孫雪玉 于亞男 王婷 江月萍
·病例報(bào)告·
神經(jīng)纖維瘤病1型伴胰腺神經(jīng)內(nèi)分泌瘤一例
孫雪玉 于亞男 王婷 江月萍
患者女,38歲。1年前無明顯誘因出現(xiàn)上腹部陣發(fā)性隱痛,加重2個(gè)月,外院上腹部增強(qiáng)CT示胰管截?cái)嘈元M窄,入我院進(jìn)一步檢查與治療。有神經(jīng)纖維瘤病1型(neurofibromatosis type 1, NF1)病史,且患者母親和弟弟也患有該病。體檢:貧血貌,全身皮膚見散在疣狀物及牛奶咖啡斑點(diǎn),上腹部劍突下輕壓痛。實(shí)驗(yàn)室檢查:紅細(xì)胞3.56×1012/L,血紅蛋白75 g/L,平均紅細(xì)胞體積71fl,平均紅細(xì)胞血紅蛋白296 g/L,鐵蛋白4.35 g/L,血膽紅素及血CEA、CA19-9正常。內(nèi)鏡超聲:十二指腸降段乳頭側(cè)黏膜明顯腫脹,胰頭見一低回聲區(qū),約2.1 cm×2.0 cm,累及十二指腸壁,胰腺體、尾胰管明顯擴(kuò)張,診斷為胰頭占位性病變,胰腺癌可能。于黏膜腫脹處取活檢并行免疫組化染色,考慮胰腺神經(jīng)內(nèi)分泌腫瘤(PNENs, G1級(jí))。擇期行胰十二指腸切除術(shù)。術(shù)中于胰頭處捫及1.5 cm×2 cm大小質(zhì)硬腫塊,將胰頭、鉤突、膽管下端、部分胃及十二指腸組織整塊切除。病理學(xué)檢查診斷為PNENs(G2級(jí)),浸透十二指腸壁,周圍淋巴結(jié)未見癌轉(zhuǎn)移。免疫組化: Syn(+),CgA(+),Ki-67陽性率約為2%,CD31染色見間質(zhì)脈管內(nèi)有癌栓。術(shù)后隨訪4個(gè)月到2年,未見疾病進(jìn)展或腫瘤復(fù)發(fā)。
討論 神經(jīng)內(nèi)分泌腫瘤(neuroendocrine neoplasms,NENs)是一組起源于神經(jīng)內(nèi)分泌細(xì)胞的異質(zhì)性腫瘤,發(fā)病率約為5.25/10萬[1],胃腸胰神經(jīng)內(nèi)分泌腫瘤(GEP-NENs)最為常見,占65%~75%[2]。PNENs約占GEP-NENs的30%[3],分為功能性和非功能性兩類。前者中胰島素瘤和胃泌素瘤較常見,生長抑素瘤、胰高血糖素瘤等較為罕見[4]。非功能性PNENs約占50%[5],通常由于腫瘤體積增大壓迫周圍組織引起梗阻、黃疸或體檢時(shí)發(fā)現(xiàn),或在腫瘤發(fā)生轉(zhuǎn)移時(shí)進(jìn)一步檢查發(fā)現(xiàn)。
NF1屬常染色體顯性遺傳病,發(fā)病率為1/3 000~4 000,約50%的患者有家族史,其突變基因位于常染色體17號(hào)染色體長臂。該基因突變使其編碼的NF蛋白對(duì)細(xì)胞增殖分化的調(diào)控減弱,導(dǎo)致良、惡性腫瘤的發(fā)生[6]。NF1主要表現(xiàn)為皮膚咖啡牛奶斑、多發(fā)性神經(jīng)纖維瘤和腋窩雀斑[7]。
約5%~10%的GEP-NENs與遺傳性疾病有關(guān)[8]。目前約有8種遺傳性綜合征能誘發(fā)NENs,包括多發(fā)性內(nèi)分泌腺瘤病1型和2型(MEN1型和MEN2型)、腦視網(wǎng)膜血管瘤病(VHL綜合征)、NF1、結(jié)節(jié)性硬化癥等[9],以MEN1型和MEN2型最常見。Relles等[10]報(bào)道并發(fā)的NF1患者中40%為生長抑素瘤、34%為胃腸道間質(zhì)瘤、8%為腺癌、6%為類癌、5%為神經(jīng)纖維瘤;發(fā)生腫瘤的靶器官60%為十二指腸、31%為壺腹區(qū)、5%為胰腺、4%為膽管或膽囊。全球醫(yī)學(xué)期刊報(bào)道的此類病例僅8例[11-18],本例為第9例。9例NF1患者伴發(fā)的腫瘤中胰島素瘤4例、非功能性PNENs 3例、生長抑素瘤2例。性別無差異,年齡38~75歲,平均56歲。胰島素瘤均位于胰腺體尾部,非功能性PNENs和生長抑素瘤均位于胰頭部[19]。臨床癥狀主要有腹痛、體重下降、貧血以及由激素引起的特異性表現(xiàn)等,如胰島素瘤引起的發(fā)作性低血糖、暈厥等,生長抑素瘤引起的糖尿病、腹瀉或脂肪瀉、膽石癥等。78%的生長抑素瘤為惡性,且大部分發(fā)生轉(zhuǎn)移[20]。9例NF1中2例生長抑素瘤均發(fā)生了轉(zhuǎn)移、1例神經(jīng)內(nèi)分泌瘤發(fā)生轉(zhuǎn)移。對(duì)NF1并發(fā)PNENs的患者,手術(shù)是首選的治療方式,常采用胰十二指腸切除術(shù)。
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(本文編輯:呂芳萍)
10.3760/cma.j.issn.1674-1935.2017.03.015
266003 山東青島,青島大學(xué)附屬醫(yī)院消化科(孫雪玉、于亞男、江月萍),感染科(王婷)
江月萍,Email: yuepingmd@hotmail.com
2017-03-08)