病历摘要：

“发现左乳肿物1年余，右乳肿物1周”入院。

2010年12月6日双乳钼靶片示：双乳呈混合型Ⅳb（纤维囊性增生为主），左乳外上区多发肿块不除外恶变可能，建议手术，右乳外上区良性增生结节，BI-RADS：III，左乳BI-RADS：V；

查乳腺彩超示：符合双侧乳腺增生声像，左乳头外上象限低回声团块，考虑为实性占位，不除外恶变可能，建议病理检查，右乳低回声肿块，考虑纤维腺瘤可能。

专科检查：双乳外形欠对称，左乳12－2点位距乳头2cm可触及一肿物，大小约4.0×5.0cm，质硬，边界欠清，表面欠光滑，活动度欠佳，与皮肤、胸壁无粘连。右乳11点位距乳头2cm可触及一肿物，大小约1.5×1.5cm，质韧，边界尚清，表面尚光滑，活动度一般，与皮肤、胸壁无粘连。

临床诊断：

1.乳房肿物（左乳癌？）2.乳房肿物（右乳增生结节？）3.乳腺增生（双侧）

大体病理检查：

送检（左侧）乳腺肿物切除标本：6.0cm×4.0cm×1.0cm，切面见大小为1.5cm×1.3cm灰红结节。

其中一张切片，免疫组化顺序为：ER，CK5/6，CD10

Papillomas can display focal proliferations of a mildly
atypical, monotonous cell population identical to lowgrade
DIN (DIN 1/ADH/DCIS, grade 1; Figures 5, A
through F, and 6, A through C). When DIN 1 occupies
less than a third of the papillary lesion, the term atypical
papilloma has been used. If at least a third, but less than
90% of the lesion displays such changes, the designation
of carcinoma arising in a papilloma has been used.

When completely excised, these 2 groups do not seem to differ in clinical behavior, as observed in a retrospective study that used this quantitative approach. It is noteworthy that
although 90% was used as the cut-off point, none of the
lesions had atypical areas that occupied more than 65%
to 70% of the papillary lesion. Currently, to avoid the term
carcinoma, we designate all such lesions as papillomas with
DIN 1/atypical papilloma (Table 1).

-Ueng, S.H., T. Mezzetti, and F.A. Tavassoli, Papillary neoplasms of the breast: a review. Arch Pathol Lab Med, 2009. 133(6): p. 893-907.

Lewis JT, Hartmann LC, Vierkant RA, Maloney SD, Shane Pankratz V, Allers TM,Frost MH, Visscher DW. An analysis of breast cancer risk in women with single, multiple, and atypical papilloma.

Am J Surg Pathol. 2006 Jun;30(6):665-72.

Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA. lewis.jason@mayo.edu

Breast papillomas may be single or multiple and associated with atypical ductal or lobular hyperplasias (ADH/ALH). The risk of breast carcinoma development in patients with papillomas, particularly those with multiple or atypical lesions,is incompletely defined. Fibrocystic lesions were histopathologically classified in a benign breast disease cohort of 9155 who underwent biopsy from 1967 to 1991,with papilloma assessment in 9108.

Individuals with papillomas (N=480) were classified into 4 groups:

1）single papilloma (SP, N=372),

2）single papilloma with ADH or ALH (SP+A, N=54),

3）multiple (>5) papillomas (MP, N=41),

4）multiple papillomas with ADH or ALH (MP+A, N=13).

Those without papillomas were classified as nonproliferative (NP, N=6053), proliferative without atypia (PDWA, N=2308), and ADH/ALH [atypical hyperplasia (AH), N=267]. The relative risk of cancer development within our cohort was compared to that expected in the general population using standardized incidence ratios.

The relative risk of breast cancer development associated with SP [2.04, 95% confidence interval (CI)1.43-2.81] was greater than NP (1.28, 95% CI 1.16-1.42) but similar to PDWA (1.90, 95% CI 1.66-2.16).

The risk associated with SP+A (5.11, 95% CI 2.64-8.92) was highly elevated but not substantively different than atypical hyperplasia (4.17, 95% CI 3.10-5.50).

Patients with MP are at increased risk compared with PDWA or SP (3.01, 95% CI 1.10-6.55), particularly those with MP+A (7.01, 95% CI 1.91-17.97). There was a marginal increase in breast cancer risk (16%) among patients with proliferative disease if a papilloma was present, but this did not reach statistical significance (P=0.29).

The observed frequency of ipsilateral(vs. contralateral) breast cancer development in papilloma subsets was not significantly different than other patient groups.

We conclude that：

1）SP imparts a cancer risk similar to conventional proliferative fibrocystic change. The presence of papilloma in, or associated with, atypia does not modify the risk connotation of ADH/ALH overall.

2）MP constitutes a proliferative breast disease subset having unique clinical and biologic behavior.

   这篇文献研究了乳腺乳头状瘤伴或不伴不典型导管或小叶增生、多发性乳头状瘤伴或不伴不典型导管或小叶增生与非乳头状乳腺增生或不典型增生发生乳腺癌的危险性。红笔字处讲的：多发性乳头状瘤的危险性为3.01; 多发性乳头状瘤伴ADH/ALH的危险性为7.01。明显高于其他组。这说明了鉴别诊断的临床意义。

 同意Dr.abin的意见。然而，那个所谓“低级别DCIS”小灶，对于治疗的意义值得探讨。个人认为，非典型性乳头状瘤（或乳头状瘤伴ADH）其中仅小灶所谓“低级别DCIS”，与非典型性乳头状瘤（或乳头状瘤伴ADH）在临床治疗上没有太多的不同，对于预后随访可能有指导意义。再说，非典型性乳头状瘤（或乳头状瘤伴ADH）的非典型性增生与所谓“低级别DCIS”本身就是很难区别的，特别是要诊断小灶的所谓“低级别DCIS”。

1 不典型乳头状瘤 足够诊断

2 ADH 足够诊断

3 DCIS 有争议 （根据楼主补充的HE图和免疫组化，窃以为够得上低级别DCIS）

 好病例，学习了，感谢！

就算是DCIS，也应该是低级别的，请问它与ADH的区别在临床治疗上有什么意义吗？国内跟国外的是否一致？

引用一些诊断标准：

区分不典型乳头状瘤和乳头状瘤伴DCIS的标准

区分不典型乳头状瘤和乳头状瘤伴DCIS的标准不统一。
一些专家将含有局限区域非高级别DCIS的乳头状瘤（例如，DCIS范围＜3mm或DCIS占病变的比例＜30%）定义为“乳头状瘤伴非典型性“或”非典型乳头状瘤”，而当DCIS较大或占病变更多比例时则诊断为乳头状瘤伴DCIS。
另有人提出当乳头状瘤的非典型增生区域具有DCIS的结构和细胞学特征时，不论其范围如何，均诊断为乳头状瘤伴DCIS。
-Stuart J,et al(黄文斌等译).乳腺病理活检解读，P207.

ADH和DCIS的量化鉴别

<非典型性导管增生章节的论述>：

1、将一个或一个以上完全累及的导管 横切面合计≤2mm规定为ADH上限；
2、另一些学者则要求两个区域具有典型的细胞形态和结构：①增生细胞单一性，②核/浆比增大；③细胞核等距或极规则分布；④圆形核；⑤可出现或不出现染色质浓染；⑥拱形、筛状、实性和/或微乳头型。

<低级别导管内癌章节的论述>：

低级别DCIS由小的单一性细胞组成，生长方式呈拱形、微乳头、筛状或实性，核大小一致，染色质均匀，核仁不明显，核分裂象罕见。

1、某些诊断标准要求单个导管横切面全部被特征性细胞和结构替代，

2、而有些则要求2个管腔或者1个以上导管横切面直径达到2mm。
-Tavassoli FA,et al.乳腺及女性生殖器官肿瘤病理学和遗传学.

复习以上标准：DCIS及乳头状瘤合并DCIS与ADH的诊断分歧主要是病变的“质”和“量”是否达到DCIS诊断标准的问题。

本例“质”是否达标？“量”是否达标？

大家在日常工作中是如何把握以上标准的？

请大家继续发表意见，谢谢!