ECP 2023 Abstracts

S122 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Background & objectives: Time reduction between surgery and adju- vant therapy for non-small cell lung cancer improves (NSCLC) patient survival. We have tested the perioperative combination of confocal microscopy and real-time sequencing to provide faster and simpler workflow for the molecular profiling of NSCLC. Methods: Three fresh lung adenocarcinoma tumour tissue samples were perioperatively imaged with the Histolog® Scanner confocal micro- scope. Tissue areas relevant for molecular profiling were immediately sampled by the pathologist thanks to confocal images and analysed with the IdyllaTM real-time PCR based molecular testing. Obtained molecular profiles were compared with the output of standard-of-care assessments performed on diagnostic FFPE bioptic materials. Results: High cellularity tumour areas were identified with confocal imaging and sampled in less than 10 minutes allowing to start molecu- lar profiling right away and get the results of this assessment 2-3h after surgery. Treatment with Histolog® Scanner confocal microscope does not consume tissue nor negatively impact subsequent assessment in histopathology. Results of the molecular assessments obtained through the combination of confocal microscopy and automated sequencing were in complete agreement (100% concordance) with the output of standard-of-care assessment for the three cases. These included one KRAS, one EGFR mutated adenocarcinomas, and one with the absence of ALK, ROS, NTRK, RET fusions, or METex14 skipping. Conclusion: We report here a promising proof-of-concept for a fast and simple postoperative molecular analysis of NSCLCs. The use of on-site confocal imaging of full NSCLC surgical specimens allows the rapid retrieval of appropriate specimens for a fast automated sequencing. Tumour molecular profiling can be obtained on the day of the surgery. After confirmation on more cases, this approach could be implemented to simplify the molecular pathology workflow and provide in a timely manner useful information for the patient targeted treatment. PS-20-013 Studying tumour heterogeneity and its functional consequences in tumour growth in vitro and in vivo I. Vamvakaris*, K. Potaris, K. Tsilingiri, A. Chalari, Z. Kanaki, C. Karakostas, G. Zachou, I. Pateras, P. Constantoulakis, G. Christopou- lou, V. Georgoulias, A. Klinakis *SOTIRIA, Greece Background & objectives: In recent years it has been shown that tumours are highly heterogeneous “mosaic” tissues. The genetic differ- ences leading to this mosaicism as well as the significance for tumour growth and metastasis are poorly understood. Methods: Non-small cell lung cancer tumours were used to generate patient-derived xenografts and organoid cultures. We have compared the growth potential of squamous cell carcinomas to that of adenocarcino- mas. Furthermore, we have evaluated the capacity of different bits of the same tumour to grow both in mice and in culture. Tumour heterogeneity has been assessed with haematoxylin/eosin and specific staining. Results: In agreement with others, we have shown that squamous cell carcinomas have significantly higher engraftment rates, with around 80% of squamous cell carcinomas successfully establishing patient derived xenografts for at least 3 passages, compared to less than 50% for adenocarcinomas. Further, we observe that different areas of the same tumour engraft with not only different success rates but also dif- ferent latencies for those bits that do engraft successfully. This hetero- geneity is evident in tumour samples as small as 1cm2 as shown also by the histopathological analyses. The molecular basis of these differences is not yet clear and is the subject of ongoing studies in our laboratory. Conclusion: We show here that beyond the already described intra- tumour heterogeneity, to a certain extent there is also important inter- tumour heterogeneity. Whether this arises from genetic or epigenetic differences and whether invasive clones originate in specific areas of the tumour are important issues that need to addressed. PS-20-014 Pathomorphological features of AL-amyloidosis of the upper and lower respiratory tract O. Vasyukova*, Z. Gioeva, L. Mikhaleva, R. Vandysheva, K. Midiber, N. Gutyrchik, V. Pechnikova, D. Areshidze, M. Kozlova *Avtsyn Research Institute of Human Morphology of Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", Russia Background & objectives: Respiratory system is one of the target organs that can be affected by the pathologic protein aggregation in both systemic and localized forms of the amyloidosis. Objective: to describe pathomorphological features of AL-amyloidosis of the upper and lower respiratory tract. Methods: In this study, clinical findings, biopsy and surgical speci- mens were assessed in 17 patients with amyloidosis of the upper and lower respiratory tract. Amyloid deposits were identified in tissue sec- tions using Congo red stain and polarized light microscopy. Immuno- histochemical analysis was carried out with monoclonal and polyclonal antibodies against different amyloid types. Results: Amyloidosis of the respiratory tract was diagnosed in 7 male and 10 female patients, age range 42-88 years. The main clinical mani- festations included hoarseness, cough and dyspnea. Six cases were classified as localized laryngeal amyloidosis, including 4 cases of AL- kappa and 2 cases of AL-lambda amyloidosis. Lung involvementwas reported in 8 patients (6 patients with AL-lambda amyloidosis, 2 with AL-kappa amyloidosis). Three cases of diffuse pulmonary amyloidosis demonstrated the deposits within the interstitium and blood vessels. Amyloid tumour-like interstitial deposits were detected in 5 patients. Diffuse tracheal and bronchial involvement in amyloidosis was found in 3 cases (two cases of AL-kappa- and one - AL-lambda amyloidosis). Conclusion: Amyloidosis of the respiratory system is a rare disease. Localized amyloid deposits in the respiratory tract can be treated surgi- cally, while diffuse interstitial and vascular amyloid deposition which typically occurs in systemic amyloidosis requires combination therapy comprising surgery, transplantation, chemotherapy. This study was supported by RSF, grant No. 23-15-00138. PS-20-015 Placental transmogrification of the lung: a clinicopathological analysis of a case series and literature review C. Vieru*, J.C. Ruiz Tello, M.Á. Tribaldos Villar, M.J. Bonilla Pérez, A. Jiménez García, Á. Panizo Santos, M. García Martos *Hospital General Universitario Gregorio Marañón, Spain Background & objectives: Placental Transmogrification of the Lung (PTL), first described in 1979, is a rare benign disease with unclear pathogenesis, frequently associated with emphysematous or cystic lung lesions, pulmonary fibrochondromatous hamartomas and pulmonary lipomatosis. Morphologically resemble immature placental villi with- out placental properties. Methods: We reviewed all cases diagnosed as pulmonary hamartoma or bulla over a period of 11 years (2012-2023) in two university Span- ish hospitals. We identified several cases of PTL and retrospectively analysed clinical, radiological, histopathological and immunopheno- typic features. Results: 15 cases were retrieved, 9 associated with hamartomas and 6 detected as focal lesions in bullectomy specimens. There were 10 males and 5 females with 55,26 years mean age and 80% smoking background. Hamartomas were detected incidentally on radiology as solitary well- defined lung lesion (0,7-3 cm) and half of bullectomy specimens were obtained in pneumothorax context. Microscopically, pulmonary paren- chyma surrounding main lesions focally showed papillary structures resembling immature placental villi, lined by hyperplastic penumocytes and containing myxoid-edematous fibroadipose stroma with a variable