BACKGROUND: The presence of a lymphoma associated with a solid synchronous neoplasm or collision neoplasm has been rarely in the literature, and a detailed characterization of these cases is lacking to date. OBJECTIVE: To describe the main clinicopathological features of synchronous/collision tumors. METHODS: A systematic search in PubMed, Scielo, and Virtual Health Library literature databases for cases or case series of synchronous or collision lymphoma and other solid neoplasms reported up to March 2021 was performed. Three reviewers independently screened the literature, extracted data, and assessed the quality of the included studies. The systematic review was performed following the Preferred Reporting Items for Systematic Meta-Analyses guidelines. RESULTS: Mean age of patients was 62.9 years (52.9% men). A total of 308 cases were included (62% synchronous and 38% collision). The most frequent location of both synchronous and collision tumors was the gastrointestinal tract with the most common solid neoplasm being adenocarcinoma, and the most frequent lymphoma diffuse large B-cell lymphoma (21.7%) and mucosa-associated lymphoid tissue lymphoma (20.4%). Of the total number of mucosa-associated lymphoid tissue lymphomas and gastric adenocarcinomas, the presence of Helicobacter pylori infection was documented in 47.3% of them. Only 2% of all cases had a previous history of lymphoma. Thus, in most cases (98%), lymphoma was discovery incidentally. In addition, nodal lymphoma was associated with metastasis in 29 (9.4%) cases as collision tumor, most commonly (90%) in locoregional lymph nodes of the solid neoplasm. CONCLUSIONS: The frequent association of some type of B-cell lymphoma and adenocarcinoma in synchronous/collision tumors of the gastrointestinal tract points to common pathogenic mechanisms in both neoplasia, particularly related to chronic inflammation in this location. In most cases, lymphoma identified in locoregional lymph nodes or distant of a carcinoma seems to represent an incidental finding during the carcinoma diagnostic/therapeutic approach. A synergy between carcinoma and lymphoma (involving inflammation and immunosuppression mechanisms) may favor tumor progression and dissemination. A better understating of the interactions lymphoma/carcinoma in the setting of synchronous/collision tumors may help to improve patient management and prognosis.

Perilymphatic micronodular pattern as a manifestation of pulmonary amyloidosis on high-resolution computed tomography.

The term amyloidosis describes a group of diseases caused by the fibrillar deposit of poorly folded proteins in tissues with a secondary alteration of their function. Diffuse parenchymal lung disease associated with amyloidosis is rare and is most often diagnosed in autopsy. A 45-year-old male patient presented an acute episode of cough with mucoid expectoration. He had also dyspnea, dry cough, chest pain, and constitutional symptoms of 6 months of evolution. Initially the case was treated as acute pneumonia. After taking radiological images of the thorax, a diagnostic suspicion of lymphangitic spread of neoplasia was assumed. Histopathological findings of an open pulmonary biopsy demonstrated interstitial thickening with perivascular eosinophilic invasion. Congo Red staining and immunohistochemistry studies were done and turned out to be positive for amyloid. The perilymphatic micronodular pattern as a radiological manifestation of parenchymal pulmonary amyloidosis has been very rarely described in the literature, therefore it must be considered as a differential diagnosis in patients with this pattern in CT scan and should be an incentive for its histopathological study once a neoplasm is ruled out.