来源：美国匹兹堡大学医学院赵澄泉

整理：慧馨

病例一

网友讨论：

mingfuyu：Intra-cystic papillary carcinoma? I think it is a special form of invasive ductal carcinoma with good prognosis. I forgot the details of this type. I remember that it mimics DCIS but myoepithelial markers support invasive ca.

冰上舞蹈：神经内分泌癌

cy3163：倾向囊内乳头状癌.建议做免疫组化标记:P63和CK5/6以进一步明确诊断

赵澄泉老师（cqzhao） ：

网友讨论继续：

yourself ：Intraductal papilloma with “atypia” or DCIS

Liu_Aijun ：这是导管内乳头状病变。需在“瘤”与“癌”之间鉴别。从HE看，细胞形态一致，核增大，圆形或卵圆形，染色质丰富而细腻，可见1－2个小核仁。乳腺癌癌细胞的特点之一就是“太一致”，易被误为神经内分泌癌。从IHC看，肌上皮细胞在异型上皮细胞巢周围分布，而不是深入乳头轴心内。综上，考虑为导管内乳头状瘤伴重度不典型增生、癌变，或癌在导管内乳头状瘤内。

alqblk：认为是导管内乳头状瘤

天山望月：请教cqzhao老师：是否需标记ER?在增生性病变，ER表达分布不均匀，而在癌则是弥漫强阳性，不知对否？请赐教。 

sjp：导管内乳头状瘤。

stevenshen：Intraductal papilloma with ADH or DCIS or intraductal papillary carcinoma. Nice pictures. Thanks.

笃行者：导管内乳头状肿瘤。按照WHO标准，如果达到以下两个标准中任何一项即可诊断导管内乳头状癌：（1）肿瘤90%以上的区域肌上皮消失，无论有无明显上皮增生。或/和（2）肿瘤90%以上的区域呈现低级别导管内癌图像，无论有无肌上皮存在。如果达不到以上标准，则可诊断不典型导管内乳头状瘤。

听雨：导管内乳头状瘤 伴重度不典型增生 管壁无浸润

abin：下一步应该确定增生的性质：UDH/ADH/DCIS？形态非常一致，范围也足够大，考虑增生的性质为DCIS。IHC检测ER、CK5、CAM5.2等有助于鉴别。那么参照第2条标准，如果DCIS范围>90%，考虑导管内乳头状癌。如果<90%为不典型乳头状瘤。另一种诊断名称“导管内乳头状瘤伴DCIS”可能也比较合适。

liz1972：Intraductal papilloma with ADH or DCIS .

chaohuj：导管内乳头状瘤伴DCIS

赵澄泉老师：

Thank for reviewing this case.

Histologically, the papillary lesion demonstrates papillary-like proliferation with uniform cells. I cannot appreciate the obvious myoepithelial cell distribution within the lesion or surrounding the entire papillary lesion. Some cystic space can be seen in the low power. My impression is that this is a papillary carcinoma with cyst and without myoepithelial linging surrounfing the lesion. So I released the case in the same day and diagnosed as intracyatic papillary caricinoma (IPC) or encapsulated papillary carcinoma (EPC). I still ordered IHC for myoepithelial markers. I was surprised to read the ihc rslides above in the second day. Myoepithelial cells are present surrounding the papaillary lesion (ruled out EPC) and focally within the papillary lesion. The final diagnosis is DCIS involving the papilloma. I revised my diagnosis and noticed the surgen immediately enven though the clinical treatment is the same. The lesson I learn is that I will do IHC for papillary lesion until the cases are classic intraductal papilloma.

The case confused me is that cytologic features of the papillae or glands are exactly same in the entire papillary lesion regardless the areas with or without myoepithelial cells.

If you still think this is a intraductal papilloma after the IHC. Suggest that you read the book chapter of paillary lesion and the interpretation of myoepithelial markers again. A lot of papillary structures loss the myoepthelial cells in this case. It should not be a benign intraductal papilloma.

There are no good standards for diagnosis papillary lesion such as atypical papilloma, DCIS arising from papillaoma, papillary carcinoma. Tavasoli who worked at AFIP for many years before 2002 ( you may read her breast book if you are interested in breast pathology) used 1/3 as cut line. Atypical papilloma: atypical proliferation less than 1/3 of the papillary lesion. DCIS: atypical proliferation >1/3 to 90%; Papillary carcinoma: atypical >90%. Now most people used the criteria: atypical papilloma--focal atypical proliferation like ADH; DCIS arising from papillaoma--focal atypical proliferaiton like DCIS; papillary carcinoma---DCIS almost (or 90%) or entirely involving the papillary lesion. Pathologically or clinically there are no differences between DCIS arising or involving papilloma and papillary carcinoma. Both are types of DCIS. Also you can call small papillary ca as DCIS, papillary pattern.

In the US excional biospy will always be performed if atypical papilloma is diagosed in the breast core biopsy. 

I do not have the experience about the usage of ER in the diagnosis of papillary lesion. I think it will not be useful.

abin 译：

谢谢大家参与讨论。

组织学上，乳头状病变呈乳头样增生，细胞一致。我不能识别病变内或整个乳头状病变周围是否存在明显的肌上皮细胞。低倍镜下可见囊性腔隙。我的印象是有囊的乳头状癌，病变周围没有肌上皮衬覆。因此同一天我发了报告，诊断为囊内乳头状癌（IPC）或者有囊包裹的乳头状癌（EPC）。但是我仍然安排做了肌上皮标记。第二天看到免疫组化结果时，我很惊讶。乳头状病变周围存在肌上皮细胞（可排除EPC），乳头状病变内部也局灶存在肌上皮！最后诊断是DCIS累犯乳头状瘤。我修改了诊断并且立即通知外科医生，尽管临床处理相同。我从中学到的教训是：乳头状病变要做免疫组化，直到确信它确实是典型的导管内乳头状瘤。

令我困惑的是，肌上皮存在的区域或无肌上皮的区域，整个乳头状病变中的乳头或腺体内的细胞学特征非常一致。

如果看过免疫组化之后，你仍然认为它是导管内乳头状瘤，建议你再次阅读乳头状病变和肌上皮标记物的有关章节。本例中大部分乳头状结构丢失肌上皮。它不应该是良性的导管内乳头状瘤。

对于不典型乳头状瘤、起源于乳头状瘤内的DCIS、乳头状癌，这些乳头状病变没有形成较好的诊断标准。Tavasoli在2002年以前在AFIP工作过多年，如果你对乳腺病理有兴趣，可能读过她的书。她使用1/3作为分界线。不典型乳头状瘤：不典型增生<1/3乳头状病变；起源于乳头状瘤内的DCIS：不典型增生介于1/3~90%之间；乳头状癌：不典型增生>90%。现在大多数接受以下标准：不典型乳头状瘤：与ADH相似的局灶不典型增生；起源于乳头状瘤内的DCIS：与DCIS相似的局灶不典型增生；乳头状癌：几乎全部（或90%）为DCIS或DCIS完全累犯乳头状病变。

至于DCIS起源于乳头状瘤，还是DCIS累犯乳头状瘤，病理学或临床上无法区分。二者都属于DCIS的不同类型。你也可以把小灶乳头状癌称为DCIS，乳头状型。

在美国，如果粗针穿刺活检诊断了不典型乳头状瘤，通常要进行切除活检。

在乳头状病变中我没有使用ER的经验。我认为这没有帮助。

病例二

网友讨论：

天山望月：我先试着分析一下，不当之处请赵老师指导，谢谢！囊内2种构像，周边似筛孔状，但管腔大小不等，腔圆或扁，腔面上皮呈柱状，上皮细胞单一，有核仁核沟。中央管腔不规则，周围似增生的肌上皮，间质胶原化。猜：UDH?不排除ADH？请标记CK5/6,34BE12

abin：好图！谢谢Dr.cqzhao！这例很费思量。导管内乳头状瘤，伴导管内增生性病变----UDH？ADH？第一眼看结构，好像有“筛孔”，而且比较“圆”。倾向于ADH。再看图4，有边窗，“筛孔”的腔缘并不光滑，又有顶泌现象，于是又转向UDH。再看细胞：形状大小染色都不一致，分布不均匀，更加倾向于UDH。

赵澄泉老师：I do not use IHC such as CK5/6 or 34BE12 because IHC stains are not useful for this kind of cases. It seems that most of the people in China use IHC for helping dx of UDH, ADH and DCIS. Are you sure that they are useful in your clinical practice?

abin：我代替天山望月回答Dr.cqzhao的提问。国内确实还在用免疫组化帮助鉴别UDH/ADH/DCIS，可能反映了国内知识更新不够及时。经过最近在网上学习，特别是Dr.cqzhao和Dr.Stevenshen的多次强调，我才更正了原先坚持的观点。 

天山望月：谢谢Dr.cqzhao和abin！谢谢Dr.cqzhao和Dr.Stevenshen的提醒！HE上的形态学改变是诊断的基础，看来，我要加强基础的练习了，不能依靠免疫组化。不知此例最后诊断如何？期待Dr.cqzhao讲解。

stevenshen：It is true that "H&E形态学改变是诊断的基础"; but if 免疫组化 really help can you to reach a "correct" diagnosis, you should still consider use it.  I enjoyed all Dr. Zhao's cases.  For these photos alone, I consider it "intraductal papilloma with ADH". Thanks.

赵澄泉老师：

This case is an easy one. It is a small peripheral papilloma. The key of the case is that the focal atypical proliferation is ADH or DCIS. the differential dx of ADH and low grade DCIS is difficult for some cases. You can check my discussion with Abin's excellent translation in the topic 57岁女性，乳腺肿物 floor 77.

Criteria for distinguishing between atypical papilloma (papilloma with ADH) and papilloma with DCIS vary. Some authorities define atypical papilloma that contain linited areas of non-high grade DCIS (<3 mm in size) or in which it occupies <30 of the papilloma and render a dx of papilloma with DCIS when the foci are larger or occupy = or >30 of the papilloma. Others render a papilloma with DCIS when the atypical proliferation in papilloma demonstrates architectural and cytologic features of DCIS regardless of its size.

Clinical signigicance of ADH or DCIS in a papilloma is not well defined.Some studies indicated that a substantially increased risk (7.5 fold) for the development of breast cancer, wherase others have found that the level of breast cancer risk associated with with atypia was similar to that of patients with ADH elsewhere in the breast (4-5 fold). Now most people think papilloma with ADH or DCIS are best managed by complete excision with careful follow-up.

Now about this case: As 天山望月 described , It is easy to notice the focal atypical proliferation with uniform, monotonous, rounded cell population. Extracelluar lumens within the cell proliferation are noted . They are relatively  round and rigid with a punched-out apperance. The size of the focus is very small which occupies <30% of the papilloma. I think it is a good example of atypical papilloma or papilloma with ADH.

For interesting,  I showed the cases to four of my colleques. Three called atypical papilloma and one called papilloma with DCIS. He though the focal atypia was good for DCIS regardless of the size. So do not fell bad if you have some difficulty for diagnosis of these cases.

Final dx: Atpical papilloma.

Thank every one for discussing this case.

abin译：

这一例比较简单，为周围型乳头状瘤。本例的关键是局性性不典型增生为ADH或DCIS。某些病例中ADH与低级别DCIS的鉴别比较困难。

不典型乳头状瘤（乳头状瘤伴ADH）与乳头状瘤伴DCIS之间的区分标准不一致。一些作者定把不典型乳头状瘤定义为“有限范围的非高级别DCIS（大小<3mm，或其面积<30%）”，超过此范围即为乳头状瘤伴DCIS。当乳头状瘤中不典型增生呈DCIS的结构和细胞学牲时，另一些作者称为乳头状瘤伴DCIS，不管其大小。

乳头状瘤中ADH或DCIS的临床意义还不明确。一些研究提示以后进展为乳腺癌的风险增加（7.5倍），而另一些研究发现其与乳腺其它部位ADH的风险相似（4-5倍）。目前大多数认为乳头状瘤伴ADH或DCIS最好完整切除并密切随访。

再说本例。正如天山望月描述的，容易注意到局灶性不典型增生，一致、单调的圆细胞群。腔隙圆而僵硬，似凿出的外观。面积整个乳头状瘤的<30%。我认为这是一个不典型乳头状瘤或乳头状瘤伴ADH的好例子。

有趣的是，我的四位同事中，三位认为是不典型乳头状瘤，另一位认为是乳头状瘤伴DCIS，他认为局灶性不典型性足够DCIS而不管其范围。因此如果对这些病例诊断感到困难，也不必沮丧。

最终诊断：不典型乳头状瘤。

谢谢所有参与讨论的人。

第三例

网友讨论：

zhongshihua：考虑乳腺分泌型癌，有三种结构二型细胞:（1）小囊腔组成的微囊结构，有的合并成大的空腔而与甲状腺滤泡相似；（2）致密的实性结构；（3）小管结构,由许多含分泌物的小管腔组成.

Elizabeth：Interesting case! thanks for sharing.

(1) the tumor is structurally composed of 3 patterns : microcystic pattern closely simulating thyroid follicles, solid pattern and tubular pattern. The cystic spaces and tubles are filled with eosinophilic serection.

(2)the tumor has two populations of cells with bland looking.

serectory carcinoma

赵澄泉老师（cqzhao）：Shandong lao xiang, check the text book and you will know the resutl, i am sure.

Congratulation.

This is an easy case for diagnosis. I showed here just becasue this ca is arare type. This case was one I had recut from AFIP when I worked there.

Wish my shandong  老乡 can give us a short summary of epideminology, clinical features, histopathology abd prognosis about the secretory carcinoma. Thanks,

Could I know which hospital you work now if you do not mind?

cz

IHC stains are not necessary for most of the cases. Most of the cases are positive for S-100, negative for ER

   谢谢！