Search

Background: Primary pulmonary paragangliomas are extremely rare neuroendocrine tumor, counting less than 1% of all paragangliomas. The incidence of paragangliomas range between 2– 8 per million in a year. The most common site of origin is the superior paraaortic region between the diaphragm and the lower renal poles (approximately 46% of all cases), and particularly in and around the renal hilus. Most pulmonary paragangliomas are nonfunctional and result in no evident clinical symptoms. Some patients develop respiratory symptoms, such as a cough, chest pain, or dyspnea, as in our case. Case presentation: A 71-year-old woman came to our attention for cough. Active smoker of 56 p/y, her medical history consisted of a myocardial infarction, anxious-depressive syndrome, hypertension, diabetes, obesity (BMI 37.3) and Hashimoto thyroiditis. The chest radiography revealed a rounded opacity of the middle lobe. Then, a computerized tomography (CT) showing the presence of a 2.6 cm solid lesion, oval in shape, with regular margins, located in the medial segment of the middle lobe. On gross examination, a well-demarcated neoplasm, with white-brown cut surface and solid consistency was found. The tumor cells appear to be arranged in a typical nest pattern supported by a thin vascular framework producing the classic ‘zellballen’ or basket pattern. Immunohistochemical staining showing positivity for CgA, Syn and S100 (immunostaining revealed of the presence of the classic “substentacular” cells). Conclusion: Primary pulmonary paragangliomas are rare entities and their differential diagnosis with carcinoid tumors, more typical for this site, is not always easy and lies in subtle morphological and immunophenotypic differences. A correct diagnosis is important since, in 50% of the patients, mutations in tumor susceptibility genes have been reported, thus a genetic testing and counseling should be considered.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural surface that includes three major histologic subtypes, epitheliod, sarcomatoid and biphasic. Epithelioid mesothelioma is usually associated with better prognosis. The genetic mechanisms driving MPM, the possible target mutations and the correlation with overall survival remain largely unsettled. We performed target exome sequencing in 29 cases of MPM aimed at identifying somatic mutations and, eventually, their correlation with phenotypic traits and prognostic significance. We found that KRAS mutations, occurring in 13.7% of cases, were associated with shortened median survival (7.6 versus 32.6 months in KRAS wild-type; p = 0.005), as it was the occurrence of any ≥3 mutations (7.6 versus 37.6 months; p = 0.049). Conversely, the presence of KDR single nucleotide polymorphism p.V297I (rs2305948) resulted in a favorable variable for survival (NR versus 23.4 months; p = 0.026). With the intrinsic limitations of a small number of cases and patient heterogeneity, results of this study contribute to the characterization of the mutation profile of MPM and the impact of selected somatic mutations, and possibly KDR polymorphism, on prognosis.