case_images: PMC8488436_01
case_images: In this figure of a 47-year-old-woman, axial images (A, B) of contrast enhanced computed tomography (CT, A) and T1 weighted, fat suppressed magnetic resonance imaging (B) demonstrates an intensely enhancing 2.7 x 2.0 cm mass (arrows; A, B) at the bifurcation of right common carotid artery causing splaying of right internal and external carotid arteries. The anterior maximum intensity projection (MIP, C-E) of 18F-fluorodopa (18F-FDOPA) positron emission tomography (PET) demonstrates an uptake in the carotid region (arrow, C). This mass was identified as a right carotid body paraganglioma. Six years later, follow-up functional PET/CT imaging with 18F-FDOPA (D) and 68Ga-DOTATATE (E) shows no evidence of pheochromocytoma/paragangliomas (PHEOs/PGLs). Similarly, whole-body CT (not shown here) imaging and neck MRI (not shown here) were negative for PHEOs/PGLs.
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case_images: PMC8488436_01_fendo-12-731096-g001.jpg
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case_images: Whole-body CT and neck MRI revealed a 2.7 x 2.0 cm mass in the right neck suggestive of carotid body PGL (Figures 1A, B). The mass was also positive on 18F-fluorodopa (18F-FDOPA) PET/CT scan (Figure 1C). Six years after surgery, based on follow-up imaging with whole-body 18F-FDOPA (Figure 1D) and 68Ga-DOTATATE PET/CT (Figure 1E), as well as whole-body CT and neck MRI, there was no evidence of any recurrent or new PGL.
case_images: Hematoxylin and eosin staining revealed typical morphology of neuroendocrine tumors (A). Immunohistochemistry showed strong IDH2 mutant expression in the tissue specimen from the index patient (B). Immunoblotting showed the expression of the IDH2 mutant enzyme in cancer tissue. Ectopic expression of IDH2 was used as a positive control (C). Sanger sequencing showed a somatic mutation of the IDH2 gene in cancer tissue. The variant is not seen in blood DNA (D). Mass spec analysis revealed the presence of high-level D-2-HG in cancer tissue. The level of L-2-HG was found not significantly changed. A non-IDH-mutated tumor specimen was used as a control (E). ****p < 0.0001; ns, no significance.
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case_images: PMC8488436_01_fendo-12-731096-g002.jpg
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case_images: Histopathological examination confirmed the typical PGL morphology (Figure 2A). The tumor tissue from the patient exhibited strong immunopositivity for the IDH2 mutant enzyme (Figure 2B). The IDH2 mutant was expressed in the protein lysate from the patient, but not in PGLs with other genetic backgrounds as described above (Figure 2C). The specificity of the IDH2 mutant antibody was confirmed by testing the ectopic expression of the IDH2 R172G variant in hPheo1 cell (Figure 2C). A follow-up Sanger sequencing confirmed the presence of IDH2 c.514A>G variant, which leads to R172G amino acid substitution (Figure 2D). We identified 15.39 pmol/microg protein, which was significantly higher than in non-IDH-mutant cancer tissue (0.0059 pmol/microg protein, Figure 2E, ****p<0.0001). The level of L-2-HG was found not significantly changed between the tested samples (Figure 2E, IDH2WT: 0.01436 pmol/microg protein, IDH2R172G: 0.2407 pmol/microg protein).