劉俊嬌 張津浦 高文慧 白玥 遲迪 錢忞
【摘要】神經(jīng)母細(xì)胞瘤是常見的小兒顱外實(shí)質(zhì)性惡性腫瘤,但腹膜后囊性的神經(jīng)母細(xì)胞瘤罕見。該文報道1例腹膜后囊性神經(jīng)母細(xì)胞瘤患兒,其為男性,于40+5周時出現(xiàn)胎心率下降、產(chǎn)程未發(fā)動而通過剖宮產(chǎn)術(shù)娩出。產(chǎn)前5 d患兒母親于孕檢時發(fā)現(xiàn)胎兒存在腹腔囊腫,患兒出生后行熒光原位雜交技術(shù)基因擴(kuò)增檢測示N-myc基因擴(kuò)增。生后第2日患兒即在全身麻醉下接受腫物切除術(shù),經(jīng)病理檢查確診為腹膜后囊性神經(jīng)母細(xì)胞瘤,術(shù)后常規(guī)予抗感染及對癥、支持等治療,患兒恢復(fù)良好,出院后末次隨訪暫未見腫瘤復(fù)發(fā)或轉(zhuǎn)移。N-myc基因擴(kuò)增與預(yù)后不良相關(guān),故對于N-myc基因擴(kuò)增的神經(jīng)母細(xì)胞瘤患兒宜盡早實(shí)施手術(shù)治療以提高其生存率。
【關(guān)鍵詞】腹膜后囊性神經(jīng)母細(xì)胞瘤;先天性心臟病;腹裂;先天性巨結(jié)腸; N-myc基因
【Abstract】Neuroblastoma is the most common extracranial solid tumor in children, whereas the retroperitoneal cystic neuroblastoma is rarely encountered. In this article, one child of retroperitoneal cystic neuroblastoma was reported. The male infant presented with a decline in the fetal heart rate at a gestational age of 40+5 weeks. He was delivered by cesarean section due to no signs of imminent delivery. At 5 d before delivery, abdominal cysts were found in the fetus during pregnancy examination. Fluorescence in situ hybridization (FISH) was applied to neuroblastoma for detection of N-myc oncogene amplification after birth. At 2 d after birth, the infant underwent tumor resection under general anesthesia. He was diagnosed with retroperitoneal cystic neuroblastoma by pathological examination. Anti-infection, symptomatic and supportive therapies were delivered after surgery. The child was properly recovered and discharged. No tumor recurrence or metastasis was noted during the final follow-up. The amplification of N-myc was significantly correlated with poor clinical prognosis. For children with retroperitoneal cystic neuroblastoma with N-myc amplification, surgical treatment should be performed as early as possible to enhance the survival rate.
【Key words】Retroperitoneal cystic neuroblastoma;Congenital heart disease;Gastroschisis; Congenital megacolon;N-myc
神經(jīng)母細(xì)胞瘤是常見的小兒顱外實(shí)質(zhì)性惡性腫瘤,其發(fā)病率僅次于白血病和腦惡性腫瘤,但腹膜后囊性神經(jīng)母細(xì)胞瘤較少見[1]。該病多在幼兒期被發(fā)現(xiàn),可通過病理檢查及骨髓涂片活組織檢查(活檢)確診。該文報道1例在胎兒期發(fā)現(xiàn)腹腔囊腫并于出生后接受手術(shù)切除行病理檢查確診為神經(jīng)母細(xì)胞瘤的患兒。
病例資料
一、主訴及體格檢查
患兒男,于40+5周時出現(xiàn)胎心率下降、產(chǎn)程未發(fā)動,其母親于2019年9月10日在我院產(chǎn)科接受急診剖宮產(chǎn)術(shù)將其娩出,出生時體質(zhì)量3300 g。
產(chǎn)前5 d患兒母親于孕檢時發(fā)現(xiàn)胎兒存在腹腔囊腫,故患兒出生后即被轉(zhuǎn)至新生兒科作進(jìn)一步檢查和治療?;純耗赣H既往身體健康,本次孕檢除發(fā)現(xiàn)胎兒腹腔囊腫外無其他異常。否認(rèn)相關(guān)疾病家族史?;純后w格檢查:生命體征、胸、肺、腹及神經(jīng)肌肉等均無異常。
二、實(shí)驗(yàn)室及輔助檢查
血常規(guī):血紅蛋白150.0 g/L,紅細(xì)胞4.01 ×1012/L,白細(xì)胞17.9×109/L,血小板196.0×109/L。甲狀腺功能:FT3 4.3 pmol/L,F(xiàn)T4 15.1 pmol/L,高靈敏TSH 10.0 mIU/L。神經(jīng)元特異性烯醇化酶(NSE)15.2 ng/ml,鐵蛋白367.4 ng/ml。尿香草扁桃酸(VMA) < 2.0 mg/24 h。腹腔彩色多普勒超聲檢查(彩超):肝腎間隙探及一無回聲光團(tuán),壁較薄,透聲差,充滿密集回聲,大小約5.0 cm×3.4 cm×4.0 cm,邊界尚清,形態(tài)尚規(guī)則,內(nèi)有多發(fā)大小不等分隔,彩色多普勒血流顯像(CDFI):未見明顯血流信號。右腎略受壓,與后腹膜關(guān)系密切。診斷提示:腹腔囊性腫物,首先考慮腹膜后來源。腎臟MRI平掃+彌散成像:右后腹肝臟后方、腎臟前方可見囊狀長T1、長T2信號,其內(nèi)可見分隔影,大小約40 mm×42 mm×44 mm。右側(cè)腎臟呈受壓改變;左腎大小、形態(tài)、信號未見明顯異常。診斷提示:右側(cè)腹膜后異常信號,不排除腎上腺囊性占位性病變。
三、治療及隨訪
患兒于2019年9月11日在全身麻醉下接受腫物切除術(shù)。術(shù)中見腹膜后有一大小約5.0 cm×4.0 cm×3.0 cm的類圓形腫物(圖1A),呈囊性,切除囊腫后行病理檢查,結(jié)果顯示:腹膜后病變呈囊腫性改變,囊壁內(nèi)可見神經(jīng)母細(xì)胞瘤成分,囊內(nèi)有出血,有少量腫瘤細(xì)胞,囊壁外可見腎上腺皮質(zhì),病變符合先天性囊腫性神經(jīng)母細(xì)胞瘤表現(xiàn),腫瘤為低分化亞型,有絲分裂核碎裂指數(shù)(MKI)為低級別,囊壁外未見腫瘤浸潤。熒光原位雜交技術(shù)基因擴(kuò)增檢測示N-myc基因擴(kuò)增(圖1B)。術(shù)后常規(guī)予抗感染及對癥、支持等治療,患兒恢復(fù)良好,于術(shù)后15 d出院。隨訪至2019年12月1日暫未見腫瘤復(fù)發(fā)或轉(zhuǎn)移。
討論
神經(jīng)母細(xì)胞瘤屬于交感神經(jīng)系統(tǒng)腫瘤,其病因?yàn)樵谂咛ピ缙?,原始神?jīng)嵴產(chǎn)生交感神經(jīng)元細(xì)胞,后者移行至其他部位而形成神經(jīng)母細(xì)胞和腎上腺髓質(zhì)的嗜鉻母細(xì)胞,從而形成正常組織或腫瘤。只要具有交感神經(jīng)元細(xì)胞的部位均有可能產(chǎn)生神經(jīng)母細(xì)胞瘤,如顱內(nèi)、頸后側(cè)部、眼眶,但大多發(fā)生在腎上腺,先天性神經(jīng)母細(xì)胞瘤少見,發(fā)生在腹膜后更為罕見。另外,神經(jīng)母細(xì)胞瘤很少出現(xiàn)囊性變,因?yàn)槠渫ǔ:泄腆w成分,故腹膜后的囊性神經(jīng)母細(xì)胞瘤極為罕見[1]。
神經(jīng)母細(xì)胞瘤的臨床表現(xiàn)有熊貓眼、霍納綜合征、腹部腫塊、肝腫大、皮下結(jié)節(jié)等,本例患兒即表現(xiàn)為腹腔囊腫。神經(jīng)母細(xì)胞瘤與先天性心臟病的臨床表現(xiàn)是否有相關(guān)性尚不清楚,Testori等[2]在基因水平上發(fā)現(xiàn)兩者的神經(jīng)嵴細(xì)胞起源存在共同遺傳基礎(chǔ)。Rosa等[3]報道1例神經(jīng)母細(xì)胞瘤患者,他們懷疑在播散性的惡性腫瘤如轉(zhuǎn)移性神經(jīng)母細(xì)胞瘤中出現(xiàn)的凝血缺陷可能與腹裂的病因有關(guān),因?yàn)樵撊毕菘赡苁窃趹言? ~ 4周時受形成的血栓形成影響所致,但他們尚無法確定2個事件是否有同時發(fā)生的可能性,仍需行大樣本量的研究證實(shí)。在生物學(xué)方面,本例患者NSE和VMA均無明顯升高。神經(jīng)母細(xì)胞瘤患者大多出現(xiàn)NSE升高,這對于診斷此病有一定的價值,有研究者分析了50例成人神經(jīng)母細(xì)胞瘤中的NSE,結(jié)果提示NSE水平可作為監(jiān)測腫瘤的治療效果和復(fù)發(fā)的指標(biāo)[4]。但本例患兒NSE正常,結(jié)合文獻(xiàn)提示僅靠NSE診斷神經(jīng)母細(xì)胞瘤存在一定的陰性可能,這是否與患者年齡有關(guān)尚未明確。檢測神經(jīng)母細(xì)胞瘤患者體內(nèi)的兒茶酚胺有一定的指導(dǎo)意義,但不必在囊性神經(jīng)母細(xì)胞瘤患者中檢測兒茶酚胺水平,因?yàn)槟倚陨窠?jīng)母細(xì)胞瘤缺乏固體成分,故較少出現(xiàn)血清和尿中兒茶酚胺水平升高,這與本例的檢測結(jié)果一致[1]。另外,新的遺傳學(xué)研究顯示PHOX2B基因多態(tài)性在先天性巨結(jié)腸和神經(jīng)母細(xì)胞瘤中具有較強(qiáng)的生物學(xué)適用性,是與神經(jīng)發(fā)育障礙相關(guān)疾病的治療靶點(diǎn)[5]。超聲檢查有助于診斷先天性神經(jīng)母細(xì)胞瘤,MRI有助于確定腫塊來源于腹膜后,兩者結(jié)合可更有效診斷先天性腹膜后神經(jīng)母細(xì)胞瘤[6]。
神經(jīng)母細(xì)胞瘤是異質(zhì)性非常強(qiáng)的腫瘤,大部分發(fā)病隱匿,診斷時已發(fā)生全身轉(zhuǎn)移并迅速進(jìn)展而致命,但臨床上亦存在無干預(yù)腫瘤可自然消退的現(xiàn)象。該病的預(yù)后主要與年齡、腫瘤分期、病理類型有關(guān),囊性神經(jīng)母細(xì)胞瘤的遠(yuǎn)期預(yù)后尚可,因?yàn)槠鋵儆诤币姷淖儺愋停ǔ0l(fā)生于較小年齡的患者,且很少發(fā)生轉(zhuǎn)移[1]。N-myc基因擴(kuò)增和腫瘤的分化差、快速進(jìn)展、預(yù)后不佳密切相關(guān),是預(yù)測腫瘤進(jìn)展的強(qiáng)有力的生物學(xué)指標(biāo)[7]。對于N-myc陰性的神經(jīng)母細(xì)胞瘤患兒,其有可能自然消退,但必須密切隨訪觀察,必要時及早予綜合干預(yù),包括行手術(shù)及化學(xué)治療[8]。本例患兒N-myc基因擴(kuò)增,立即予以手術(shù)切除腫瘤是非常正確的,這對于預(yù)防嚴(yán)重的后遺癥非常有利。一項(xiàng)大型研究顯示,胎兒生長異常和先天性畸形可能與神經(jīng)母細(xì)胞瘤的風(fēng)險增加有關(guān),另外補(bǔ)充葉酸和母乳喂養(yǎng)在預(yù)防神經(jīng)母細(xì)胞瘤方面具有潛在的重要性,這需要作進(jìn)一步研究以確定其作用[9]。
本例較罕見,其腹腔囊腫在胎兒期即被發(fā)現(xiàn),位于腹膜后,出生后立即予以手術(shù)切除,通過病理檢查明確神經(jīng)母細(xì)胞瘤的診斷,其NSE及VMA均為陰性,但熒光原位雜交技術(shù)檢測示N-myc基因擴(kuò)增,提示預(yù)后不佳,故立即予以手術(shù)切除腫瘤。術(shù)后繼續(xù)密切隨訪患兒,以便在出現(xiàn)腫瘤復(fù)發(fā)或轉(zhuǎn)移時能盡早予以干預(yù)。
參 考 文 獻(xiàn)
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(收稿日期:2019-12-02)
(本文編輯:洪悅民)