ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 GATA3, CK5/6, CD44 and CK20 (AUC 0.951, 0.959, 0.871 and 0.938, respectively). Conclusion: All markers significantly correlated with the respec- tive subtype assigned by transcriptomic analysis and with each other. For luminal carcinomas, the AUC for CK20 was lower (0.816, sensitivity/specificity: 67%/87%) than GATA3 (0.965, sen- sitivity/specificity: 86%/96%). Similarly, CD44 had a lower AUC for basal carcinomas (0.617, sensitivity/specificity: 57%/69%) than CK5/6 (0.852, sensitivity/specificity: 91%/70%). While the markers may be complementary, CK5/6 and GATA-3 have the best AUC and should be considered as "first-line" in assigning a surrogate luminal or basal subtype. PS-26-021 Clinicopathologic assessment of MTAP status in muscle inva- sive urothelial carcinoma E. Olkhov-Mitsel, E. Slodkowska, M. Downes* *Sunnybrook Health Sciences Centre, Canada Background & objectives: Methylthioadenosine phosphorylase (MTAP) deficiency correlates with 9p21 loss and susceptibility to antifolate therapy, is frequent in metastatic urothelial carcinoma, but underexplored in the primary muscle invasive setting. We determined MTAP status and associated clinicopathologic features in a cystectomy cohort. Methods: A triplicate core tissue microarray with 302 muscle invasive carcinomas (T2= 50, T3=62, T4=90) was stained for MTAP (Abnova, clone 2G4). Staining was interpreted as nega- tive when carcinoma was completely negative with appropri- ate internal controls. MTAP status was correlated with patient data, molecular subtype, stage, underlying mutation status, prior therapy, overall (OS) and relapse free (RFS) survival using SPSS. Results: MTAP loss occurred in 87/302 (28.8%). There was no correlation with T-stage, nodal status, patient sex or age. MTAP was retained in 99% of luminal genomically unstable subtype, 65% of basal subtype and 50% of luminal- Uro type carcinomas (p<0.001). MTAP loss was strongly correlated with FGFR3 mutations, and MTAP retention with TP53 mutations (p=0.0062). Cases with MTAP loss had shorter OS (14.7 months vs 23.3 months MTAP retained) and RFS (11.2 months vs 18.2 months MTAP retained), p>0.05. Within the luminal-Uro group, loss of MTAP predicted for reduced RFS (p=0.031) but not OS. All analyses were also performed excluding cases with neoadju- vant chemotherapy (n= 59) with similar results. Conclusion: Loss of MTAP occurs in <30% of primary muscle invasive urothelial carcinomas. It does not associate with stage suggesting loss is acquired early in the disease. There were no statistically significant association with outcome parameters or neoadjuvant chemotherapy status. MTAP loss was associated with FGFR3 mutations. Within the luminal-Uro molecular subtype, MTAP loss defined a group with shorter RFS and assessment of MTAP may be most beneficial in this cohort. Funding: LMMD Strategic Innovation Fund Grant 2021, Sunny- brook Health Sciences Centre PS-26-022 Neuroendocrine carcinomas of the urinary bladder: a large case series of a rare entity R. Maragliano*, G.M. Pini, L. Nicolini, C. Patriarca, M. Colecchia, F. Sessa, S. Uccella *Department of Medicine and Surgery, Unit of Pathology, Univer- sity of Insubria, Varese, Italy Background & objectives: Urinary bladder (UB) is the extra-pulmo- nary and extra-digestive organ with the highest frequency of neuroen- docrine neoplasms (NENs). The recognition of UB-NENs and their distinction from high grade non-neuroendocrine (HG nonNE) UB carcinomas represent a challenge in diagnostic practice. Methods: With the aim of clarifying the clinicopathological features of UB-NENs and of establishing differential diagnostic criteria for their distinction from HG nonNE carcinomas, we ret- rospectively reviewed a series of 78 cases collected from three Italian Institutions and originally diagnosed as UB-NENs or HG carcinomas with NE markers expression. The latest diagnostic criteria proposed for NENs by WHO/IARC were strictly applied. Results: The histopathological review identified 51 UB-NENs, including 23 neuroendocrine carcinomas (NECs) and 28 mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs). Pres- ence of neuroendocrine morphology (architectural and cytologi- cal), intense and diffuse expression of one/two neuroendocrine markers, and absence of urothelium-related markers were used to separate NECs from HG nonNE carcinomas. MiNENs were diagnosed when two separate components were morphologically identified and immunohistochemically confirmed. Small cell mor- phology was more frequent than large cell one, both in pure and mixed neoplasms. PDL-1 expression was lower in UB-NENs than in HG nonNE carcinomas. Clinically, patients were old males with smoking habits; NECs showed poorer prognosis than HG nonNE carcinomas, significantly improved by treatment with neoadjuvant chemotherapy. Conclusion: With this study, we were able to identify true UB- NENs and to distinguish them from HG nonNE carcinomas of the same site, clarifying the clinicopathological features of these rare entities. We highlight the prognostic impact of UB-NENs diagno- sis, also when mixed with a nonNE component, which confers a very poor outcome to patients, improved by the administration of neoadjuvant chemotherapy. Although very preliminary, data on PDL1 expression suggest a therapeutic chance with immune check- point blockage also in these rare malignancies. PS-26-023 Retrospective report-based review of kidney biopsies and resec- tions with a focus on oncocytoma N. Nikzad, I. El-Shinnawy, S. Salama, A. Kapoor, M. Bonert* *Pathology, McMaster University, Canada Background & objectives: Synoptic reporting combined with the automated categorization of free text reports (ACFTR) and patholo- gist review allows insight to practice patterns. This project examined kidney biopsies for mass lesion and kidney resections, and matched specimens by an anonymized patient identifier (API). Methods: All non-medical kidney biopsies with and without resec- tions accessioned 2011-2020 were retrieved from one referral cen- tre, matched by API and categorized by diagnosis and diagnostic group (DxGrp) (malignant (MAL)/suspicious (SUSP)/insufficient (INS)/benign (BEN)). All recent biopsy report categorizations were reviewed/classified by pathologists. APIs were categorized into biopsy only (BxOnly) and biopsy+surgery(Bx+Sx). Biopsies and surgeries were tabulated by the most recent pathology. Results: The data set contained 948 patients; these were 641 BxOnly and 307 Bx+Sx. BxOnly by DxGrp 374(MAL)/3( SUSP)/58(INS)/206(BEN); Bx+Sx(by Sx diagnosis) was: 293(MAL)/0(SUSP)/ 0(INS)/14(BEN). 84 patients had two biop- sies, 9 had three and two had four; the INS rate for the preced- ing biopsies was: 24.2%, 27.3% and 0%. Oncocytoma(ONC) was seen in 109/948 patients. Four patients had a prior ONC biopsy diagnosis linked to surgery; on resection: two were oncocytoma, S173