case_images: PMC7568619_01
case_images: Radiological and histological evaluation and ALK translocation in patient 1. (A-G) Chronological records of computed tomography (CT) images. The dates of the CTs were indicated below the images. (A) The baseline showed ascites and diffused peritoneal thickening with multiple focal masses and nodules. (B) The lesion was in partial regression after 3 months of crizotinib treatment. (C) A metastatic tumor mass of about 2.3 x 1.0 cm behind the spleen and a small amount of peritoneal effusion were present when the patient became resistant to crizotinib. (D) The mass behind the spleen was stable after two months of alectinib treatment. (E) The tumor behind the spleen was enlarged again when it became resistant to alectinib. (F) A recurrence lesion of 5.1x3.4 cm at the porta hepatis and perisplenic space. (G) The tumor was relieved after receiving ceritinib. (H) Micrograph of hematoxylin and eosin (HE) staining of the tumor biopsy at diagnosis (original magnification x40). (I) FISH image of the tumor biopsy at diagnosis labeled by an ALK probe (original magnification x40). (J) Diagram of ALK translocation. A 3' end fragment of ALK starting from exon 20 is fused behind base 34 of RRBP1 intron 21.
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case_images: Computed tomography (CT) demonstrated substantial ascites and diffuse peritoneal thickening (Figure 1A). Subsequently, IMT was diagnosed on January 30, 2018, based on the above information and pathological evaluation of the laparoscopic peritoneal biopsy (Figure 1H). Fluorescence in-situ hybridization (FISH) revealed a rearrangement in the ALK gene (Figure 1I). WES and RNA-Seq confirmed the 5' end of ALK exon 21 was fused to the 3' end of a 34 bp piece of RRBP1 intron 21, creating a fusion gene consisted of RRBP1 exons 1-21 on the N-terminal and ALK exons 20-29 on the C-terminal (Figure 1J). Following the treatment, the ascites subsided, and the abdominal distension and general condition of the patients were improved (Figure 1B). However, a follow-up CT scan on August 1, 2018, showed a ~2.3 x 1.0 cm metastatic tumor mass behind the spleen and a small amount of peritoneal effusion (Figure 1C). ALK inhibitor alectinib at 600 mg b.i.d. was prescribed. After two months, the disease was stable as shown in CT and the abdominal distension was relieved (Figure 1D). Still, a third CT scan on January 2, 2019, revealed PD with enlarged size of the tumor behind the spleen (Figure 1E). The patient was continued on alectinib for another four months, until a new (4th) CT scan in May 2019 demonstrated a 5.1 x 3.4 cm opacity at the porta hepatis and perisplenic space (Figure 1F). He was able to achieve a PR (Figure 1G) and is under follow-up to this date.
case_images: PMC7568619_02
case_images: Radiological and histological evaluation and ALK translocation in patient 2. (A-H) Chronological records of CT images. The dates of the CTs were indicated below the images. (A) A mass of about 6.6 x 9.6 cm in the pelvic cavity invading to the right ureter and right iliac vessels. (B and C) Multiple recurrences and metastases at the right abdominal cavity, pelvic cavity and abdominal wall region. (D and E) The size of the pelvic tumor was reduced after crizotinib treatment. (F and G) The lesions at the abdominal and pelvic cavity were stable after alectinib treatment. (H) The lesions in the abdominal cavity had progressed against alectinib treatment. (I) Micrograph of HE staining of the tumor biopsy at diagnosis (original magnification x40). (J) FISH image of the tumor biopsy labeled by an ALK probe (original magnification x40). (K) Diagram of ALK translocation. A 3' end fragment of ALK starting from exon 12 is fused behind TNS1 exon 18.
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case_images: CT scan on January 23, 2018, displayed a mass of ~6.6 x 9.6 cm in the pelvic cavity invading to the right ureter and right iliac vessels, which caused severe hydronephrosis and renal failure (Figure 2A). Parallel pathological examination showed hyper-proliferation (mitoses 38/50 HPF), spindle-shaped cells, necrosis and partial mucoid degeneration in the postoperative tissues (Figure 2I). ALK translocation event (Figure 2J and K). A 3' end fragment of ALK including exons 18-29 was fused to exon 18 of TNS1 therefore formed a TNS1-ALK translocation and the ALK kinase domain was preserved. Five months later, multiple recurrences and metastases were found in the right abdominal cavity, pelvic cavity and abdominal wall in CT imaging (Figure 2B and C). August 2018 showed tumor shrinkage (Figure 2D and E). At the end of September 2018, the lesions were stable although the patient still suffered severe pain in the right leg, indicating true progression, so another biopsy was taken and subjected to WES and RNA-Seq. October 26, 2018. One month after that, the disease had been stabilized (Figure 2F and G). Unfortunately, the lesions in the abdominal cavity soon grew quickly as shown in the CT images of February 12, 2019 (Figure 2H), with the largest one reaching 10.7 x 7.17 cm.