Small cell lung cancer with SYN2::PPARG fusion.

INTRODUCTION: Small cell lung cancer (SCLC) accounts for 15% of lung cancers worldwide. It is an aggressive tumor that is typically diagnosed at an advanced stage. Treatment involves chemo-immunotherapy and/or radiotherapy. Identifying druggable targets activated by specific genetic alterations represents a significant challenge in improving patient outcomes. METHODS: We conducted a retrospective examination of molecular findings in lung cancer patients' records from 2021 to 2022. We discovered a unique case of SCLC harboring the SYN2-PPARG fusion. Histopathological analysis confirmed the diagnosis of SCLC. CASE REPORT: A 60-year-old woman, a heavy smoker, came to our attention due to a persistent cough with slight hemoptysis. Imaging, including axial contrast-enhanced computed tomography, revealed an advanced disease with extra-thoracic spread. Tumor histology showed a sheet-like proliferation of small-sized cells with a neuroendocrine phenotype and a high proliferation tumor cell fraction. Molecular genetic analysis using NGS approach revealed a fusion involving the SYN2 and PPARG genes. CONCLUSION: The SYN2-PPARG fusion has recently been documented in sinonasal adenocarcinoma and has been reported in only a single SCLC case previously. Highlighting the molecular heterogeneity within this aggressive form of lung cancer could potentially aid in the selection of specific therapies.

Klippel-Trenaunay syndrome as a rare cause of chronic thromboemboembolic pulmonary hypertension.

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum-maximum 26-50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

Bronchial Paraganglioma with SDHB Deficiency.

Though most paragangliomas arise as sporadic tumors, the recent advantages in the genetic screening revealed that about 30 % of paragangliomas are linked to hereditary mutations, such as those involving SDH genes. A 22-year-old woman carrying a left main bronchus tumor underwent surgery in our institution. Her past medical history included a GIST without KIT or PDGFRA mutation. The histological examination revealed a nested proliferation of medium-sized cells expressing neuroendocrine markers (chromogranin A and synaptophysin). The neoplastic cells failed to express SDHB gene product. These findings led us to the final diagnosis of bronchial paraganglioma in the setting of Carney-Stratakis syndrome. Bronchial paragangliomas are exceedingly rare tumors with polymorphous clinical presentation, and usually benign clinical course. Though most paragangliomas are sporadic, some tumors are associated with specific hereditary disease, especially those occurring in young patients or in combination with other neoplasms.

The role of endobronchial ultrasound-guided fine needle aspiration in the diagnosis of pleural mesothelioma.

OBJECTIVE: The aims of the present study were to investigate the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of malignant pleural mesothelioma (MPM), and to identify specific clinical settings in which this procedure can be recommended. METHODS: We retrospectively reviewed the clinical and pathological files of patients having undergone EBUS-TBNA from February 2011 to October 2014 to investigate thoracic lesions. Among 736 patients, we identified four of them with a diagnosis of MPM achieved primarily through EBUS-TBNA. The diagnosis was made on formalin-fixed paraffin-embedded cell blocks, by checking the expression of mesothelial and carcinomatous-specific markers. RESULTS: In all patients, the collected tissue was adequate, and the histological analysis in association with immunohistochemistry led us to the diagnosis of malignant pleural mesothelioma. In three patients, the diagnosis of mesothelioma was clinically suspected, as patients presented with diffuse pleural thickening. In two patients, videothoracoscopy was not possible owing to the 'dry' presentation of the pleural disease and the site of thickening. In this setting, EBUS-TBNA was considered, at a multidisciplinary consensus meeting, as the most adequate available method to obtain a histological diagnosis. CONCLUSION: EBUS-TBNA may be a valuable diagnostic technique in the field of pleural pathology in selected clinical settings. More specifically 'dry' mesothelioma forming para-tracheal nodules or masses not accessible by surgery or by computed tomography/ultrasonogaphy-guided needle biopsy constitutes a good indication to perform EBUS-TBNA.

Deep-seated rectal/anal basaloid carcinoma: useful immunocytochemistry in rare squamous cell carcinoma variants.

OBJECTIVES: To report the cytological aspects of ano-rectal basaloid carcinoma (BC) variant in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) conventional and liquid-based cytology (LBC), in a series of 10 cases of deep-seated squamous cell carcinomas (SCC), and to discuss the diagnostic difficulties in interpreting the morphology and immunocytochemical findings. METHODS: Ten cases of EUS-FNA smears and LBC specimens of deep-seated pelvic masses were retrospectively collected from January 2001 to November 2006. RESULTS: Ten EUS-FNA specimen cases were SCC, eight corresponding to usual SCC and two to BC-variant. Of these two cases, only one was correctly diagnosed by EUS-FNA specimen, whereas in the second case, the initial cytological diagnosis was poorly differentiated adenocarcinoma and the final diagnosis of basaloid carcinoma variant was established on surgical resection. Immunocytochemistry (ICC) using CK7, CK20 and CK34betae12 on FNA specimens confirmed the diagnosis retrospectively. CONCLUSION: The diagnosis of basaloid variant of SCC in a rectal location can be very difficult, both on account of the uncommon location and because of the low specificity of morphological aspects on EUS-FNA smears. The immunocytochemical technique, including a limited spectrum of keratins (CK7, CK20, CK34betae12, and p63) is necessary to avoid this diagnostic pitfall.