PMC9997097_01
Microscopic examinations: Cytological and immunocytochemical examinations performed on the aspirated pleural fluid show the presence of tumour cells (images 1 and 2) and ERG nuclear positivity (image 3). Characteristic histological features of angiosarcoma: proliferating atypical tumour cells forming anastomosing vascular channels. The lining endothelial cells display marked atypia (image 4). Tumour cells showed strong cytoplasmic CD31 and nuclear ERG positivity (images 5 and 6). Based on the morphology and the immunophenotype, the lesion corresponded with the diagnosis of angiosarcoma, grade 2.
fonc-13-999810-g001.jpg
PMC9997097_01_fonc-13-999810-g001.jpg
f1
All these were suggestive of angiosarcoma ( Figure 1 ). CD31 cytoplasmic positivity ( Figure 1 ). Cytokeratin (AE1-AE3) and CD34 were negative and no WT1 and CAMTA1 nuclear positivity was observed.
Schematic illustration of the in-frame KHDRBS1-NTRK3 fusion (Circos plot and schematic diagram were created using MAFTOOLS and Biorender, respectively) and confirmation using the NTRK3 break apart FISH probe. The following breakpoints were identified using the FusionCatcher software: chr1:32039573A and chr15:88033045 for KHDRBS1 and NTRK3, respectively.
fonc-13-999810-g002.jpg
PMC9997097_01_fonc-13-999810-g002.jpg
f2
TRK inhibitor ( Figure 2 ). This fusion was validated by fluorescence in situ hybridisation ( Figure 2 ).
Radiological response as determined by Magnetic Resonance imaging before treatment (22.01.21), following administration of the CWS 2012 protocol (06.04.21) and NTRK inhibitor therapy (Larotrectinib) (10.09.21), respectively. Follow-up MRI is performed every three months; the latest images show a sustained response to Larotrectinib therapy as no visible tumour mass is detectable (29.03.22). While a limited therapeutic response upon completion of chemotherapy, a remarkable and sustained complete remission from Larotrectinib was observed.
fonc-13-999810-g003.jpg
PMC9997097_01_fonc-13-999810-g003.jpg
f3
Overall, a remarkable and sustainable clinical and radiological response to larotrectinib has been achieved. ( Figure 3 ).