PMC7412810_01
Imaging features of the lesion. a, b Axial and sagittal post-contrast MRI demonstrates an avidly enhancing lesion in the L1 pre-vertebral soft tissues. There is anterior displacement of the aorta (Ao, black arrow) and inferior vena cava (IVC, white arrows). There is invasion of the L1 vertebral body, with cephalad and caudad extension of disease and secondary pressure erosion of the ventral cortices of T12 (black arrowhead) and L2 (white arrowhead) vertebral bodies. c Concurrent contrast-enhanced CT image at the level of L1 shows an avidly enhancing mass (between large black arrows) with invasion of the L1 vertebral body. The CT shows rim of sclerosis in the vertebral body indicative of secondary invasion from a soft tissue mass. The aorta and inferior vena cava (black and white arrows, respectively) are anteriorly displaced. d Contrast-enhanced CT at end of therapy shows significant decrease in size and degree of enhancement of the mass (between large black arrows). Mass effect on the aorta and inferior vena cava (black and white arrows, respectively) has also decreased
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Fig1
He underwent MRI which demonstrated the lesion extending from T12-L2 and measured 8.7 cm x 3.9 cm x 6.9 cm (Fig. 1a, b). Early response assessment after 1 month demonstrated a near-complete loss of enhancement and density of the mass, with the hounsfield units dropping from 200 on the initial scan to 55-60 at follow up (Figs. 1a, b, and 4).
Pre-treatment biopsy. a H&E sections demonstrate monotonous, bland, spindle cell proliferation admixed with mature fat and occasional ectatic blood vessel. Immunohistochemical studies reveal that areas of the tumor cells had reactivity for c S-100, c CD34, and d pan-trk. Measurement bars = 100 microm
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Fig2
Subsequent biopsy revealed a spindle cell mesenchymal tumor with monotonous, bland spindle cells admixed with mature fat and occasional ectatic blood vessels (Fig. 2).
LMNA-NTRK1 fusion confirmed by RT-PCR. a Schematic diagram showing the predicted in-frame LMNA-NTRK1 fusion protein joining the 5' LMNA filament domain to an intact 3' NTRK1 tyrosine kinase domain (KD). The red dashed lines denote the 1q chromosomal positions of LMNA and NTRK1, respectively. b RT-PCR Sanger sequencing trace confirming the fusion breakpoint at chr1:156100564 (LMNA, NM_005572.3, exon 2) and chr1:156844698 (NTRK1, NM_002529.3, exon 11). LTD, lamin tail domain; Ig, Tyrosine-protein kinase receptor C2 Ig-like domain
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Fig3
A custom-designed, clinically-validated anchored multiplex PCR-based targeted next-generation sequencing (NGS) RNA fusion panel that covers 485 exons from 81 genes and is optimized for formalin-fixed, paraffin-embedded (FFPE) samples, revealed a fusion between exon 2 of LMNA (NM_005572.3; chr1:156100564) and exon 11 of NTRK1 (NM_002529.3; chr1:156844698), predicted to encode an in-frame LMNA-NTRK1 fusion protein retaining the C-terminal kinase domain of NTRK1 (Fig. 3a). The fusion transcripts were confirmed with orthogonal RT-PCR and Sanger sequencing (Fig. 3b).
Post treatment. Contrast-enhanced MR images demonstrating mass involving vertebrae (a) axial and (b) sagittal showing decrease in the size of the lesion compared to baseline (Fig. 1). c Gross specimen (sagittal) demonstrating a tan-white pink mass involving the paraspinal soft tissue and protruding into the underlying vertebrae body associated with sclerosis. Measurement bar = 1 cm
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Fig4
Early response assessment after 1 month demonstrated a near-complete loss of enhancement and density of the mass, with the hounsfield units dropping from 200 on the initial scan to 55-60 at follow up (Figs. 1a, b, and 4).
Response to therapy as assessed by RECIST 1.1. Response plateau was achieved at week 12, with 45% decrease in size of the lesion
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Fig5
He had an excellent therapeutic response, with a 45% reduction in tumor size by RECIST criteria, measuring 4.0 x 2.8 cm (Fig. 5).
Post-treatment histological changes. a H&E sections demonstrate marked hyalinization and decreased cellularity with scattered foci of b residual tumor cells admixed with lymphocytes. Measurement bars = 100 microm
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Fig6
Histologically, there was extensive treatment response (> 95%) with decreased cellularity, marked hyalinization and focal areas of viable tumor cells (Fig. 6).