failed to poste the photos and try again.

Your diagnosis

Differential diagnoses

What immunostains will be useful?

回赵老师：请原谅我不求甚解，我是学习了陈国璋教授的讲课资料后，在实际工作中验证并接受了这个观点。不仅是乳头状病变，ER对UDH和低级别DCIS的鉴别也有帮助。我只有陈国璋教授的资料，其他的数据和文献就无法提供啦。

sorry again

Usual ductal hyperplasia: Key features
“Mixed and disorderly”
Interspersed spaces vary in size and shape; spaces tend to be peripherally located
Cells often have indistinct cell borders, and are unevenly spaced
Nuclei are often oval, with grooves and pseudoinclusions
Nuclei show streaming
May have some admixed apocrine cells
Cytokeratin profile: mixed (CK5+, CAM5.2+)
ER: heterogeneous
Low-grade DCIS: Key features
“Uniform”
Interspersed spaces, if present, are round and rigid
Cells often have distinct cell borders, and are evenly spaced
Nuclei are often round, with hyperchromasia
Pagetoid spread (lifting up residual luminal cells), if present, favors diagnosis of DCIS
Cytokeratin profile: one type of cells -- glandular cells (CK5-, CAM5.2+)
ER: usually uniform strong

 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.

Thanks,

cqz

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。
谢谢，
cqz

 使用ER帮助诊断乳头状病变，来自陈国璋教授的讲课资料。

Papilloma or Papillary DCIS / intracystic papillary carcinoma?
--One of the most difficult diagnostic problems
--Solving problem by immunohistochemistry:
    Abundant myoepithelial cells in the cores of papillae in papilloma, but not in the papillae of papillary carcinoma [Note: Myoepithelium is absent around the cyst in intracystic papillary carcinoma]
    CK5 (preserved in papilloma)
    ER (uniform strong staining favors carcinoma)

 To Dr. Abin:

Agree that myoepithelial markers are useful for the differential dx of papillary lesions.

I am not sure the ER, as I mentioned that I have no experience about ER in papillary lesion. My impression is that epithelial cells in most papilloma cases are also positive for ER. Could you let me know the original study (not text book) papers or study results. Hope to learn the differences in details about the positive rate of ER ,and extention and intensity of the stains among papilloma, atypical papilloma, and papillary DCIS in these studies.

Thanks

cqz

 WHO: Introductal papillary neoplasms: it mentioned the following 5 types

Central papilloma

Peripheral papilloma

Atypical papilloma

Intraductal papillary carcinoma

Intracystic papillary carcinoma

I copied the original sentence from WHO book about the definition of intraductal papillary carcinoma:

Intraductal papillary carcinoma's diagnosis requires that 90% ir more of the papillary processes are totally devoid of a myoepithelial cell layer regardless of presence or absence of notavle epithelial proliferation, and/or that any of the recognized patterns of low grade DCIS occupies 90% or more of the lesion.

So the lesions between atypical papilloma and intraductal papillary carcinoma will be called as DCIS involving or arising from papilloma, even though it is not mentioned in WHO book. But it has be used for a long time in the literature and in the clinical diagnosis.

So DCIS involving papilloma and intraductal papillary ca are the same disease process with the different degree. The botoom line  is that they are kinds of of DCIS with the same clinical managment.

Hope it can help,

 To Abin and Lili:

ER for differential dx of papillary lesion.

I asked one of our previous GYN/Breast fellow who did a lot of research in papillary lesions and works as a breast pathologist in another institute now. I copied her response below.