Histopathological features of SMARCA4-deficient thoracic malignancies: Data from resource-limited setting.

person Nune Karapetyan Yeolyan Hematology and Oncology Center, Yerevan, Armenia info_outline Nune Karapetyan, Davit Zohrabyan, Parandzem Khachatryan, Liana Safaryan, Lilit Harutyunyan, Armen Avagyan, Aramayis Galumyan, Gevorg Voskanyan, Gor Geghamyan, Sergo Mkhitaryan, Mikayel Arustamyan, Meri Ghayamyan, Sona Karamyan, Mariam Khachatryan, Armen Arzumanyan, Mariam Hovhannisyan, Samvel Bardakhchyan, Armen Mkhitaryan

Authors person Nune Karapetyan Yeolyan Hematology and Oncology Center, Yerevan, Armenia info_outline Nune Karapetyan, Davit Zohrabyan, Parandzem Khachatryan, Liana Safaryan, Lilit Harutyunyan, Armen Avagyan, Aramayis Galumyan, Gevorg Voskanyan, Gor Geghamyan, Sergo Mkhitaryan, Mikayel Arustamyan, Meri Ghayamyan, Sona Karamyan, Mariam Khachatryan, Armen Arzumanyan, Mariam Hovhannisyan, Samvel Bardakhchyan, Armen Mkhitaryan Organizations Yeolyan Hematology and Oncology Center, Yerevan, Armenia, Nersisyan 7 str., Yerevan, Armenia, Yerevan State Medical University, Yerevan, Armenia, Mikaelyan Institute of Surgery, Yerevan, Armenia, Wigmore Clinic, Yerevan, Armenia, Astghik Medical Center, Yerevan, Armenia, National Center of Oncology named after V.A. Fanarjyan, Yerevan, Armenia, IRA Medical Group Radiotherapy Center, Yerevan, Armenia, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia, Immune Oncology Research Institute, Yerevan, Armenia, Histogen Practical Scientific Center of Pathology, Yerevan, Armenia Abstract Disclosures Research Funding No funding sources reported Background: SMARCA4 deficient tumors are rare malignancies that develop due to inactivating mutation in switch/sucrose-nonfermenting chromatin remodeling complexes (SWI/SNF). This is an aggressive type of non-small cell lung cancer (NSCLC) with a poor prognosis and mediocre treatment response. The trials and observational research on SMARCA4 deficient thoracic malignancies are lacking, especially in limited resource settings. This study aims to analyze pathological and immunohistochemical (IHC) profiles of patients with SMARCA4 deficient thoracic malignancies in Armenia. Methods: The current research utilizes a retrospective cohort single-center study design. The study setting was the only pathology center in Armenia that runs an IHC panel for SMARCA4/BRG1 protein evaluation. For data collection purposes, a census sampling has been done and all the pathology reports of SMARCA4 deficient thoracic malignancies were reviewed. The study timeframe was from 24 February 2021 up to 11 December 2023. Descriptive statistics through portions were done to analyze the data. Results: In total, 19 patients with SMARCA4 deficient thoracic malignancies were diagnosed. The male-to-female ratio was 15:1 and the median age was 63 years (range: 50-73 years). Of those cases, 21% (n = 4) were excluded from the current analysis as histopathological examination of those tissue samples was not performed. The diagnosis was based on an IHC evaluation to obtain a second opinion. The tissue histopathological architecture was represented: 60% (n = 9) solid, 6.67% (n = 1) trabecular, and 6.67% (n = 1) papillary. Of those samples, 66.7% (n = 10) had hyperchromatic/polymorphic nuclei and 33.3% (n = 5) pleomorphic nuclei. Similarly, the evaluated sample cells have 53.3% (n = 8) eosinophilic, 13.3% (n = 2) clear, and 13.3% (n = 2) scant cytoplasm. All 19 cases were included in the descriptive analysis of the IHC profile as examinations were performed for all the subjects. The IHC profile of the cohort is presented in the table. Ki67 was checked in 47.4% (n = 9) of cases with 70-75% median expression. In general, the most frequently examined markers were TTF1, p40, Chromogranin, and AE1/3. Conclusions: In conclusion, the study shed light on SMARCA4 thoracic tumors spread in Armenia. Considering the rarity of the disease, further research is required to investigate the actual prevalence of SMARCA4 deficient thoracic tumors and treatment approaches in Armenia. IHC Markers Tested N (%) Positive N (%) IHC Markers Tested N (%) Positive N (%) AE1/3 9 (47.3) 5 (55.5) CK20 6 (31,5) 0 (0) INSM1 3 (15,7) 2 (66,6) Vimentin 2 (10,5) 1 (50) CK7 8 (42) 3 (37,5) NUT 3 (15,7) 0 (0) Chromogranin 9 (46,6) 0 (0) CAM5,2 2 (10,5) 2 (100) Desmin 2 (10,5) 1 (50) HepPar 2 (10,5) 1 (50) TTF1 14 (73,6) 1 (7) CD45 4 (21) 0 (0) p40 13 (68) 0 (0) SALL4 3 (15,7) 1 (33,3) CD65 4 (21) 0 (0) SMARCA4 loss 19 (100.0) 0 (0)