case_images: PMC10540086_01
case_images: Clinicopathological features of gastric differentiated GIST. (A) CT examination revealed a mass located on the lesser curvature of gastric antrum. (B) The gastrectomy specimen showed a gray-white mass with hemorrhage and small cystic changes in the cut surface. (C) Microscopically, somewhere tumor cells were predominantly epithelioid cells arranged in multinodular pattern (HE*40). (D) The epithelioid cells were mild with variably eosinophilic cytoplasm, reminiscent of SDH-deficient GIST(HE*200). (E) There were some moderate to severe atypical cells spotted in the mild epithelioid cell groups (HE*200). (F) Conversely, sheet of anaplastic spindle cells was present elsewhere, similar to the pattern seen in the biopsy specimen (HE*40). (G) The anaplastic cells showed highly pleomorphic nuclear with brisk mitoses, accompanied with proliferation of mesenchymal fibroblasts (HE*400). (H) Undifferentiated small round cells were noticed (HE*400).
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case_images: The CT examination revealed a mass located on the lesser curvature of the gastric antrum, measuring 4.1x9.1 cm2 ( Figure 1A ). The cut surface was grayish-white in appearance with the hemorrhage and small cystic changes ( Figure 1B ). In some areas, tumor cells were predominantly epithelioid cells in a multinodular pattern, involving the gastric wall ( Figure 1C ). HPFs ( Figure 1D ). However, some moderate to severe atypical cells were sparsely noticed ( Figure 1E ). Another part of the area was dominated by the spindle cells, similar to the pattern seen in the biopsy specimen ( Figure 1F ). The spindle cells showed a fascicular or sheet-like architecture, with ill-defined cell borders, variably amphophilic or palely eosinophilic cytoplasm, highly pleomorphic nucleus, dense chromatin, and brisk mitoses (about 75 per 50 HPFs) ( Figure 1G ). Multinucleated giant tumor cells and undifferentiated small round cells were frequently noticed ( Figure 1H ).
case_images: Immunophenotype and clinical behavior of the differentiated SDH-deficient GIST. (A) The two zones were abruptly transitioned (HE*200). The mild epithelioid cells showed a positive reaction for CD117 (B), DOG-1 (C) and a negative reaction for CKpan (D) and P53 (E), while the analpastic spindle cells were on the contrary. However, both components lost the expression of SDHB (FG) while the internal controls, such as the background vascular endothelial cells (F) and non-neoplastic fibroblasts (G), were positively stained. Metastatic epithelioid cells (H) expressing C-KIT (I) were observed in the gastric omental lymph nodes.
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case_images: The two zones were abruptly transitioned and showed a different immunophenotype ( Figures 2A-E ). However, the staining for the SDH-B was negative in both areas ( Figures 2F, G ). A total of 32 lymph nodes were examined, and two of them revealed the metastatic epithelioid cells ( Figure 2H ) expressing C-KIT ( Figure 2I ), DOG-1, and CD34, which corresponded to the conventional SDH-deficient GIST.
case_images: Molecular features of the differentiated SDH-deficient GIST. The classical area and the differentiated area presented with SDHC truncation mutation (A). FISH assays verified MDM2 amplification in the dedifferentiated region (C), compared with the classic region (B).
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case_images: Although there was no difference in the KIT or PDGFRA genotype between the two zones, the SDHC mutation (p.S48*) terminating the SDHC protein translation prematurely, was identified from both zones ( Figure 3A ). Using a commercially available Vysis LSI MDM2 dual-color probe (Abbott Laboratories), the FISH assays were performed on 3-microm-thick sections from the FFPE tumor tissue blocks, confirming that the copy number of the MDM2 signal increased in the dedifferentiated region ( Figures 3B, C ).