乳腺MRI檢查對乳腺癌個體化治療的作用

劉佩芳，鮑潤賢

MRI成像技術具有極好的軟組織分辨率和無射線輻射特點，對乳腺檢查具有獨到的優(yōu)勢，已有的大量研究結果表明乳腺MRI檢查對于乳腺良、惡性腫瘤的診斷和鑒別診斷、對乳腺癌分期、治療后隨訪以及評估腫瘤血管生成和腫瘤生物學行為及預后方面，與乳腺X線和超聲檢查相比可獲得更多、更準確的信息，在某些方面起著后兩者不能替代的作用[1-4]。本文結合臨床病例從影像學角度重點闡述乳腺MRI對首發(fā)癥狀以腋淋巴結轉移癌患者尋找乳腺原發(fā)灶、對乳腺癌保乳術前評估、對一側已確診為乳腺癌檢出對側同時性乳腺癌以及MR引導下乳腺病變定位和活檢在乳腺癌個體化治療方面的作用。

1 乳腺MRI對首發(fā)癥狀以腋淋巴結轉移癌患者尋找乳腺內原發(fā)灶的作用

臨床上約近1.0%的乳腺癌患者僅表現(xiàn)為腋淋巴結腫大，經活檢病理及免疫組化診斷為轉移癌并提示原發(fā)灶可能來自乳腺，而臨床乳腺觸診、X線和超聲檢查均為陰性[5]。以往臨床上對部分這類患者的傳統(tǒng)治療手段為行同側乳腺根治術或改良根治術，以期切除其原發(fā)腫瘤，但術后并非所有病例的病理結果都能檢出癌灶。2005年美國乳腺外科醫(yī)師協(xié)會(American Society of Breast Surgeons，ASBS)對776名醫(yī)師的調查結果表明：約43%的醫(yī)師對這類患者選擇手術治療；37%選擇放療；其余則選擇觀察或由患者選擇治療方案或行PET進一步檢查等[6]。因此對首發(fā)癥狀為腋淋巴結轉移癌患者術前了解乳腺內是否存在癌灶以及對癌灶的準確定位和范圍評估對臨床進一步制訂個體化的治療方案至關重要。近年來隨著乳腺MRI檢查越來越多的應用于臨床，對于腋淋巴結轉移癌患者尋找乳腺內原發(fā)癌灶已成為臨床醫(yī)生公認的乳腺MRI檢查適應證之一，已有研究表明MRI對檢出腋淋巴結轉移癌患者的乳腺內原發(fā)癌灶具有較高敏感性，約80%的病例可通過MRI檢查檢出乳腺內原發(fā)癌灶[7-9]。筆者一組研究結果顯示[10]，以腋淋巴結轉移癌為首診且臨床乳腺觸診、X線和超聲檢查均為陰性的33例患者，MRI檢出乳腺內原發(fā)癌灶的準確性為83.33%，相對于臨床常見的一般乳腺癌而言，以腋淋巴結轉移癌為首診且臨床乳腺觸診和X線、超聲檢查均為陰性的乳腺癌MRI表現(xiàn)以小灶性的腫塊性病變(圖1)和導管性或段性強化的非腫塊性病變(圖2)為常見表現(xiàn)類型。乳腺MRI檢查可作為腋淋巴結轉移癌且臨床乳腺觸診、X線和超聲檢查均為陰性患者尋找乳腺內原發(fā)灶的常規(guī)檢查手段。

圖1 患者系右腋下淋巴結轉移性癌，雙乳臨床觸診、X線和超聲檢查均未發(fā)現(xiàn)惡性病變，乳腺MRI診斷右側乳腺癌，行右乳腺根治術，經全乳取材病理診斷為右乳外上非特殊型浸潤性導管癌。圖1A～D分別為右乳腺MRI平掃和動態(tài)增強后1 min、2 min、8 min，顯示右乳外上方不規(guī)則強化結節(jié)(箭)；圖1E為動態(tài)增強后病變時間-信號強度曲線圖，顯示為流出型曲線；圖1F為DWI圖像(b=500 s/mm2)，顯示該病變呈較高信號，ADC值為0.80×10-3 mm2/s；圖1G：雙乳X線內外側斜位，雙乳未見明顯惡性病變征象Fig 1 Clinically,mammographically,and ultrasonographically (not shown) occult breast carcinoma visualized by MRI in the patient with axillary lymph node metastasis.Histology proved invasive ductal carcinoma of the right breast.MR images before(Fig 1A),1 min (Fig 1B),2 min (Fig 1C) and 8 min (Fig 1D) following injection of contrast medium showed a strong early enhancing nodule (arrow) with irregular shape in the right breast.Kinetic curve (Fig 1E) demonstrated rapid initial enhancement with washout pattern.Axial DWI (b=500 sec/mm2) (Fig 1F) showed obviously high signal intensity lesion with ADC value of 0.80×10-3 mm2/sec.Mediolateral oblique views of both breasts (Fig 1G) showed negative findings.

圖2 患者系左腋下淋巴結轉移性癌，免疫組化檢查提示原發(fā)灶來自乳腺，乳腺MRI檢查考慮左側乳腺癌，行左乳腺根治術后經全乳取材病理診斷為左乳外下非特殊型浸潤性導管癌。圖2A～C分別為左乳腺MRI平掃和動態(tài)增強后1 min、8 min，顯示左乳下方不規(guī)則斑點狀異常強化病灶(箭)；圖2D為強化后延遲期橫斷面，顯示左乳強化病變沿導管走行分布(箭)Fig 2 Clinically,mammographically,and ultrasonographically (not shown) occult breast carcinoma visualized by MRI in the patient with axillary lymph node metastasis.Histology revealed invasive ductal carcinoma not otherwise specifi ed of the left breast.MR images before (Fig 2A),1 min (Fig 2B) and 8 min (Fig 2C) following injection of contrast medium showed clumped and stippled enhancement nodules (arrow) in the left breast.Axial delayed enhanced image (Fig 2D) demonstrated linear clumped and stippled enhancement (arrows).

圖3 (左乳腺)非特殊型浸潤性導管癌，組織學Ⅱ級，淋巴管癌栓(+++)，乳頭(+)，腋下淋巴結11/25。圖3A為左乳X線頭尾位，圖3B為左乳X線內外側斜位，顯示左乳中上方高密度不規(guī)則單發(fā)腫物。圖3C為左乳病變不同層面VR圖，圖3D～3F分別為左乳腺增強后病變不同層面圖；圖3G為左乳MIP圖，顯示左乳頭深面從內側至外側均可見多發(fā)、大小不等不規(guī)則異常強化，其中較大腫塊(箭)相符于X線所見病變，其余多發(fā)的異常強化病變于X線上未顯示Fig 3 Invasive ductal carcinoma not otherwise specifi ed of the left breast (Grade II),nipple (+),axillary lymph node 11/25 (+).Craniocaudal (Fig 3A) and mediolateral oblique (Fig 3B) views of the left breast demonstrated a solitary irregular high density mass with ill-defi ned margins.Volume rendering images (Fig 3C),contrastenhanced images (Fig 3D-3F) at different slices,and MIP image (Fig 3G) showed multiple enhanced lesions in the left breast.The largest one (arrow) corresponds to the mass shown on mammogram.The other multifocal lesions could not be identifi ed on mammograms.

2 乳腺MRI對乳腺癌患者保乳術前評估的作用

近年來隨著醫(yī)學的發(fā)展、綜合治療水平的提高和乳腺癌患者對生活質量的要求，乳腺癌保乳手術以其兼顧乳腺癌療效和患者生活質量的優(yōu)勢已成為乳腺癌治療中的幾種主要方法之一，但對保乳手術而言為了減少術后復發(fā)率，必須嚴格掌握適應證，臨床醫(yī)師需在術前盡可能準確判斷癌灶的位置、范圍和有無多灶或多中心腫瘤。相關研究和我們的臨床實踐表明，MRI對乳腺癌特別是對浸潤性較強的乳腺癌范圍的評估與組織病理學結果最為接近，而臨床乳腺觸診和X線檢查對這類病變范圍常常低估(圖3)，在浸潤性小葉癌中，術前MRI檢查改變治療方案達24%[11-14]。關于乳腺癌中的導管原位癌(ductal carcinoma in situ,DCIS)，盡管其預后明顯好于浸潤性癌且臨床多適合行保乳手術治療，但其生物學特性具有明顯的異質性，另外，DCIS較浸潤性癌易呈多中心性，DCIS的多中心性直接影響到保乳手術的效果并增加了局部復發(fā)的危險性，MRI因其本身具有的成像優(yōu)勢不僅可對DClS特別是高核級DCIS早期檢出，更重要的是可對其準確確定病變范圍，對僅表現(xiàn)為鈣化的DCIS或伴廣泛導管內癌成分的浸潤性癌，X線上很難依靠鈣化準確評估病變范圍，即使聯(lián)合超聲檢查或進行術前穿刺活檢，也難以保證局部切除范圍充足，而出現(xiàn)手術切緣反復陽性或保乳手術失敗或術后復發(fā)等問題，對此，MRI則有助于對病變范圍的準確評估[15,16](圖4)。乳腺多灶或多中心性癌發(fā)生率為14%～47%，明確診斷乳腺癌是否為多灶或多中心性是臨床醫(yī)生考慮能否行保乳手術的一個最重要因素，文獻報道在擬行保乳手術前行動態(tài)增強MRI檢查的病例中，約有11%～19.3%的病例因發(fā)現(xiàn)了多灶或多中心病變而改變了原來的治療方案，由局部切除術改為乳腺切除術，動態(tài)增強MRI、X線和超聲三種影像學檢查方法對于多灶、多中心性乳腺癌診斷的準確性分別為85%～100%、13%～66%和38%～79%[11,17-20](圖5)，因此，對擬行保乳手術的患者術前行MRI檢查具有較高的臨床價值。Fischer等[21]對乳腺癌患者術前行MRI檢查價值評估的回顧性研究結果表明，保乳術前行MRI檢查和未行MRI檢查患者的術后復發(fā)率分別為1.2%和6.8%，其差異具有統(tǒng)計學意義，術前MRI檢查對保乳手術患者可降低復發(fā)率。Turnbull等[22]進行的多中心研究結果表明術前行MRI檢查的816例患者中50例因MRI發(fā)現(xiàn)了其他病灶而改變了臨床處理方式，由腫瘤局部擴大切除術改為全乳切除，其中35例病理證實MRI診斷正確，即70%的患者受益于術前乳腺MRI檢查，臨床上得到了及時和正確的治療。此外，對于進行保乳手術治療以及行放射治療后的患者，動態(tài)增強MRI檢查亦有利于發(fā)現(xiàn)殘留病灶、鑒別手術或放療后瘢痕和腫瘤復發(fā)[23]。

圖4 (左乳腺)非特殊型浸潤性導管癌(浸出成分較少，可見廣泛導管原位癌)。圖4A：左乳X線頭尾位，圖4B：左乳X線內外側斜位，圖4C：左乳鈣化區(qū)局部放大，顯示左乳中上方多發(fā)不定形及模糊的細小鈣化，成簇和段性分布，局部腺體結構不良，未見明確腫塊。圖4D～4G分別為MRI平掃和動態(tài)增強后1、2、8 min，圖4H：動態(tài)增強后病變時間-信號強度曲線圖,圖4I：矢狀面MIP圖,圖4J：橫軸面MIP圖，顯示左乳上方偏內側局限片狀不均勻明顯強化，呈段性分布，病變區(qū)時間-信號強度曲線呈平臺型，病變范圍顯示清楚Fig 4 Invasive ductal carcinoma not otherwise specified associated with extensive ductal carcinoma in situ of the left breast.Craniocaudal(Fig 4A) and mediolateral oblique (Fig 4B) views of the left breast and magnifi cation view (Fig 4C)for the region of microcalcifications.Multiple clusters of amorphous microcalcifications with varying density demonstrated segmental distribution,no defi ned mass.MR images before(Fig 4D),1 min (Fig 4E),2 min (Fig 4F) and 8 min (Fig 4G) following injection of contrast medium and time-signal intensity curve (Fig 4H),sagittal (Fig 4I),and axial (Fig 4J) maximum intensity projection images demonstrated more extensive,segmental distribution marked enhanced lesion in the upper inner quadrant of the left breast.Kinetic curve demonstrated rapid initial enhancement with plateau pattern.

3 乳腺MRI對一側已確診為乳腺癌患者檢出對側同時性乳腺癌的作用

在乳腺癌患者中，盡管部分患者僅以一側病變而就診，但存在雙側同時性乳腺癌的可能。MRI雙側乳腺同時成像可及時發(fā)現(xiàn)對側乳腺癌，為臨床醫(yī)生制訂合理、有效的治療方案提供影像學信息，使患者在一次手術中雙乳病變均可得到治療成為可能，既可早期發(fā)現(xiàn)對側臨床隱匿性乳腺癌改善預后，又能節(jié)省醫(yī)療資源、減輕患者負擔。已有研究結果表明，隨著MRI對乳腺癌術前分期應用的增多，在對病側乳腺檢查的同時，對側乳腺癌MRI檢出率為2%～9%[22,24-26]，對一側已診斷為乳腺癌的患者，MRI可作為診斷對側是否存在臨床隱性乳腺癌的一種有效的檢查方法(圖6、7)。

圖5 (左乳腺)雙發(fā)癌，左乳外上非特殊型浸潤性導管癌，組織學Ⅱ級；左乳中上浸潤性篩狀癌。圖5A：右、左乳X線頭尾位，圖5B：右、左乳X線內外側斜位，顯示雙乳腺呈多量腺體型乳腺，其中左乳內可見高密度不規(guī)則單發(fā)腫塊(箭)。圖5C～5F分別為MRI平掃和動態(tài)增強后1 min、2 min、8 min，圖5G～5J分別為不同層面MRI平掃和動態(tài)增強后1 min、2 min、8 min，圖5K為左乳矢狀面MIP圖,圖5L為橫軸面MIP圖，圖5M、5N：左乳病變不同層面VR圖，顯示左乳稍外上和中上方兩個不規(guī)則明顯異常強化腫物，時間-信號強度曲線呈流出型Fig 5 Double lesions of the left breast cancer.Invasive ductal carcinoma not otherwise specifi ed localized in the upper outer quadrant and invasive cribriform carcinoma localized in the medially upper region.Craniocaudal (Fig 5A) and mediolateral oblique (Fig 5B) views of both breasts showed a solitary irregular high density mass (arrow) with ill-defi ned margins in the left breast.MR images before (Fig 5C,Fig 5G),1 min (Fig 5D,Fig 5H),2 min (Fig 5E,Fig 5I) and 8 min (Fig 5F,Fig 5J) following injection of contrast medium at different slices,sagittal (Fig 5K) and axial (Fig 5L) maximum intensity projection,and volume rendering images at different slices (Fig 5M,Fig 5N) demonstrated two irregular marked enhanced masses with spiculated margins.The kinetic curves (not shown) demonstrated rapid initial enhancement with washout pattern for the both lesions.

圖6 (雙側乳腺)同時性乳腺癌。該患者X線檢查可疑左乳癌，術前行MRI檢查以進一步明確左乳診斷和病變范圍，MRI診斷雙則乳腺癌。手術病理診斷：(左乳腺)導管原位癌，組織學Ⅱ級，伴灶性早期浸潤，乳頭(+)見灶性導管內癌；(右乳腺)非特殊型浸潤性導管癌，組織學Ⅱ級。圖6A：右、左乳X線頭尾位，圖6B：右、左乳X線內外側斜位，圖6C：左乳鈣化區(qū)局部放大，顯示左乳外上局限多發(fā)細小鈣化。圖6D～6G分別為左乳MRI平掃和動態(tài)增強后1 min、2 min、8 min，圖6H～6K分別為右乳MRI平掃和動態(tài)增強后1 min、2 min、8 min，顯示左乳較大范圍段性分布異常強化，同時右乳上方可見不規(guī)則明顯強化腫物，邊緣毛刺Fig 6 Bilateral synchronous breast cancer.Histology revealed ductal carcinoma in situ associated with focal microinvasion of the left breast (grade II),nipple (+),and invasive ductal carcinoma not otherwise specifi ed of the right breast (grade II).Craniocaudal(Fig 6A),mediolateral oblique (Fig 6B),and magnifi cation (Fig 6C) for the region of microcalcifi cations views demonstrated multiple amorphous microcalcifications of varying density in upper outer quadrant in the left breast.MR images before (Fig 6D,Fig 6H),1 min (Fig 6E,Fig 6I),2 min (Fig 6F,Fig 6J) and 8 min (Fig 6G,Fig 6K) following injection of contrast medium demonstrated extensively segmental enhancement in the left breast corresponding to microcalcifi cations on mammograms and irregular enhanced mass with spiculated margins that could not be identifi ed on mammograms in the right breast.

4 MRI引導下乳腺病變定位和活檢

近年來隨著日趨發(fā)展成熟的乳腺MRI檢查更多的應用于臨床，MRI對乳腺觸診、X線和超聲檢查均為陰性即以往所謂的“隱匿性”乳腺病變發(fā)現(xiàn)的越來越多，明顯提高了乳腺癌的早期診斷率，同時MRI發(fā)現(xiàn)的“隱匿性”病灶往往屬臨床分期較早的病變如乳腺原位癌，適合行保乳手術，從而可減少創(chuàng)傷較大的根治性手術率，減輕患者和社會負擔并提高生活質量，因此，2007年美國癌癥協(xié)會乳腺癌篩查指南中提出將MRI作為乳腺癌高危人群篩查的影像學檢查方法[27]。但伴隨的問題是由于MRI對乳腺癌診斷具有高敏感性即高陰性預期值，對一個陰性乳腺MRI檢查結果，一般具有較大把握排除乳腺癌，但高敏感性相應帶來的假陽性結果使部分患者可能接受了過度治療，為了避免出現(xiàn)這一問題，就需要醫(yī)療機構配備有MR引導下乳腺病變活檢裝置和經驗豐富的醫(yī)生，對MRI發(fā)現(xiàn)的可疑病灶行MR引導下的定位或組織病理學檢查，該技術能夠在MRI下準確定位病變或獲取組織學標本，從而避免不必要的外科過度治療，為臨床選擇和實施個體化治療方案起到保駕護航的作用。

總之，由于MRI成像特點，近年來我國開展乳腺MRI檢查的臨床和研究工作越來越多，其在臨床上發(fā)揮的作用也已得到了認可，但乳腺MRI檢查與乳腺X線攝影相比，起步較晚，為了使乳腺MRI檢查在我國目前的國情下得到更佳合理的應用，既能最大限度地發(fā)揮其特有的優(yōu)勢，又能避免由于不正確或不恰當的使用給患者和臨床醫(yī)生帶來困惑，節(jié)省醫(yī)療資源，還需國內同行不斷的共同努力。

圖7 (雙側乳腺)同時性乳腺癌。該患者X線和超聲檢查診斷左乳癌，右乳正常，臨床準備行左側保乳手術，手術前行MRI檢查診斷雙則乳腺癌。手術病理診斷雙乳腺非特殊型浸潤性導管癌。圖7A：右、左乳X線頭尾位；圖7B：右、左乳X線內外側斜位，顯示左乳中上腫塊(箭)，邊緣毛刺，未見鈣化，右乳未見腫物及鈣化。圖7C～7F分別為左乳MRI平掃和動態(tài)增強后1 min、2 min、8 min，圖7G～7J分別為右乳MRI平掃和動態(tài)增強后1 min、2 min、8 min，顯示左乳腺內上不規(guī)則分葉狀腫塊，動態(tài)增強后腫塊呈明顯強化；右乳腺中上方沿導管走行方向呈串珠狀異常強化Fig 7 Bilateral synchronous breast cancer.Histology revealed invasive ductal carcinoma not otherwise specifi ed bilaterally.As in this patient,MRI was proving helpful in establishing the presence of synchronous,clinically and mammographically unsuspected bilateral breast cancers.Craniocaudal (Fig 7A) and mediolateral oblique (Fig 7B) views of the both breasts showed an irregular high density mass (arrow) in the left breast and negative findings in the right breast.Ultrasound (not shown) diagnosed carcinoma in the left breast and normal in the right breast.MR images before (Fig 7C,Fig 7G),1 min (Fig 7D,Fig 7H),2 min (Fig 7E,Fig 7I) and 8 min (Fig 7F,Fig 7J) following injection of contrast medium of both breasts demonstrated irregular mass with spiculated margins in upper inner quadrant of the left breast corresponding to the lesion seen on the left mammogram and string enhancement nodules ductal distribution that could not be seen on mammograms in the right breast.

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