Solitary Intraductal Papilloma
These lesions have also been classified as central papillomas. Clinically, patients with solitary intraductal papillomas most commonly present with unilateral nipple discharge which is usually clear but may be blood-stained. These lesions vary in size from 2 to 3 mm up to 1 to 2 cm in maximum dimension. When the pathologist is presented with a case of an excision for nipple discharge, it is best to examine the duct by opening it longitudinally with the help of a dissecting microscope. Microscopically, these solitary papillomas are composed of a cuboidal or columnar epithelium covering a fibrovascular core. Beneath the epithelial lining, myoepithelial cells are present. Apocrine metaplasia is commonly seen in these papillomas and rarely seen in situ papillary carcinoma. Squamous metaplasia is frequently seen, especially in areas of infarction. The degree of fibrosis associated with papillomas varies tremendously. Some papillomas show extensive fibrosis with entrapped epithelial elements that may mimic carcinoma. In cases such as this, the use of myoepithelial markers may prove very helpful. Patients with single central papillomas do not have a significantly increased risk for developing breast cancer.¹ 

Ductal Adenoma
Ductal adenomas are a variant of intraductal papillomas and thought to develop through extensive sclerosis of intraductal papillomas.²  They usually have very thick walls and the proliferation, in contrast to an intraductal papilloma, appears to be adherent to the wall. Ductal adenomas, sclerosing papillomas and intraductal papillomas all may have entrapped epithelium in their wall and, one should take caution not to interpret this as evidence of invasion. All of these lesions are characterized by a mixture of epithelial and myoepithelial cells and, when in doubt, myoepithelial cell markers may be helpful in the differential diagnosis.^3,4 

Nipple Adenoma
The term "nipple adenoma" is not specific by refers to any proliferative lesion involving the nipple. These lesions may be papillary or have the appearance of florid sclerosing adenosis. They tend to be superficial and they may cause a mass in the nipple or erode and ulcerate mimicking Paget's Disease.^5-10  Microscopically, these lesions may be papillary or resemble adenosis. These lesions are benign but their cellularity and tendency to cause skin ulceration may be alarming features to the pathologist.

Multiple or Peripheral Papillomas
In contrast to central papillomas, multiple peripheral papillomas are much more likely to be associated with atypical ductal hyperplasia or ductal carcinoma in situ. In some series, 40% to 60% of these lesions, when serially sectioned, are associated with either atypical ductal hyperplasia or ductal carcinoma in situ.^11-14 

Intracystic Carcinoma
Intracystic carcinoma of the breast is essentially ductal carcinoma in situ in a very enlarged ductal space. The amount of the lesion that is occupied by ductal carcinoma in situ, in order to be considered intracystic carcinoma, varies by author. Some authors use the term "atypical papilloma" for lesions showing low-grade ductal carcinoma in situ involving less than 1/3 of the lesion.¹²  It is my philosophy to diagnose something as carcinoma within a papilloma if it would be diagnosed as carcinoma if it were outside of the papilloma. However, the prognosis for intracystic papillary carcinoma or intracystic carcinoma is excellent. The major factor to be concerned about is, is it the sole lesion, i.e., is there ductal carcinoma in situ adjacent to it? If the only lesion is the intracystic lesion, excision alone is curative.¹⁵  Otherwise, they should be treated as ductal carcinoma in situ. Microscopically, these lesions generally have a fairly thick wall, you may have entrapped epithelium within this wall, but that does not indicate invasion. The ductal carcinoma in situ may be papillary in nature or have a cribriform or solid pattern.

Papillary Ductal Carcinoma In Situ
Papillary ductal carcinoma in situ is a lesion that, on one hand, is difficult to distinguish from intraductal papillomas and, on the other hand, from invasive papillary carcinoma. It is characterized by lesions with fibrovascular cores with columnar epithelium that is hyperchromatic and may resemble a colonic adenoma. A particularly difficult part in the differential diagnosis of these lesions is the fact that they have cells with clear cytoplasm underlying the epithelium. These cells mimic myoepithelial cells but, in fact, have been demonstrated to be epithelial in origin and have been termed globoid.¹⁶  An excellent differential diagnosis of papillary tumors of the breast is the classic paper by Kraus and Neubecker.¹⁷ 

References

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