ECP 2023 Abstracts

S343 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 E-PS-21-021 Insights into synchronous squamous non-small cell lung cancer genomics – a case viewpoint into the broader literature M.M. Köteles*, G. Olteanu *Emergency County Hospital Bihor, Romania Background & objectives: The most common synchronous primary lung carcinoma (SPLC) is, statistically, squamous cell carcinoma (SCC). Here we report a case of SPLC SCC that was molecularly dis- sected and used as a viewpoint for a review of the literature. Methods: A 77-year-old female patient presented to our hospital with two lung tumours in the right upper lobe (RUL), she underwent lobec- tomy with pathological diagnosis and staging of both tumours. Next, for both tumours’ next-generation sequencing (NGS) from the corre- sponding formalin-fixed paraffin-embedded (FFPEs) tissue blocks was performed with COSMIC variant ID calling. The results were used for a literature review viewpoint. Results: Both tumours, diagnosed as NSCLC nonkeratinizing squamous cell carcinoma, had pathological stages of pT1cN0R0 and pT2aN0R0. The pT1c tumour exhibited NGS-detected EGFR (COSM18419), BRAF (COSM449) missense mutations, and sev- eral p53 gene nonsense and missense mutations alongside KIT (COSM12708) and VHL missense mutations (COSM14387). In con- trast, the pT2a tumour displayed different genomic alterations, includ- ing PTEN (COSM23657), PIK3CA (COSM163484), RB1, and FLT3 (COSM28047) missense mutations. P53 nonsense and missense altera- tions also occurred but with differing amino acid level changes. Nota- bly, previous SCC literature emphasizes TP53, PIK3CA, and FGFR1 as frequent findings, differing from the tumours described here. Conclusion: NGS profiling may be useful for establishing the rela- tionship between tumours, with a significant role in the differential diagnosis between intrapulmonary metastasis and synchronous primary lung cancer. For this case, our findings showed different molecular pro- files with only one relevant similarity, the same missense SMARCB1 genomic alteration, with akin allele frequency and identical amino acid change, supporting the anticipated diagnostic of synchronous tumours. E-PS-21-022 SMARCA4-deficient lung adenocarcinoma—case report A. Lapa*, N. Coimbra, A. Coutada, P. Rodrigues Veiga *IPO-Porto, Portugal Background & objectives: SMARCA4-deficient lung adenocarcinoma is rare, usually poorly differentiated and typically affects young male smokers. It usually presents as a TTF1-negative tumour with preponder- ant solid pattern and aggressive behaviour, leading to short survival rates. Methods: A 41-year-old ex-smoker male was evaluated due to 1-month long persistent pain, located at the right hemithorax. The patient had a medical history of a right-sided pneumothorax that was conserva- tively treated. TC-scans showed a 4,3x3,3cm pulmonary lesion, with extensive pleural contact, but no clear evidence of bone involvement. An extensive surgical resection was performed. Results: The histopathological examination showed a poorly- differ- entiated adenocarcinoma, with solid and acinar patterns and loss of SMARCA4 expression. Spreading through airspaces, lymph-vascular permeation and invasion of parietal pleura and thoracic wall were pre- sent. PD-L1 expression was between 5 and 10% and expression of cytokeratin was diffuse. Genetic testing showed no mutations in EGFR, ALK, ROS1, KRAS, BRAF, MET or RET genes, but two mutations in TP53 gene were found. Genetic testing for SMARCA4 is still pending. Less than two months after surgery, local relapse with metastatic mul- tifocal pleural disease was found, leading to a new staging of T4N0M1. The patient is currently undergoing palliative treatment. Conclusion: Testing for loss of expression of SMARCA4 is recom- mended in poorly-differentiated thoracic tumours given the dismal prognosis and limited therapeutic solutions of the entities harbouring this alteration. Debate is still ongoing if SMARCA4-deficient adenocar- cinoma should be considered a separate entity. Nevertheless, although both lose the expression of SMARCA4, it should be distinguished from SMARCA4-deficient undifferentiated tumours. Additional genetic testing beyond the recommended for NSCLC, including members of the SWI/ SNF complex, might be considered until final entity definition is achieved. E-PS-21-023 Late presentation: a case of tuberous sclerosis complex associated lymphangioleiomyomatosis A. Lazim*, A. Arriola, M. Mollaee *Temple University Hospital, USA Background & objectives: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease, may occur sporadically or with tuberous scle- rosis complex (TSC). It is characterized by a proliferation of abnormal smooth muscle in the pulmonary interstitial spaces leading to cystic destruction, respiratory failure, pneumothorax. Methods: LAM is the most common lung manifestation of TSC and can be seen in both males and females. Sporadic LAM occurs mostly in young reproductive-aged females. Here we report a 35-year-old Span- ish female with TSC, and medical history significant for intellectual disability, seizures, blindness, ash leaf spots, and retinal hamartoma. Results: She had subependymal giant cell astrocytoma status post resection with a 9 cm fat containing cystic mass of the kidney likely angiomyolipoma on MRI, who presented with severe shortness of breath and cough. High-resolution computed tomographic imaging of the chest revealed numerous bilateral cysts and multiple sub centimetre nodules. She underwent right upper and middle lobe wedge surgery with bullectomy and pleurodesis. Histological examination revealed cysts with subtle abnormal smooth muscle proliferation in the cysts’ wall and multifocal micronodular pneumocyte hyperplasia. Immuno- histochemical stains showed positivity for SMA and HMB-45 in the abnormal smooth muscle areas confirming the LAM diagnosis. Conclusion: LAM has been underreported and should be included in the differential diagnosis in any young female with respiratory dys- function, pneumothorax, or pleural effusion. In patients with TSC, early screening and regular follow-up of organs including lung should be considered to establish diagnosis of LAM to minimize subsequent complications and associated morbidity and mortality. E-PS-21-024 Thymic high grade neuroendocrine neoplasm with carcinoid mor- phology: rare occurrence A. Lazim*, A. Arriola, M. Mollaee *Temple University Hospital, USA Background & objectives: High grade neuroendocrine carcinoma of the thymus are extremely rare. WHO classifications of pulmonary/ thymic neuroendocrine tumours (TNETs) classify these tumours into low and high grade. A subset of TNETs identified have low grade morphological features and high mitotic counts. Methods: We report a rare case of a 59-year-old woman who presented with progressively enlarging anterior mediastinal mass. The imaging study revealed 7.5 cm mass abutting the distal SVC, anterior and lat- eral wall of the right atrium. Following neoadjuvant chemotherapy, the thymic mass was resected en block with adhesed pericardium and portion of the lung. Results: On histology, the tumour lacked characteristic features of large cell neuroendocrine carcinoma (LCNEC) such as peripheral palisading, prominent nucleoli. There were 18 mitotic figures per10 HPF, exten- sive necrosis, and direct invasion into adjacent parietal pericardium and lung parenchyma. Ki-67 was 35%, further supporting the notion that this is a high-grade tumour. This case is a rare occurrence and has