背景:副神经节瘤很少发生在鞍区/鞍区。这里,我们报告了1例恶性副神经节瘤患者,其原发性鞍区位置具有异常的遗传和影像学特征。
方法:一名31岁男性,患有轻度高血压,头痛,恶心,和呕吐。磁共振成像(MRI)显示鞍区/鞍区肿瘤块,而内分泌检查发现部分垂体功能减退,这表明这是一种无功能的垂体肿瘤。开始抗高血压治疗和激素替代治疗。经蝶窦神经外科手术可减少肿瘤。然而,由于广泛的组织坏死,无法进行组织学诊断。疾病稳定4年后,残留的肿瘤显示需要伽玛刀放射外科治疗。放射外科手术四年后,MRI显示明显的肿瘤进展,导致第二次神经外科手术。这一次,病理和免疫组织化学结果显示副神经节瘤。间肾上腺素和去甲肾上腺素的血浆水平正常。对从血液中提取的DNA进行基因测序小组,排除了17个易感基因中的种系突变。病人颈部出现了新的肿瘤,进行了第三次手术。免疫组织化学显示肿瘤细胞中缺乏ATRX(α地中海贫血/智力低下综合征X连锁)蛋白,表明ATRX基因突变。对肿瘤DNA进行的分子遗传学分析显示ATRX和TP53基因异常的组合;以前在副神经节瘤中没有报道过。MRI和68Ga-DOTANOCPET/CT显示了该疾病的全部程度。开始使用生长抑素LAR和177Lu-DOTATATE肽受体放射性核素治疗(PRRT)的治疗。
结论:虽然罕见,在鞍区/鞍区肿瘤病变的鉴别诊断中应考虑副神经节瘤,即使没有典型的影像学特征。副神经节瘤中的ATRX基因突变是恶性行为的早期预测因子,并且当靶向突变的ATRX的药物治疗变得可用时,是潜在的新型治疗标记。
BACKGROUND: Paraganglioma occurs rarely in the sellar/parasellar region. Here, we report a patient with malignant paraganglioma with primary sellar location with unusual genetic and imaging features.
METHODS: A 31-year-old male presented with mild hypertension, headache, nausea, and vomiting. A sellar/parasellar tumor mass was revealed by magnetic resonance imaging (MRI), while an endocrine work-up found partial hypopituitarism, suggesting that it was a non-functioning pituitary tumor. Antihypertensive therapy and hormone replacement were initiated. Tumor reduction was achieved with transsphenoidal neurosurgery. However, histological diagnosis was not possible due to extensive tissue necrosis. After 4 years of stable disease, the residual tumor showed re-growth requiring gamma knife radiosurgery. Four years after the radiosurgery, MRI showed a significant tumor progression leading to a second neurosurgery. This time, pathological and immunohistochemical findings revealed paraganglioma. Plasma levels of metanephrine and normetanephrine were normal. A gene sequencing panel performed on DNA extracted from blood excluded germline mutations in 17 susceptibility genes. The patient developed new tumor masses in the neck, and the third surgery was performed. Immunohistochemistry demonstrated lack of ATRX (alpha thalassemia/mental retardation syndrome X-linked) protein in tumor cells, indicating an ATRX gene mutation. Molecular genetic analysis performed on tumor DNA revealed a combination of ATRX and TP53 gene abnormalities; this was not previously reported in paraganglioma. MRI and 68Ga-DOTANOC PET/CT revealed the full extent of the disease. Therapy with somatostatin LAR and 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) was initiated.
CONCLUSIONS: Although rare, paraganglioma should be considered in the differential diagnosis of sellar/parasellar tumor lesions, even in the absence of typical imaging features. ATRX gene mutation in paraganglioma is an early predictor of malignant behavior and a potential novel therapeutic marker when pharmacological therapy targeting mutated ATRX becomes available.