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肝血管平滑肌脂肪瘤的临床特征与预后分析
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1.中南大学湘雅二医院 普通外科，湖南 长沙 410011;2.中南大学湘雅二医院 病理科，湖南 长沙 410011;3.中南大学湘雅二医院 放射科，湖南 长沙 410011

作者简介:

陈伦，中南大学湘雅二医院硕士研究生，主要从事肝脏肿瘤方面的研究。

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湖南省自然科学基金资助项目（2022JJ30809）。


Clinical characteristics and prognostic analysis of hepatic angiomyolipoma
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1.Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, China;2.Department of Pathology, the Second Xiangya Hospital, Central South University, Changsha 410011, China;3.Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha 410011, China

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    摘要:

    背景与目的 肝血管平滑肌脂肪瘤（HAML）是一种罕见的肝脏良性肿瘤，部分HAML较难与其他肝脏良、恶性肿瘤相鉴别。其临床诊断困难，治疗策略及预后仍不清楚。本研究探讨HAML的临床、影像与病理特征，以及治疗策略和预后情况，以期为该病的临床诊治提供参考。方法 回顾性分析中南大学湘雅二医院普通外科2012年1月—2023年12月收治的46例HAML患者的临床特征、病理、影像及随访资料。结果 46例HAML患者中，男性12例（26.1%），女性34例（73.9%）；发病年龄20~70岁（中位年龄46岁）。29例发病时无明显临床症状，17例表现为腹部不适，6例合并乙型病毒性肝炎，7例合并肾血管平滑肌脂肪瘤（RAML）。无病例合并结节性硬化症。肿瘤标记物（AFP、CEA、CA19-9、异常凝血酶原Ⅱ）均无明显异常。根据其中4例HAML患者的临床数据，HAML平均增长速度0.46 cm/年，中位增长速度0.39 cm/年。影像学表现多样，超声、CT和MRI对HAML术前影像学诊断的准确率分别为3.8%、34.1%、40.9%。46例样本中，共有左肝病变26例（56.5%），右肝病变18例（39.1%），尾状叶病变2例（4.3%）。1例为多发且局限于左肝，余45例均为单发。肿瘤直径为1~15 cm（中位直径4.3 cm）。41例病理结果报告为良性，5例病理结果报告为恶性；上皮样型HAML有10例。免疫组化显示，HMB-45、Melan-A阳性率均为100%，SMA阳性率为95.1%，CD34阳性率为89.7%，S-100阳性率为54.5%。随访0.25~12年，失访16例。1例术后19个月复发，2年后死于肺腺癌（本中心术后病理证实），另1例术后5年死于肺癌（外院病理证实）；2例死亡均与HAML无关，余28例患者均健康，无复发转移。结论 HAML好发于中年女性，常无明显症状，肿瘤生长缓慢，通过影像学诊断容易误诊。病理诊断为HAML诊断的金标准，HMB-45、Melan-A阳性是HAML特异性指标。绝大多数HAML病理为良性，少数为恶性。患者整体预后良好，上皮样型HAML和恶性HAML有复发风险，建议积极随访。手术切除是HAML的有效治疗方法。

    Abstract:

    Background and Aims Hepatic angiomyolipoma (HAML) is a rare benign liver tumor that can be difficult to distinguish from other benign and malignant liver tumors. The clinical diagnosis is challenging, and the treatment strategies and prognosis remain unclear. This study was performed to explore the clinical, imaging, and pathological characteristics, as well as the treatment strategies and prognosis of HAML, to provide a reference for its clinical diagnosis and treatment.Methods The clinical, pathological, imaging, and follow-up data of 46 cases of HAML treated in the Department of Hepatobiliary and Pancreatic Surgery of the Second Xiangya Hospital of Central South University from January 2012 to December 2023 were retrospectively analyzed.Results Among the 46 HAML patients, 12 were male (26.1%) and 34 were female (73.9%), with an age range of 20 to 70 years (median age of 46 years). Twenty-nine cases were asymptomatic at onset, 17 presented with abdominal discomfort, 6 had concurrent hepatitis B, and 7 had concurrent renal angiomyolipoma (RAML). No cases were associated with tuberous sclerosis. Tumor markers (AFP, CEA, CA19-9, and abnormal prothrombin Ⅱ) were not significantly abnormal. Based on clinical data from 4 HAML patients, the average growth rate of HAML was 0.46 cm/year, with a median growth rate of 0.39 cm/year. Imaging characteristics were diverse, with the accuracy rates of preoperative imaging diagnosis of HAML being 3.8% for ultrasound, 34.1% for CT, and 40.9% for MRI. Among the 46 samples, 26 cases (56.5%) had left liver lesions, 18 cases (39.1%) had right liver lesions, and 2 cases (4.3%) had caudate lobe lesions. One case had multiple lesions confined to the left liver, and the remaining 45 cases had single lesions. Tumor diameters ranged from 1 to 15 cm, with a median diameter of 4.3 cm. Pathological results indicated that 41 cases were benign, while 5 cases were malignant; 10 cases were epithelioid HAML. Immunohistochemistry showed 100% positivity for HMB-45 and Melan-A, 95.1% for SMA, 89.7% for CD34, and 54.5% for S-100. Follow-up ranged from 0.25 to 12 years, with 16 cases lost to follow-up. One case recurred 19 months after the operation and 2 years later died of lung adenocarcinoma (confirmed by postoperative pathology at our center), and another case died of lung cancer 5 years after the operation (confirmed by pathology at an external hospital). Both deaths were unrelated to HAML. The remaining 28 patients were healthy with no recurrence or metastasis.Conclusion HAML predominantly occurs in middle-aged women, often without apparent symptoms, and grows slowly, making it prone to misdiagnosis through imaging. Pathological diagnosis is the gold standard for HAML, with HMB-45 and Melan-A positivity being specific indicators. The majority of HAML cases are benign, with a minority being malignant. Overall prognosis is good, but epithelioid and malignant HAML have a risk of recurrence, warranting active follow-up. Surgical resection is an effective treatment for HAML.

    表 1 46例HAML患者一般临床特征[n（%）]Table 1 General clinical characteristics of the 46 HAML patients [n (%)]
    表 4 上皮样型和非上皮样型HAML病理特征[n（%）]（续）Table 4 Pathological features of epithelioid and non-epithelioid HAML [n (%)] (continued)
    表 3 上皮样型和非上皮样型HAML病理特征[n（%）]Table 3 Pathological features of epithelioid and non-epithelioid HAML [n (%)]
    表 5 46例HAML患者免疫组化检测情况Table 5 The immunohistochemical staining results in the 46 HAML patients
    表 6 Table 6
    图1 46例HAML患者各个年龄段分布图Fig.1 Age distribution of the 46 HAML patients
    图2 4例HAML患者肿瘤生长曲线Fig.2 Tumor growth curves of 4 HAML patients
    图3 经典型HAML影像学表现与病理学特征 A-D：分别为轴位CT平扫、增强扫描动脉期、静脉期、延迟期图像，肝S2可见混杂密度结节（红色箭头），为脂肪密度和软组织密度，增强扫描软组织成分明显强化；E：术后大体观，S2切面见2个结节，均灰白灰黄，鱼肉状，大结节2.2 cm×2.0 cm×1.5 cm，紧邻肝被膜，考虑HAML，小结节1.0 cm×0.7 cm×0.5 cm，距肝被膜0.3 cm，与S4、S6结节均为神经内分泌肿瘤（G1级）；F：S2大结节HE染色图像（×100），镜下见肿瘤组织由脂肪组织、血管及上皮样、卵圆形细胞构成，结合免疫组化符合HAML；G：S2大结节肿瘤细胞HMB-45免疫组化染色阳性（×100）；H：S2小结节肿瘤细胞CgA免疫组化染色阳性（×100）Fig.3 Imaging and pathological characteristics of classic HAML A-D: CT images of axial plain scan, and enhanced arterial phase, venous phase, and delayed phase scans, respectively, and a mixed-density nodule in liver segment S2 (red arrow) is visible, showing both fat and soft tissue density, with marked enhancement of the soft tissue component on the enhanced scan; E: Postoperative gross specimen, the S2 section shows two nodules, both gray-white to gray-yellow and fish-flesh-like in appearance, the larger nodule measures 2.2 cm × 2.0 cm × 1.5 cm, adjacent to the liver capsule, suggesting HAML, the smaller nodule measures 1.0 cm × 0.7 cm × 0.5 cm, located 0.3 cm from the liver capsule, and nodules in S4 and S6 are both neuroendocrine tumors (G1 grade); F: HE staining of the large nodule in S2 (×100), microscopically, the tumor tissue comprises fat tissue, blood vessels, and epithelioid, oval-shaped cells, and combined with immunohistochemistry, the findings are consistent with HAML; G: Immunohistochemical staining of tumor cells in the large nodule in S2 shows HMB-45 positivity (×100); H: Immunohistochemical staining of tumor cells in the small nodule in S2 shows CgA positivity (×100)
    图4 经典型HAML影像学表现与病理学特征 A-D：分别为轴位CT平扫、增强扫描动脉期、静脉期、延迟期图像，肝S4可见类圆形混杂稍低密度影（红色箭头），大小约89 mm×83 mm，其内可见脂肪成分，增强扫描强化不均，软组织区呈持续明显强化，其内脂肪成分强化不明显，动脉期可见肿块由肝左右动脉分别供血；E-F：HAML的HE染色，镜下见囊壁样组织，纤维组织增生，周边梭形、短梭形细胞增生，局灶可见脂肪样组织（×100）；G：肿瘤细胞Melan-A免疫组化染色阳性（×100）；H：肿瘤细胞HMB-45免疫组化染色阳性（×100）Fig.4 Imaging and pathological characteristics of classic HAML A-D: CT images of axial plain scan, and enhanced arterial phase, venous phase, and delayed phase scans, respectively, a roundish, slightly hypodense lesion (red arrow) is visible in liver segment S4, measuring approximately 89 mm × 83 mm, the lesion contains fat components and shows heterogeneous enhancement on the enhanced scan, with significant persistent enhancement in the soft tissue areas but not in the fat components, and in the arterial phase, the tumor is supplied by both the left and right hepatic arteries; E-F: HE staining of HAML, Microscopically, cyst-like wall structures and fibrous tissue proliferation are observed, with spindle and short spindle cell proliferation at the periphery, and focal areas of fat-like tissue (×100); G: Immunohistochemical staining of tumor cells shows Melan-A positivity (×100); H: Immunohistochemical staining of tumor cells shows HMB-45 positivity (×100)
    图5 肌瘤型HAML影像学表现（术前误诊为肝腺瘤）与病理学特征 A-D：分别为轴位CT平扫、增强扫描动脉期、静脉期、延迟期图像，肝左叶见一类圆形稍低密度影（红色箭头），增强动脉期及静脉期均匀明显强化，延迟期廓清；E：术后大体观（左肝肿块1个），7.0 cm×5.5 cm×3.0 cm，紧邻肝被膜，切面灰白质中，附少许肝组织；F：HE染色（×40），镜下见肿瘤细胞，浸润周围肝组织，瘤细胞异型性明显，可见核仁，可见瘤巨细胞，可见凝固性坏死，浸润性生长，肿块较大等因素均提示为恶性HAML；G：肿瘤细胞HMB-45免疫组化染色阳性（×100）；H：肿瘤细胞Melan-A免疫组化染色阳性（×100）Fig.5 Imaging (preoperatively misdiagnosed as hepatic adenoma) and pathological characteristics of myomatous HAML A-D: CT images of axial plain scan, and enhanced arterial phase, venous phase, and delayed phase scans, respectively, a roundish, slightly hypodense lesion (red arrow) is visible in the left lobe of the liver. The lesion shows uniform, significant enhancement in both the arterial and venous phases, and clearing in the delayed phase; E: Postoperative gross specimen (a single tumor in the left liver), measuring 7.0 cm × 5.5 cm × 3.0 cm, located near the liver capsule. The cut surface is gray-white with some attached liver tissue; F: HE staining (×40), microscopically, tumor cells are seen infiltrating the surrounding liver tissue, with significant atypia, visible nucleoli, giant tumor cells, coagulative necrosis, and infiltrative growth. These features suggest malignant angiomyolipoma; G: Immunohistochemical staining of tumor cells shows HMB-45 positivity (×100); H: Immunohistochemical staining of tumor cells shows Melan-A positivity (×100)
    图6 肌瘤型HAML影像学表现（术前误诊为肝癌）与病理学特征 A-D：分别为轴位CT平扫、增强扫描动脉期、静脉期、延迟期图像，肝右叶见一大小约106 mm×87 mm混杂密度肿块（红色箭头），边界欠清，增强扫描动脉期不均匀强化，静脉期持续强化，延迟期部分区域强化减退，肿块内见多发新生血管影，病灶大部分边缘清晰，与胆囊分界欠清，E-F：HE染色（×100），由较多脂肪、血管及圆形细胞构成，瘤细胞胞浆丰富、红染或透明，灶性轻度异型；G：肿瘤细胞Melan-A免疫组化染色阳性（×100）；H：肿瘤细胞HMB-45免疫组化染色阳性（×100）Fig.6 Imaging (misdiagnosed as hepatocellular carcinoma before surgery) and pathological characteristics of myomatous HAML A-D: CT images of axial plain scan, and enhanced arterial phase, venous phase, and delayed phase scans, respectively, a mixed-density mass (red arrow) approximately 106 mm × 87 mm is visible in the right lobe of the liver, with unclear boundaries, the enhanced scan shows heterogeneous enhancement in the arterial phase, persistent enhancement in the venous phase, and partial decrease in enhancement in the delayed phase, multiple new blood vessels are visible within the mass. Most of the lesion has clear edges, but the boundary with the gallbladder is unclear; E-F: HE staining (×100), the tumor is composed of numerous fat cells, blood vessels, and round cells, and tumor cells have abundant cytoplasm, appearing red or clear, with focal mild atypia; G: Immunohistochemical staining of tumor cells shows Melan-A positivity (×100); H: Immunohistochemical staining of tumor cells shows HMB-45 positivity (×100)
    图7 脂肪瘤型HAML影像学表现与病理学特征 A-D：分别为增强CT平扫、动脉期、静脉期、延迟期，肝S5、8可见一浅分叶状占位性病变（红色箭头），大小约6.3 cm×5.1 cm×5.7 cm，边界清楚，密度尚均匀，CT值约-86 HU，增强未见强化，内可见小血管影；E：术后送检碎组织大体观，切面灰黄质软；F：HE染色（×100），镜下全为血管及脂肪组织Fig.7 Imaging and pathological characteristics of lipomatous HAML A-D: CT images of enhanced plain, arterial phase, venous phase, and delayed phase scans, respectively, a slightly lobulated mass (red arrow) is visible in liver segments S5 and S8, measuring approximately 6.3 cm × 5.1 cm × 5.7 cm, the mass has clear boundaries and relatively uniform density, with a CT value of about -86 HU, and o enhancement is observed, but small blood vessels are visible within the lesion; E: Postoperative gross specimen of fragmented tissue, with a gray-yellow, soft cut surface; F: HE staining (×100), microscopically, the lesion consists entirely of blood vessels and fat tissue
    图8 血管瘤型HAML影像学表现与病理学特征 A-D：分别为轴位CT平扫、增强扫描动脉期、静脉期、延迟期图像，肝左叶包膜下见线状高密度灶，肝实质内见多发大小不一类圆形低密度灶，大者位于肝S7/8交界处（红色箭头），大小约8.0 cm×6.8 cm×7.0 cm，边缘较清晰，增强扫描早期各病灶呈不均匀、明显强化，其后进一步向心性填充，呈“快进慢出”式强化；E：HE染色（×100），肝细胞水肿变性，有小片坏死，灶性区域纤维血管增生，少数细胞核增大；F：肿瘤细胞HMB-45免疫组化染色阳性（×100）Fig.8 Imaging and pathological characteristics of angiomatous HAML A-D: CT images of axial plain scan (A), and enhanced arterial phase, venous phase, and delayed phase scans, respectively, a linear high-density lesion is visible under the capsule in the left lobe of the liver, with multiple roundish low-density lesions of varying sizes within the liver parenchyma, the largest lesion is located at the junction of liver segments S7 and S8 (red arrow), measuring approximately 8.0 cm × 6.8 cm × 7.0 cm, the lesion has relatively clear edges, and in the early phase of the enhanced scan, the lesions show heterogeneous, marked enhancement, followed by further centripetal filling, presenting a fast in, slow out enhancement pattern; E: HE staining (×100), Microscopically, hepatocytes show hydropic degeneration, with small areas of necrosis, focal regions of fibrous vascular proliferation, and some cells with enlarged nuclei; F: Immunohistochemical staining of tumor cells shows HMB-45 positivity (×100)
    图9 上皮样型HAML的大体及镜下表现和肿瘤免疫组化特征 A：肝中叶切除术后大体观，切面见9 cm×9 cm×3.2 cm肿块，灰黄质软，鱼肉状；B：肝肿块HE染色图像（×100）；C：肝肿块HE染色（×200），镜下见较多上皮样透明细胞、嗜酸性细胞；D：肝肿块Melan-A免疫组化阳性（×100）；E：术后10个月HE染色（×100），中分化肺腺癌；F-H：术后19个月复发后行肝穿刺活检，HE染色（×100），镜下见大多角细胞增生，胞浆红而宽，呈上皮样细胞形态，局灶可见围绕血管生长，细胞核增大，有核内包涵体；肿瘤细胞HMB-45免疫组化染色阳性（×100）；肿瘤细胞Melan-A免疫组化染色阳性（×100）Fig.9 Gross and microscopic appearance and immunohistochemical features of epithelioid HAML A: Postoperative gross specimen from a middle liver lobectomy showing a tumor measuring 9 cm × 9 cm × 3.2 cm, with a gray-yellow, soft, fish-flesh-like cut surface; B: HE-stained image of the liver tumor (×100); C: HE-stained image of the liver tumor (×200), showing numerous epithelioid clear cells and eosinophilic cells; D: Immunohistochemical staining of the liver tumor shows Melan-A positivity (×100); E: HE-stained image of a moderately differentiated lung adenocarcinoma 10 months postoperatively (×100);F-H: HE-stained image of a liver biopsy performed 19 months postoperatively after recurrence (×100), microscopically, there is proliferation of large polygonal cells with abundant red cytoplasm, resembling epithelioid cells, with focal perivascular growth, the nuclei are enlarged with intranuclear inclusions, tumor cells show HMB-45 positivity and Melan-A positivity on immunohistochemical staining (×100)
    表 2 46例HAML患者影像学检查情况Table 2 Imaging examination results of the 46 patients with HAML
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陈伦,何柳青,吴静,何超.肝血管平滑肌脂肪瘤的临床特征与预后分析[J].中国普通外科杂志,2024,33(7):1078-1090.
DOI:10.7659/j. issn.1005-6947.2024.07.007

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