Case presentationFirst onsetA 19-years-old female was first found with occupation about 6.2 cm × 5.7 cm in the right adrenal five years ago based on CT scan at a regular physical examination, accompanied with fever and headache with high blood pressure. Tumor resection was performed, and pathological diagnosis was right pheochromocytoma. The patient was regularly subjected to follow-up.Secondary onsetDuring this hospitalization, CT scan found multiple tumor occupation in left adrenal and paraganglion region zones with round nodular shadows. Meanwhile, she had fever and headache with high blood pressure. Based on medical history and examination, she was diagnosed as left pheochromocytoma. Meanwhile, the occupying lesions in right lung and pancreas were found, located in extrabasal segment of inferior lobar and head respectively.Case characteristicsThe case characteristics were summarized: 1. A 12y female; 2. Tumor occupation was first found in right adrenal; 3. Tumor resection was performed and the pathological diagnosis was pheochromocytoma; 4. Multiple round nodular shadows were found in left adrenal and paraganglion region zones after five years; 6. The symptoms were fever and headache with high blood pressure; 7. The diagnosis was pheochromocytoma (PCC) and paraganglioma (PGL) (Combined PPGLs); 8. The occupying lesions located in right lung and pancreas were scanned and diagnosed with masses.Diagnostic methodThe patient was followed up regularly. Based on personal medical history, symptoms and imaging examinations, the patient was diagnosed as PPGLs combined with right lung and pancreas occupation.Multidisciplinary team discussion based on professional board indicated the following views: (1) The diagnosis was possibly considered as atypical VHL type II. Further qualitative diagnosis relied on genetic examination; (2) Other lesions like retina tumor should be examined. (3) PPGLs was surgically resected for pursuing pathological diagnosis. (4) The occupying lesions in right lung and pancreas were performed with puncture biopsy for further diagnosis. The diagnosis and treatment workflow were shown in Fig. 1.

Case 2This 10 year old girl presented with intermittent fever for the past one month. Her birth history was unremarkable. She was the fourth child of nonconsanguineous parents. Her family history was not significant for tumor occurrence. Physical examination revealed a blood pressure level of 160/100 mmHg (95p: 120/79 mmHg) and a heart rate of 110 beats per minute. Laboratory tests showed an elevated 24 h urinary VMA level of 83 mg/day. Abdominal MRI revealed a 44x33 mm, well circumscribed mass with a necrotic core in the left adrenal gland. Subtotal adrenalectomy was performed and histologic examination showed that the tumor was PCC. During two years of follow-up, a 20x19x12 mm mass was detected in the right adrenal gland on abdominal MRI. PET-computed tomography (CT) with 68Ga-DOTA‐DPhe1, Tyr3‐octreotate (68Ga- DOTATATE) showed increased uptake in the right adrenal gland and a 11x10 mm nodular lesion in the corpus of the pancreas (Figure 2). The tumoral masses in the adrenal gland and pancreas were removed. Histologic investigation of adrenal and pancreas specimens confirmed the diagnosis of PCC and PNET (World Health Organisation grade 3) respectively. One year later, an 8x7 mm lesion in the pancreas, compatible with recurrence, was observed on abdominal MRI and confirmed with 68 Ga-DOTATATE PET-CT. Splenectomy and subtotal pancreatectomy were performed for removal of the lesion. Histologic examination of the pancreatic lesion reported a neuroendocrine tumor. Bilateral PCC with PNET suggested the diagnosis of VHL disease. Molecular genetic analysis of the VHL gene revealed a heterozygous missense mutation c. 386 T>G (p.Leu129Pro) which has been previously described. No additional VHL tumor developed during three years follow up.

10412Y12Y13NNNNNc.500G>AExon 3p.Arg167GlnMissense