双语病例——间变性星形细胞瘤

朗读老师：朱勤勤     衢州市人民医院

翻译老师： 温满盈    东莞市大朗医院放射科

审校老师：姜春雷   青岛市第九人民医院

History: A 43-year-old man with no significant medical history was referred for three weeks of right facial weakness that progressed to include right arm and hand weakness, right leg weakness, and word-finding difficulty. Prior to referral, a CT scan in the emergency department demonstrated a mass-like lesion.

MR brain and MR spectroscopy (MRS) scans with diffusion-tensor imaging (DTI) were also performed. Click on the image below to enlarge.

病史：男性，43岁，主诉三个星期前无明显诱因出现右侧面肌无力，后进展为右侧上肢、下肢无力，唤词困难。急诊CT发现颅内肿瘤样病变。

头颅MR、MRS及DTI扫描图像如下

Findings and diagnosis

· MR brain: Diffuse expansile lesion with T2/FLAIR hyperintensity with patchy multifocal enhancement extending from the left corona radiata through the posterior limb of the left internal capsule, left thalamus, left cerebral peduncle, the pons, and left cerebellar peduncle, and into the medulla oblongata.

· MRS: Single-voxel MR spectroscopy of a focal abnormal area in the left cerebral peduncle with echo time (TE) of 144 msec demonstrates elevated choline peaks (3.2 ppm) with depressed NAA (2.0 ppm) and creatine (2.0 ppm) peaks.

· DTI: Color-encoded structural orientation map of the fiber tracts shows significant loss of the normal directional encoded color of the posterior limb of the left internal capsule. Corresponding fractional anisotropy (FA) map shows indistinctness and reduced signal intensity of the fibers of the posterior limb. Findings are highly suggestive of tumoral infiltration and likely disruption of the cortical spinal tract.

影像与诊断

颅脑MR：左侧放射冠、内囊后肢、丘脑、大脑脚、桥脑、小脑脚及延髓见弥漫性膨胀性病变，T2/FLAIR呈高信号，增强呈不均匀多灶性斑片状强化。

MRS：选择左侧大脑脚病变中心位置，回波时间144ms，显示胆碱峰升高（3.2ppm），NAA（2.0ppm）和Cr(2.0ppm）峰下降。

DTI（弥散张量成像）：彩色纤维束结构成像显示左侧内囊后肢正常的定向编码色显著消失。内囊后肢纤维束在相对应的各向异性分数图上显示模糊、信号强度减低。图像高度提示肿瘤浸润以及皮质脊髓束可能中断。

Differential diagnosis

· Glioma

· Cerebral metastasis

· Tumefactive demyelination

· Subacute cerebral infarct

Diagnosis: Glioma - anaplastic astrocytoma

鉴别诊断

胶质瘤

脑内转移瘤

肿瘤样脱髓鞘病变

亚急性脑梗死

诊断：胶质瘤-间变型星形细胞瘤

Pathophysiology

Anaplastic astrocytoma (AA) is a malignant, diffusely infiltrating neuroepithelial tumor originating from the astrocytes of the central nervous system (CNS). According to the World Health Organization (WHO) classification system for glial tumors, it is a high-grade tumor (grade III/IV) characterized by hypercellularity, mitotic activity, and nuclear atypia without necrosis. Twenty-five percent of AAs arise de novo, while 75% result from transformation of lower-grade astrocytoma. Malignant progression of AA may result in glioblastoma multiforme (WHO grade IV/IV). Exposure to ionizing radiation, particularly at a young age, as well as rare Mendelian disorders including neurofibromatosis types 1 and 2, tuberous sclerosis, and Li-Fraumeni syndrome are the only well-established risk factors for the development of AA.

病理生理

间变型星形细胞瘤（AA）是一种来源于中枢神经系统星形细胞的神经上皮肿瘤，具有恶性、弥漫浸润特性。根据WHO胶质瘤分型，AA属于高级别肿瘤（III/IV级），具有细胞密集，核分裂活跃，核异型性无坏死的特点。25%的AA属于原发，75%由低级别星形细胞瘤演变而来。AA有恶变为多形性胶质母细胞瘤（IV/IV级）的可能。AA致病的危险因素，目前已经明确的有低龄电离辐射，罕见的遗传性疾病，例如神经纤维瘤病1,2型、结节性硬化、李-佛美尼综合症。

Epidemiology

AA is uncommon, accounting for 4% of all malignant CNS tumors, with an annual incidence of less than 1 per 100,000. It most commonly occurs in the 40- to 50-year age group. There is a male predilection of 3:2.

流行病学

AA少见，仅占恶性中枢神经系统肿瘤的4%，年发病率低于十万分之一。好发于40-50岁人群，男女发病率约3:2。

Clinical presentation

The majority of patients with AA present with new focal neurologic deficits. Other presenting symptoms can include seizures, cognitive change, and headache. Symptom onset is usually within three months of diagnosis.

临床表现

AA病人大部分表现为局灶性神经功能缺失，其他症状包括癫痫、认知改变，头痛。症状发作通常在诊断三个月之内发生。

Imaging features

· Contrast-enhanced MRI: AA is hypointense compared to myelinated white matter on T1-weighted imaging and heterogeneously hyperintense on T2-weighted imaging. Although contrast enhancement is commonly associated with high-grade glioma including AA, it is not sensitive nor specific. For this reason, further evaluation with advanced MR techniques including perfusion-weighted imaging, diffusion-tensor imaging, and MR spectroscopy is recommended.

· Perfusion-weighted MR: Due to increased neoangiogenesis in high-grade gliomas, it is typical to see increased relative cerebral blood volume or regional cerebral blood flow in the tumor. In a gadolinium-contrast perfusion-weighted study, this change in the microvascular environment is represented by decreased signal intensity on T2* sequences and signal increase on T1-weighted sequences. Arterial spin labeling is another perfusion-weighted technique that does not require contrast, which demonstrates signal reduction in the tumor relative to the surrounding tissue.

影像特征

增强MRI：相对于脑白质，AA在T1加权图像呈低信号，T2呈混杂高信号，虽然高级别胶质瘤多数会强化，包括AA，但不具有敏感性和特异性。因此，更先进的MR技术检查非常必要，例如PWI，DTI和MRS 。

MR灌注成像：由于高级别胶质瘤新生血管增多，典型的可以看到肿瘤内相关脑血容量或局部脑血流增多。在轧对比剂灌注研究中，这种微血管环境的改变，表现在T2*序列上信号减低和T1加权序列上的信号增高。动脉自旋标记（ASL）是一种无需造影剂的灌注加权技术，它表现为肿瘤较周围组织信号减低。

· DTI: Increased tumor cellularity restricts the diffusion of water molecules, resulting in decreased apparent diffusion coefficient (ADC) values. Diffusion-tensor imaging utilizes directional variations in ADC, also known as anisotropic diffusion, to visualize the dominant white-matter tracts. Disruptions in the major white-matter tracts caused by the tumor can aid in delineating tumor boundaries for improved surgical resection.

DTI：肿瘤细胞密集限制了水分子的扩散，导致表观弥散系数值下降。DTI利用ADC值的定向变化，也就是各向异性扩散，将主要的白质纤维束可视化。肿瘤导致白质纤维束破坏，有助于确定肿瘤边界，进而提高手术切除率。

· MRS: Variations in concentrations of the tissue metabolites choline (Cho), NAA, Cr, lactate (Lac), and free lipids (Lip) can be used to aid diagnosis of high-grade glioma on MR spectroscopy. Cho is involved in cell membrane synthesis and used as a marker for cell turnover. NAA is correlated with neuronal density and viability and acts as a surrogate for neuronal integrity. Cr serves as a reserve for high-energy phosphates and is a marker for bioenergy metabolism. Compared to normal tissues, high-grade gliomas demonstrate elevated Cho, decreased NAA, and stable or reduced Cr concentration resulting in increased Cho/NAA and Cho/Cr ratios. Elevated Lac and Lip reflect hypoxia and tumor necrosis, respectively, suggestive of high-grade glioma.

MRS：利用组织代谢产物的变化可以帮助高级别胶质瘤的诊断。比如胆碱，NAA，肌酸，乳酸和游离脂质等。胆碱参与细胞膜的合成并作为细胞更新的标志。NAA跟神经元密度和活力有关，代表神经元的完整性。Cr用作高能磷酸盐的储备，是能量代谢的标志。相对正常组织，高级别胶质瘤导致CHO峰升高，NAA下降，肌酸平稳或下降，以至于CHO/NAA和CHO/Cr比值升高。升高的乳酸峰反映组织缺氧，升高的脂质峰反映肿瘤的坏死，均提示高级别胶质瘤。

Treatment/prognosis

Definitive diagnosis of AA is made histologically following biopsy or excision. It is further classified according to molecular alterations including 1p/19q codeletion, IDH1, ATRX, and p53 mutations. Treatment is guided by molecular subtyping and typically includes maximal surgical resection followed by radiotherapy and/or chemotherapy. Prognosis is dependent on molecular subtyping, tumor localization, patient age, mental status, and neurological function as graded with the Karnofsky performance scale. Nearly all patients with malignant glioma will die of progressive disease despite treatment, with a median overall survival of three years and a five-year survival rate of 28%.

治疗/预后

AA的确诊依靠组织活检或手术切除。根据分子学进一步分级，包括1P/19P缺失，IDH1，ATRX，和p53突变等。治疗根据分型，典型的包括最大可能的手术切除，联合放疗和/或化疗。预后取决于分型，肿瘤位置、病人年龄、精神状态和神经功能的卡氏量表分级。无论治疗与否，几乎所有恶性胶质瘤的病人最终都会随着疾病的进展而死亡。中位生存期3年，5年生存率28%。