前哨淋巴结活检(sentinel lymph node biopsy, SLNB)已常规应用于浸润乳腺癌患者中,但是对粗针穿刺活检(core needle biopsy, CNB)诊断为乳腺导管原位癌(ductal carcinoma in situ, DCIS)的患者行SLNB,国际治疗指南未明确共识并且存在争议[1-2]。原则上DCIS患者不需要行SLNB,但由于CNB诊断为DCIS有较高的低估风险[3-4],在临床实践中为了避免这种风险都会进行SLNB[5],由此导致相当多的DCIS患者原本不需要却进行了SLNB。如何将那些不需要SLNB的患者筛选出来,是本研究的主要目的。为了解SLNB对于CNB诊断DCIS的临床意义,现将复旦大学附属妇产科医院乳腺外科从2012年1月至2018年12月收治并手术的DCIS患者行回顾性分析。
资料和方法患者资料 2012年1月至2018年12月我院乳腺外科收治并行SLNB的DCIS患者,纳入标准:(1)CNB提示DCIS并未见浸润性灶;(2)成功完成SLNB。排除标准:未在我院行SLNB。
器材 使用美国ATL公司的Ultramark 3000型带ESP功能B超仪,探头频率为5~12 mHz。穿刺活检采用14/16 g巴德手动式穿刺活检枪,或者麦默通8 g真空负压活检系统。
穿刺方法 患者取平卧位,患侧背部用枕头适当垫高。常规消毒铺巾,0.5%利多卡因局部麻醉。穿刺活检后的标本经4%甲醛固定后送病理检查。加压包扎穿刺部分及残腔区域。
巴德穿刺活检在超声引导下使用14/16 g穿刺活检枪刺入皮下组织,当针尖到达肿块边缘时,激发活检针,使针芯推入肿块内部切割组织,拔出探针,取出组织条,每个病灶取3~4条。
麦默通穿刺活检在超声引导下使用8 g旋切刀通过3 mm切口置入肿块后方,刀槽对准病灶,真空辅助系统抽吸旋切,直至肿块完全切除。
纳入标准参考中国抗癌协会乳腺癌诊治指南与规范(2017版) [5]:(1)乳腺超声发现未扪及的可疑乳腺占位性病变,BI-RADS≥4类或部分3类病灶。(2)可扪及乳腺肿块,且超声提示相应部位有乳腺内占位性病变,需要行微创活检或切除以明确诊断。
手术方法 (1)保留乳房肿瘤扩大切除术(保乳术):DCIS的切缘距离大于2 mm,若切缘2次阳性,行乳房切除术;(2)乳房切除术;(3)SLNB:使用亚甲蓝染料法行SLNB。在乳晕旁2处不同部位皮下注射1%亚甲蓝2 mL,注射后局部按摩10 min,后于胸大肌外缘处做弧形切口,逐层切开,寻找到蓝染淋巴管后沿其追踪,将所有蓝染淋巴管进入的第一个蓝染淋巴结以及周边触诊发现的肿大淋巴结作为SLN送检。取出的SLN行快速冰冻活检,随后与肿瘤标本同行石蜡切片、HE染色检查。
统计学方法 采用SPSS 19.0统计学软件处理,采用精确概率法或非参数检验法。所有检验取双侧检验,P < 0.05为差异有统计学意义。
结果患者临床病理特征 共169例病例符合纳入标准,平均年龄为(47.2±9.3)岁,中位SLN数目为3枚(1~9枚);肿瘤大小≤2 cm 116例(68.6%),> 2 cm 53例(31.4%);伴有广泛细小钙化(钙化范围大于2 cm或者呈多灶性表现)的38例(22.5%),不伴有的131例(77.5%);保乳29例(17.2%),乳房全切140例(82.8%)。使用14/16 g穿刺活检针者93例(55%),8 g真空负压活检系统76例(45%)。前哨淋巴结活检阳性7例;病理类型:纯导管原位癌为117例(69.2%),原位癌伴微浸润28例(16.6%),浸润性导管癌24例(14.2%)(表 1)。
[n=169, n(%)] | |||||||||||||||||||||||||||||
Characteristic | Number of patients | ||||||||||||||||||||||||||||
Age | |||||||||||||||||||||||||||||
≤50 y | 103 (60.9) | ||||||||||||||||||||||||||||
> 50 y | 66 (39.1) | ||||||||||||||||||||||||||||
Tumor size | |||||||||||||||||||||||||||||
≤2 cm | 116(68.6) | ||||||||||||||||||||||||||||
> 2 cm | 53(31.4) | ||||||||||||||||||||||||||||
MIC | |||||||||||||||||||||||||||||
Yes | 38(22.5) | ||||||||||||||||||||||||||||
No | 131(77.5) | ||||||||||||||||||||||||||||
CNB method | |||||||||||||||||||||||||||||
14/16-gauge | 93(55) | ||||||||||||||||||||||||||||
8-gauge VAB | 76(45) | ||||||||||||||||||||||||||||
Type of surgery | |||||||||||||||||||||||||||||
Breast conserving | 29(17.2) | ||||||||||||||||||||||||||||
Mastectomy | 140(82.8) | ||||||||||||||||||||||||||||
SLN status | |||||||||||||||||||||||||||||
Positive | 7(4.1) | ||||||||||||||||||||||||||||
Negative | 162(95.9) | ||||||||||||||||||||||||||||
Final pathological result | |||||||||||||||||||||||||||||
Pure DCIS | 117 (69.2) | ||||||||||||||||||||||||||||
DCIS with microinvasion | 28 (16.6) | ||||||||||||||||||||||||||||
Invasive breast cancer | 24 (14.2) | ||||||||||||||||||||||||||||
MIC: Microcalcification; CNB: Core needle biopsy; VAB: Vacuum-assisted biopsy; SLN: Sentinel lymph node; DCIS: Ductal carcinoma in situ. |
患者分层分析 根据病理结果将患者分成纯导管内癌组(117例,69.2%)和微浸润/浸润性癌组(52例,30.8%),比较两组间的肿瘤大小、影像学表现、术前活检和手术方式。与纯导管内癌组相比,微浸润/浸润性癌组肿瘤 > 2 cm、伴有广泛钙化、14/16 g粗针穿刺、乳房切除术的比例均高于纯导管内癌组,P均 < 0.05,差异具有统计学意义(表 2)。
[n(%)] | |||||||||||||||||||||||||||||
Variables | Pure DCIS (n=117) | Microinvasion /Invasive breast cancer (n=52) | χ2 | P | |||||||||||||||||||||||||
Tumor size | |||||||||||||||||||||||||||||
≤2 cm | 98 (84.5) | 18 (15.5) | 40.39 | < 0.001 | |||||||||||||||||||||||||
> 2 cm | 19 (35.8) | 34 (64.2) | |||||||||||||||||||||||||||
MIC | |||||||||||||||||||||||||||||
Yes | 11 (28.9) | 27 (71.1) | 37.34 | < 0.001 | |||||||||||||||||||||||||
No | 106 (80.9) | 25 (19.1) | |||||||||||||||||||||||||||
CNB method | |||||||||||||||||||||||||||||
14/16-gauge | 47 (50.5) | 46 (49.5) | 33.92 | < 0.001 | |||||||||||||||||||||||||
8-gauge VAB | 70 (92.1) | 6 (7.9) | |||||||||||||||||||||||||||
Type of surgery | |||||||||||||||||||||||||||||
Breast conserving | 25 (86.2) | 4 (13.8) | 4.73 | ||||||||||||||||||||||||||
Mastectomy | 92 (65.7) | 48 (34.3) | 0.03 | ||||||||||||||||||||||||||
MIC:Microcalcification; CNB: core needle biopsy; VAB: Vacuum-assisted biopsy; DCIS: Ductal carcinoma in situ |
7例(4.1%)患者SLNB为阳性;均为14/16 g穿刺活检针诊断患者,8 g真空负压活检系统患者SLNB结果均为阴性。这7例SLNB阳性的患者中1例孤立细胞转移,1例微转移,5例宏转移。7例SLNB阳性的患者均行乳房全切手术,29例保乳手术患者SLNB结果均为阴性(表 3)。
Case | CNB method | Type of surgery | Final histological diagnosis | LVI | SLN | Axillary clearance |
1 | 14/16-gauge | Mastectomy | Microinvasive carcinoma < 0.1 cm | Y | Macrometastasis in 3/3 LNs | 23/24 LNs positive Total: 26/27 LNs positive |
2 | 14/16-gauge | Mastectomy | IDC, 3 cm grade 2 | N | Macrometastasis in 1/5 LNs | 0/11 LNs positive Total: 1/16 LNs positive |
3 | 14/16-gauge | Mastectomy | IDC, 1.4 cm grade 1 | Y | Micrometastasis in 2/4 LNs | 0/10 LNs positive Total: 2/14 LNs positive |
4 | 14/16-gauge | Mastectomy | IDC, 2.2 cm grade 3 | Y | Macrometastasis in 1/6 LNs | 0/8 LNs positive Total: 1/14 LNs positive |
5 | 14/16-gauge | Mastectomy | IDC, 2.7 cm grade 3 | Y | Macrometastasis in 2/4 LNs | 0/13 LNs positive Total: 2/17 LNs positive |
6 | 14/16-gauge | Mastectomy | IDC, 2.4 cm grade 2 | N | Macrometastasis in 1/3 LNs | 0/12 LNs positive Total: 1/15 LNs positive |
7 | 14/16-gauge | Mastectomy | IDC, 2.2 cm grade 2 | N | ITC | N/A |
SLN: Sentinel lymph node; LVI: Lymphovascular invasion; IDC: Invasive ductal carcinoma; ITC: Isolated tumour cells; LN: Lymph node. Y: Yes, N: No. |
患者预后结果 从术后开始截至2019年6月,169例患者中有143例(84.6%)患者获得随访,时间4~86个月,中位随访时间49个月。浸润性癌组1例患者在术后8个月出现肝转移,术后18个月死亡,其余患者均无进展。纯导管内癌组2例出现对侧乳腺癌,1例为DCIS,术后17个月复发,另1例为浸润性癌,术后28个月复发;其余患者疾病均无进展。
讨论CNB是目前确诊乳腺癌的常用方式,其中包括14/16 g自动穿刺活检枪和8 g真空负压辅助穿刺活检系统。CNB可能出现病理结果低估,虽然总体比例并不高,但诊断DCIS的低估比率却不低,低估率在30%左右[3-4],因此临床上为了规避这种风险都会尽可能行SLNB[5]。然而这样临床治疗方式导致相当多的导管原位癌患者原本不需要却进行了SLNB。SLNB并非无并发症,相对腋窝淋巴结清扫来说,其不良反应很少[6-9],但是它仍然会引起少数患者淋巴水肿、上肢疼痛、麻木和染料过敏反应[10-11]。如何避免这种过度活检也成为乳腺外科医师临床工作中的一大挑战。
很多研究都证实DCIS的患者前哨淋巴结的转移率都非常低,并且质疑对于这部分患者SLNB的必要性[12-14]。但是还有研究认为CNB诊断的DCIS低估率较高,所以对于CNB诊断为DCIS的患者应该行SLNB[15-17]。此外,还有人认为SLNB适用于有高危险因素的DCIS患者[18-20]。Susan等[21]的研究中,共纳入181例CNB穿刺诊断DCIS的患者,并且完成了SLNB。7例(4%)患者SLNB阳性,6例(3.5%)是孤立细胞转移,1例(0.5%)为宏转移,总体转移比例低于5%。近期日本一个回顾性研究也显示:术前诊断为DCIS的患者行SLNB,其前哨淋巴结宏转移比例仅为0.9%[22]。在我们的研究中,7例前哨淋巴转移的患者中,孤立细胞转移1例,微转移1例,宏转移5例,总体转移比例也低于5%。另外,本研究还显示8g真空负压辅助穿刺活检系统病理低估率只有7.9%,明显低于14/16 g自动穿刺活检枪检测,主要原因是8 g真空负压活检系统获取的组织量明显多于14/16 g自动穿刺活检枪;而且8 g真空负压活检系统患者SLNB结果均为阴性。目前国内8 g真空负压辅助活检系统更多用于乳房良性肿块微创切除术(病灶切除),而不是单纯的组织学活检;结合我们之前研究结果,相较于14/16 g自动穿刺活检枪检测,采用8 g真空负压辅助系统活检的主要是那些肿块相对更小、术前影像学诊断考虑良性病变(BI-RADS分类3-4A)可能性更大的低风险患者[23]。因此对于采用8 g真空负压活检系统诊断为DCIS患者,是可以避免行SLNB的。
目前,中国大陆地区的保乳率普遍在10%~15%,明显低于欧美国家。NCCN专家共识认为[24],DCIS保乳切缘小于1 mm是不够的,DCIS安全切缘距离为2 mm;可以看出DCIS的切缘所需安全距离比浸润性癌更严格。实际临床实践过程中,由于DCIS患者保乳切缘要求更严格,同时全乳切除术对DCIS患者是一种治愈性处理方法,导致临床医师和患者的保乳意愿不高,因此本研究中患者的保乳比例不高。但在我们的研究中,29例保乳患者病理低估率明显低于乳房切除患者(P=0.018),并且保乳患者前哨淋巴均未见癌转移。分析其原因为:我们之前的研究[23]显示肿瘤大于2 cm、影像学检查见广泛细小钙化是CNB诊断DCIS低估的独立危险因素,国外的研究也得出了相似的结果[25]。在本研究中,由于DCIS患者保乳切缘要求更严格,我们会选择肿块≤2 cm、影像学检查均未见广泛细小钙化的患者进行保乳手术。因此我们选择保乳手术时就提前对患者进行了筛查,避免了肿块 > 2 cm、影像学检查见广泛细小钙化的具有病理低估高危因素的患者进行保乳手术,而这部分保乳患者是可以豁免SLNB。Susan等[21]研究认为:对于CNB穿刺诊断为DCIS低复发风险的保乳患者,可以考虑不行SLNB。基于上述结果,对于危险因素较少的保乳患者,SLNB可能是不必要的。
综上所述,CNB诊断DCIS的患者SLNB阳性率非常低,其中大部分患者SLNB是不必要的,特别是8 g真空负压活检系统和保乳患者。另外本研究存在一定的局限性:(1)研究结果出自我院单中心数据,并不能代表国内的整体情况,还需进一步扩大样本量。(2)本研究是回顾性分析,需要后期前瞻性队列研究进一步验证对于8 g真空负压活检系统和保乳患者不行SLNB对预后的影响。
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