case_images: PMC10940343_01
case_images: Computed tomography (CT) of lung (left) and pancreas (right). In 2012, CT showed a mass in left upper lobe (A). No lesion was seen in the pancreas (B). In 2016, CT found a small rise at the left edge of the main pulmonary artery ((C), red arrowhead). Then in 2017, CT revealed a low-density mass measuring 60mmx50mmx30 mm in the body of pancreas, the mass being mildly enhanced and homogeneous, the pancreatic duct dilatated, and the splenic artery slightly compressed (D). In 2020, there was a tumor in the left middle and upper mediastinal mass measuring 70mmx56mmx53mm, pressing the left pulmonary artery ((E), red arrowhead). In 2022, on the left side of the mediastinum, a mass-like soft tissue mass was seen, with a larger size than the lesion in 2020 (F). The timeline of the patient's clinical history is presented (G).
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case_images: A computed tomography (CT) scan at the time revealed a mass in the left upper lobe ( Figure 1A ), initially diagnosed as a solitary fibrous tumor (SFT). No pancreatic lesion was observed then ( Figure 1B ). One year after the pneumonectomy, a follow-up CT ( Figure 1C ) scan showed a small shadow near the main pulmonary artery, considered to be a postoperative change, without further treatment. In 2017, an abdominal CT scan ( Figure 1D ) uncovered a well-demarcated pancreatic tumor (60mmx50mmx30mm), leading to middle segment pancreatectomy and LGFMS diagnosis. In 2020, a CT ( Figure 1E ) scan showed a mass (70mmx56mmx53mm) in the left upper lobe and middle mediastinum, pressing on the left pulmonary artery. A chest CT scan ( Figure 1F ) revealed a larger mass occupying the left thoracic cavity, with pleural and pericardial effusions. The timeline of the patient's clinical history is presented ( Figure 1G ). There was no necrosis, and the average number of mitotic figures was approximately 1-2/10 high power fields (HPFs).
case_images: Morphological features and immunophenotype of LGFMS, a primary, metastasized, and dedifferentiated tumor. Primary lung tumor (A-D). Hematoxylin & eosin (HE) staining in the low-power view showed spindle cells were densely composed and arranged in a fascicular manner (A). Spindle to stellate cells were sparsely distributed in the fibrous to myxoid background, with the surrounding alveolar epithelial cells entrapped in the tumor (B). Curvilinear and branching capillary-sized blood vessels were observed, some of which were dilatated as staghorn vessels (C). Giant collagen rosettes characterized by a central zone of eosinophilic collagen surrounded by spindle to oval tumor cells (D). Metastatic pancreatic tumor (E, F). Pancreatic tissues were limitedly involved in the tumor cells (E). Bland spindle cells sparsely distributed in a mucus background with thin-walled branching vessels (F). Dedifferentiated mediastinal tumor (G-I). Anaplastic cells were present beneath the squamous metaplasia bronchial surface epithelium (G). The tumor cells were round, polygonal to epithelioid with high degree of nuclear pleomorphism and abu4ndant eosinophilic cytoplasm, and some cells showed vacuolated changes in cytoplasm (H). Mitosis was active (I, red arrowheads), and pathological mitosis could be seen ((I), the red arrowhead below). Immunohistochemistry (J-O). The pancreatic tumor cells strongly expressed MUC4 (J). The Ki-67 proliferation index was about 5%+ (K), but negative for p53 (L). The mediastinal tumor cells were strongly positive for MUC4 (M) as well. The Ki-67 proliferation index was averagely 50% (N). The p53 staining was strongly and diffusely expressed (O).
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case_images: Histologically, the left lung mass was composed of bland spindle-shaped cells with a fibrous stroma and thin-walled blood vessels in the background ( Figure 2A ). Although the tumor cells appeared mild and amicable, the surrounding bronchial and alveolar epithelia were observed entrapped in the tumor ( Figure 2B ). Some vessels were slender, while others were dilatated as staghorn vessels ( Figure 2C ). Focally, epithelioid cells were present, and a giant collagen rosette was witnessed ( Figure 2D ). There was no necrosis, and the average number of mitotic figures was approximately 1-2/10 high power fields (HPFs). Sheets of anaplastic cells were observed beneath the squamous metaplasia bronchial surface epithelium ( Figure 2G ). Tumor cells displayed a round, polygonal to epithelioid shape with significant nuclear pleomorphism and some vacuolated cytoplasmic changes in a disordered arrangement ( Figure 2H ). Mitosis was active, with visible pathological mitotic figures ( Figure 2I ). Immunohistochemistry of the lung and pancreatic masses showed strong MUC4 expression ( Figure 2J ), but were negative for S-100, CD117, CK, EMA, Desmin, CD34, SMA, and beta-Catenin. The Ki-67 index was about 5%+ ( Figure 2K ). TTF-1, P40, STAT6, and SOX10. The Ki-67 index averaged 50% ( Figure 2N ). Additionally, the mediastinal tumor cells strongly and diffusely expressed p53 ( Figure 2O ), while the pancreatic tumor cells did not ( Figure 2L ).
case_images: Molecular characterization of pancreatic and mediastinal tumors. Two fusions and one extra green signal were detected in more than 30% of tumor cells by FUS break-apart fluorescence in situ hybridization (FISH) test in pancreatic (A) and mediastinal (B) masses. Genetically, next-generation sequencing (NGS) test of the mediastinal mass revealed that FUS exon 6 was fused to CREB3L2 exon 5 (C) and the TP53 had an H193Y mutation (D). By direct sequencing of RT-PCR product in pancreatic tumor, chimeric transcripts were detected between FUS exon 6 and CREB3L2 exon 5 (E), but TP53 mutation was not detected (F).
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case_images: There was no necrosis, and the average number of mitotic figures was approximately 1-2/10 high power fields (HPFs). Dual-color break-apart commercial probes of FUS (Anbiping, Guangzhou, China) were used for fluorescence in situ hybridization (FISH) assays, showing separate signals in over 30% of pancreatic and mediastinal tumor cells ( Figures 3A, B ), indicating FUS rearrangement. Next-generation sequencing (NGS) was performed on the mediastinal mass, revealing a FUS exon 6::CREB3L2 exon 5 fusion ( Figure 3C ) and H193Y mutation of TP53 ( Figure 3D ). Otherwise, reverse transcription polymerase chain reaction (RT-PCR) on the pancreatic tumor confirmed the presence of the same FUS exon 6::CREB3L2 exon 5 fusion as the mediastinal mass ( Figure 3E ), but TP53 mutation was absent ( Figure 3F ).