ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 608 samples of 76 different normal tissue types was analysed by immunohistochemistry to determine the expression of CDH16 in cancer and to assess the diagnostic utility of immunohistochemical CDH16 analysis. Results: Among normal tissues, a membranous CDH16 immu- nostaining predominated in thyroid, kidney, cauda epididymis, and in mesonephric remnants. In the thyroid, CDH16 staining was seen in all normal samples, 83% of follicular adenomas, 58% of follicu- lar carcinomas, but in only 9% of papillary carcinomas (p<0.0001). CDH16 positivity was particularly frequent in nephrogenic adeno- mas (100%), oncocytomas (98%), chromophobe (97%), clear cell (85%), and papillary (76%) renal cell carcinomas (RCCs), clear cell (56%), mucinous (36%), and endometroid (16%) carcinomas as well as carcinosarcomas (18%) of the ovary, adenocarcinomas of the cervix uteri (40%), serous (33%), clear cell (33%), and endometroid carcinomas (18%) of the endometrium and in various subtypes of neuroendocrine neoplasms (4-26%). Conclusion: Given the massive loss of CDH16 expression in >90% of papillary carcinomas of the thyroid, CDH16 is a highly useful diagnostic marker for these tumours. CDH16 immunohistochemistry is also useful for the identification of nephrogenic adenomas and the distinction of renal cell carcinomas from other neoplasms. OFP-09-002 Pediatric thyroid nodules: a multi-institutional study from India based on the applicability of the Bethesda System with analysis of the risk of malignancy (ROM) and comparison with adult thyroid nodules C. Rana*, N. Nigam, S. Agarwal, P. Mishra, A. Bychkov *King George’s Medical University, India Background & objectives: This study analyses the paediatric thyroid nodules based on the Bethesda system and compares the risk of malignancy (ROM) with adults (>18 yrs) across various Bethesda categories. It also compares young adults (19-21 yrs) with the other two age groups. Methods: This is a retrospective multi-institutional, where archival thyroid cytology and histology data were retrieved. The cases were segregated into paediatric (<18 years), young adult (19-21 years), and adults (>18 years) age groups. The Bethesda distribution across the different age groups and diagnosis on follow-up resection were collated. The ROM in the various categories was compared across the different age groups. Results: A total of 5,958 FNA for thyroid swelling were performed over a period of 5 years. The paediatric patients constituted 3.3% (n=199) of all the cases. Follow-up histology was available in 2276 patients. The malignancy was significantly higher in patients <18b yrs as compared to adults (18 % vs. 12.7% p-value 0.02). Interest- ingly, surgical resection rates were also higher in paediatric groups in almost all the categories except benign. Similar to the paediatric age group, the young adult patients also underwent a significantly higher number of resections as compared to adults. The risk of malignancy was comparable between paediatric and young adults age groups. Conclusion: There was no significant difference in the distribu- tion of Bethesda categories between the adult and paediatric age groups. When resected, paediatric patients are more likely to har- bour malignancies than adults with thyroid nodules as the overall risk of malignancy is higher in children as compared to adults. Importantly, the young adult group (19-21 yrs) may behave in a similar manner to paediatric suggesting a reconsideration of the upper age limit, however, more studies are required to further vali- date this finding. OFP-09-003 Diagnostic utility of menin immunohistochemistry in multiple endocrine neoplasia type 1 syndrome patients A.S. Kok, A.V. Verschuur*, F.H. Morsink, M.F. van den Broek, J.A. Offerhaus, G.D. Valk, M.R. Vriens, B.P. Nesselrooij, W.M. Hackeng, L.A. Brosens *Department of Pathology, University Medical Center Utrecht, Utrecht University, The Netherlands Background & objectives: The diagnosis of multiple endocrine neoplasia type 1 (MEN1) syndrome is confirmed with a germline mutation in the MEN1 gene. As 5-25% of patients suspected of MEN1 remain without definitive genetic diagnosis we investigate the added value of menin immunohistochemistry. Methods: From 16 MEN1 syndrome patients 31 parathyroid adenomas were collected. As control group, 61 parathyroid adenomas were collected from 32 non MEN1 syndrome patients, these included sporadic (n=30), multiple endocrine neoplasia type 2A (n=1) and hyperparathyroidism-jaw tumour (n=1) patients. Menin immunohistochemistry was performed and its use for identification of MEN1 syndrome related tumours was assessed. Results: 14 out of 16 MEN1 syndrome patients and 3 out of 32 non MEN1 patients showed nuclear menin loss on immunohistochem- istry. On average 1,9 tumours were resected per patient. Using a cut-off of at least one tumour showing menin loss on immunohisto- chemistry per patient, the sensitivity and specificity in diagnosing MEN1 syndrome was 87,5% and 90,1% respectively. Using a cut off of 2 tumours showing menin loss on immunohistochemistry, the specificity raised to 100%. Menin immunostaining on two cases with a germline variance of unknown significance in the MEN1 gene illustrates the additional value of menin immunohistochem- istry in MEN1 diagnosis. Conclusion: Menin immunohistochemistry is useful in the recognition of MEN1 syndrome and in the genetic analysis of patients with inconclusive MEN1 germline testing. OFP-09-004 BRAF mutation and AXL (hyper)expression as markers of high risk for persistent/recurrent papillary thyroid cancer (PTC) M. Martini*, C. Pizzimenti, A. Ieni, A. Campennì, L. Giovanella, G. Fadda *Università degli Studi di Messina, Italy Background & objectives: Thyroidectomy followed with 131-radi- oiodine therapy (RIT) is the main treatment for differentiated thy- roid cancer (DTC) patients with an excellent response rate. The understanding of the PTC molecular mechanisms may be useful to identify patients with higher risk of persistent disease. Methods: We analysed 42 low (n=32) or intermediate (n=10) risk PTC patients subjected to total-thyroidectomy and RIT with abla- tive or adjuvant purpose. The response to treatments were evalu- ated 6-12 months after RIT. The mutational status of BRAF, RAS, TERT, PIK3 and RET, the expression of PD-L1 (as CPS score) and AXL gene and CD4/CD8 ratio were analysed on surgical pathol- ogy specimens. Results: Thirty patients had an excellent response (ER), 6 an inde- terminate/incomplete bio-chemical response (BIndR/ BIR) and 6 a structural incomplete response (SIR). A significant correlation was found between BRAF mutation and high expression of AXL gene (p= 0.001) and between these parameters and persistent/recur- rent disease, respectively (p=0.02 and p=0.03). BRAF mutation and high expression of AXL gene were also correlated to PD-L1 expression (p=0.004 and p=0.002). Moreover, PTC patients with persistent disease showed significantly higher PD-L1 and AXL expression and lower level of CD4/CD8 ratio (p=0.021, p=0.032 S35