ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 J. Lobo*, M. Rechsteiner, B.M. Helmchen, N.J. Rupp, A. Weber, H. Moch *IPO Porto, Portugal Background & objectives: Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) shows frequent CK20 positivity and TSC muta- tions. In contrast, frequency of CK20 expression and presence of TSC mutations are unclear in TFEB-amplified RCC and TFEB-translocated RCC, which frequently express Melan A. Methods: Herein, we compare 6 ESC RCC with 4 TFEB-amplified/ translocated RCC. We assess the frequency of CK20 and Melan A expression by immunohistochemistry, and of TSC mutations by next generation sequencing. TFEB alterations were confirmed by fluorescence in situ hybridization (FISH). Results: All tumours showed voluminous eosinophilic cells with granular cytoplasm, prominent nucleoli, and most showed admix- ture of solid and cystic areas. CK20 expression was found in all 6 ESC RCC and in all RCCs with TFEB alterations. Melan A positiv- ity was identified in 5/6 ESC RCC and 4/4 RCC with TFEB altera- tions. We found TSC mutations in 2 ESC RCCs, including in one case also harbouring a CIC fusion, unreported to date. However, we also identified a TSC mutation in one TFEB-amplified RCC. Conclusion: ESC RCC represents an emerging renal tumour entity with some histological, immunohistochemical and molecular over- lap to TFEB-amplified/translocated RCC. FISH for TFEB aids in this differential diagnosis in challenging cases. Funding: JL is recipient of a fellowship from FCT – Fundação para a Ciência e Tecnologia (SFRH/BD/132751/2017). H.M. receives a Swiss National Science Foundation grant (No. S-87701-03-01). PS-26-003 Reliability of histological subtyping of penile squamous cell carcinoma in assessing HPV tumour status L. Dorofte*, S. Davidsson, G. Lillsunde Larsson, M. Karlsson *Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden Background & objectives: HPV-positive penile tumours have been asso- ciated with higher survival rates. However, HPV analysis is unavailable in many low-income countries. We investigated if histological assessment of penile squamous cell carcinoma subtypes can replace HPV testing in determining HPV-related/non-HPV-related tumour status. Methods: We reviewed paraffin-embedded tumour tissue from 345 penile cancer patients, surgically treated between 2009 and 2018 at Örebro University Hospital, Sweden. The histological subtype of squamous cell carcinoma was assessed according to the WHO criteria and ISUP recommendations. HPV-DNA genotyping was performed using the PCR method Anyplex II HPV28. Concordance was assessed by calculating Cohen’s kappa (κ). Results: A good concordance was found between histological subtype of squamous cell carcinoma and HPV tumour-status with a Cohen’s kappa (κ) of 0,72 corresponding to 86,6% agreement. Of the 46 discordant cases, five had HPV-related histology (mixed subtypes) but were HPV-negative. The remaining 41 cases had non-HPV- related histology (85% usual subtype, 15% mixed subtypes) but were HPV-positive. Noteworthy is that in 21 of the cases with non-HPV-related histology, foci of undifferentiated PeIN was found. In addition, four cases with both undifferentiated PeIN and lichen sclerosus et atrophicus in the tumour margin, 14 cases with both differentiated PeIN and lichen sclerosus et atrophicus and two cases without preneoplastic lesion were identified. Conclusion: Good concordance between histological subtype of penile squamous cell carcinoma and HPV genotyping shows that when necessary, histological assessment is a good alternative, at least in less resourceful settings, to PCR-based HPV analysis in determining if penile tumours are HPV or non-HPV-related. Dis- cordant cases most likely depend on subjectivity in histological assessment but can also suggest a HPV infection in a non-HPV- related tumour. PS-26-004 Benign clear cell clusters in non-tumoral nephrectomy specimens M. Conde Ferreiros*, J. Dominguez de Dios, A. Bellas Pereira, C. Fachal Bermúdez, P. Sanmiguel Fraile, C. Gómez de María, I. Antón Badiola, J. González Carreró Fojón, J.A. Ortiz Rey *Complejo Hospitalario Universitario de Vigo, Department of Pathology, Spain Background & objectives: Clear cell clusters (CCCs) constitute a benign change occasionally found in the kidney (Virchows Arch. 2021;479:57-67). They must be recognised to avoid a misdiagnosis of renal carcinoma. Etiopathogenesis of CCCs and their frequency in atrophic kidneys are not known. Methods: 157 consecutive non-tumoral nephrectomy surgical specimens were retrospectively reviewed. Immunohistochemical stainings were performed using an enzyme-conjugated multimer complex (OptiView DAB Detection Kit, Ventana) in an automatic stainer (Benchmarck Ultra). Heat antigen retrieval was done in the automatic stainer. Electron microscopy studies were performed on FFPE tissue. Ultrathin sections were examined with a Philips CM100 electron microscope. Results: Six cases (3,82%) showed CCCs. This change was multi- focal and found in 100% of the samples of five cases and in 83% of the slides of the other one. They were in the renal cortex, predomi- nantly in a subcapsular location. CCCs were composed by large cells with clear/foamy cytoplasm, forming predominantly solid nests, as well as occasional tubules with narrow lumina. Adjacent renal parenchyma showed interstitial fibrosis with tubular atrophy, glomerulosclerosis, and sclerosis of vessel walls. CCCs were CK7, Ksp-cadherin and EMA positive, and negative for RCC marker and AMACR with focal immunoreactivity for CD10. Ultrastructurally, cytoplasms were filled of disrupted organellas with mitochondrial and endoplasmic reticulum ballooning degeneration. Conclusion: CCCs are rare in nonfunctioning / atrophic kidneys (<5%). It is a multifocal change in the cortex, often subcapsular. Ultrastructural appearance suggests that they are caused by intracellular oedema of tubular cells with disruption of organellas. CCCs show a distal tubule immunophenotype except focal positivity for CD10. The absence of atypia, the subcapsular location and the coexistence of atrophy / ischemic changes help to the diagnosis. PS-26-006 B7-H3 immune checkpoint molecule in prostate cancer C. Ntala*, J. Salmond, A. Blomme, I. Ahmad, H. Leung *Department of Pathology, Western General Hospital, Edinburgh, United Kingdom Background & objectives: B7-H3 is a newly discovered member of the B7 family of immune checkpoint molecules with both immune and non-immune functions. We investigated the relationship of B7-H3 to the tumour microenvironment as well as its non-immune functions in prostate cancer (PCa). Methods: We developed a discovery tissue microarray from 94 PCa patients who underwent radical prostatectomy with curative intent. This was stained manually with B7-H3 and correlated to S168