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case_images: A summary and comparison of CSF characteristics at different stages of the disease.
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case_images: Two weeks later, the patient was admitted to our hospital's neurology department, and her clinical course is detailed in  Figure 1 .
case_images: On first admission to the hospital, the brain MRI cystic-solid occupying lesion in the medulla oblongata (A), the solid part showed significant enhancement, while the cystic part was not enhanced (B). Abdominal CT showed an elliptical soft tissue density shadow over the head of the pancreas (C), approximately 4.6x3.6 cm in size, with significant enhancement and several small cyst-like non-enhancing hypodensities in the pancreas (D). A long T2 edema band is seen around the thoracic medulla, which ranges from T4 to T12 segments. Long T1 (E) and long T2 (F) signal in the medulla oblongata and upper cervical medulla stripes, and foci of punctiform seen after enhancement (G). A round dotted lesion of the posterior spinal cord of the seventh cervical medulla with visible enhancement and localized spinal tail sign (H).
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case_images: A cranial magnetic resonance imaging (MRI) showed space-occupying lesions in the medulla oblongata ( Figures 2A, B ), ultrasound scans revealed multicentric renal cysts in both kidneys, and a cystic solid mixed density mass in the pancreas was later identified as PanNENs through enhanced CT ( Figures 2C, D ), chest radiograph shows thickened pleura, and Sanger sequencing identified a heterozygous mutation site in the VHL gene, leading to a diagnosis of VHL syndrome. In 2015, she developed neck pain, weakness of the right limb, and urinary and fecal disorders, then multiple occupying lesions were detected by spinal cord MRI ( Figure 2E ), and a total of 3 masses in C1, C2-3, and C6-7 were surgically resected, measured 2x1x2mm, 3x2x4mm, 2x1.5x1.0mm, respectively. In 2021, the patient suffered dizziness, headache, and unsteady gait again, and imaging revealed space-occupying lesions in the right cerebellar hemisphere, junction of the medulla oblongata and cervical medulla ( Figures 2F-H ), 3 masses were surgically resected, measured 2.5x2x2cm, 1.5x1x1.5cm, 5x6x2mm, which were confirmed to be HBs by postoperative pathology.
case_images: Renal histopathology of the patients showed that the tumor cells were polygonal and columnar in shape, with abundant and transparent cytoplasm, rounded nuclei, partially irregular, uniformly distributed chromatin in the form of fine granules, inconspicuous nucleoli, and localized vascular dilatation in the tumor tissue (A, B). Thoracic medullary mass from the patient's mother (C, D) after surgical resection are subjected to hematoxylin and eosin staining and pathological diagnoses are hemangioblastoma.
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case_images: SMA immunolabelled positive vascular tufts, scattered KP1 and LCA positive cells with GFAP positive gliosis at the margins, the pathological diagnosis was hemangioblastoma. She was diagnosed with renal occupancy in 2008 and underwent resection of the target lesion, which was confirmed as RCC by postoperative pathology ( Figures 3A, B ).
case_images: Whole-exome sequencing peak diagram. (A) The proband, her mother and son carried a heterozygous variant at the VHL c.353T > C site. (B) The other family members and the 187 healthy individuals did not carry this heterozygous mutation.
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case_images: This specific mutation leads to the replacement of leucine with proline at amino acid 118 of the encoded protein, which may primarily account for the VHL syndrome that occurred in the proband ( Figure 4 ).
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