表現(xiàn)為間質(zhì)性肺炎的肺腺癌15例臨床分析

李建東,郝淑玲,王 斐

(陸軍總醫(yī)院呼吸科,北京 100700；*通訊作者,E-mail:ljdzy@hotmail.com)

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表現(xiàn)為間質(zhì)性肺炎的肺腺癌15例臨床分析

李建東*,郝淑玲,王 斐

(陸軍總醫(yī)院呼吸科,北京 100700；*通訊作者,E-mail:ljdzy@hotmail.com)

目的 提高對肺腺癌臨床表現(xiàn)及影像學(xué)多樣性的認(rèn)識(shí),減少誤診。 方法 回顧性分析2012-07～2015-05收治的15例表現(xiàn)為肺間質(zhì)性肺炎的肺腺癌臨床資料及診治經(jīng)過,總結(jié)其臨床特點(diǎn)、影像學(xué)表現(xiàn)及與間質(zhì)性肺炎的差異,提出診斷線索和方法。 結(jié)果 15例患者中,男8例,女7例,年齡在44-78歲,平均(56.8±8.2)歲。臨床表現(xiàn)為不同程度咳嗽、咳痰、進(jìn)行性呼吸困難,6例患者發(fā)熱,體溫在37.8-38.8 ℃。13例肺部可聞及爆裂音。14例患者部分腫瘤標(biāo)志物增高。15例肺功能彌散功能下降,14例患者血?dú)夥治鰹棰裥秃粑ソ?。胸部CT表現(xiàn)為磨玻璃影,實(shí)變、小結(jié)節(jié)影,網(wǎng)格影。15例患者經(jīng)抗感染治療無效。12例患者進(jìn)行性呼吸困難給予甲強(qiáng)龍治療,咳嗽,呼吸困難好轉(zhuǎn),肺部爆裂音減少,動(dòng)脈血氧分壓上升至70-80 mmHg,但胸部CT無明顯吸收。經(jīng)皮肺活檢病理診斷為肺腺癌。5例患者拒絕治療出院,隨訪3例死亡,生存期2-3個(gè)月,2例失訪。8例患者給予化療(GP,DP方案),患者病情好轉(zhuǎn),后隨訪8例患者死亡,生存期8-10月。2例EGFR基因突變患者給予化療(GP方案)及吉非替尼治療,患者病情明顯好轉(zhuǎn),肺部病變明顯吸收,隨訪3年,病情穩(wěn)定。 結(jié)論 肺腺癌臨床、影像學(xué)無特異性,表現(xiàn)形式呈多樣性,尤其是部分肺腺癌臨床與影像學(xué)類似間質(zhì)性肺炎,易造成誤診。提高對這類型表現(xiàn)的肺腺癌的認(rèn)識(shí),在臨床診療過程中發(fā)現(xiàn)肺癌的診斷線索,積極行經(jīng)皮肺活檢病理檢查,明確診斷。

肺腺癌; 間質(zhì)性肺炎; 胸部CT

近年來肺腺癌的發(fā)病率顯著增高[1],肺腺癌臨床表現(xiàn)無特征性,多以咳嗽起病,可有痰中帶血,癥狀呈多樣性,影像學(xué)表現(xiàn)復(fù)雜,大部分表現(xiàn)為團(tuán)塊影、結(jié)節(jié)影,部分肺癌影像學(xué)表現(xiàn)類似肺炎。近年來我科收治15例以咳嗽、咳痰、進(jìn)行性呼吸困難為首發(fā)癥狀,雙肺彌漫性間質(zhì)性病變?yōu)楸憩F(xiàn)的肺腺癌病例,給予糖皮質(zhì)激素治療,呼吸困難明顯好轉(zhuǎn),臨床表現(xiàn)為間質(zhì)性肺炎,后經(jīng)皮肺活檢診斷為肺腺癌?，F(xiàn)報(bào)道如下并結(jié)合文獻(xiàn)進(jìn)行復(fù)習(xí),提高對肺腺癌臨床表現(xiàn)多樣性的認(rèn)識(shí),減少誤診率。

1 材料與方法

1.1 研究對象

選取2012-07～2015-05入住我院呼吸科經(jīng)皮肺活檢明確診斷為肺腺癌患者15例,其中男8例,女7例,年齡在47-77歲,平均(57.5±8.2)歲。吸煙5例。病程2周至3月,平均(1.69±0.984)月。15例患者既往健康13例,慢性阻塞性肺病2例,均無間質(zhì)性肺疾病病史。

1.2 診斷標(biāo)準(zhǔn)

結(jié)合患者病史、臨床癥狀、體征,實(shí)驗(yàn)室檢查及胸部X線表現(xiàn),經(jīng)皮肺活檢組織病理學(xué)診斷。

1.3 方法

回顧性總結(jié)15例患者的病史、癥狀體征、實(shí)驗(yàn)室檢查、胸部X線表現(xiàn)、組織病理結(jié)果及診療過程,并隨訪。

2 結(jié)果

2.1 臨床表現(xiàn)

15例患者中13例表現(xiàn)為不同程度咳嗽、咳痰,均無咳大量泡沫痰,2例患者干咳,15例患者均表現(xiàn)為進(jìn)行性呼吸困難,10例患者活動(dòng)受限,2例患者需無創(chuàng)呼吸機(jī)治療。6例患者發(fā)熱,體溫在37.8-38.8 ℃。13例患者肺部可聞及爆裂音。

2.2 實(shí)驗(yàn)室及肺功能檢查

15例患者中12例血常規(guī)正常,2例輕度輕度貧血,血紅蛋白在90-110 g/L。10例患者肝腎功能正常,2例患者谷丙轉(zhuǎn)氨酶增高,為50-105 U/L,3例患者白蛋白減低,為30-34 g/L。6例患者血沉增快,為30-55 mm/h。12例患者CEA增高,在5.9-80.7 ng/ml(參考值為0-4.6 ng/ml),6例患者CA125增高,65.9-116.6 U/ml(參考值為0-35 U/ml),1例患者CA15-3增高,為42.2 U/ml(參考值為0-25 U/ml),7例CA19-9增高,65.4-746.6 U/ml(參考值為0-39 U/ml),6例CA724增高,6.0-61.4 U/ml(參考值為0-5.3 U/ml),6例NSE增高,17.5-27.2 U/ml(參考值為0-15.2 U/ml),僅1例患者腫瘤標(biāo)志物正常。

15例患者血?dú)夥治鰴z查,14例為Ⅰ型呼吸衰竭,動(dòng)脈血氧分壓40-58 mmHg,1例動(dòng)脈血氧分壓87 mmHg。

肺功能檢查15例患者中13例限制性通氣功能障礙,2例混合型通氣功能障礙,15例患者均一氧化碳彌散功能減低,一氧化碳彌散量占預(yù)計(jì)值百分比為32%-75%。

2.3 胸部CT

15例患者胸部CT表現(xiàn)為雙肺彌漫性斑片、實(shí)變影,磨玻璃影,小結(jié)節(jié)影,網(wǎng)格影。胸部CT表現(xiàn)為雙肺多發(fā)性,非對稱磨玻璃影12例,雙肺斑片、實(shí)變影伴支氣管充氣征6例,雙肺小結(jié)節(jié)影4例,網(wǎng)格影4例,幾種征象常共存(見圖1，2)。圖1為52歲女性患者,入院時(shí)胸部CT:雙肺散在分布直徑小于1.0 cm結(jié)節(jié),雙上肺明顯,雙肺上葉及右肺中下葉見斑片、實(shí)變影,支氣管充氣征(見圖 1A-C)。患者化療、吉非替尼治療1年后胸部CT:雙肺多發(fā)淡薄小結(jié)節(jié)影,右肺及左肺上葉見彌漫性斑點(diǎn)及條片影,局部呈磨玻璃密度改變(見圖 1D-F)。圖2為59歲女性,入院時(shí)胸部CT:雙肺多發(fā)性磨玻璃影,右肺為著。

A-C.入院時(shí)胸部CT,雙肺散在分布直徑小于1.0 cm結(jié)節(jié),雙上肺明顯;雙肺上葉及右肺中下葉見斑片、實(shí)變影,右肺為著,內(nèi)見支氣管充氣征;D-F.患者化療、吉非替尼治療1年后胸部CT,雙肺多發(fā)淡薄小結(jié)節(jié)影;右肺及左肺上葉見彌漫性斑點(diǎn)及條片影,局部呈磨玻璃密度改變圖1 52歲女性患者胸部CT結(jié)果Figure 1 Chest computed tomography finding of a 52-year-old female patient

雙肺多發(fā)性磨玻璃影,右肺為著圖2 59歲女性患者入院時(shí)胸部CT結(jié)果Figure 2 Chest computed tomography finding of a 59 year-old female patient

2.4 病理

15例患者均經(jīng)皮肺活檢組織病理檢查為肺腺癌(見圖3,4),其中7例呈貼壁生長,4例呈乳頭狀生長,4例呈部分貼壁,乳頭樣生長。11例患者行EGFR基因檢測,2例exon21突變。

肺腺癌,貼壁型生長圖3 圖1患者經(jīng)皮肺活檢病理結(jié)果Figure 3 Histopathological finding of figure 1 patient obtained from percutaneous lung biopsy

肺腺癌,貼壁型生長圖4 圖2患者經(jīng)皮肺活檢病理結(jié)果Figure 4 Histopathological finding of figure 2 patient obtained from percutaneous lung biopsy

2.5 治療經(jīng)過

15例患者住院后均給予廣譜抗菌藥物抗感染治療,12例患者因呼吸困難明顯,給予甲強(qiáng)龍治療(甲強(qiáng)龍80 mg/d,后逐漸減量,總劑量在1 320-1 600 mg),2例無創(chuàng)呼吸機(jī)治療,經(jīng)甲強(qiáng)龍治療后,患者體溫正常,咳嗽、咳痰、呼吸困難好轉(zhuǎn),雙肺爆裂音減少,復(fù)查血?dú)夥治鲅醴謮荷仙?0-80 mmHg,但復(fù)查胸部CT病灶無明顯吸收。15例患者經(jīng)皮肺活檢診斷為肺腺癌。2.6 轉(zhuǎn)歸

15例患者經(jīng)病理診斷明確后,5例患者拒絕治療出院,隨訪3例死亡,生存期2-3個(gè)月,2例失訪。8例患者給予化療(GP方案,鹽酸吉西他濱1 250 mg/m2,d1,d8,靜脈滴注;順鉑75 mg/m2,d1,靜脈滴注;DP方案,多西他塞75 mg/m2,d1,靜脈滴注;卡鉑300 mg/m2,d1,靜脈滴注),患者病情好轉(zhuǎn),后隨訪8例患者均死亡,生存期8-10月。2例EGFR基因突變患者給予化療(GP方案)及吉非替尼(250 mg/d,口服)治療,患者病情明顯好轉(zhuǎn),肺部病變明顯吸收,隨訪3年,病情穩(wěn)定。

3 討論

肺癌是世界上發(fā)病率和死亡率最高的惡性腫瘤之一,近年來肺腺癌已成為最常見的組織類型,目前肺腺癌占肺癌的46.5%[2]。肺腺癌起源于支氣管黏膜腺,部分起源于Clara細(xì)胞,Ⅱ型肺泡上皮細(xì)胞,多見于周圍型肺癌。肺腺癌無特異性癥狀、體征及胸部X線特征,其臨床表現(xiàn)及影像學(xué)呈多樣性,極易誤診。

本組15例患者以咳嗽、進(jìn)行性呼吸困難起病,多數(shù)肺部可聞及爆裂音,胸部CT表現(xiàn)為磨玻璃、實(shí)變、小結(jié)節(jié)影及網(wǎng)格影,抗感染治療無效,糖皮質(zhì)激素治療呼吸困難可緩解,臨床過程類似間質(zhì)性肺炎,后經(jīng)皮肺活檢診斷肺腺癌。

本組患者具有以下特點(diǎn):①年齡在47-77歲,平均(57.5±8.2)歲,男 ∶女為1.14 ∶1。②均表現(xiàn)咳嗽、進(jìn)行性呼吸困難,近半數(shù)患者發(fā)熱,為輕中度發(fā)熱,多數(shù)患者(86.7%,13/15)肺部均可聞及爆裂音。患者均無大量泡沫痰。③胸部CT表現(xiàn)為雙肺磨玻璃影、實(shí)變影、多發(fā)性小結(jié)節(jié)影、網(wǎng)格影,幾個(gè)征象多共存。④大部分患者(93.3%,14/15)出現(xiàn)Ⅰ型呼吸衰竭。⑤肺一氧化碳彌散功能減低。⑥多數(shù)患者(93.3%,14/15)一種或多種腫瘤標(biāo)志物增高。⑦病理均為肺腺癌,為貼壁或乳頭型生長,或兩者兼有之。

本組患者雖然臨床過程及影像學(xué)表現(xiàn)酷似間質(zhì)性肺炎,但可發(fā)現(xiàn)肺癌的診斷線索。①多數(shù)患者可有多種腫瘤標(biāo)志物增高。②糖皮質(zhì)激素治療雖可減輕患者呼吸困難癥狀,但肺部病灶無明顯吸收。③胸部CT多表現(xiàn)為磨玻璃影、實(shí)變影、小結(jié)節(jié)影、網(wǎng)格影等幾種征象共存,雙側(cè)不對稱與間質(zhì)性肺炎略有不同,結(jié)節(jié)影較間質(zhì)性肺炎多見[3-7]。④經(jīng)皮肺活檢是明確診斷簡便、安全的手段。

慢性間質(zhì)性肺疾病合并肺癌的發(fā)生率較高[8],本組患者表現(xiàn)與慢性間質(zhì)肺病合并肺癌不同。其原因?yàn)?①慢性間質(zhì)性肺炎既往有相關(guān)的病史,如結(jié)締組織疾病史,緩慢的進(jìn)行性呼吸困難,胸部CT表現(xiàn)為網(wǎng)格、蜂窩陰影,雙肺胸膜下病變?yōu)橹?與本組患者表現(xiàn)不符。②慢性間質(zhì)性肺炎多緩慢進(jìn)展,在彌漫性間質(zhì)疾病基礎(chǔ)出現(xiàn)團(tuán)塊、結(jié)節(jié)影[9],與本組患者起病即為磨玻璃、實(shí)變、結(jié)節(jié)影等不同。③慢性間質(zhì)性肺炎合并肺癌,腫瘤病理類型為腺癌、鱗癌、小細(xì)胞,呈多樣性,而本組患者均為腺癌,可能與肺腺癌的生長特性有關(guān),而呈現(xiàn)為間質(zhì)性肺炎表現(xiàn)。

本組患者表現(xiàn)與急性間質(zhì)性肺炎有差別。急性間質(zhì)性肺炎病因不明,平均發(fā)病年齡在50-55歲,表現(xiàn)為發(fā)熱、頭痛、肌痛等流感樣癥狀,咳嗽,進(jìn)行性加重的呼吸困難,迅速發(fā)展為Ⅰ型呼吸衰竭,大多數(shù)患者需要呼吸支持,糖皮質(zhì)激素治療效果差,死亡率達(dá)到70%[3,6,7]。本組患者病情進(jìn)展相對緩慢,糖皮質(zhì)激素治療可緩解呼吸困難,但病灶無明顯吸收,可能與腫瘤細(xì)胞刺激局部炎性水腫有關(guān)?；颊呓谒劳雎什桓?與急性間質(zhì)性肺炎不同。

由此,我們推測,可能存在著一種類型的肺腺癌,具有與一般肺腺癌不同的生物學(xué)特性,其生長方式浸潤肺間質(zhì),臨床上表現(xiàn)為呼吸困難,肺部爆裂音,Ⅰ型呼吸衰竭,胸部CT表現(xiàn)為磨玻璃、實(shí)變、結(jié)節(jié)影、網(wǎng)格影,可能為肺腺癌的一種表型,表現(xiàn)了肺腺癌的異質(zhì)性。但這需要進(jìn)一步研究。

綜上所述,肺腺癌臨床表現(xiàn)、影像學(xué)無特異性,表現(xiàn)形式呈多樣性,尤其是部分肺腺癌臨床表現(xiàn)與影像學(xué)檢查類似間質(zhì)性肺炎,易造成臨床醫(yī)生誤診。提高對這類型表現(xiàn)的肺腺癌的認(rèn)識(shí),熟悉其臨床、影像學(xué)表現(xiàn)形式及與間質(zhì)性肺炎差異,在臨床診療過程中發(fā)現(xiàn)肺癌的診斷線索,積極行經(jīng)皮肺活檢病理檢查,明確診斷。

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Clinical analysis of 15 cases of lung adenocarcinoma presenting as interstitial pneumonia

LI Jiandong*,HAO Shuling,WANG Fei

(DepartmentofRespiration,PLAArmyGeneralHospital,Beijing100700,China;*Correspondingauthor,E-mail:ljdzy@hotmail.com)

ObjectiveTo improve the understanding of the clinical manifestation and radiologic imaging diversity of lung adenocarcinoma and reduce misdiagnosis.MethodsClinical and imaging data of 15 cases of lung adenocarcinoma presenting as interstitial pneumonia were retrospectively analyzed.The data were collected form Army General Hospital from July 2012 to May 2015.ResultsAll the 15 cases(8 males and 7 females,aged 47-77 years old,mean 57.5±8.2 years old) had the symptoms of cough,expectoration and dyspnea in varying degrees.Six cases of them had fever(37.8-38.8 ℃).Coarse crackles was heard in one or two lung fields of 13 patients.Blood tumor markers were elevated in 13 patients.Monoxide diffusion function was reduced in 15 patients.Blood gas analysis presented typeⅠ respiratory failure in 14 patients.Chest computed tomography showed ground glass opacities,consolidation with air bronchograms,small nodules shadows and reticulation shadow in two lung fields.The patients all were treated with broad-spectrum antibiotics and the symptoms were not improved.Among 15 patients,12 patients with progressive dyspnea received corticosteroid therapy,and then the dyspnea of the patients was improved and the crackles of lung was reduced.Arterial oxygen partial pressure of the patients raised to 70-80 mmHg,but the pulmonary lesion of chest CT scan was not absorbed.The patients all were diagnosed as lung adenocarcinoma by percutaneous lung biopsy.Five patients refused chemotherapy and discharged.Three patients died after 2-3 months from the onset and two patients were lost for follow up.Eight patients received chemotherapy and survived for 8-10 months.Two patients with EGFR gene mutation were treated with chemotherapy combined with epidermal growth factor receptor inhibitor-gefitinib and still survived after three-year follow-up.ConclusionClinical manifestation and imaging of lung adenocarcinoma are diverse and non-specific,and even some of them present as interstitial pneumonia.Clinicians must improve the understanding of the lung adenocarcinoma and obtain actively pathologic diagnosis by precutaneous lung biopsy.

lung adenocarcinoma; interstitial pneumonia; chest CT scan

李建東,男,1962-10生,碩士,副主任醫(yī)師

2017-02-23

R734.2

A

1007-6611(2017)06-0571-04

10.13753/j.issn.1007-6611.2017.06.013