ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 two were unclassified renal cell carcinoma (RCC). Four additional patients had incidental ONC on biopsy and biopsy-unrelated sur- gery: surgery for contralateral RCC (1 patient), ONC biopsy after prior surgery for ONC (1 patient), ONC biopsies after surgery for RCC (2 patients). Conclusion: The approach used allows a large amount of data to be analysed with limited effort. Oncocytoma on biopsy rarely goes to surgery in our environment. The findings support an approach that includes kidney biopsy for the management of renal masses, and allows selected patients to avoid surgery. Reliable pathologic classifications, combined with follow-up data, are essential for safe conservative patient management strategies. PS-26-024 Synaptophysin, CD117, and GATA3 as a diagnostic immuno- histochemical panel for small cell neuroendocrine carcinoma of the urinary tract G.H. Kim*, Y.M. Cho, S. Kim, J. Park, S.Y. Yoon, G. Jeong, D. Shin, H. Ju, S.U. Jeong *Department of Pathology, Asan Medical Center, Seoul, Republic of Korea Background & objectives: Although the diagnosis of small cell neu- roendocrine carcinoma (SCNEC) is based on its characteristic histol- ogy, immunohistochemistry (IHC) is commonly employed to confirm neuroendocrine differentiation (NED). The challenge is that SCNEC may yield negative results for traditional neuroendocrine markers. Methods: To establish an IHC panel that could detect even tradi- tional marker-negative SCNEC of the urinary tract, 17 neuronal, basal, and luminal markers were examined on 47 SCNEC cases as a discovery cohort. A decision tree algorithm was employed to analyse the immunoreactivity. An external cohort of eight SCNEC cases and transmission electron microscopy (TEM) were used to validate the model. Results: Among the 17 markers, the decision tree diagnostic model selected 3 markers to classify NED with 98.4% accuracy. The extent of synaptophysin (>5%) was selected as the initial parameter, the extent of CD117 (> 20%) as the second, and then the intensity of GATA3 (negative or weak immunoreactivity) as the third for NED. The importance of each variable was 0.758, 0.213, and 0.029, respectively. In all cases with ≤5% of synaptophysin- immunoreactive area in the discovery and external cohorts showed > 20% of CD117 expression and their NED status was confirmed by the demonstration of electron dense neurosecretory granules of the tumour cells by the TEM. Conclusion: We propose a decision tree-based IHC model consist- ing of two inclusion markers synaptophysin and CD117 and one exclusion marker GATA3 for the diagnosis of SCNEC of the uri- nary tract. Since SCNEC is an aggressive tumour type and requires therapeutic approaches that differ from those used for urothelial carcinoma, an accurate diagnosis of SCNEC is critical and this model may help pathologists accurately diagnose SCNEC in daily practice. PS-26-025 Molecular correlates of somatic-type malignancies arising in male germ cell tumours N. Wyvekens*, L.M. Sholl, Y. Yang, I. Tran, V. Vasudevaraja, B.C. Dickson, K.I. Al-Obaidy, N. Baniak, K. Collins, J. Gordet- sky, M. Idrees, C. Kao, F. Maclean, A. Matoso, S. Wobker, C.D.M. Fletcher, M. Hirsch, J.L. Hornick, M. Snuderl, A.M. Acosta *Brigham and Women’s Hospital/Harvard Medical School, USA Background & objectives: A subset of male germ cell tumours (GCTs) with aggressive clinical behaviour shows overgrowth of com- ponents resembling extra-testicular malignancies (e.g. sarcomas, carci- nomas). The molecular mechanism of somatic-type tumour transforma- tion in GCT is incompletely understood. Methods: Following IRB approval, FFPE tumour material was retrieved from archives of participating institutions. Targeted NGS using a 447 gene panel was performed on 36 somatic-type malig- nancies (SMs), 10 matched conventional GCTs, and 20 SYSTs. A subset of 9 SM cases underwent fusion panel RNA sequencing. DNA methylation profiling was performed on 9 SYSTs, 15 SMs and 10 matched conventional GCTs. Results: The median age at SM diagnosis was 34 years. The most common histotypes of SM were sarcoma, ENT/PNET, and carcinoma in 61%, 28%, and 6% of cases, respectively. KRAS and TP53 mutations were each identified in 28% of SM cases. Evidence of i(12p) was seen in 89% of cases. 97% of cases showed complex copy number profiles. MDM2 amplifications were detected in 15% of cases. Matched conventional GCTs and SMs harboured similar mutational and copy number profiles. Fusion panel RNA sequencing detected no oncogenic gene fusions. Irrespective of histotype, SMs had similar DNA methylation profiles that were different from profiles of matched conventional GCTs. Conclusion: SMs in GCTs are molecularly unrelated to their true somatic counterparts. Instead, they are characterized by complex copy number profiles and mutations that are otherwise rare in GCT. Mutational profiles of SMs and matched conventional GCTs are almost identical. Different SM histotypes show similar mutational and DNA methylation profiles, indicating that identification of SM components of GCTs may be more important than precise sub-clas- sification. DNA methylation profiling of additional tumour types (sarcomas, sarcomatoid/glandular YSTs, carcinomas) is ongoing. PS-26-026 TFF3 in ERG/SPINK1 subsets of sporadic prostate cancer I.D. Caruntu*, S.E. Giusca, B. Gafton, I. Prutianu, B.M. Manole, A. Rusu, A.D. Timofte *"Grigore T. Popa" University of Medicine and Pharmacy, Romania Background & objectives: TFF3 is a potential candidate for molecular prostate cancer subtyping, that could predict patients¢ clinical evolu- tion. Our study focuses on TFF3 immunohistochemical expression in specific subsets of prostate adenocarcinoma defined by ERG/SPINK1 status, correlated with clinico-pathological parameters and biochemi- cal recurrence. Methods: The study group comprised 105 radical prostatectomy samples, immunohistochemically investigated using anti-TFF3, anti-ERG and anti-SPINK1 antibodies. TFF3 was semi-quantita- tively assessed as low and high. Four subgroups were character- ized based on positive and negative ERG/SPINK1 profile. For each subset, relationships between TFF3 immuno-expression and age, Gleason score, Gleason grade, tumour stage, capsular, peri- neural, lympho-vascular invasion, and biochemical recurrence were statistically analysed. Results: In the predominant subset ERG+/SPINK1- (63 cases/59.04%), TFF3 over-expression was statistically correlated with Gleason score (p=0.02), Gleason grade and tumoral stage (p=0.00001). All 12 cases in ERG-/SPINK1+ subset (11.42%) over-expressed TFF3, with less favourable features: younger age of onset (75% under 65 years), higher Gleason grade (83.33%, >3), invasive tumour profile (91.66% capsular and perineural invasion). High-expression TFF3 indicated shorter time to bio- chemical recurrence in ERG-/SPINK1+ subset compared to low- expression TFF3, and all other ERG/SPINK1 subsets. ERG-/ S174