Context

Patients choosing to retain the nipple when undergoing therapeutic or prophylactic mastectomy are at risk for cancers arising at that site.

Objective

To identify cases of invasive carcinoma arising within the nipple and to investigate their clinical, imaging, biologic, and staging features.

Design

Carcinomas were identified by prospective review of surgical and consult cases at 4 hospitals.

Results

The 24 patients identified presented with symptoms related to the nipple. Mammography did not detect the cancer in most cases. Ten patients (42%) had skin changes from ductal carcinoma in situ involving nipple skin (Paget disease), with small foci of invasion into the dermis, and 6 of those 10 carcinomas (60%) stained positive for human epidermal growth factor receptor 2 (HER2). The remaining 14 patients (58%) presented with a nipple mass or with skin changes. These were larger invasive carcinomas of both ductal and lobular types. Only 2 of those 14 carcinomas (14%) were HER2+. Three of 15 patients (20%) undergoing lymph node biopsy had a single metastasis. No patients have had recurrent disease.

Conclusions

Rare, invasive, primary nipple carcinomas typically present as subtle nipple thickening or an exudative crust on the skin. Imaging studies are often nonrevealing. A variety of histologic and biologic types of carcinomas occur, similar to cancers arising deeper in the breast. Although the carcinomas invaded into the dermis, some with skin ulceration, the likelihood of lymph node metastasis was no higher than carcinomas of similar sizes. Patients who choose to preserve their nipple(s) should be aware of the possibility of breast cancer arising at that site and to bring any observed changes to the attention of their health care providers.

Removal of the nipple along with the breast for the treatment or prevention of cancer has long been advocated because of observations of nipple involvement at the time of diagnosis and cancers arising after subcutaneous mastectomies and in nipples transplanted to the thigh for later reconstruction.15  More recently, the necessity of removing the nipple has been questioned and nipple-sparing mastectomy is now an accepted procedure for selected patients.5,6  Subsequent carcinoma in patients undergoing therapeutic mastectomy is most often from recurrence of the prior carcinoma. However, for patients undergoing mastectomy for risk reduction, preservation of the nipple creates the possibility that a carcinoma could arise directly from breast tissue at that site.

Very little has been published concerning breast cancers originating from the nipple. Because of the anatomic structure of the nipple, it is possible these cancers could have unusual clinical, imaging, or biologic features. In addition, a cancer in the dermis of the nipple could possibly portend a less-favorable prognosis because cancers invading into the skin and/or in a superficial location and/or close to the nipple are more likely to metastasize to lymph nodes.710  We sought to identify a contemporary series of invasive carcinomas arising in the nipple and to identify similar cases in the published literature to better inform patients at risk for this type of cancer.

Eight of the authors prospectively identified cases in their practices in 2015 and 2016 at Brigham and Women's Hospital (Boston, Massachusetts; J.E.B., B.T.H., D.A.D., S.C.L.), Brigham and Women's Faulkner Hospital (Boston, Massachusetts T.J.W., X.H.), the University of Louisville Hospital (Louisville, Kentucky; M.A.S.), and Newton-Wellesley Hospital (Newton, Massachusetts; A.J.G.). More than 8000 cases of invasive breast cancer were diagnosed at the 4 hospitals during that period. Cases included surgical specimens as well as cases seen in consultation. Carcinomas were defined as originating in the nipple if most of the invasive carcinoma was located in the nipple papilla and adjacent dermis, above the smooth muscle of the areola. Focal invasion below the smooth muscle was allowed if less than 1 cm and smaller in size than the carcinoma in the nipple. Epidermal cancers of the skin or skin appendages, such as squamous cell carcinoma or basal cell carcinoma, were not included. If there was a history of breast cancer, the nipple cancer had to be considered a new primary carcinoma based on clinical features, location, and pathologic findings. Clinical notes, breast imaging reports, pathology reports, and glass slides were reviewed. The study received institutional review board approval.

The papilla of the nipple has a median height of 0.6 cm (0 to 1.9 cm) and approximately 23 lactiferous sinuses traverse this area to open onto the overlying epidermis at duct orifices (Figure 1).11  Glass slides were reviewed to document that the invasive carcinoma was primarily present within the papilla.

Figure 1

Nipple-invasive primary carcinomas arise within the papilla of the nipple. Only small areas of invasion below the smooth muscle layer of the nipple and areola were allowed in the study (asterisks). The lymphatic plexus associated with the nipple is located in the superficial subcutaneous tissue (dotted line) (hematoxylin-eosin, original magnification ×20).

Figure 2. Extensive involvement of the nipple epidermis by tumor cells (Paget disease) is associated with focal invasion directly into the dermis. The patient presented with a scaling crust of the skin (hematoxylin-eosin, original magnification ×40).

Figure 1

Nipple-invasive primary carcinomas arise within the papilla of the nipple. Only small areas of invasion below the smooth muscle layer of the nipple and areola were allowed in the study (asterisks). The lymphatic plexus associated with the nipple is located in the superficial subcutaneous tissue (dotted line) (hematoxylin-eosin, original magnification ×20).

Figure 2. Extensive involvement of the nipple epidermis by tumor cells (Paget disease) is associated with focal invasion directly into the dermis. The patient presented with a scaling crust of the skin (hematoxylin-eosin, original magnification ×40).

Twenty-four invasive carcinomas originating in the nipple were identified. All occurred in women. The mean age was 63 years (range, 37–86 years). The carcinomas could be separated into 2 groups based on clinical presentation and the site of origin of the invasive carcinoma.

Paget Disease With Invasion From Nipple Skin into the Dermis

Ten of the 24 patients (42%) presented with skin changes from ductal carcinoma in situ (DCIS), involving the nipple epidermis (Paget disease), and associated with direct invasion into the dermis from the epidermis (Table 1). Nine of the 10 patients (90%) presented with exudative crust, erythema, pruritus, and/or bleeding due to disruption of the epidermis by the tumor cells. One of the 10 patients (10%) presented with pigmentation related to melanocytic proliferation associated with the tumor cells. The areas of invasion arose from the tumor cells in the epidermis (Figure 2). The authors previously reported a series of 7 similar patients.12  The 10 carcinomas reported in the current study represent new cases, identified after the conclusion of the prior study.

Table 1

Clinical and Pathologic Features of Patients With Paget Disease and Dermal Invasion

Clinical and Pathologic Features of Patients With Paget Disease and Dermal Invasion
Clinical and Pathologic Features of Patients With Paget Disease and Dermal Invasion

Of the 10 cases, mammography was negative in 8 cases (80%) and showed calcifications associated with the DCIS in 2 cases (20%). Ultrasound was performed in 1 of the 10 cases (10%) and showed skin thickening. Magnetic resonance imaging (MRI) was performed in 4 of the 10 cases (40%) and showed skin enhancement in 3 of those 4 cases (75%) and was negative in 1 case (25%).

Of the 10 patients, 8 (80%) had microinvasion (<0.1 cm) and 2 (20%) had invasive carcinomas measuring 0.2 cm and 0.36 cm, extending from the epidermis into the dermis. Six of the 10 cancers (60%) were positive for HER2 by immunohistochemistry (3+), and the remaining 4 cases (40%) had equivocal results. Fluorescence in situ hybridization to evaluate HER2 amplification was not performed. Four of the 10 carcinomas (40%) were negative for estrogen receptor (ER) and progesterone receptor (PR). No lymphovascular invasion was observed. Five of the 10 patients (50%) had lymph node sampling with negative results. At a mean follow-up of 15 months (range, 6–27 months), no recurrences were reported.

Invasive Carcinoma Arising Within Nipple Ducts or Lobules

Fourteen of the 24 patients (58%) had carcinomas arising within the nipple dermis, but not specifically from tumor cells in the nipple epidermis (Table 2). Four of the 14 patients (29%) had symptoms for several months up to a year before diagnosis. A subtle nipple mass, thickening, or retraction was the only indication of the cancer for 7 of the 14 patients (50%; Figure 3). One of the 14 patients (7%) had a mass with distortion of the nipple (Figure 4), and the remaining 6 patients (43%) had skin changes without a mass. Although the skin changes over the underlying invasive carcinoma were similar to Paget disease (ie, exudative crust, erythema, and/or pruritus), only 2 of those 6 patients (33%) actually had Paget disease. Those 2 patients had invasive cancers measuring 2.7 cm and 4 cm. Whether the first site of invasion originated in the epidermis could not be determined, as was seen in the previously discussed cancers. One of the 14 patients (7%) had Paget disease that was focal and clinically occult.

Table 2

Clinical and Pathologic Features of Invasive Carcinomas Originating from Ducts or Lobules in the Nipple

Clinical and Pathologic Features of Invasive Carcinomas Originating from Ducts or Lobules in the Nipple
Clinical and Pathologic Features of Invasive Carcinomas Originating from Ducts or Lobules in the Nipple
Figure 3

This carcinoma is ductal in type, as were most of the carcinomas in this study. The carcinoma was detected because of increased firmness of the nipple without skin changes. Mammography did not show the lesion as the carcinoma is completely confined to the nipple (hematoxylin-eosin, original magnification ×20).

Figure 4. This nipple is markedly distorted by an invasive ductal carcinoma involving the papilla. Although there is very focal Paget disease in the overlying epidermis, there were no skin changes noted clinically (hematoxylin-eosin, original magnification ×20).

Figure 5. This invasive lobular carcinoma was detected as a palpable nipple mass involving the papilla and the adjacent dermis. Lobular carcinoma in situ was present in the lactiferous sinuses (hematoxylin-eosin, original magnification ×20).

Figure 3

This carcinoma is ductal in type, as were most of the carcinomas in this study. The carcinoma was detected because of increased firmness of the nipple without skin changes. Mammography did not show the lesion as the carcinoma is completely confined to the nipple (hematoxylin-eosin, original magnification ×20).

Figure 4. This nipple is markedly distorted by an invasive ductal carcinoma involving the papilla. Although there is very focal Paget disease in the overlying epidermis, there were no skin changes noted clinically (hematoxylin-eosin, original magnification ×20).

Figure 5. This invasive lobular carcinoma was detected as a palpable nipple mass involving the papilla and the adjacent dermis. Lobular carcinoma in situ was present in the lactiferous sinuses (hematoxylin-eosin, original magnification ×20).

Ten of the 14 patients (71%) underwent mammographic evaluation that showed no abnormality in 7 of the 10 cases (70%), skin thickening in 1 case (10%), distortion in 1 case (10%), and calcifications in the remaining case (10%). Ultrasound was performed for 5 of the 14 patients (36%) and showed a mass in 3 cases (60%) and no changes in 2 cases (40%). An MRI was performed for 3 of the 14 patients (21%) and showed a mass in 1 of the 3 patients (33.3%), skin thickening in 1 patient (33.3%), and no changes in 1 patient (33.3%).

Three of the 14 carcinomas (21%) invaded into and ulcerated the epidermis and would be classified as American Joint Committee on Cancer (AJCC) T4b.13  Five of the 14 carcinomas (36%) invaded into the epidermis but did not cause ulceration. The remaining 6 carcinomas (43%) did not involve the epidermis. Of the 14 cancers, 8 (57%) were only present in the papilla and smooth muscle, 2 (14%) focally invaded below smooth muscle (<0.1 cm), and 4 (29%) invaded below the smooth muscle for 0.5 to 0.9 cm. In all cases, most of the invasive carcinoma was present in the papilla of the nipple.

The histologic type for these 14 cases was ductal in 7 cases (50%), lobular in 3 cases (21%), and with features of both in 4 cases (29%). Size ranged from 1.4 cm to 4 cm (mean, 2.1 cm). Very large carcinomas were excluded from the study because the site of origin within the nipple could not be determined. The larger carcinomas in the study invaded laterally in the dermis, above and into the smooth muscle of the areola (Figure 5). Well (5 of 14 cases; 35.7%), moderate (5 of 14 cases; 35.7%), and poorly (4 of 14 cases; 28.6%) differentiated carcinomas were observed. Twelve of the 14 carcinomas (86%) were positive for ER and negative for HER2 (“luminal-like”), and the remaining 2 carcinomas (14%) were positive for both ER and HER2. Of the 14 carcinomas, 7 (50%) were associated with DCIS (3 of the 7 [43%] with Paget disease) and 3 of the 14 (21%) with lobular carcinoma in situ (LCIS). The in situ carcinomas were present in lactiferous sinuses. An in situ component was not identified in 4 of the 14 cases (29%).

Dermal lymphovascular invasion was identified in 4 of the 14 cases (29%). None of those patients had a clinical presentation of inflammatory carcinoma. Ten of the 14 patients (71%) (mean size of invasive carcinomas, 2 cm) underwent lymph node sampling, and 3 of the 10 (30%) had a metastasis in a single node (2 macrometastases and 1 micrometastasis) (Table 2). All of the lymph node metastases arose from poorly differentiated carcinomas, and 2 of those 3 carcinomas (67%) were HER2 positive. One of the 14 patients (7%) had isolated tumor cells in a node. No recurrences have been reported at a mean follow-up of 2 years (range, 1–6 years).

The first, and only previous, large series of carcinomas originating in the nipple was published in 1956.14  Of approximately 10 000 cases of malignant disease of the breast in patients undergoing surgery at the Mayo Clinic in 46 years, only 25 (0.25%) originated in the nipple (excluding cases of skin cancer and carcinomas associated with more than focal Paget disease). We also found that those cancers are quite unusual, only encountering them rarely in surgical and consult cases (24 cases in >8000 cases [0.3%]). A major difficulty in identifying these cancers in databases or in the literature is the absence of a specific term to describe them. We propose nipple-invasive primary carcinoma as a term which, if used, could assist in future studies.

The cases we identified fell into 2 main groups. The first group presented with extensive skin changes secondary to Paget disease, with invasion arising directly from tumor cells in the epidermis (Table 1). We and others12,1521  have previously reported on 22 cases of “invasive Paget disease” (Table 3). The additional 10 cases reported in this study confirm the previous findings. The areas of invasion are small because larger carcinomas cannot be identified as specifically arising from tumor cells involving the skin.22  Because of the association with Paget disease, most overexpress HER2. Of the 22 patients undergoing lymph node sampling, only 1 patient (4.5%) has had a lymph node macrometastasis (Table 3). That patient was unusual in that there were multiple areas of dermal invasion (the largest, 3.5 mm).21  No cases of distant metastasis or recurrence have been reported.

Table 3

Published Cases of Paget Disease and Dermal Invasiona

Published Cases of Paget Disease and Dermal Invasiona
Published Cases of Paget Disease and Dermal Invasiona

Carcinomas that did not qualify for the first group were larger and presented as a nipple mass or thickening and/or were due to skin changes from the underlying mass (Table 2). Twenty published studies were identified that reported 48 patients with cancers that were described as being similar to the second group of nipple-invasive carcinomas in the current study (Table 4).14,2240  Except for the first series from the Mayo Clinic, the rest of the studies were reports of 1 to 2 patients. As in the cases in the current study, most patients presented with nipple masses and/or with skin changes related to the carcinoma. Paget disease was only reported in 4 of the 48 cases (8%). Imaging studies were reported for 12 of the 48 patients (25%) and showed a mass in 6 of the 12 patients (50%), calcifications in 2 patients (17%), and had negative findings in 4 patients (33%). Carcinomas not observed in the current study were those associated with a benign nipple adenoma or papilloma.23,25,28,34 

Table 4

Published Cases of Invasive Breast Carcinomas Originating From Ducts or Lobules in the Nipple

Published Cases of Invasive Breast Carcinomas Originating From Ducts or Lobules in the Nipple
Published Cases of Invasive Breast Carcinomas Originating From Ducts or Lobules in the Nipple
Table 4

Extended

Extended
Extended

Ductal was the most common histologic type, followed by lobular, “neuroendocrine,” and “basaloid.” Twelve of the 48 published cancers (25%) reported a modified Bloom Richardson grade. Of those 12, 3 (25%) were well differentiated, 5 (42%) were well to moderately or moderately differentiated, and 4 (33%) were poorly differentiated. The mean size was 1.6 cm (range, <0.1–3.5 cm).

For 9 of the 48 published cancers (19%), both ER and HER2 were determined. Five cases (56%) were ER+ and HER2 (“luminal-like”), 1 (11%) was ER+ and HER2 equivocal, 1 (11%) was ER and HER2+, and 2 (22%) were ER and HER2 (“triple negative” or “basal-like”) (Table 4). Two of the 4 cancers (50%) associated with Paget disease were tested, and were both HER2+.

A total of 58 of the published cases had lymph node sampling, and of those, 18 (31%) had positive nodes, including 1 of 17 patients (6%) in the first group (Table 3) and 17 of 41 patients (41%) in the second group (Table 4). The mean size of carcinomas with both size and lymph node status reported in the second group was 1.8 cm (Table 4). Only 5 of the 18 cancers (28%) with lymph node metastases had both grade and tumor markers reported. Three of those 5 cancers (60%) were poorly differentiated and either positive or equivocal for HER2. Two of these 3 cases (67%) were negative for ER. The remaining 2 cancers (40%) were moderately differentiated, ER+, and HER2. The number of positive nodes was reported in 8 of the 18 cases (44%). Seven of the 8 cases (88%) had only 1 positive node, and the remaining cancer (12%), associated with 8 lymph node metastases, was ER and HER2+.22 

The published cases of carcinomas arising in the nipple and the additional cases identified for this study demonstrate that, apart from the invasive carcinomas arising in association with Paget disease, which are predominantly HER2+, carcinomas arising in the nipple are similar to carcinomas arising in the remainder of the breast. They include different histologic types, grades, and biologic types. A specific type of carcinoma arising from the special structures of the nipple was not identified. Therefore, these cancers may arise from similar structures as those found in the remainder of the breast. Lobules are present within the papilla in up to 26% of nipples (17 of 65 nipples [26%] in 1 study41) and could be the site of origin. Another possibility is that carcinoma in situ arose deeper in the breast and extended into the lactiferous ducts with invasion occurring in the nipple. Five of the 24 carcinomas (21%) in this study were associated with DCIS deeper in the breast.

Carcinomas involving the skin, superficially located, and/or close to the nipple are associated with a higher risk of lymph node metastases.710  This may be due to those carcinomas passing through the dense, subareolar plexus of lymphatics as they invade from deeper in the breast into the dermis (Figure 1).42  In the cases in this study and in the published cases, the number of carcinomas with lymph node metastases was comparable to cancers of similar size and was not markedly increased.43  This may be due to those carcinomas being located above the lymphatic plexus. Only the larger carcinomas may have invaded deep enough to encounter the areolar lymphatics. Three of the 24 carcinomas (12.5%) reported in this study had lymph node metastases. Two of the 3 carcinomas (67%) with lymph node metastases invaded below the smooth muscle of the areola (both with macrometastases) and 1 (33%) did not (the carcinoma with a micrometastasis). The association of skin involvement with an increased likelihood of lymph node metastasis may be a surrogate for the presence of invasion through the lymphatic plexus rather than being due to skin involvement itself.7 

Women opting to undergo prophylactic nipple-sparing mastectomies rather than total mastectomies accept the risk of a carcinoma arising in the nipple. Although some surgeons advocate removing the central core of tissue from the nipple, it is unclear how successful that technique is in practice and the procedure has not been standardized.44  The observed risk of subsequent cancer after nipple-sparing prophylactic mastectomy is quite low—only 9 cases in 776 patients (1.2%) in 3 studies.30,45,46  Only 1 of the 9 cancers (11%) occurred at the nipple. Therefore, residual breast tissue in the skin flaps or in far lateral areas of the breast appears to provide a greater risk than the nipple itself. The current study has shown that the rare cancers that originate in the nipple are similar to other breast cancers and do not carry an extremely high risk of nodal metastasis. Patients undergoing this procedure should be aware that cancers arising in the nipple can have a subtle presentation and can reach a substantial size before being detected by imaging. In addition, they should bring any skin changes (erythema, exudative crust, pigmentation, or pruritus) or nipple thickening to the immediate attention of their health care providers.

1
Allison
AB.
Howorth
MB
Jr.
Carcinoma in a nipple preserved by heterotopic auto-transplantation
.
N Eng J Med
.
1978
;
298
(
20
):
1132
.
2
Khandekar
JD.
Carcinoma in a heterotopically auto-transplanted nipple
.
Cancer
.
1979
;
43
(
6
):
2502
2503
.
3
Rose
JH
Jr.
Carcinoma in a transplanted nipple
.
Arch Surg
.
1980
;
115
(
9
):
1131
1132
.
4
Cucin
RL.
Gaston
JP.
Case report: implantation of breast cancer in a transplanted nipple: a plea for preoperative screening
.
CA Cancer J Clin
.
1981
;
31
(
5
):
281
283
.
5
Dominici
LS.
Morrow
M.
Mittendorf
E.
Bellon
J.
King
TA.
Trends and controversies in multidisciplinary care of the patient with breast cancer
.
Current Probl Surg
.
2016
;
53
(
12
):
559
595
.
6
Rusby
JE.
Smith
BL.
Gui
GP.
Nipple-sparing mastectomy
.
Brit J Surg
.
2010
;
97
(
3
):
305
316
.
7
Güth
U.
Huang
DJ.
Schötzau
A.
Dirnhofer
S.
Wight
E.
Singer
G.
Breast cancer with non-inflammatory skin involvement: current data on an underreported entity and its problematic classification
.
Breast
.
2010
;
19
(
1
):
59
64
.
8
Ansari
B.
Morton
MJ.
Adamczyk
DL.
et al.
Distance of breast cancer from skin and nipple impacts axillary nodal metastases
.
Ann Surg Oncol
.
2011
;
18
(
11
):
3174
3180
.
9
Torstenson
T.
Shah-Khan
MG.
Hoskin
TL.
et al.
Novel factors to improve prediction of nodal positivity in patients with clinical T1/2 breast cancers
.
Ann Surg Oncol
.
2013
;
20
(
10
):
3286
3293
.
10
Eom
YH.
Kim
EJ.
Chae
BJ.
Song
BJ.
Jung
SS.
The distance between breast cancer and the skin is associated with axillary node metastasis
.
J Surg Oncol
.
2015
;
111
(
7
):
824
828
.
11
Rusby
JE.
Brachtel
EF.
Michaelson
JS.
Koerner
FC.
Smith
BL.
Breast duct anatomy in the human nipple: three-dimensional patterns and clinical implications
.
Breast Cancer Res Treat
.
2007
;
106
(
2
):
171
179
.
12
Sanders
MA.
Dominici
L.
Denison
C.
Golshan
M.
Wiecorek
T.
Lester
SC.
Paget disease of the breast with invasion from nipple skin into the dermis: an unusual type of skin invasion not associated with an adverse outcome
.
Arch Pathol Lab Med
.
2013
;
137
(
1
):
72
76
.
13
American Joint Committee on Cancer
.
Breast
.
In
:
Edge
S.
Byrd
DR.
Compton
CC.
Fritz
AG,
Greene
FL.
Trotti
A.
eds
.
AJCC Cancer Staging Manual. 7th ed
.
New York, NY
:
Springer;
2011
:
345
376
.
14
Congdon
GH.
Dockerty
MB.
Malignant lesions of the nipple exclusive of Paget's disease
,
Surg Gynecol Obstet
.
1956
;
103
(
2
):
185
192
.
15
Chao
C.
Edwards
MJ.
Wolfson
S.
Sewell
C.
Edwards
D.
McMasters
KM.
Paget's disease of the male breast: an unusual case of dermal invasion
.
Breast J
.
2003
;
9
(
3
):
254
.
16
Soler
T.
Lerin
A.
Serrano
T.
Masferrer
E.
Garcia-Tejedor
A.
Condom
E.
Pigmented Paget disease of the breast nipple with underlying infiltrating carcinoma: a case report and review of the literature
.
Am J Dermatopathol
.
2011
;
33
(
5
):
e54
e57
. doi:.
17
Duan
X.
Sneige
N.
Gullett
AE.
et al.
Invasive Paget disease of the breast, clinicopathologic study of an underrecognized entity in the breast
.
Am J Surg Pathol
.
2012
;
36
(
9
):
1353
1358
.
18
Hanna
M.
Jaffer
S.
Bleiweiss
IJ.
Nayak
A.
Minimally invasive mammary Paget's disease without an underlying breast carcinoma
.
Virchows Arch
.
2013
;
463
(
3
):
471
473
.
19
Lee
H-W.
Kim
TE.
Cho
SY.
et al.
Invasive Paget disease of the breast: 20 years of experience at a single institution
.
Human Pathol
.
2014
;
45
(
12
):
2480
2487
.
20
Tang
X.
Umemura
S.
Kumaki
N.
et al.
A case report of pigmented mammary Paget's disease mimicking nevus of the nipple
.
Breast Cancer
.
2014
;
21
(
3
):
370
374
.
21
Saluja
K.
Sahoo
S.
Invasive Paget disease of the nipple of luminal-B subtype with axillary lymph node metastasis in a 60-year-old white woman
.
Lab Med
.
2015
;
46
(
4
):
332
337
.
22
Ozerdem
U.
Swistel
A.
Antonio
LB.
Hoda
SA.
Invasive Paget disease of the nipple: a brief review of the literature and report of the first case with axillary nodal metastases
.
Int J Surg Pathol
.
2014
;
22
(
6
):
566
569
.
23
Bhagavan
BS.
Patchefsky
A.
Koss
LG.
Florid subareolar duct papillomatosis (nipple adenoma) and mammary carcinoma: report of three cases
.
Hum Pathol
.
1973
;
4
(
2
):
289
295
.
24
Cauble
WG.
Carcinoma of the nipple
.
Kans Med
.
1986
;
87
(
5
):
134
135
.
25
Rosen
PP.
Caicco
JA.
Florid papillomatosis of the nipple: a study of 51 patients, including nine with mammary carcinoma
.
Am J Surg Pathol
.
1986
;
10
(
2
):
87
101
.
26
Menon
RS.
van Geel
AN.
Cancer of the breast with nipple involvement
.
Br J Cancer
.
1989
;
59
(
1
):
81
84
.
27
Kasuga
Y.
Oohashi
T.
Nagai
N.
Tsuchiya
S.
Sugenoya
A.
Primary scirrhous carcinoma of the nipple with symptoms simulating Paget's disease: report of a case
.
Surg Today
.
1993
;
23
(
4
):
356
359
.
28
Jones
MW.
Tavassoli
FA.
Coexistence of nipple duct adenoma and breast carcinoma: a clinicopathologic study of five cases and review of the literature
.
Mod Pathol
.
1995
;
8
(
6
):
633
636
.
29
Ohsumi
S.
Nozaki
I.
Takashima
S.
Mandai
K.
Invasive ductal carcinoma of the nipple: a case report
.
Breast Cancer
.
1996
;
3
(
3
):
215
218
.
30
Hartmann
LC.
Schaid
DJ.
Woods
JE.
et al.
Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer
.
N Engl J Med
.
1999
;
340
(
2
):
77
84
.
31
Glazebrook
KN.
Morton
MJ.
Reynolds
C.
Carcinoma of the breast mimicking an areolar dermal lesion
.
J Ultrasound Med
.
2007
;
26
(
8
):
1083
1087
.
32
Mecca
P.
Busam
K.
Primary male neuroendocrine adenocarcinoma involving the nipple simulating Merkel cell carcinoma—a diagnostic pitfall
.
J Cutan Pathol
.
2008
;
35
(
2
):
207
211
.
33
Ahmed
A.
Basit
A.
Isolated adenocarcinoma of the nipple
.
BMJ Case Rep
.
2011
. doi:.
34
Kawasaki
T.
Suda
M.
Kondo
T.
et al.
Microinvasive neuroendocrine carcinoma arising from a central papilloma of the breast
.
J Clin Pathol
.
2011
;
64
(
6
):
549
551
.
35
Erben
Y.
Ghosh
K.
Nassar
A.
Gimenez
D.
Jakub
JW.
Invasive lobular carcinoma of the nipple
.
Breast J
.
2012
;
18
(
3
):
280
281
.
36
Kawasaki
T.
Mochizuki
K.
Yamauchi
H.
et al.
High prevalence of neuroendocrine carcinoma in breast lesions detected by the clinical symptom of bloody nipple discharge
.
Breast
.
2012
;
21
(
5
):
652
656
.
37
Shafqat
G.
Khan
S.
Minhas
K.
Afzal
S.
Infiltrating ductal carcinoma of breast presenting as areolar dermal lesion
.
J Coll Physicians Surg Pak
.
2012
;
22
(
5
):
323
325
.
38
Moennich
J.
Ort
R.
High
W.
Brown
M.
Breast carcinoma masquerading as basal cell carcinoma of the nipple
.
JAAD Case Rep
.
2015
;
1
(
6
):
361
363
.
39
Pasquali
P.
Freites-Martinez
A.
Camacho
E.
Fortuno
A.
A painful nipple: a rare presentation for an infiltrating lobular carcinoma
.
Breast J
.
2015
;
22
(
1
):
117
118
.
40
Solus
JF.
Goyal
A.
Duncan
LM.
Nazarian
RM.
Basaloid carcinoma of the breast mimicking cutaneous basaloid neoplasms
.
Am J Dermatopathol
.
2015
;
37
(
9
):
e102
e106
. doi:.
41
Kryvenko
ON.
Yoon
JY.
Chitale
DA.
Lee
MW.
Prevalence of terminal duct lobular units and frequency of neoplastic involvement of the nipple in mastectomy
.
Arch Pathol Lab Med
.
2013
;
137
(
7
):
955
960
.
42
Suami
H.
Pan
W.
Mann
GB.
Taylor
GI.
The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human cadaver study
.
Annals Surg Oncol
.
2007
;
15
(
3
):
863
871
.
43
Andea
AA.
Wallis
T.
Newman
LA.
Bouwman
D.
Dey
J.
Visscher
DW.
Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma
.
Cancer
.
2002
;
94
(
5
):
1383
1390
.
44
Murthy
V.
Chamberlain
RS.
Defining a place for nipple sparing mastectomy in modern breast care: an evidence based review
.
Breast J
.
2013
;
19
(
6
):
571
581
.
45
Sacchini
V.
Pinotti
JA.
Barros
A.
et al.
Nipple-sparing mastectomy for breast cancer and risk reduction: oncologic or technical problem?
J Am Coll Surg
.
2006
;
203
(
5
):
704
714
.
46
Yao
K.
Liederbach
BS.
Tang
R.
et al.
Nipple-sparing mastectomy in BRCA1/2 mutation carriers: an interim analysis and review of the literature
.
Ann Surg Oncol
.
2015
;
22
(
2
):
370
376
.

Author notes

The authors have no relevant financial interest in the products or companies described in this article.