PMC7446511_01
Gadolinium-enhanced magnetic resonance imaging scans of the abdomen before and at 6 weeks and 12 weeks after starting ceritinib. Images before treatment demonstrate large-volume ascites, bilateral hydronephrosis, and widespread peritoneal soft tissue deposits particularly within the pelvis (all findings marked by green arrows). Follow-up imaging 1 month after treatment was started showed a significant reduction in tumor bulk in these areas and reduction in volume of ascites. Hydronephrosis has resolved. At 12 weeks after treatment, there is a further reduction in the volume of peritoneal disease and ascites.
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Images before treatment showed large-volume ascites, bilateral hydronephrosis, and widespread peritoneal soft tissue deposits particularly within the pelvis and around the liver with scalloping of the liver margin (Fig 1).
(A) Peritoneal biopsy with a neoplasm showing a tubulopapillary and solid growth pattern (original magnification x5). (B) Higher magnification (original magnification x 20) shows relatively bland tumor cells with slightly irregular nuclei and inconspicuous nucleoli. Hematoxylin and eosin stain was used for (A) and (B).
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Even though necrosis and mitotic activity (less than 1 mitosis per 10 high-power fields) were not evident, growth pattern, cytonuclear atypia of the tumor cells, and immune profile fulfilled the criteria for malignant epithelioid mesothelioma (Figs 2A and 2B).
Next-generation sequencing data showing the STRN-ALK fusion. (A) Alignment of 176 paired-end reads spanning both breakpoints in STRN and ALK are shown on the human reference genome (hg19). Position of depicted genomic regions are labeled in blue at the top. The breakpoints in STRN and ALK were found in intron 3 (chr2:37,134,246-37,134,536) and intron 19 (chr2:29,447,483-29,447,805), respectively. (B) Schematic representation of the STRN-ALK fusion showing the 700-amino-acid (AA)-long fusion gene, with 137 AAs originating from the N terminus of STRN and the remaining 562 AAs originating from the C terminus of ALK. Although the Striatin domain in the STRN-ALK fusion is likely nonfunctional because of its premature truncation at its C-terminal region, the tyrosine kinase domain of ALK remains intact.
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Genetic alterations in the NF2 gene were not detected nor were additional oncogenic drivers known to be present in malignant mesotheliomas (Fig 3).
(A) Immunohistochemical staining showing strong expression of ALK protein (original magnification x40). (B) ALK fluorescent in situ hybridization break-apart probes showing one fused red-green signal and one red signal in 96% of the tumor cells compatible with 5' ALK deletion (original magnification x100).
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ALK (clone 5A4; Fig 4A). A FISH analysis revealed a 5' ALK deletion in 96% of the tumor cells (Fig 4B).