Paget's Disease of the Breast
CancerIndex Home - Guide to Internet Resources for Cancer Home > Cancer Types > Breast Cancer > Paget's Disease of the Breast

Paget’s disease is a type of breast cancer that occurs in the ducts adjacent to the nipple and areola and spreads to the skin of the nipple and the areola. It accounts for less than 2 percent of all breast cancer cases, predominantly in women but with rare cases in men. Symptoms can be similar to eczema. Paget’s disease is usually associated with ductal carcinoma in situ (DCIS), limited to the nipple and areola area of the breast.

Menu: Paget's Disease of the Breast

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Breast Cancer

Information Patients and the Public (7 links)


Information for Health Professionals / Researchers (3 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Sanders MA, Dominici L, Denison C, et al.
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):72-6 [PubMed]
CONTEXT: Paget disease is an uncommon skin manifestation of breast cancer, associated with either invasive carcinoma or ductal carcinoma in situ in the underlying breast. In very rare cases, tumor cells within the epidermis invade through the basement membrane of the skin into the dermis.
OBJECTIVES: To identify a series of cases of Paget disease with direct dermal invasion and to investigate the clinicopathologic features and outcome.
DESIGN: Cases were identified during a 6-year period from the files of 2 hospitals. The clinical histories, imaging studies, and pathology reports were reviewed.
RESULTS: Seven patients were identified, 5 with microinvasion (<0.1 cm) and 2 with 0.2- or 0.3-cm invasive carcinomas in the dermis. No lymphovascular invasion was seen. Sentinel nodes were negative in 3 patients who underwent biopsy. Five patients were treated with breast conservation with radiation. Three patients were at high risk for breast cancer because of prior breast cancer, Li-Fraumeni syndrome, or radiation for Hodgkin disease. The latter 2 patients underwent bilateral mastectomies. Three patients received hormonal therapy and 1 oophorectomy. No patient received chemotherapy. At follow-ups ranging from 4 to 66 months (median, 20 months), there have been no recurrences.
CONCLUSIONS: Patients with direct dermal invasion from Paget disease had a favorable outcome during the available follow-up period. This type of dermal involvement must be distinguished from locally advanced invasive carcinomas with skin invasion classified as T4b in the American Joint Cancer Commission staging system, as cancers with other types of skin invasion are associated with a poor prognosis.


Psoma E, Nikolaidou O, Stavrogianni T, et al.
A rare case report of a primary large-cell neuroendocrine carcinoma of the breast with coexisting Paget disease.
Clin Imaging. 2012 Sep-Oct; 36(5):599-601 [PubMed]
Neuroendocrine carcinomas are malignancies deriving from neuroendocrine cells existing in various sites of the body, most commonly in the lungs and gastrointestinal tract. Primary neuroendocrine carcinomas of the breast are extremely rare, and their diagnosis is confirmed by positive neuroendocrine markers. We describe a case of a 46-year-old woman with a palpable mass in her left breast for the previous 3 months. The tumor was resected and a primary large-cell neuroendocrine tumor of the breast was confirmed by histopathologic examination. Paget disease of the nipple was noted as well.


Zheng S, Song QK, Zhao L, et al.
Characteristics of mammary Paget's disease in China: a national-wide multicenter retrospective study during 1999-2008.
Asian Pac J Cancer Prev. 2012; 13(5):1887-93 [PubMed]
The aim of this study was to detail characteristics of mammary Paget's disease (PD) representing the whole population in China. A total of 4211 female breast cancer inpatients at seven tertiary hospitals from seven representative geographical regions of China were collected randomly during 1999 to 2008. Data for demography, risk factors, diagnostic imaging test, physical examination and pathologic characters were surveyed and biomarker status was tested by immunohistochemistry. The differences of demography and risk factors between PD with breast cancer and other lesions were compared using Chi-square test or t-test, with attention to physical examination and pathological characters. The percentage of PD was 1.6% (68/4211) in all breast cancers. The mean age at diagnosis was 48.1, and 63.2% (43/68) patients were premenopausal. There is no difference in demography and risk factors between PD with breast cancer and other breast cancer (P>0.05). The main pattern of PD in physical exam and pathologic pattern were patients presenting with a palpable mass in breast (65/68, 95.6%) and PD with underlying invasive cancer (82.4%, 56/68) respectively. The rate of multifocal disease was 7.4% (5/68). PD with invasive breast cancer showed larger tumor size, more multifocal disease, lower ER and PR expression and higher HER2 overexpression than those in other invasive breast cancer (P<0.05). These results suggested that PD in China is a concomitant disease of breast cancer, and that PD with underlying invasive cancer has more multiple foci and more aggressive behavior compared with other breast invasive cancer. We address the urgent needs for establishing diagnostic and therapeutic guidelines for mammary PD in China.


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):1353-8 [PubMed]
Mammary Paget disease (MPD) is considered an intraepidermal manifestation of an underlying mammary carcinoma. In contrast to extramammary Paget disease, invasion of mammary Paget cells into the dermis (invMPD) has not been reported, except for 2 cases described in Rosen's textbook. Our study was designed to identify the presence of dermal invasion of mammary Paget cells and characterize the associated clinicopathologic features. Slides from 146 MPD patients were retrieved. Six cases of invMPD were identified. One case of invMPD was not associated with an underlying breast cancer, 1 was associated with invasive ductal carcinoma (IDC), 1 with ductal carcinoma in situ (DCIS) with microinvasion, and 3 with DCIS only. The underlying breast carcinomas was separate from the area of invMPD. The depth of invasion, measured from the dermal-epidermal junction to the focus of deepest invasion, ranged from 0.02 to 0.9 mm. The horizontal extent ranged from 0.01 to 4.0 mm. Lymph node with isolated tumor clusters was present in case 1, which had no underlying carcinoma but had the greatest extent of invasion, and in case 3, which had DCIS with microinvasion. One patient (case 1) died of unrelated causes 2 years later, and the remaining patients were alive without disease at last follow-up. In summary, we describe 6 cases of MPD with invasion of Paget cells into the dermis and provide histopathologic criteria for the diagnosis of this rare and underrecognized entity. Further studies are required to determine whether invasion in MPD has clinical significance.


Marques-Costa JC, Cuzzi T, Carneiro S, et al.
Paget's disease of the breast.
Skinmed. 2012 May-Jun; 10(3):160-5; quiz 165 [PubMed]
The initial presentation of Paget's disease of the breast is an eczematous lesion, similar to contact dermatitis, in the skin of the breast at the areola and/or nipple and is refractory to usual topical treatments. It is frequent among women, especially those in their 50s and 60s. Most cases are associated with an in situ or underlying invasive breast neoplasia. The histopathology is usually diagnostic, with immunohistochemistry useful for its differentiation from melanoma and other types of tumors. Treatment should always be surgical with invasive procedures for the effective and complete removal of the breast tumor.


Lohsiriwat V, Martella S, Rietjens M, et al.
Paget's disease as a local recurrence after nipple-sparing mastectomy: clinical presentation, treatment, outcome, and risk factor analysis.
Ann Surg Oncol. 2012; 19(6):1850-5 [PubMed]
BACKGROUND: Paget's disease is a rare clinical and histological type of local recurrence (LR) after breast cancer treatment both in case of conservative surgery or nipple-sparing mastectomy (NSM) with or without intraoperative radiation.
METHODS: We performed an analysis of 861 NSM with electron beam intraoperative radiotherapy (ELIOT) patients treated at the European Institute of Oncology from 2002 to 2008, focused on Paget's disease local recurrence.
RESULTS: In 861 patients (713 invasive carcinoma and 148 intraepithelial neoplasia), there were 36 local recurrences (4.18%), and among these were 7 Paget's disease local recurrences (0.8%). Median follow-up was 50 months. Four cases presented with nipple areola complex (NAC) erosions, two crusted lesions, and one ulcerated NAC. The average latency period from the NSM to Paget's disease local recurrence is 32 months (range, 12-49). Complete NAC removal was performed in all seven recurrences. The average follow-up after NAC removal was 47.4 months (range, 20-78). We found neither locoregional relapse nor metastatic event in this group. All patients were alive without disease.
CONCLUSIONS: Paget's disease local recurrence can be found in a significant proportion after NSM. Any suspicious lesion on NAC requires prompt pathological confirmation. Primary carcinoma with ductal intraepithelial neoplasia or invasive ductal carcinoma with extensive in situ component, negative hormonal receptor, high pathological grade, overexpression of HER2/neu, and "HER2 positive (nonluminal)" subtype tend to be significantly associated with more Paget's disease local recurrence and should be followed carefully.


Marczyk E, Kruczak A, Ambicka A, et al.
The routine immunohistochemical evaluation in Paget disease of the nipple.
Pol J Pathol. 2011; 62(4):229-35 [PubMed]
Paget disease (PD) of the nipple with coexisting intraductal (DCIS) and invasive carcinoma of the breast comprises 0.6-1.8% of all malignant epithelial neoplasms of this organ. Unlike invasive ductal carcinoma, there are many controversies concerning histological features of PD and the significance of the immunohistochemical characteristics of this neoplasm, which limits the optimal treatment protocols. Therefore, we decided to verify the immunohistochemical markers of PD basing on the retrospective analysis of postoperative material from 69 patients treated surgically. Microscopic examination revealed partial (7 cases) or total (62 cases) replacement of the squamous epithelium of the nipple with nests of atypical glandular cells spreading in an area ranging from 0.2 to 2.5 cm. DCIS coexisting with the PD lesions was present in all examined patients, and infiltrating carcinoma occurred in 31 (44.9%) patients. Both intraepidermal and DCIS components presented c-erbB2 overexpression. Positive estrogen and progesterone receptor staining was observed only in 7 (10.1%) and 2 (2.7%) tumours, respectively. Ki-67 proliferation index of PD cells ranged from 10% to 30%, whereas in DCIS it varied from 4% to 20%. The value of Ki-67 index exceeding 25% in the intraepidermal component of PD was associated with worse overall survival rate.


Spizuoco A, Jain RD, Stockton T, et al.
Mammary Paget disease in Darier disease: beware the wolf in sheep's clothing.
Am J Dermatopathol. 2012; 34(4):449-51 [PubMed]
This case describes new onset mammary Paget disease arising in the background of Darier disease. Clinically and histologically, lesions of Darier disease can mask the lesions of mammary Paget disease. A high index of suspicion is necessary to diagnose Paget disease in a patient with Darier disease, for a potentially fatal disease could easily be missed.


Ortiz-Pagan S, Cunto-Amesty G, Narayan S, et al.
Effect of Paget's disease on survival in breast cancer: an exploratory study.
Arch Surg. 2011; 146(11):1267-70 [PubMed]
OBJECTIVE: To explore whether Paget's disease (PD) has an effect on outcome in patients with breast cancer.
DESIGN: Retrospective analysis of comprehensive pathology database, medical records, and slides of samples showing pathologic features.
SETTING: UMass Memorial Health Care.
PATIENTS: All patients with breast cancer and PD with records in a prospectively maintained database between January 1, 1990, and December 31, 2008, were identified. Each participant was matched (criteria: age within 5 years, year of treatment, and stage of breast cancer) with 2 controls (1:2 ratio).
MAIN OUTCOME MEASURES: Overall and disease-free survival were analyzed using Kaplan-Meier statistics and Cox proportional hazards modeling, accounting for matching in the latter analyses by using robust standard error estimates.
RESULTS: Mean (SD) follow-up was 47 (33) months. Treatment involved mastectomy in 29 (91%) PD vs 16 (25%) non-PD patients (P < .001), radiotherapy in 14 (44%) PD vs 53 (83%) non-PD patients (P < .001), and hormonal therapy in 14 (44%) PD vs 33 (52%) non-PD patients (P = .004). Biological markers were not significantly different except for ERBB2 (formerly HER2 or HER2/neu) overexpression in 14 (44%) PD vs 16 (25%) non-PD patients (P = .008). The PD group had an overall 5-year survival of 81.2% vs 93.8% of the non-PD group (Kaplan-Meier log-rank, P = .03). The unadjusted hazard ratio for the PD vs non-PD group was 5.31 (95% CI, 1.74-16.27; P = .003). The corresponding hazard ratio after adjusting for local and systemic treatment was 2.26 (95% CI, 0.46-11.06; P = .32).
CONCLUSIONS: These exploratory data show that PD may have a negative effect on breast cancer survival. This finding needs to be substantiated in larger data sets.


Lim HS, Jeong SJ, Lee JS, et al.
Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation.
Radiographics. 2011 Nov-Dec; 31(7):1973-87 [PubMed]
Paget disease is a rare malignancy of the breast characterized by infiltration of the nipple epidermis by adenocarcinoma cells. The clinical features of Paget disease are characteristic and should increase the likelihood of the diagnosis being made. An important point is that more than 90% of cases of Paget disease are associated with an additional underlying breast malignancy. Paget disease is frequently associated with ductal carcinoma in situ (DCIS) in the underlying lactiferous ducts of the nipple-areolar complex; it may even be associated with DCIS or invasive breast cancer elsewhere in the breast, at least 2 cm from the nipple-areolar complex. Nevertheless, mammographic findings may be negative in up to 50% of cases. Magnetic resonance (MR) imaging can be useful in patients with Paget disease for evaluation of the nipple-areolar complex and identification of an additional underlying malignancy in the breast. The appropriate surgical treatment must be carefully selected and individualized on the basis of radiologic findings, especially those obtained with breast MR imaging.


Hida T, Yoneta A, Nishizaka T, et al.
Pigmented mammary Paget's disease mimicking melanoma: report of three cases.
Eur J Dermatol. 2012 Jan-Feb; 22(1):121-4 [PubMed]
Pigmented mammary Paget's disease (PMPD) is a rare subtype of mammary Paget's disease. The differential diagnosis of PMPD and melanoma is difficult clinically and sometimes histopathologically. Here we present three cases of PMPD with a variable-sized lesion. All cases showed an irregular-shaped black-brown macule, one of which was accompanied by nipple retraction. Dermoscopically, all cases showed reticular pigmentation with or without irregular black dots, regression structures and streaks, which were indistinguishable from those of melanoma. In all but one of the cases, preoperative examinations confirmed the presence of a subcutaneous mammary lesion. All patients underwent a total mastectomy with the histopathological results indicating invasive ductal carcinoma. These cases emphasize how difficult it is to distinguish PMPD from melanoma. Dermoscopic features also mimic those of melanoma, but the reticular pigmentation seen in all cases could be a feature specific to PMPD. For suspicious cases, histopathological assessment using immunohistochemistry is highly recommended.


Dominici LS, Lester S, Liao GS, et al.
Current surgical approach to Paget's disease.
Am J Surg. 2012; 204(1):18-22 [PubMed]
BACKGROUND: Paget's disease constitutes between 1% and 3% of all breast malignancies, which makes defining standard surgical therapy difficult. We sought to identify preoperative factors that would select patients for successful breast conservation.
METHODS: Fifty-one patients with Paget's disease underwent surgical therapy between October 1998 and January 2010. Clinical presentation of Paget's disease, preoperative imaging, pathologic tumor characteristics, as well as surgical, radiation, and adjuvant therapies were reviewed.
RESULTS: Thirty-seven percent underwent breast conservation whereas 63% underwent mastectomy. Twelve patients presented with a palpable mass, and all were treated with mastectomy. Twenty-two patients underwent a mammogram, identifying extensive abnormality requiring mastectomy. Magnetic resonance imaging added to surgical planning in 52% of patients who participated in the study. None of our patients had a local/regional recurrence at 29 months of follow-up evaluation.
CONCLUSIONS: Paget's disease of the breast can be treated with breast conservation in a properly selected subset of patients. Successful breast conservation was achieved in patients without a palpable finding, a benign mammogram, and a normal magnetic resonance imaging scan.


Onoe S, Kinoshita T, Tamura N, et al.
Feasibility of breast conserving surgery for Paget's disease.
Breast. 2011; 20(6):515-8 [PubMed]
INTRODUCTION: The standard treatment for Paget's disease of the breast is mastectomy. Since it is frequently associated with underlying carcinoma, many surgeons are reluctant to choose breast conserving surgery for Paget's disease.
PATIENTS AND METHODS: We retrospectively analyzed a series of 59 patients with Paget's disease who had undergone mastectomy at the National Cancer Center Hospital between 1963 and 2009.
RESULTS: In 55 of 59 cases (93%) there was underlying carcinoma in the ipsilateral breast. Clinically, 27 (46%) patients had no evidence of other tumors, but 23 (85%) had underlying histopathologically confirmed carcinoma. Based on the data from this subset, cone excision with a 3-cm radius and a 4-cm radius could completely resect any underlying malignancy in 74% and 85% of patients, respectively.
CONCLUSION: As Paget's disease is frequently accompanied by underlying intraductal and/or invasive carcinoma, patients should be carefully selected for breast conserving surgery.


Nardelli AA, Stafinski T, Menon D
Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease: a state of the science review.
BMC Dermatol. 2011; 11:13 [PubMed] Free Access to Full Article
BACKGROUND: Paget's disease is a rare skin disorder occurring in the breast (mammary) or in the groin, genital, peri-anal and axillary regions (extra-mammary). Typical treatment involves surgical excision, which in the case of extra-mammary Paget's disease, can lead to significant morbidity. Photodynamic therapy (PDT) which uses a topical or intravenous photosensitizing agent that is activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to assess the effectiveness of photodynamic therapy in the treatment of Paget's disease.
METHODS: Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for mammary and extra-mammary Paget's disease was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale.
RESULTS: 21 retrospective and 2 prospective non-comparative studies were identified and included in the review: 9 case reports with 1-2 patients and 14 case series with 1-16 patients. These reports totalled 99 patients with 133 extra-mammary Paget's lesions and 3 patients (with 3 lesions) with mammary Paget's disease. Follow-up periods were typically one year or less, with 77/133 extra-mammary lesions exhibiting complete response to PDT. One recurrent mammary skin lesion and two mammary lesions treated concomitantly with surgery also exhibited complete responses.
CONCLUSIONS: Evidence of the effectiveness of PDT for Paget's disease is promising, but limited. This may, in part, be explained by the rarity of the condition, making controlled comparative clinical trials challenging.


Soler T, Lerin A, Serrano T, et al.
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):e54-7 [PubMed]
Paget disease of the breast represents a cutaneous manifestation of an underlying breast malignancy. The rare finding of a pigmented Paget disease mimicking melanoma represents a diagnostic problem. We report a case of a pigmented lesion involving the breast nipple with an underlying infiltrating breast carcinoma, and we describe the clinical presentation, histological findings, and immunohistochemical features with a review of reported cases.


Vohra P, Ljung BM, Miller TR, et al.
Paget's disease of the breast masquerading as squamous cell carcinoma on cytology: a case report.
Diagn Cytopathol. 2012; 40(11):1015-8 [PubMed]
Paget's disease is an uncommon manifestation of breast carcinoma occurring in 1-2% of female patients with breast cancer. Here, we present a case of Paget's disease of the breast, which was initially interpreted as squamous cell carcinoma on cytology. This case report raises two issues. First, histological and cytological specimens of Paget's disease show a mixed population of epithelial cells including squamous cells with reactive changes and malignant glandular cells. In the current case, a mixed population of atypical keratinizing and nonkeratinizing epithelial cells was initially interpreted as squamous cell carcinoma of cutaneous origin. The marked reactive changes in the squamous epithelium involved by Paget's disease should be recognized. Second, this case is an unusual clinical presentation for Paget's disease of the breast as the nipple-areolar complex and underlying breast tissue were surgically absent at the time of diagnosis. Clinical suspicion, along with an awareness of the cytologic features and clinical presentation of Paget's disease, can help in reaching the correct diagnosis in a timely fashion.


Sek P, Zawrocki A, Biernat W, Piekarski JH
HER2 molecular subtype is a dominant subtype of mammary Paget's cells. An immunohistochemical study.
Histopathology. 2010; 57(4):564-71 [PubMed]
AIMS:   To test the hypothesis that the similarity of the molecular subtypes of Paget's cells to the molecular subtypes of the underlying breast carcinomas favours the epidermotrophic theory of the origin of Paget's cells.
METHODS AND RESULTS:   The immunohistochemical expression of markers that define particular molecular subtypes of breast carcinomas were analysed. The whole analysis was performed by means of tissue microarrays in mammary Paget's disease and in the underlying breast carcinoma(s). Human epidermal growth factor receptor type 2 (HER2)-overexpression subtype [oestrogen receptor (ER(-) ); HER2(+) ] was a dominant molecular subtype of Paget's cells (37 of 43 analysed cases; 86%). Luminal B (ER(+) ; HER2(+) ) and luminal A (ER(+) ; HER(-) ) subtypes were identified in 12% and 2% of cases, respectively. None of the analysed tumours presented a basal-like phenotype. A similar distribution of molecular subtypes was identified in the underlying in situ breast carcinomas (HER2 subtype, 82%; luminal A, 6%; luminal B, 6%; basal-like, 6% of cases) and in the invasive component (HER2 subtype, 84%; luminal A, 8%; luminal B, 8%; basal-like, 0% of cases).
CONCLUSIONS:   HER2 molecular subtype is the dominant, but not the sole subtype seen in Paget's cells of the nipple. A similar distribution of molecular subtypes in both Paget's cells and in the underlying carcinomas strongly suggests their common origin.


Giger O, Caduff R, O'Meara A, et al.
Frequent expression of the breast differentiation antigen NY-BR-1 in mammary and extramammary Paget's disease.
Pathol Int. 2010; 60(11):726-34 [PubMed]
While mammary Paget's disease (MPD) is clearly linked to breast cancer, the histogenesis of extramammary Paget's disease (EMPD) is controversial. Recently NY-BR-1, a differentiation antigen expressed in the breast and in skin adnexal structures was identified. Its protein expression is restricted to normal and neoplastic breast epithelium and to adnexal tumors of the skin. In this study, we examine NY-BR-1 expression by immunohistochemistry in 24 MPD cases with synchronous ductal carcinoma in situ or invasive breast cancer. Results were compared with 26 cases of EMPD of men (n= 4) and women (n= 22) as well as in apoeccrine glands of the axilla and mammary-like glands of the anogenital region. We found NY-BR-1 positivity in 18 of 24 MPD (75%) and in 21 of 26 EMPD (80.8%). All apoeccrine glands of the axilla and mammary-like glands of the anogenital region were NY-BR-1-positive. NY-BR-1 expression is a common finding in MPD and in EMPD. When considering the diagnosis of Paget's disease, NY-BR-1 is a useful diagnostic marker. Furthermore NY-BR-1 positivity in apoeccrine glands of the axilla and anogenital region suggests a potential histogenetic link between these structures and Paget's disease.


Siponen E, Hukkinen K, Heikkilä P, et al.
Surgical treatment in Paget's disease of the breast.
Am J Surg. 2010; 200(2):241-6 [PubMed]
BACKGROUND: The aim of this study was to evaluate the outcomes of surgical treatment of Paget's disease of the breast, with special emphasis on magnetic resonance imaging (MRI) and sentinel node biopsy (SNB).
METHODS: The study included 58 consecutive patients with Paget's disease treated from 1995 to 2006.
RESULTS: Twenty-five patients had ductal carcinoma in situ, and 31 had invasive carcinoma. MRI was performed in 14 patients, with positive findings in 7 patients, 5 of whom had negative findings on conventional imaging. The overall mastectomy rate was 76%. Eighteen patients underwent SNB, and 26 patients underwent full or partial axillary clearance. Fourteen patients had no axillary surgery. One patient had local recurrence after breast conservation, and another had axillary recurrence after negative results on SNB. Six patients had distant metastases. Four patients died of breast cancer.
CONCLUSIONS: Paget's disease is frequently associated with peripheral or multicentric cancer. MRI may be helpful when considering breast conservation or omitting axillary nodal staging.


Lage D, Volpini Cde A, Sasseron Mda G, et al.
Paget's disease: the importance of the specialist.
An Bras Dermatol. 2010 May-Jun; 85(3):365-9 [PubMed]
A twenty-six-year-old woman with a two-year history of an erythematous, scaly lesion on the left nipple was being followed up by her gynecologist and treated using a topical corticoid for chronic eczema albeit with no improvement. She was referred to this department where a diagnosis of Paget's disease of the breast associated with a ductal carcinoma in situ was made. Paget's disease is uncommon prior to the fourth decade of life and the great majority of cases are associated with breast carcinomas. Differential diagnosis must be made between this condition and nipple eczema. As shown in the present case report, late diagnosis results in poor prognosis and higher morbidity since mutilating procedures then become necessary.


Usui K, Ochiai T, Abe I, et al.
Apocrine gland carcinoma of the mammary skin concomitant with pagetoid phenomenon.
J Dermatol. 2010; 37(4):350-4 [PubMed]
We reported a 52-year-old woman with an apocrine gland carcinoma of the mammary skin concomitant with pagetoid phenomenon. She had a 23-year history of a small nodular lesion on the lower left part of her right breast with a 1-year history of the pigmented plaque spreading peripherally around the nodule. Our diagnosis revealed that the nodule was an apocrine gland carcinoma and the intraepidermal neoplastic cells with pagetoid spread in the pigmented plaque were derived from the apocrine gland carcinoma. No Paget's cells were detected in the right nipple, and no tumor cells were observed in the sentinel lymph node and underlying mammary gland tissue. We also investigated the immunohistochemical changes in this case. They showed that both intraepidermal neoplastic cells with pagetoid spread and tumor cells of the apocrine gland carcinoma were positive with cytokeratin-7 and human epidermal growth factor receptor-2 (HER-2)/neu overexpression. The results of the present study conclude that the intraepithelial spread of tumor cells in the mammary skin distant from the nipple occurred as a pagetoid phenomenon, and that HER-2 may have a key role in pagetoid phenomenon of an underlying apocrine gland carcinoma, as well as in mammary Paget's disease.


El Harroudi T, Tijami F, El Otmany A, Jalil A
Paget disease of the male nipple.
J Cancer Res Ther. 2010 Jan-Mar; 6(1):95-6 [PubMed]
Breast cancer occurring in the mammary gland of men is infrequent. It accounts for 0.8% of all breast cancers, which is less than one per cent of all newly diagnosed male cancers and 0.2% of male cancer deaths. However, Paget disease of the male nipple is extremely rare. We report a single case of Paget disease with infiltrative ductal carcinoma of the breast in a 61-year-old man.


Kaić G, Stoos-Veić T, Ostović KT, et al.
Misleading presentations of malignant breast diseases--role of clinical cytology.
Coll Antropol. 2010; 34(1):193-5 [PubMed]
We described two examples with misleading presentations to draw attention to the role of clinical cytology as apart of multidisciplinary approach to breast lesions. In the first case--Paget's disease of the nipple, there was no obvious clinical and radiological evidence of breast cancer, while the second case--primary non-Hodgkin lymphoma of the breast imitated advanced breast carcinoma. The question is whether accurate and fast diagnoses can be made without cytological examinations. It must be kept in mind that first-hand clinical information and contact with the patient is necessary in rendering accurate cytological diagnoses.


Park S, Suh YL
Useful immunohistochemical markers for distinguishing Paget cells from Toker cells.
Pathology. 2009; 41(7):640-4 [PubMed]
AIMS: Toker cells (TCs) are normal components of the nipple epidermis. Because of their morphological and immunohistochemical similarities to mammary Paget cells (PCs), their presence may lead to a mistaken diagnosis of Paget's disease. The objective of this study was to identify immunohistochemical markers that are able to distinguish TCs from mammary PCs.
METHODS: Nipple tissue, derived from surgical specimens following radical mastectomy for breast cancer, was obtained from 30 cases diagnosed with TCs and 30 cases of mammary Paget's disease (MPD). The tissue was examined by immunohistochemistry using antibodies to c-erbB-2, cytokeratin (CK)7, Ki-67 and oestrogen receptor (ER).
RESULTS: TCs were consistently positive for CK7 and ER but negative for c-erbB-2. TCs either did not express Ki-67 or expressed very low levels with only 1-3 positive cells per high-power field. In contrast, MPD tended strongly to express both Ki-67 and c-erbB-2.
CONCLUSIONS: Results suggested that TCs and mammary PCs differ substantially in their expression of ER, c-erbB-2 and Ki-67, although they share immunoreactivity to CK7. Both Ki-67 and c-erbB-2 were consistently positive in mammary PCs but almost always negative in TCs, while ER was consistently positive in TCs. Therefore, a combination of these markers may allow TCs to be distinguished from mammary PCs.


Ellis PE, Maclean AB, Crow JC, et al.
Expression of cyclin D1 and retinoblastoma protein in Paget's disease of the vulva and breast: an immunohistochemical study of 108 cases.
Histopathology. 2009; 55(6):709-15 [PubMed]
AIMS: Loss of retinoblastoma protein expression and overexpression of cyclin D1 have been implicated in the development and progression of some cancers. Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon conditions and the pathogenesis of these diseases is still unclear. The aim was to examine the expression of the retinoblastoma and cyclin D1 proteins in PDV and PDB and to correlate any differences between PDV and PDB, and in the presence or absence of an underlying carcinoma.
METHODS AND RESULTS: Seventy-two archival cases of PDV including 10 with invasive disease and 36 cases of PDB were evaluated immunohistochemically for the expression of cyclin D1 and retinoblastoma protein. Forty-four percent (32/72) of cases of PDV showed loss of expression of the retinoblastoma protein, compared with 67% (24/36) of PDB cases. Fifty-nine percent (41/69) of PDV overexpressed cyclin D1. In PDB, 8% (3/34) overexpressed cyclin D1. There were no significant differences in the expression of retinoblastoma and cyclin D1 in PDV cases with or without underlying invasive disease. There were significant differences between the expression of retinoblastoma (P = 0.03) and cyclin D1 (P < 0.001) in PDV compared with PDB.
CONCLUSIONS: The differences in the expression of cyclin D1 and retinoblastoma may indicate the differences in the pathogenesis of PDV and PDB.


Buxant F, Fayt I, Noel JC
Assessment of proliferating activity in Paget's disease of the nipple by double stain immunohistochemistry.
Eur J Gynaecol Oncol. 2009; 30(5):500-2 [PubMed]
Paget disease of the nipple is a rare disease characterized by the presence of malignant glandular cells within the squamous epithelium of the nipple. The most common hypothesis to explain the development of Paget's disease is an intraepithelial epidermotropic migration of malignant epithelial cells originating from an underlying intraductal carcinoma. Although the immunohistochemical properties of Paget cells in the nipple have been extensively studied, their proliferating characteristics remain paradoxically poorly studied. In the present study we have investigated the proliferating activity of Paget cells in the nipple by using double stain immunohistochemistry with both Ki-67 (a protein which is expressed in all active parts of the cell cycle) and cytokeratin 7 (a highly sensitive marker of Paget cells). Ten cases of Paget's disease and the associated intraductal carcinomas (n = 10) and/or invasive carcinomas (n = 4) were tested. The mean Ki-67 index was in Paget's disease (26% +/- 10), in intraductal carcinomas (23% +/- 8) and/or in invasive carcinomas (20% +/- 8) (p > 0.05). This is the first report to convincingly demonstrate by specific double stain immunohistochemistry that Paget's disease and underlying intraductal carcinomas share a close proliferating activity.


Kim HS, Seok JH, Cha ES, et al.
Significance of nipple enhancement of Paget's disease in contrast enhanced breast MRI.
Arch Gynecol Obstet. 2010; 282(2):157-62 [PubMed]
PURPOSE: To evaluate significance of nipple enhancement of Paget's disease in contrast enhanced (CE) breast MRI.
METHODS: Ten patients of biopsy proven Paget's disease were included in this study. Preoperative mammogram and ultrasonogram (US) were obtained in all 10 patients, and 8 patients underwent CE breast MRI prior to surgery. Mammographic and US findings were reviewed retrospectively. On MRI, morphology (flattening or asymmetry or thickening) and enhancement of pathologically involved nipple were analyzed comparing with the opposite side, and also reviewed the abnormal enhancing lesion in the breast parenchyma.
RESULTS: Morphologic changes of the nipple were detected in 2 out of 10 patients by mammogram and 6 out of 10 patients by US. On MRI, morphologic change was also revealed in 7 patients and abnormal enhancement of involved nipple was observed in all 8 patients. Associated parenchymal enhancing lesions were proved to be DCIS (7 out of 10) and invasive ductal carcinoma (2 out of 10). Remaining one patient had no underlying breast parenchymal malignancy.
CONCLUSION: CE breast MRI allows for the correct detection of nipple involvement of Paget's disease even when clinical information or mammographic/US findings are not provided.


Song Y, Wang Z, Xu H, et al.
Paget's disease is associated with eleven cancerous regions: a case report and therapeutic strategy.
J Huazhong Univ Sci Technolog Med Sci. 2009; 29(5):677-8 [PubMed]
Paget's disease of the breast is an uncommon disorder that accounts for 1% to 3% of all mammary tumors. The incidence of underlying carcinoma associated with Paget's disease has been reported in 82% to 100% of cases. The finding of underlying carcinoma reaches almost 100% when a palpable lump is also present. In this rare case, we described a patient presenting with Paget's disease but no palpable lump. However, we found 11 independent regions which were all invasive ductal carcinoma after the operation. Considering this patient, we should pay more attention to a multifocal and multicentric breast carcinoma associated with Paget's disease. Furthermore, we believe the mammography examination and a modified radical mastectomy are the most appropriate treatments for this population in clinical practice.


Liu W, Iqbal J, Khoury T
Mammary Paget's disease and extra-mammary Paget's disease: two morphologically similar but biologically different diseases.
J Cutan Pathol. 2010; 37(11):1145-9 [PubMed]
BACKGROUND: The cells of origin of mammary Paget's disease (MPD) and extra-mammary Paget's disease (EMPD) have been a controversial subject. The purpose of this study is to examine the expression of the human epidermal growth factor receptor 2 (HER2) pathway members in these two diseases.
DESIGN: HER2, AKT, pAKT, PTEN, epidermal growth factor receptor (EGFR) and pEGFR were examined in 16 MPD and 14 EMPD cases. HER2 was graded on a scale from 0 to 3. A score of 3 was considered positive. For AKT, pAKT, PTEN, EGFR and pEGFR, a semi-quantitative scoring system was used. A score >100 was considered positive. Fisher's exact test was used to analyze the data.
RESULTS: HER2 was overexpressed in 87.5% MPD and 35.7% EMPD. While AKT was expressed in all cases, pAKT was expressed in 87.5% MPD and 92.9% EMPD. Both EGFR and pEGFR were negative in all cases. PTEN was positive in 62.5% MPD and 71.4% EMPD. For pAKT+ group, HER2-/PTEN+ was recorded in 0% MPD and 38.5% EMPD (P = .01).
CONCLUSIONS: In a subset of EMPD, AKT is not activated by HER2 overexpression or by loss of PTEN, which is not the case in MPD. These data suggest that these two diseases are biologically different.


Seetharam S, Fentiman IS
Paget's disease of the nipple.
Womens Health (Lond Engl). 2009; 5(4):397-402 [PubMed]
Paget's disease of the nipple is an unusual epidermal presentation of underlying breast cancer. It presents as eczematous change or erythematous ulceration, but may also be an incidental histological finding in a mastectomy specimen. Approximately half of the underlying cancers are invasive, the remainder being ductal carcinoma in situ, and only rarely is there no associated malignancy. Routine clinical and mammographic assessment may significantly underestimate the extent of disease, but MRI may increase the sensitivity in detecting occult malignancy. Mastectomy maximizes local control; however, selected cases can be treated by nipple conisation with radiotherapy. Sentinel node biopsy is the standard of care for axillary staging in the clinically and ultrasonically node-negative case. Almost all invasive cases overexpress human EGF receptor-2 and, therefore, are likely to benefit from adjuvant chemotherapy and herceptin.


This page last updated: 22nd May 2013
Displaying links verified within last 2 weeks at time of update.

CancerIndex Logo

Home
Site Map
Cancer Types
Treatments
Locations
Glossary
Search

Patients/Public
Health Professionals
Researchers

About

Disclaimer
© 1996-2013