湯武裝 張麗 張曉雷 胡秀秀

腦膜癌病25例臨床分析

湯武裝 張麗 張曉雷 胡秀秀

目的 探討腦膜癌病的臨床特點和診斷依據(jù)。 方法 對25例確診為腦膜癌病患者的臨床資料及腦脊液細胞學資料進行回顧性分析。結果 25例腦膜癌病患者中, 臨床表現(xiàn)為頭痛24例, 惡心、嘔吐21例, 腦膜刺激征陽性20例, 視乳頭水腫12例, 意識障礙6例, 四肢無力6例, 視力減退5例,癲癇發(fā)作5例, 精神癥狀5例, 聽力障礙3例, 頭暈3例, 發(fā)熱2例, 頸痛1例；20例患者頭顱CT/MRI均未見腦膜異常, 5例行頭顱MRI增強掃描可見2例腦膜強化, 1例腦皮質(zhì)腫脹, 1例腦積水, 1例小腦蚓部左側可疑結節(jié)；腰椎穿刺腦脊液壓力升高12例, 蛋白升高16例, 糖、氯降低14例, 23例患者行腦脊液細胞學檢查均發(fā)現(xiàn)異型細胞, 17例患者行腦脊液免疫組化染色均發(fā)現(xiàn)轉移癌；17例患者經(jīng)臨床及病理學確定其原發(fā)腫瘤, 來源于肺癌10例(其中1例肺癌合并前頰黏膜鱗癌)、胃癌3例、賁門癌2、乳腺癌1例、可疑卵巢癌1例, 8例來源未明。結論 腦膜癌病為惡性腫瘤顱內(nèi)轉移的特殊形式, 臨床表現(xiàn)復雜, 缺乏特異性, 早期以顱內(nèi)壓升高為主；頭顱MRI增強掃描對腦膜癌病診斷有一定指導意義；腦脊液細胞學檢查結合免疫組化染色是腦膜癌病確診的主要依據(jù)。

腦膜癌病；腦脊液細胞學；免疫細胞組化；MRI增強掃描

腦膜癌病(meningeal carcinomatosis, MC)亦稱癌性腦膜炎,是指腦和脊髓的軟膜內(nèi)轉移性腫瘤細胞彌漫播散或呈多數(shù)的局灶性浸潤, 臨床表現(xiàn)腦、顱神經(jīng)和脊髓受損的癥狀, 為中樞神經(jīng)系統(tǒng)轉移癌的一種特殊分布類型, 在實體腫瘤患者中發(fā)生率約為5%［1］。該病起病隱匿, 臨床表現(xiàn)及影像學檢查均缺乏特異性, 易于誤診和漏診。以往認為MC很少見, 近年來隨著臨床認識水平的提高, 以及癌癥患者生存期的延長,使得MC的發(fā)病率也呈明顯上升趨勢。本文對南京腦科醫(yī)院近年來收治的25例腦膜癌病患者臨床資料進行回顧性分析如下。

1 臨床資料

1.1 一般資料 收集2006年11月～2011年5月南京醫(yī)科大學附屬腦科醫(yī)院神經(jīng)內(nèi)科住院的, 經(jīng)腦脊液細胞學確診的腦膜癌病患者25例, 其中男11例, 女14例；年齡32～64歲,平均 (52±7.72)歲, 其中＞50歲15例(60%)；病程3～300 d,平均(41.5±8.1)d。7例患者既往有明確的惡性腫瘤病史, 包括胃癌3例, 賁門癌、肺癌、前頰黏膜鱗癌、乳腺癌各1例。

1.2 臨床表現(xiàn)與體征 起病形式多為亞急性(18例病程≤30 d)或慢性起病, 病情進展較快, 首發(fā)癥狀為頭痛24例(96%), 惡心、嘔吐21例(84%), 頭暈3例(12%), 發(fā)熱2例(8%)。臨床有意識障礙6例(24%), 四肢無力6例(24%), 視力減退5例(20%), 癲癇發(fā)作5例(20%), 精神癥狀5例(20%), 聽力障礙3例(12%), 頭昏1例(4%), 頸痛1例(4%)；腦膜刺激征陽性20例(80%)、可疑陽性1例(4%), 視乳頭水腫12例(48%)。

1.3 影像學檢查 20例患者頭顱CT和(或)頭顱MRI平掃均未發(fā)現(xiàn)腦膜異常信號, 僅5例為多發(fā)性腔隙性腦梗死, 2例右額葉異常信號, 1例枕大池囊腫, 1例脫髓鞘腦病, 1例第五、第六腦室形成, 余10例未見明顯異常；5例行頭顱MRI增強掃描, 其中2例腦膜強化, 1例腦皮質(zhì)腫脹, 1例腦積水伴右顳葉軟化, 1例小腦蚓部左側可疑結節(jié)；4例行頭顱靜脈血管成像(MRV)檢查, 均未見異常。

1.4 腦脊液檢查 25例患者均行腰椎穿刺腦脊液(cerebrospinal fluid, CSF) 檢查, CSF壓力≥200 mmH2O 13例(52%), 正常10例, 2例未測壓。CSF白細胞升高［(10～70)×106/L］ 8例(32%)；蛋白含量增高16例(64%), 正常8例, 降低1例；糖及氯化物降低14例(56%), 正常11例(44%)。細胞學檢查發(fā)現(xiàn)異型細胞23例(92%), 其中17例行CSF細胞免疫組化染色均發(fā)現(xiàn)轉移癌。

1.5 原發(fā)腫瘤來源 根據(jù)病史、臨床表現(xiàn)及相關病理學檢查等尋找原發(fā)腫瘤來源, 本組25例MC患者中, 有17例患者(68%)找到原發(fā)腫瘤, 來源于肺癌10例(其中1例合并前頰黏膜鱗癌)、胃癌3例、賁門癌2例、乳腺癌1例、可疑卵巢癌1例；8例患者未查明原發(fā)腫瘤, 其中7例血清CEA明顯升高, 3例血清CA199明顯升高。

2 討論

腦膜癌病是指原發(fā)病灶的癌細胞選擇性浸潤軟腦膜、腦和脊髓蛛網(wǎng)膜下腔, 并隨血管周圍間隙侵入腦皮質(zhì)引起的一系列臨床綜合征。腫瘤細胞通過血行轉移或淋巴轉移種植播散, 腦膜轉移的原發(fā)惡性腫瘤可來自中樞神經(jīng)系統(tǒng), 也可來源于中樞神經(jīng)系統(tǒng)以外。前者多見于室管膜癌、彌漫性腦膜膠質(zhì)瘤［2］、中樞神經(jīng)系統(tǒng)淋巴瘤［3］等。后者以肺癌、胃腸道癌、乳腺癌、黑色素瘤最常見［4,5］。報道指出仍有大約20%～40%的腦膜癌病原發(fā)病灶不明［6］。本組患者均為神經(jīng)系統(tǒng)以外的惡性腫瘤轉移, 以肺癌最為多見, 占40%, 其次為消化道腫瘤,占20%, 乳腺癌占5%, 基本符合轉移規(guī)律, 本組25例腦膜癌病患者8例來源未明(32%), 結果與既往研究［6］基本相符。

腦膜癌病病理上為腫瘤細胞廣泛浸潤軟腦膜, 顱底神經(jīng)根和腰骶神經(jīng)根也是易受累部位。因此腦膜癌病主要有腦部癥狀、顱神經(jīng)癥狀、脊神經(jīng)癥狀等三組表現(xiàn)。腫瘤細胞轉移到腦膜后引發(fā)局部炎性反應, 影響到CSF的循環(huán)及顱內(nèi)壓力改變, 因此頭痛、惡心嘔吐、腦膜刺激征是患者最常見的表現(xiàn)［7］。顱高壓或腦膜轉移性病灶刺激皮質(zhì)可能導致癇性發(fā)作；過高的顱內(nèi)壓可以抑制皮質(zhì)功能, 造成精神癥狀及或意識障礙等。隨著癌細胞沿軟腦膜或腦脊膜的擴散, 侵犯顱神經(jīng)和脊神經(jīng)根而出現(xiàn)相應的臨床表現(xiàn)。本組25例患者中24例有頭痛, 21例出現(xiàn)惡心嘔吐, 6例存在意識障礙, 癲癇發(fā)作5例,精神癥狀5例, 頭暈3例, 腦膜刺激征陽性者20例, 可疑陽性1例, 視乳頭水腫12例。即幾乎所有病例均以腦部癥狀起病, 且以顱內(nèi)壓升高為突出表現(xiàn)。本組5例視力減退, 聽力障礙3例, 以第Ⅱ、Ⅸ對顱神經(jīng)受累為主；1例頸痛為脊神經(jīng)根受累表現(xiàn)。

影像學檢查對腦膜癌病診斷幫助有限, 頭顱CT/MRI平掃陽性率不高, 且定性困難［8］, 頭顱MRI增強掃描可提高陽性率。國外報道［9］經(jīng)腦脊液細胞學病理證實的腦膜癌病患者中, 2/3頭顱MRI增強有陽性發(fā)現(xiàn)。本組患者頭顱CT或MRI平掃均未發(fā)現(xiàn)腦膜異常信號；5例頭顱MRI增強掃描僅2例有腦膜強化, 另外3例分別表現(xiàn)為腦皮質(zhì)腫脹、腦積水伴右顳葉軟化及小腦蚓部左側可疑結節(jié)。腦膜強化是由于腫瘤炎性反應, 腦膜內(nèi)層血管高度擴張, 使血管通透性增加所致, 所以腫瘤轉移早期時腦膜可以不強化。對腦膜癌病的早期診斷CT或MR平掃價值不高, 頭顱MR增強掃描對診斷有一定的輔助作用。

腦脊液細胞學檢查對腦膜癌病的診斷非常重要, 是主要的確診依據(jù)。CSF細胞學檢查發(fā)現(xiàn)腫瘤細胞是確診腦膜癌病的金標準, 其敏感性為75%～90%, 特異性為100%［10］。本組25例患者CSF細胞學檢查發(fā)現(xiàn)23例有異型細胞, 敏感性92%, 與文獻報道［10］一致。常規(guī)及生化檢查可見白細胞輕～中度增加, 蛋白升高16例(64%), 糖及氯化物降低14例(56%),這是由于癌細胞浸潤破壞了血腦屏障導致CSF生成吸收障礙, 以及腫瘤代謝消耗所致。

CSF細胞學檢查中的常規(guī)邁-格-姬(MGG)染色只能從形態(tài)學角度觀察細胞, 對細胞的定性有很大局限性, 有時難以與慢性腦膜炎時出現(xiàn)的變性細胞鑒別, 而腫瘤細胞變性時也會失去其惡性的特性而難以辯認。免疫組化染色可明確細胞組織學性質(zhì), 補充單一細胞學檢查的不足, 通過免疫組化染色與腦脊液細胞學檢查結合可檢出腦脊液細胞學檢查陰性的病例, 明顯提高了對癌細胞的檢出率［12］。本組17例患者行CSF細胞免疫組化染色檢查, 結果全部呈現(xiàn)典型染色,因此CSF細胞免疫組化染色檢查與細胞學檢查結合可提高腦膜癌病的診斷敏感性, 減少腦膜癌病的漏診率。

本文為臨床資料的回顧性分析, 樣本量少, 存在一定的局限性?？傊? 對中老年患者, 特別是有腫瘤病史者, 不明原因的顱內(nèi)壓升高, 定性困難的腦膜炎及臨床表現(xiàn)多樣而缺乏特異性的患者, 且頭顱CT或MRI檢查無明顯異常者, 要考慮有腦膜癌病的可能。應盡早行反復的CSF細胞學檢查,有條件的聯(lián)合腦脊液免疫組織化學染色, 必要時行頭顱MRI增強掃描, 并在此基礎上進一步尋找原發(fā)灶, 做到早診斷早治療, 避免漏診和誤診。

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Clinical analysis of 25 cases of meningeal carcinomatosis

TANG Wu-zhuang,ZHANGli, ZHANG Xiao-lei,et al.
Department of Neurology, Yixing People’s Hospital Aftiliated to Jiangsu Universily,Yixing 214200, China

Objective To investigate the clinical features and diagnostic evidence of meningeal carcinomatosis (MC).Methods The clinical data and cerebrospinal fluid(CSF) cytology data of 25 cases diagnosed as meningeal carcinomatosis were retrospectively reviewed.Results In 25 patients of MC, there were 11 men and 14 women and the mean age was (52±7.72) years old.24 cases of patients with headache, 21 cases of patients with nausea and vomiting, meningeal irritation sign was positive in 20 cases, papilledema were found in 12 cases, disturbance of consciousness were found in 6 cases, four limbs weakness were found in 6 cases, vision loss were found in 5 cases, seizures were found in 5 cases, psychiatric symptoms were found in 5 cases, hearing-impaired were found in 3 cases, dizziness were found in 3 cases, fever were found in 2 cases, neck pain were found in 1 case.No meningeal enhancement were found in cranial CT and (or) cranial MRI scan among 20 patients, 5 patients underwent cranial MRI enhanced scan showed 2 cases of meningeal enhancement, 1 case of swelling of the cerebral cortex, 1 case of hydrocephalus and 1 case of the left cerebellar vermis suspicious nodules.CSF pressure increases in 12 cases, 16 cases of protein increase, and 14 cases of sugar and chlorine decrease.23 patients with CSF cytology were found atypical cells, and 17 patients with CSF immunohistochemical staining were found metastatic cancer.Primary tumor source of 17 patients were found by the clinical and pathological, 10 cases were diagnosed with lung cancer (from which 1 case was mergered former buccal mucosa squamous cell carcinoma), 3 cases were diagnosed with gastric cancer, 2 cases were diagnosed with cardia cancer, 1 case of breast cancer, 1 case of suspicious ovarian cancer, and 8 cases of unknown source.Conclusion MC is a special form of malignant brain metastases, clinical manifestations are complex but lack of specificity.The main manifestations are increased intracranial pressure in early stage.Cranial MRI enhanced scan may provide some referential value for the diagnosis of MC.CSF cytology combined with immunohistochemical staining is the main method to diagnose MC.

Meningeal carcinomatosis；Cerebrospinal fluid cytology；Immunohistochemical staining；MRI enhancement scanning

214200 江蘇大學附屬宜興市人民醫(yī)院神經(jīng)內(nèi)科(湯武裝)；南京醫(yī)科大學附屬腦科醫(yī)院老年神經(jīng)科(張麗 張曉雷胡秀秀)

胡秀秀, E-mail：xxh198312@sina.com