There is a wide spectrum of lesions that are papillary in the
breast. This ranges from the solitary intraductal papilloma to multiple peripheral papillomas to
intracystic papillary carcinoma, invasive papillary carcinoma and, finally, invasive micropapillary
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
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
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
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 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
- Page DL, Dupont WD. Premalignant conditions and markers of elevated risk in the breast and their
management. Surg Clin North Am 1990; 70:831-851.
- Azzopardi JG, Salm R. Ductal adenoma of the breast: A lesion which can mimic carcinoma. J Pathol
- Lammie GA, Millis RR. Ductal adenoma of the breast. A review of fifteen cases. Hum Pathol 1989;
- Gusterson BA, Sloane JP, Middwood C, et al. Ductal adenoma of the breast - a lesion exhibiting a
myoepithelial/epithelial phenotype. Histopathol 1987; 11:103-110.
- Handley RS, Thackray AC. Adenoma of the nipple. Br J Cancer 1962; 16:187-194.
- Perzin KH, Lattes R. Papillary adenoma of the nipple (florid papillomatosis, adenoma, adenomatosis).
A clinico-pathologic study. Cancer 1972; 29:996-1009.
- Jones DB. Florid papillomatosis of the nipple ducts. Cancer 1955; 8:315-319.
- Doctor VM, Sirsat MV. Florid papillomatosis (adenoma) and other benign tumours of the nipple and
areola. Br J Cancer 1971; 25:1-9.
- Bhagavan BS, Patchefsy A, Koss LG. Florid subareolar duct papillomatosis (nipple adenoma) and
mammary carcinoma: Report of three cases. Hum Pathol 1973; 4:289-295.
- Rosen PP, Caicco AA. Florid papillomatosis of the nipple. A study of 51 patients, including nine
with mammary carcinoma. Am J Surg Pathol 1986; 10:87-101.
- Papotti M, Gugliotta P, Ghiringhello B, Bussolati G. Association of breast carcinoma and multiple
intraduct papillomas: A histological and immunohistochemical investigation. Histopathology 1984;
- Tavassoli FA. Papillary lesions. In: Tavassoli FA, ed. Pathology of the Breast. Norwalk:
Appleton and Lange, 1992:193-228.
- Carter D. Intraduct papillary tumours of the breast. A study of 78 cases. Cancer 1977;
- Ohuchi N, Abe R, Kasai M. Possible cancerous change of intraduct papillomas of the breast. Cancer
- Carter D, Orr SL, Merino MJ. Intracystic papillary carcinoma of the breast. After mastectomy,
radiotherapy or excisional biopsy alone. Cancer 1983; 52:14-19.
- Azzopardi JG. Papilloma and papillary carcinoma. In: Azzopardi JG, ed. Problems in Breast
Pathology. London: WB Saunders Company, 1979:150-165.
- Kraus FT, Neubecker RD. The differential diagnosis of papillary tumours of the breast. Cancer 1962;