ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 A. Valent, A. Fitouri, F. Delalande, N. Joyon, P. Michenet, M. Lacroix-Triki* *Department of Pathology, Gustave Roussy, France Background & objectives: In situ hybridization (ISH) is system- atically performed for HER2 2+ invasive breast cancer. Nullisomy is a rare genomic event that may mislead the pathologist in ISH interpretation. We aimed at describe the pathological and molecu- lar features of three nullisomy cases Methods: Three cases of cen17 nullisomy breast cancer (BC) were retrieved from our archives. Clinical, pathological and treatment data were collected for each case. HER2 immunohistochemistry and HER2/cen17 fluorescent ISH were scored following the last ASCO/CAP guidelines. DNA was extracted from formalin-fixed paraffin-embedded samples and subjected to SNP array (Oncos- canTM). A Foundation One liquid CDx analysis was available for one patient. Results: All patients presented with metastatic BC, two of them from the outset. All tumours were high grade, oestrogen receptor positive. HER2 score was 2+ (n=2), or 3+ heterogeneous (n=1). All cases showed no signal in tumour cells with cen17 probe, whilst a signal was observed in normal cells. Two cases were HER2 amplified (HER2=7.9 and 9). All cases displayed a complex genomic profile with homozygous loss of the chromosome 17 centromeric region, associated to multiple quantitative chromosomic alterations. All cases showed chromosome 8q gain involving CCNE2 and MYC genes. Liquid biopsy sequencing of the lobular case additionally identified ESR1, PIK3CA, CDH1, DNMT3A, FAM123B, PTPN11 and TP53 mutations. Conclusion: Nullisomy of chromosome 17 centromeric region is a poorly known genomic event that may prove puzzling for the pathologist while reading HER2 ISH in invasive BC. Our study shows that this exceedingly rare alteration is associated to BC showing a strikingly aggressive clinical course, and displaying a consistent complex genomic profile. OFP-11 | Joint Oral Free Paper Session IT & Other Topics (Electron Microscopy / Cardiovascular Pathology) OFP-11-001 Epidermolysis bullosa: an electron microscopy study of 6 cases A. Cohn*, C. Salavastru, M. Gherghiceanu *Emergency University Hospital, Bucharest, Romania Background & objectives: Epidermolysis bullosa (EB) is a group of rare inherited disorders characterized by skin fragility and blistering after minor trauma. This study presents the ultra- structural features of six cases of EB, highlighting the diagnostic role of transmission electron microscopy (EM). Methods: Skin biopsies from six infants were processed for both light microscopy (LM) and EM. Five of six patients were younger than 1 month. Clinical presentation included skin fragility and blisters in all cases. Oral mucosa involvement was reported in one case. LM revealed a completely detached epidermis in all cases of dystrophic EB. Results: EB cases were classified based on the split level as EB simplex (EBS), junctional EB (JEB), and dystrophic EB. One case showed intraepidermal cleavage, intrakeratinocyte splitting, and tonofilament clumps suggesting generalized severe EBS. EM findings of JEB were found in one case. These included mul- tiple microsplits through the lamina lucida and a reduced number of anchoring filaments into the lamina densa. Ultrastructural features of both EBS and JEB were found in one case, revealing intra-lamina lucida splits, suprabasal cleavage, and intracytoplasmic fractures. All three cases of dystrophic EB showed a split below the lamina densa, with absent or markedly reduced anchoring fibrils between the lamina densa and collagen bundles. Conclusion: Even though TEM tends to be replaced by immunola- beling and genetic testing, ultrastructural studies are still relevant in the diagnosis of EB. Not only can EM establish the major type of EB by identifying the level of the split in the skin, but also it can provide critical prognostic information in several subtypes. Moreo- ver, EM can detect subtle changes in the dermo-epidermal junction and was proven to be superior in diagnosing EBS in absence of evident blisters. OFP-11-002 Clinico-pathologic correlation in cardiac amyloidosis: is there a substrate for the echocardiographic “relative apical spar- ing” sign? M. De Gaspari*, G. Sinigiani, S. Rizzo, M. Perazzolo Marra, M. Della Barbera, D. Mele, C. Basso, A. Cipriani *Cardiovascular Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua - Azienda Ospedaliera, Padova, Italy Background & objectives: Myocardial longitudinal strain (LS) and strain rate by speckle-tracking echocardiography play a prognostic role in cardiac amyloidosis (CA) and relative apical sparing of LS (RELAPS) is useful for early diagnosis. Our aim was to assess regional differences in amyloid burden. Methods: Retrospective study of whole hearts from autopsy with histological evidence and immunoelectron microscopy typing of CA. Amyloid burden was assessed quantitatively by histomorphometry on sodium sulphate-Alcian Blue stained transmural slides at different levels from base to apex. The parameters of myocardial LS by echocardiography performed before death were compared to the amyloid burden and basal-to- apex distribution. Results: Of the 29 hearts examined, amyloid typing identified 19 cases of immunoglobulin light chains (AL, 65.5%) and 10 tran- sthyretin (ATTR, 34.5%). A prevalent interstitial deposition was found in 20 (69%) and vascular in 9 (31%). Among the latter, all but one (88.9%) were AL. A homogeneous distribution of amy- loid was demonstrated, with a median of 25.38, 26.70 and 18.8 (P=NS) at the basal, mid and apical sections, respectively. In 11 patients, echocardiography during the same hospitalization showed a significant LS basal-to-apex gradient. A correlation was found between total histological amyloid burden and the reduction of LS at echocardiography, although the RELAPS didn’t match to a basal-to-apex gradient of amyloid. Conclusion: This clinico-pathological study demonstrates that amyloid is evenly distributed in the ventricular myocardium both in AL and ATTR. While there is a correlation between total amyloid burden and reduction of LS, the typical basal-to-apex gradient in LS at echocardiography does not appear to be explained by a gradient of amyloid burden in whole hearts. Our findings thus suggest that RELAPS is an epiphenomenon of complex interactions among amyloid infiltration, myocardial structure and consequent adaptation. OFP-11-003 Acute myocarditis in COVID-19 era: pre-pandemic and pan- demic periods compared S44