Paget's disease of the breast: diagnosis and management.

Paget's disease of the breast typically affects postmenopausal women and is associated with an underlying malignancy. Skin changes are a common presenting symptom, as well as a lump, nipple discharge, pain and changes to the nipple shape. Imaging options include ultrasound for women under the age of 35 years or mammogram and ultrasound for women over the age of 40 years. The definitive diagnostic investigation is a tissue core biopsy. Cases are discussed by a multidisciplinary team to decide on the optimal management strategy. Management options are typically surgical and include breast-conserving surgery or mastectomy in addition to oncoplastic techniques. Sentinel lymph node biopsy is performed in all patients undergoing surgery. Adjuvant chemotherapy, radiotherapy or endocrine therapy can be used to treat concomitant invasive disease or ductal carcinoma in situ.

Examining racial differences in treatment and survival among patients with Paget's disease of the breast.

BACKGROUND: The objective of this study was to evaluate racial differences in treatment (ie, surgery, chemotherapy, and radiation) and survival among patients with Paget's disease of the breast in the Surveillance, Epidemiology and End Result program. METHODS: Women >18 years old diagnosed with localized or regional Paget's disease between January 1, 2010 to December 31, 2016 in the Surveillance, Epidemiology and End Result program were included. The cohort was divided into Black and White patients. Univariable analysis compared the groups. Using propensity score matching, Black and White patients were nearest matched (1:2) on age at diagnosis; Surveillance, Epidemiology and End Result summary stage; surgery; chemotherapy; and year of diagnosis. The log-rank test evaluated the matched sample's overall survival and disease-specific survival. RESULTS: Of the 1,181 patients, the racial distribution was 1,049 (88.8%) White and 132 (11.2%) Black. A higher percentage of Black women were Medicaid insured (Black 25.8% vs White 11.1%), lived in neighborhoods with low socioeconomic status (Black 53.0% vs White 25.4%), and had regional disease than White women (Black 41.7% vs White 29%). There were no racial differences in receipt of radiation therapy (P = .90), breast surgery (P = .23), or axillary surgery (P = .25). Black patients were more likely to receive chemotherapy (Black 34.8% vs White 26.3% P = .038). In the propensity matched cohort, Black patients had a worse overall survival (P < .005) and disease-specific survival (P = .05) than White patients. CONCLUSION: In this cohort of patients with Paget's disease, despite differences in sociodemographic factors, there were no disparities in locoregional treatment. However, on matched analysis, Black patients had a worse overall survival and disease-specific survival than their White counterparts.

A monolateral pigmented lesion of the nipple.

Pigmented mammary Paget's disease is a very rare variant of mammary Paget's disease linked to an underlying carcinoma in almost all cases. We present the case of a 62-year-old female patient who came to our attention for the evaluation of a monolateral asymptomatic pigmented lesion of the right nipple, which turned out to be a pigmented mammary Paget's disease unassociated to an underlying malignancy - an extremely rare entity only anecdotally reported in literature. The two main peculiarities of our patient's lesion, the importance of immunohistochemistry in the differential diagnosis and the theories on its pathogenesis are discussed. Further studies are necessary to establish the best treatment options. Click here for the corresponding questions to this CME article.

Overall and cancer-specific survival in patients with breast Paget disease: A population-based study.

Paget disease of the breast is an uncommon malignant tumor with an inferior outcome. Therefore, establishing nomograms to predict the survival outcomes of breast Paget disease patients is urgent. Clinicopathological and follow-up data of breast Paget disease patients diagnosed between 2010 and 2016 were retrieved through the Surveillance, Epidemiology, and End Result (SEER) database. The significant factors were screened out, and then those factors were utilized to build two valuable nomograms. The discriminative ability of nomograms was investigated using concordance-index (C-index), while the predictive accuracy and benefits were evaluated using calibration curves and decision curve analysis. Finally, a total of 417 breast Paget disease patients were enrolled. Tumor grade, histological type, American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, and marital status were confirmed as independent overall survival (OS)-related factors; tumor grade, histological type, AJCC stage, and age were associated with independent cancer-specific survival (CSS)-related factors. The values of the C-index for OS nomogram acquired were 0.827 and 0.745 for training and validation cohorts, respectively. Meanwhile, the corresponding values of the C-index to CSS nomogram were 0.890 and 0.655, respectively. The calibration curves and decision curve analysis indicated that both nomograms had an excellent performance. Finally, the nomogram-based risk stratification system indicated that all breast Paget disease patients could be classified into low- and high-risk groups and showed distinct outcomes. In conclusion, two valuable nomograms incorporating various clinicopathological indicators were established for breast Paget disease patients. These prognostic nomograms provide accurate prognostic assessment for breast Paget disease patients and help clinicians select appropriate treatment strategies.

Mammary Paget's Disease Presenting as an Annular Plaque.

Dear Editor,Mammary Paget's disease (MPD) is an adenocarcinoma localized within the epidermis of the nipple and/or the areola of the breast, and it is as a rule associated with a carcinoma of the underlying lactiferous ducts, where it usually starts. MPD is relatively rare, observed in 0.7-4.3% of all breast cancers (1). We present a patient with MPD and atypical clinical finding as an annular plaque. A 74-year-old Japanese woman with a past medical history of hypothyroidism presented with a 6-month history of an itching plaque on the left areola. The patient had been treated with the application of topical steroids for a duration of approximately 5 months, and showed no clinical improvement. Physical examination showed a pink plaque encircling the nipple on the left areola (Figure 1, a). The right nipple and areola appeared normal (Figure 1, b). No palpable masses were detected within either breast. A 3.5 mm punch biopsy of the skin at the 6 o'clock position of the left areola was performed. Histological examination showed single and small aggregations of atypical cells with large hyperchromatic nuclei and pale-staining, ample cytoplasm throughout the epidermis. There was a lymphocytic infiltration in the dermis (Figure 1, c). Immunohistochemical studies were positive for CK7 and negative for S-100 and HMB45. With the diagnosis of MPD, the patient underwent a partial mastectomy of the left breast center area, consisting of surgical excision of the left nipple, the adjacent surrounding areolar skin, and subcutaneous tissues. Subsequently, radiation therapy for the residual breast was prepared. As has been described in detail by Kanitakis, the skin lesion develops insidiously as a scaly, fissured, or oozing erythema of the nipple and, more rarely, the areola. Advanced lesions present as a well-demarcated, round, ovoid, or polycyclic eczema-like plaque with a pink or red hue. It is occasionally slightly infiltrated and has an erosive, oozing, scaly, or crusted surface. The lesions are almost invariably unilateral, showing centrifugal spread. Retraction or ulceration of the nipple are often noted (1). The present case exhibited a very rare clinical finding of a plaque encircling the nipple, which has not been reported previously. It was initially difficult to establish the diagnosis of MPD, and biopsy was needed to obtain a definitive diagnosis. Differential diagnosis of MPD comprises eczema as atopic dermatitis or contact dermatitis, erosive adenomatosis, and malignant skin condition such as Bowen's disease, superficial basal cell carcinoma, or superficially spreading melanoma. As in the present case, individuals presenting with an annular plaque are often considered to have sebaceous hyperplasia. Sebaceous hyperplasia is a common, benign skin condition involving hypertrophy of the sebaceous glands, common in middle-aged or older adults (2). These lesions can be single or multiple and manifest as yellow, soft, small papules. These papules are occasionally seen around the nipple, forming an annular plaque. In general, sebaceous hyperplasia is described as yellow-colored papules among Caucasians. However, caution is needed, since it is characterized by skin-colored papules among some Asians.In the present case, some pigmentation (2 to 3 mm in diameter) was observed on the left nipple. Pigmented MPD have been reported, and the mechanism underlying the pigmentation is not yet fully understood, but it has been proposed that Paget cells may release melanocytic chemoattractants or basic fibroblast growth factors that stimulate the proliferation of melanocytes within the tumor nests (3). The possibility of physiological pigmentation cannot be ruled out in the present case; on the other hand, the possibility of pigmented MPD cannot be ruled out either, since no pigmentation was observed on the right nipple.

Paget disease of the breast: A national retrospective analysis of the US population.

BACKGROUND: Paget's disease of the breast is rare. The National Cancer Database (NCDB) is one of the largest tumor databases in the United States. METHODS: We queried the NCDB to identify male and female patients with Paget's disease of the breast who were treated from January 1, 2004, through December 31, 2015. No age limitations were applied. Descriptive statistical analysis and survival analysis were performed. RESULTS: We analyzed the demographic, disease, and treatment characteristics of 7,191 patients with Paget's disease of the breast. The median (range) age was 64 (20-90) years. Only 2.1% of patients were men, and 85.4% were white. The most common treatment was complete mastectomy (65.3%), followed by partial mastectomy (30.3%). Tumor destruction was performed in 0.1% of patients, and 4.3% of patients did not undergo any surgery. We examined survival in the subset of 6,864 patients who were treated surgically with complete mastectomy or partial mastectomy. The 5-year survival rate after surgery was 82.5% (95% CI, 81.1%-83.9%). Factors associated with shorter survival were older age, black race/ethnicity, higher tumor grade, regional lymph node metastasis, higher cancer stage, metastatic cancer, and larger tumor size. CONCLUSIONS: Paget's disease of the breast usually affects patients older than 60 years, and the most common treatment is complete mastectomy. The 5-year overall survival rate of patients with Paget's disease of the breast is greater than 80% but is lower among older and black people.

Caso Clínico: Enfermedad de Paget del Pezón / Clinical Case Report: Paget's Disease of the Nipple

INTRODUCCIÓN: La enfermedad de Paget del pezón es infrecuente y representa del 1 al 3 % de las neoplasias de mama. Está asociada con un carcinoma invasivo o in situ en el 82 al 94 % de los casos. Se presenta entre los 55 a 64 años de edad. CASO CLÍNICO: Se presenta el caso de una mujer de 58 años con zona de descamación de 1 cm2 indolora en pezón derecho y tumor de 4 cm2 en mama izquierda, ecografía y mamografía BI-RADS III. Biopsia incisional de pezón derecho que reportó enfermedad de Paget, con ampliación de márgenes. Se completó estudios de extensión con resonancia magnética que reportó lesión retro-areolar sospechosa en mama derecha y lesión nodular maligna en mama izquierda. EVOLUCIÓN: Se realizó cuadrantectomía central más neo-pezón en mama derecha, y en mama izquierda cuadrantectomía superoexterna con vaciamiento ganglionar axilar bilateral, el reporte de patología fue mama derecha negativa para malignidad, mama izquierda hiperplasia intraductal atípica con focos de carcinoma intraductal. Se administró 25 sesiones radioterapia, tras un año de seguimiento se mantiene sin recurrencia. CONCLUSIÓN: La enfermedad de Paget es poco frecuente, pero debe considerarse como diagnóstico diferencial en pacientes sobre los 55 años, su tratamiento estandarizado es quirúrgico, la adyuvancia con radioterapia aún es motivo de discusión. El autoexamen de mama, el acudir a controles periódicos a partir de los 40 años además de realizar una ecografía y mamografía nos lleva a diagnósticos tempranos con un elevado porcentaje de cirugías más conservadoras.(au)

BACKGROUND: Paget's disease of the nipple is uncommon and represents 1 to 3% of breast malignancies. It is associated with invasive or in situ carcinoma in 82 to 94% of cases. It occurs between 55 to 64 years old. CASE REPORT: We present the case of a 58 year old woman with a painless 1cm2 scaling skin lesion in the right nipple and a 4cm2 tumor in the left breast, ultrasound and mammograghy classified as BIRADS III. Incisional biopsy of the right nipple that reported Paget's¬ disease, with extension of surgical margins of resection. MRI extension studies were made; they reported suspicious retroaereolar lesion in the right breast and malignant nodular lesion in the left breast. EVOLUTION: We performed central quadrantectomy with nipple reconstruction in the right breast, and superoexternal quadrantectomy in the left breast, with bilateral axillary lymph node dissection, the pathology report was negative for malignancy in the right breast, in the left breast atypical intraductal hiperplasia with foci of intraductal carcinoma. The patient received 25 radiotherapy sessions. After one year of follow-up there is no recurrence. CONCLUSIONS: Paget's disease is rare, but should be considered as a differential diagnosis in patients over 55 years, its standardized treatment is surgery, adjuvant treatment with radiotherapy is still a matter of discussion. Breast self-exam, regular checkups in people over 40 years old, ultrasound and mammogram lead to early diagnosis with a higher percentage of conservative surgeries.(au)

Breast-Conserving Surgery in Patients With Mammary Paget's Disease.

BACKGROUND: We aimed to analyze the association between Paget's disease (PD) and breast cancer (BC) subtypes and compare the effect of breast-conserving surgery (BCS) as a local treatment with mastectomy for PD. MATERIALS AND METHODS: Data of patients with histologic type International Classification of Diseases-0-3 8540-8543 who were treated from 1973 to 2014 were retrieved from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute. A chi-square test was used to identify differences in categorical data among different groups. Overall survival (OS) was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, sequential landmark analysis, and propensity score-matched analysis. RESULTS: The study cohort included 5398 patients. Triple-negative BC accounted for the fewest patients with PD-only (1/22, 4.54%), Paget's disease-ductal carcinoma in situ (PD-DCIS) (3/48, 6.25%), and Paget's disease-invading ductal carcinoma (PD-IDC) (23/352, 6.53%). According to the results of the log-rank test and Cox analysis, the 10-year OS rates were similar for the BCS and mastectomy subgroups among patients with PD-DCIS or PD-IDC. Furthermore, there were no significant differences in survival benefits among the different surgeries after propensity score matching. Landmark analyses for OS of patients with PD-DCIS or PD-IDC surviving more than 1, 3, and 5 y showed no significant differences in survival. There were statistical differences in 10-year OS rates for patients with PD-DCIS or PD-IDC who underwent radiation therapy, or not, following BCS (both, P < 0.001). CONCLUSIONS: For patients with PD-DCIS or PD-IDC, breast conservation therapy with lumpectomy and radiation is an effective local treatment strategy, compared with mastectomy.

Characteristics and treatment of human epidermal growth factor receptor 2 positive breast cancer: 43,485 cases from the National Cancer Database treated in 2010 and 2011.

BACKGROUND: Although identification of human epidermal growth factor receptor 2 (Her2) positive breast cancer represents one of the greatest advances over the past 3 decades, it has not been studied extensively on a national level. METHODS: The National Cancer Database is a joint project of the American Cancer Society and the American College of Surgeons and contains data on about 70% of the cancer cases in the United States. Data on Her2 have been collected since 2010 and was used for this study. RESULTS: Of 298,937 cases of invasive breast cancer with known Her2 status diagnosed in 2010 and 2011, 43,485 (14.5%) were Her2 positive. Her2 positivity was greatest in Asian/Pacific Islanders and least in non-Hispanic Whites and was markedly more common in younger women. The incidence of Her2 positive tumors ranged from a low of 13.9% in the Mountain West region to a high of 16.0% in the West South Central region (P < .001). Compared with Her2 negative tumors, Her2 positive tumors were larger (2.6 vs 2.2 cm, P < .001), more likely to have positive nodes (39% vs 31% P < .001), have lymphovascular invasion (30% vs 20%, P < .001), and be high grade (56% vs 29%, P < .001). There were also differences by histology: invasive ductal 16.4%, invasive lobular 5.5%, tubular 2.3%, inflammatory 36%, and Paget's with invasion 59%. When adjusted for age, race, tumor size, and nodal status Her2 positive tumors were much more likely to receive chemotherapy (odds ratio = 5.5, confidence interval = 5.2 to 6.0) and somewhat less likely to undergo breast preservation (odds ratio = .78, confidence interval = .76 to .80). CONCLUSIONS: Her2 positive tumors have distinct epidemiologic, clinical, and treatment characteristics.

The effect of Paget disease on axillary lymph node metastases and survival in invasive ductal carcinoma.

BACKGROUND: The objective of this study was to examine the effect of Paget disease (PD) on axillary lymph node metastases and survival in patients who had concomitant invasive ductal carcinoma (PD-IDC). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women who were diagnosed with PD-IDC from 2000 to 2011, comparing baseline demographic and tumor characteristics with those who were diagnosed with IDC alone during the same period. Multivariable logistic regression was used to examine the association of PD-IDC with axillary lymph node metastasis, and breast cancer-specific survival and overall survival were compared between the PD-IDC and IDC groups using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: The study cohort included 1102 patients with PD-IDC and 302,242 controls with IDC alone. PD-IDC tumors were more likely to be centrally located (26.9% vs 5.5%; P < .001), high grade (63.5% vs 40.3%; P < .001), >2 cm in greatest dimension (47.1% vs 35.7%; P < .001), and estrogen/progesterone receptor-negative (45.2% vs 22.1%; P < .001). In adjusted analyses, patients with PD-IDC had higher odds of axillary lymph node metastasis (odds ratio, 1.83; P < .001). The unadjusted 10-year breast cancer-specific and overall survival rates were lower for the PD-IDC group compared with the IDC-alone group, although, after adjusting for disease stage, tumor characteristics, and local therapy, no significant differences in mortality risk were observed between the 2 groups (hazard ratio, 0.91; P = .24). CONCLUSIONS: PD-IDC is associated with an increased risk of axillary lymph node metastasis, but not with inferior survival, compared with IDC alone after adjustment for other disease factors.

Pigmented Paget's disease of the nipple.

Pigmented Paget's disease of the nipple (PPD) is an uncommon variant of Paget's disease. An accumulation of melanin within the lesion imparts a brow color to the affected area, so the lesion might clinically as well as histologically mimic melanoma. We present a case of PPD in a 60-year-old woman.

Mammary and extramammary Paget's disease.

Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent.

Mammary and extramammary Paget's disease

Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent.

[Diagnosis and treatment for Paget's breast cancer: state of the art].

Breast cancer is the most common cancer in women. According to WHO experts in the world each year there are revealed from 800,000 up to 1 million new cases of breast cancer. In the structure of malignant tumors morbidity among female population, in Russia in 2012 breast cancer ranked the first place (20.7%) and remained the leading malignant pathology in women. Paget's breast cancer is a rare form of breast cancer that occurs in the mouth of the excretory ducts of the nipple, which characterized by lesion of the nipple and large ducts, often with the formation of tumor in the breast. This rare abnormality occurs in 0.5-5% of all cases of breast cancer.

Paget's disease of the nipple.

Paget's disease of the breast is a disorder of the nipple-areola complex that, while rare, is often associated with an underlying carcinoma. It is characterized by eczematoid changes of the nipple. Two theories have been proposed to explain the pathogenesis of Paget's disease. The Epidermotropic, which is the most accepted theory, suggests that Paget's cells originate from ductal cancer cells that had migrated from the underlying breast parenchyma. It is supported by the predominance of breast cancer markers found in Paget's disease. This article provides an overview of Paget's disease of the breast with special attention to immunohistochemistry and raises the question of new therapeutic approaches.

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.

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.

A rare case report of a primary large-cell neuroendocrine carcinoma of the breast with coexisting Paget disease.

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.