Search

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.

BACKGROUND/AIM Paget?s disease (PD) of the breast is a very rare presentation of breast malignancy, accounting for 1?3% of all primary breast tumors. We aimed to evaluate and compare the clinicopathological featuresand clinical outcome of PD accompanied by in situ carcinoma and invasive cancer. MATERIALS AND METHODS We used the archive of our pathology laboratory retrospectively for age, gender, history of surgery, histopathological findings, treatment modalities and follow-up information. We used the Kaplan-Meier method for survival analysis. RESULTS There were 46 female patients diagnosed with PD. In 39 (84.7%) patients invasive carcinoma accompanied PD, while 7 (15.3%) patients had ductal carcinoma in situ (DCIS). The median age at diagnosis was 53.5 years. The median follow-up period was 47 months. Of the 39 invasive carcinoma 10 (25.6%) died during the follow-up period. Invasive ductal carcinoma group had a mean overall survival of rate of 57.8 ± 6.6 months. According to univariate analysis only the tumor type was found to impact overall survival (p < 0.001) Conclusions: The current study displayed the tumor type as the only parameter affecting overall survival in the invasive carcinoma group. Although it was not statistically significant, breast cancers accompanied by PD were found to be predominantly advanced stage tumors, high grade, hormon receptor negative and HER2 positive. Key words: Paget?s disease, breast carcinoma, pathology, molecular subtype, immunohistochemistry.

We read with interest the article of Francesca Maria Plutino entitled "A peculiar case of Paget's disease of the breast" and would like to make some considerations about this particular topic 1. Mammary Paget's Disease (MPD) or Paget's disease of the breast is an uncommon pathology which accounts for less than 5% of breast cancers 1-3. MPD occurs with alterations of the nipple-areolar complex (NAC) such as redness, eczema, bleeding ulceration and usually itching 1-3. In the era of personalized care, a careful multidisciplinary management is mandatory to optimize the results and minimize the risk of overtreatment 4; an adequate knowledge of the MPD, surgical skills and use of appropriate adjuvant therapies allow to reduce the risk of local recurrence and improve the aesthetic outcomes and patient's quality of life; however, a successful work can be more easily achieved thanks to the repetitive performance of some standardized tasks, such as 5: - an accurate radiological preoperative assessment with mammography and ultrasonography is important to identify associated glandular lesions; an underlying breast carcinoma (in situ and/or invasive) may be present up to about 80% to 90% of MPD although often without an evident breast mass or mammographic abnormality (2,5); therefore, all patients with MPD should also perform a magnetic resonance imaging to detect possible underlying occult breast carcinoma and define the true extent of disease 5,6; - a pathological diagnosis should be early established by nipple scrape cytology when a MPD is clinically suspected; full-thickness punch or wedge biopsy of the NAC may be necessary to accurately diagnose MPD; the histological examination must detect malignant intraepithelial carcinoma cells, also known as "Paget cells", in the epidermis of the NAC 2,3; a needle biopsy is also required for any suspicious glandular lesion identified by imaging and associated with MPD 5; - a multidisciplinary "Surgery Board" is mandatory to select the more adequate local treatment for the patient: breast-conserving surgery (BCS) followed by radiotherapy (RT) is the optimal local treatment when a NAC resection and wide local excision of any underlying cancer allows to achieve tumour-free margins and appropriate aesthetic outcomes 4,5,7; the oncoplastic techniques with the remodelling of breast tissue and placement of clips within the excision cavity as a landmark to guide adjuvant RT should always be used in BCS in order to optimize oncological and cosmetic results 5,8,9,10. Instead, skin-sparing mastectomy with immediate breast reconstruction is indicated for MPD associated to multicentric or extensive carcinoma, inadequate margins after BCS, contraindications to adjuvant RT and patient preference 5,8. Staging and surgical treatment of the axilla in MPD is based on the possible presence of underlying cancer; sentinel lymph node biopsy (SLB) is not necessary when BCS is used to treat pure MPD or MPD associate with ductal carcinoma in situ; SLB must be performed when MPD is associated with underlying invasive cancer and treated with breast-conserving surgery; SLB is always recommended when a mastectomy is performed in order to avoid complete axillary lymph node dissection in case an invasive component is revealed at final pathology of the gland (mastectomy precludes subsequent use of SLB) 5,7,8; - a multidisciplinary "Tumor Board" is crucial to choose the adjuvant treatment; whole breast radiation should be always performed after BCS and a radiation boost should be considered for the site of the resected NAC and any associated resected cancer site 2,4,5; adjuvant systemic therapies in patients with MPD should be based on biological features and the stage of the underlying cancer; no data are available to support the use of endocrine therapy in the MPD without an associated DCIS or invasive carcinoma 5. In conclusion, a dedicated multidisciplinary pathway with meticulous repetitive performance of some specific tasks could help to perform a successful work while optimizing oncological and aesthetic outcomes in patients with MPD.

Objective To provide a rare case of local recurrent Paget’s disease after nipple-sparing mastectomy (NSM) with immediate breast reconstruction with 10 years of disease-free survival and to analyze the clinical and pathological characteristics. Background Mammary Paget’s disease can be considered a rare type of local recurrence after breast cancer treatment, both in cases of conservative surgery and NSM with immediate breast reconstruction (Lohsiriwat et al, Ann Surg Oncol 19:1850-1855, 2012). Recurrent patients who present with nipple-areolar Paget’s disease usually have unfavorable primary pathological characteristics and different latency periods. However, the recurrent status in patients with favorable primary pathological characteristics and the latency periods after NSM with immediate breast reconstruction are unclear. Methods First, we present a case of local recurrent Paget’s disease in a young patient diagnosed with invasive breast carcinoma at age 30 who underwent NSM with primary silicone reconstruction. Then, the keywords “Paget’s disease” and “nipple-sparing mastectomy” were selected. Articles including the local recurrence of Paget’s disease after NSM were collected from the PubMed, Springer, and OVID databases, and the acquired relevant data were analyzed. We did not restrict our search by study design or publication date. Results Five studies describing 31 cases of local recurrent Paget’s disease after NSM with implant breast reconstruction were included. The mean patient age reported was 45 years, and the average latency period from NSM to the local recurrence of Paget’s disease was 40.2 months. Recurrent tumor histological features were Paget’s disease with ductal carcinoma in situ (DCIS) in 16 patients (50%), Paget’s disease without DCIS in 13 patients (40.6%), and Paget’s disease with ductal intraepithelial neoplasia (DIN) in 3 patients (9.4%). The primary tumor histological feature was estrogen receptor (ER)(−)/progesterone receptor (PR)(−)/human epidermal growth factor receptor (HER-2)(+) in 21 patients (77.8%). Neither locoregional relapse nor metastatic events were found in these recurrent patients who accepted NAC excision after 4–5 years of follow-up. Our reported case showed that the patient experienced pregnancy and lactation after primary adjuvant chemotherapy and endocrine therapy. However, she developed an eczematoid lesion in the NAC 120 months after breast surgery. The histopathological examination was consistent with Paget’s disease of the breast. Complete NAC and breast silicone prosthesis removal were performed. The patient accepted no systematic or local therapy and is currently alive. It is noteworthy that the biological features of the primary tumor were ER(+), PR(+), and HER-2(−); however, the recurrent tumor changed to ER(−), PR(−), and HER-2(+). Conclusions The local recurrence of Paget’s disease after NSM is uncommon; it may develop at a very early age and have a very long time to recurrence, as in our patient, who presented with recurrence 10 years after primary surgery. Surgeons should be wary of local recurrence of the nipple-areola complex after NSM in patients with ER-negative and HER-2-positive primary tumors. However, patients with ER/PR-positive and HER-2-negative tumors should not be neglected; we reported a case of an ER/PR-positive and HER-2-negative primary tumor, and ER-positive recurrent cases have the longest latency period. The local recurrence rate of Paget’s disease after NSM is low, and the prognosis is good in recurrent patients who accept further extensive NAC excision. Further systematic treatment was not considered for this patient.

We report a unique case of a post-menopausal female who presented with a lesion on the areola. A biopsy of the lesion demonstrated a pagetoid intraepithelial neoplasm suggesting a differential diagnosis of mammary Paget disease and pagetoid Bowen disease. Excision of the lesion confirmed the diagnosis of mammary Paget disease with typical histological appearance. This case is extremely rare since both keratin 7 and ERBB2 were negative, and there was no evidence of underlying in situ or invasive carcinoma.

Mammary Paget’s disease accounts for 1% to 3% of all breast tumors and manifests as a chronic eczematous lesion of the areolar skin. It can occur without any underlying neoplasia or can be present in association with an underlying invasive and/or in situ carcinoma of the breast. The present report describes a challenging nipple punch biopsy showing an infiltration of the lower third to two-thirds of the epidermis by large, ovoid, neoplastic cells. The morphology was consistent with mammary Paget's disease, although immunohistochemistry for cytokeratin-7 (CK7) was repeatedly negative. This resulted in an initial misdiagnosis and, subsequently, a delay in the patient's follow-up. Additional immunohistochemistry for GATA binding protein 3 (GATA3) and human epidermal growth factor receptor 2 (HER2), as well as a second opinion of a breast pathologist, resulted in the diagnosis of mammary Paget's disease. The aim of this article is to raise awareness among pathologists and prevent them from misdiagnosing CK7-negative Paget disease of the breast.

Mammary Paget's disease is a disorder of the nipple-areola complex of the breast that, while rare, is often associated with an underlying carcinoma. The typical aspect is usually an eczematoid change of the nipple or a red and ulcerative nipple's lesion or erythematous and crusted lesion, with or without mass-like lesion and infiltration and inversion of the nipple. It was described at first by Sir James Paget in 1874, [1] who classified the disease in mammary and extramammary type. The mammary type (Paget' s Breast Cancer: PBC) has rare frequency. PBC occurs in 0.5-5% of all cases of breast cancer, it affects the mouth of the excretory ducts of the nipple, which is characterized by lesion of nipple's large ducts. PBC can be a superficial lesion or a nodule-tumor and it can be associated with underlying carcinoma in situ (DCIS) in more than 95% of cases, especially in postmenopausal women. In a small percentage of cases, PBC can also be associated with an invasive breast cancer. Accuracy in the diagnostic phase, in order to distinguish PBC from others diseases is paramount and histological examination of lesion's biopsy has a crucial role. Prognosis and treatment depend on the type of underlying breast cancer and are based on the stage of cancer, but more importantly, on the prompt of an adequate multidisciplinary diagnostic pathway. KEY WORDS: Histopathological Report, Oncological Outcomes Paget's Breast Cancer.Gli autori presentano un peculiare caso clinico di carcinoma mammario tipo Paget, in cui si sono evidenziate delle tendenze istologiche del bio-profilo particolarmente aggressive, oltre alla rinvenuta classica manifestazione superficiale di malattia interessante la cute del complesso areola-capezzolo, e nonostante venisse riscontrato un unico focolaio micro-invasivo. Pur caratterizzandosi per la presenza infatti di un microfocolaio in un unico dotto lattifero terminale, infiltrante la cute del complesso areola-capezzolo, in questa paziente si è evidenziato uno spiccato linfotrofismo con metastatizzazione massiva dei linfonodi ascellari omolaterali, senza poter repertare un’invasività parenchimoghiandolare intermedia o poter riscontrare altro focolaio o cluster di micro-focolai nella medesima ghiandola interessata. Il comportamento biocellulare del Paget diagnosticato, definito dagli autori “skip-gland infiltration mechanism”, ha influenzato pertanto le scelte terapeutiche successive, oltre alle preferenze espresse dalla paziente, che si sono fatte convogliare in una omnicomprensiva decisione multidisciplinare di trattamento personalizzato. La particolarità del case report è proprio definita dal comportamento biologico del ritrovato istopatologico, in cui si ritrova un carcinoma intraduttale microinvasivo in un solo dotto lattifero terminale in continuità diretta con il sovrastante Paget del complesso areola-capezzolo ma con un atteggiamento biocellulare di microinvasione stromale e metastatizzazione massiva linfonodale, come pure la presenza della immunoistochimica di alto grading (Ki 67 al 30% e Her-2 score 3+) conferma. L’aspetto istologico rinvenuto e la tipizzazione immunoistochimica relativa infatti sembrano ulteriormente rafforzare concettualmente la teoria etiopatogenetica ormai ampiamente accreditata della “Epidermotropic Theory”, ma il caso presentato permette specifiche osservazioni che possono orientare verso più ampi risvolti clinico- terapeutici già a partire dalla definizione della malattia così determinata ma anche dall’attesa verifica degli outcomes successivi in base alle strategie terapeutiche prescelte, considerazioni da vagliare su casistiche allargate ad altri casi sovrapponibili.

Bilateral axillary Paget's disease in men is a rare occurrence with limited reports on its diagnosis, treatment, and prognosis. Here, we report the case of a 55-year-old Korean male, who presented with a palpable mass and eczematous skin lesion on the left axilla. An incisional biopsy and histopathologic examination indicated invasive ductal carcinoma with Paget's disease arising in the accessory breast. Magnetic resonance imaging and positron emission tomography revealed no malignancy in the normal breast and other organs. The patient was subjected to a wide excision, wherein the left axillary lymph node was dissected, followed by the administration of adjuvant chemotherapy and radiation therapy. After 17 months of disease-free survival, the patient was diagnosed with Paget's disease of the contralateral accessory breast. He underwent wide excision surgery along with radiation therapy. To the best of our knowledge, this is the first report of bilateral extramammary Paget's disease in a male.

Background We examined the vascularity of mammary Paget disease histologically to confirm the increased blood flow observed previously by clinical imaging. The relationships among blood vessel density (BVD), histopathological parameters of blood flow in the nipple, and the expression of angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) were examined. Methods We calculated the average CD34-positive BVD and podoplanin (D2–40)-positive lymphatic vessel density (LVD) and the proportion of proliferating of endothelial cells in 14 Paget disease, 3 dermatitis biopsy, and 14 age-matched control cases. As a parameter related to blood flow in the nipple, the total CD34-positive blood vessel lumen area relative to the entire nipple area was measured in each Paget disease and control case using an automated image analysis system. Immunohistochemical expression of bFGF and VEGFA in Paget cells was also examined. Results The average BVD and LVD were significantly higher in the Paget disease cases than in the dermatitis (p = 0.003) and control (p p = 0.003). The average BVD was correlated with the average LVD (r = 0.734, p r = 0.692, p p = 0.003) and control (p r = 0.818, p r = 0.503, p = 0.006). Conclusion These results provide direct histopathological evidence of a marked increase in nipple blood flow in Paget disease detected by clinical imaging. bFGF is considered to play a pivotal role in angiogenesis in mammary Paget disease.

We report a case of recurrence as Paget's disease at the core needle biopsy (CNB) entry site in a patient with microinvasive ductal carcinoma who underwent nipple-areola-skin sparing mastectomy (NASSM) and autologous reconstruction. Clinically diagnosed recurrences associated with previous needle procedures for malignant breast lesions are rare and usually occur in patients who have not received radiation therapy. The present case involved local recurrence at the skin puncture site of a patient diagnosed based on CNB findings who underwent NASSM without receiving radiation therapy. Although the removal of the CNB tract with resected breast tissue is not always emphasized, the skin puncture site should be recorded to detect abnormal skin changes after surgery for the timely detection and management of complications.

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.

Paget's disease is a rare disorder of the nipple and/or the areola that is characterized by an erythematosquamous lesion and is often associated with in situ or invasive breast carcinoma. The authors present an atypical, exuberant case that had evolved over eight years, emphasizing the importance of early diagnosis.

Introduction: Mammary Paget’s disease (MPD) is a rare cutaneous manifestation. Epidemiologically, more than half of the MPD patients concurrently have underlying invasive ductal carcinoma (MPD-IDC), and their prognosis remains poor despite multimodal treatments of breast cancer have markedly improved patients’ survival. Accordingly, it is crucial to seek out novel therapeutic targets of MPD-IDC. As an emerging biological marker, the value of androgen receptor (AR) in MPD-IDC is inconsistent. Our objectives were to investigate the associations between AR and clinicopathological factors, and to explore its prognostic value in MPD-IDC. Methods: We retrospectively analyzed data from 103 MPD-IDC patients, and immunohistochemical staining was used to determine their AR statuses. Results: AR was expressed in 44 patients (42.7%), and AR expression was significantly correlated with body mass index (BMI) (p = 0.038) and axillary lymph node (ALN) status (p = 0.025). Kaplan-Meier curves showed that AR positivity was significantly associated with better overall survival (OS) in MPD-IDC patients (p = 0.019) and estrogen receptor-negative MPD-IDC patients (p = 0.039). Multivariate Cox regression analysis revealed that AR was not an independent prognostic indicator of disease-free survival (DFS) or OS in MPD-IDC patients (p = 0.395 and p = 0.073, respectively). Conclusions: In contrast to AR-negative tumors, patients with AR-positive ones were more likely to have lower BMI, no ALN metastasis, and better OS. AR-targeted treatments for MPD-IDC may add to existing therapeutic approaches to improve their effectiveness.

Paget’s disease (PD) of the breast is an uncommon disease of the nipple usually accompanied by an underlying carcinoma, often HER2 + , and accounting for 0.5–5% of all breast cancer. To date, histogenesis of PD of the breast remains controversial, as two theories—transformation and epidermotropic—have been proposed to explain this disease. Currently, animal models recapitulating PD of the nipple have not been described. HER2-enriched DT13 breast cancer cells were injected into the mammary fat pad of NOD scid gamma null (NSG) female mice. Immunohistochemical staining and pathological studies were performed on tumor samples, and diagnosis of PD of the nipple was confirmed by expression of proteins characteristic of Paget cells (epidermal growth factor 2 (HER2), androgen receptor (AR), cytokeratin 7 (CK7), cytokeratin 8/18 (CK8/18), and mucin 1 (MUC1)). In addition, DT13 cells grown in 2D culture and in soft agar assays were sensitive to in vitro treatment with pharmacological inhibitors targeting Her2, adenylyl cyclase, mTOR, and PI3K signaling pathways. Mice developed tumors and nipple lesions that were detected exclusively on the tumor-bearing mammary fat pad. Tumor cells were positive for proteins characteristic of Paget cells. In vitro, DT13 cells were sensitive to inhibition of Her2, adenylyl cyclase, mTOR, and PI3K signaling pathways. Our results suggest that injection of HER2 + DT13 cells into the mammary fat pad of NSG mice recapitulates critical aspects of the pathophysiology of PD of the nipple, supporting the epidermotropic theory as the more likely to explain the histogenesis of this disease.

Background Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone. Methods From the Surveillance, Epidemiology, and End Results (SEER) database, 2000‐2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD‐IDC) and 1489 women who had PD with ductal carcinoma in situ (PD‐DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD. Results PD‐IDC and PD‐DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD‐IDC and P = 0.371 in PD‐DCIS), HER2 status (P = 0.788 in PD‐IDC and P = 0.643 in PD‐DCIS), and combined molecular subtype (P = 0.196 in PD‐IDC and P = 0.853 in PD‐DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD‐IDC as well as PD‐DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD‐DCIS (ICD‐O‐3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I‐III cancer) and was associated with worse survival outcomes than the other type of PD‐DCIS. Conclusions Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD‐DCIS cases were invasive breast cancer cases that required special treatment.

Paget's disease (PD) is an intraepidermal adenocarcinoma of the skin at the breast (mammary PD) or urogenital locations (extramammary PD [EMPD]). At present, there is lack of clarity on PD's pathogenesis, the relationship between its subtypes, and its lineage link with the underlying invasive carcinomas. Here we describe that mammary PD and EMPD have similar mutational profiles, with the most frequent recurrent mutations occurring in the chromatin remodeling genes, such as KMT2C (MLL3, 39%) and ARID2 (22%), with additional recurrent somatic mutations detected in genes previously not known to be mutated in cancers, such as CDCC168 (34%), FSIP2 (29%), CASP8AP2 (29%), and BIRC6 (24%). In paired mammary PD and underlying breast carcinoma samples, distinct gene mutations were detected, indicating that they represent independent oncogenic events. Finally, multistage EMPD tissue sequencing revealed KMT2C gene occurring early in EMPD oncogenesis, and that multifocal EMPD samples share the same early gene mutations, suggesting clonal origin of multifocal EMPD. Our results reveal similar genomic landscapes between mammary PD and EMPD, including early aberrations in chromatin remodeling genes. In addition, mammary PD and underlying breast ductal carcinomas represent independent oncogenic events. These findings provide approaches for developing diagnostic tools and therapeutic interventions for PD.

Pagets disease of the breast (PD) is a rare type of carcinoma that affects the skin of the nipple-areolar complex. Unresolved issues exist regarding its diagnosis and therapy. The aim of the study was to gather data on how the therapy of the disease is approached in clinical practice, and to formulate current diagnostic and therapeutic recommendations.Retrospective evaluation of data from medical records of patients with PD who underwent surgery at our department between 2001 and 2020. The data was evaluated using basic statistical methods.Sixty four female patients with the mean age of 62.5 years. In 58 women, PD was confirmed before surgery, with the median of 20 weeks from initial symptoms to diagnosis. Forty seven of the patients were operated for presumed isolated PD; in 38 cases, histopathological evaluation of the specimen revealed an associated malignancy in the mammary gland. Primary breast-conserving surgery (BCS) was performed in 46 patients; surgical revision was indicated in 17 cases. In 6 patients with PD associated with non-invasive breast cancer treated by BCS without radiotherapy (RT), a local recurrence appeared in 3 cases, which is significantly more compared to the group of patients undergoing total mastectomies (p=0.032). No local recurrence appeared in 9 cases of isolated PD treated by BCS, including 6 patients without RT. The tumors associated with PD were mostly ER-negative (44/57) and HER2-positive (22/25).In cases where PD is suspected, careful clinical examination and the use of available diagnostic imaging techniques including MRI are appropriate. BCS without RT is not an adequate oncological therapy where an associated malignancy of the breast is found.

Paget disease of the breast (PDB) is a rare form of cutaneous breast cancer. Up to date, no randomized studies evaluated the different management strategies. This systematic review investigates the role of radiotherapy and its best technical profile in the treatment of this disease, with great attention to doses and fractionation regimens.A systematic search was performed on PubMed, Embase and Scopus in order to detect case reports, case series and prospective as well as retrospective clinical studies describing histologically proven PDB and providing information about pertinent radiation treatments. Searching strategy followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines.Inclusion criteria were met by six papers, dealing with radiation treatments performed postoperatively and in exclusive settings. No evaluations were performed on preoperative radiotherapy.Actually, the standard treatment of PDB reflects oncological principles of breast carcinoma therapy, including the role of breast-preserving surgery. The traditional radiotherapic dose is 50 Gy, with daily fractionation of 2 Gy. Adjuvant radiotherapy following breast preserving surgery represents the current standard of care; prospective studies could be of help in defining the role of exclusive radiotherapy, hypofractionated schemes and smaller target volumes.

A 90-year-old male visited our hospital because redness of his left chest. An erythema of 25 mm in size with indistinct border was observed on the left nipple, and mammary' Paget's disease was diagnosed with a skin biopsy. Ultrasound examination revealed no significant findings in the mammary gland, so a left mastectomy was performed under local anesthesia. The final pathological diagnosis was mammary' Paget's disease with noninvasive ductal carcinoma in the duct. We have experienced a very rare male mammary' Paget's disease because both male breast cancer and mammary' Paget's disease are rare.

The aim of our work is to illustrate a new technique for the histological diagnosis of Paget’s disease (PD) using a core needle biopsy with a semiautomated 14-gauge needle called nipple-core needle biopsy (N-CNB). We report 3 years’ experience in our senology unit. Twenty-six women with 26 clinical of nipple–areola complex (NAC) changes with suspected PD and subjected to core needle biopsy using our new 14G semiautomated needle technique were included in our study group. Institutional review board approval was obtained for this retrospective analysis. A semiautomated biopsy gun with a 14-gauge, 15-cm-long needle was used for this new procedure. After a subcutaneous injection of anesthetic and spray-ice application to the NAC, the 14G needle was opened with the cradle exposed and positioned on the NAC with considerable pressure exerted on the same. The cradle was then closed by triggering the needle spring, and 2–4 core samples were withdrawn by moving the needle position each time. Clinical, instrumental and histological differences between the lesions that gave benign results after N-CNB and those that resulted PD were analyzed by applying the Fisher's exact test. After N-CNB, 13/26 lesions were found to be PD (50%) while 13/26 alterations were benign (50%). No malignant lesions were detected during the follow-up in patients with benign N-CNB results. The diagnosis of PD obtained with N-CNB was confirmed in all 13 cases by means of a histological analysis of the surgical specimens. No significant post-biopsy complications were recorded. Patients with PD more frequently presented nipple retraction (ρ = 0.0407) and associated suspicious (i.e., BI-RADS 4 and 5) mammographic (ρ = 0.0006) findings compared to patients whose N-CNB had given benign results and the difference was statistically significant. In conclusion, with this novel technique, we were able to obtain an easy, painless, major complication-free and accurate diagnosis of PD of the NAC using a semiautomated core needle biopsy with a 14-gauge needle.

Paget's disease is a rare disorder of the nipple and/or the areola that is characterized by an erythematosquamous lesion and is often associated with in situ or invasive breast carcinoma. The authors present an atypical, exuberant case that had evolved over eight years, emphasizing the importance of early diagnosis.

Paget's disease of the breast (PDB) is a rare breast carcinoma believed to arise from an underlying in situ or invasive ductal cancer that migrates through the epidermis causing characteristic skin changes including scaling, redness, and itching of the nipple, areola, and sometimes the surrounding skin. Although Paget's may mimic benign conditions such as contact or allergic eczema and mastitis, it should remain a strong consideration in the differential diagnosis , especially in peripartum women for whom benign conditions such as bacterial mastitis from breastfeeding are common. The workup of Paget's should focus on both making the diagnosis with nipple/skin scrape cytology or punch biopsy as well as evaluating any underlying mass with mammogram, breast ultrasound , and also a core needle biopsy , if required. Treatment focuses on management of the underlying breast cancer as usual. The purpose of this chapter is to describe the presentation of PDB as well as outline an approach to its diagnosis and management, especially in the setting of pregnancy and lactation.

No national data have been available on descriptive epidemiology of mammary Paget’s disease (MPD) in China. This population-based study aimed to estimate the prevalence of MPD and its pattens by sex, age and area in China. We conducted a population-based study using data in 2016 from China’s Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion residents. MPD cases were identified based on the diagnostic names and codes in claim data. A total of 825 patients of confirmed diagnosis of MPD were found during the study period. The prevalence of MPD in 2016 was 0.42 per 100,000 population (95% CI 0.19 to 0.73), with marked female predominance. The prevalence rates peaked at 40–59 years and ≥ 80 years in females and males, respectively. The prevalence rates varied among different regions, ranging from 0.06 (95% CI 0.00 to 0.23) in Northeast China to 1.21 (95% CI 0.07 to 3.72) in Northwest China. MPD showed marked female predominance in China. Chinese female patients were much younger, with lower prevalence than that in the United States. Obvious sex difference in the age pattern of MPD prevalence was also observed in China.

The classical Paget's disease of the nipple is histologically characterized by tumor cell infiltration originating in intraductal or invasive breast carcinoma, immunohistologically by a frequent overexpression of HER2 and clinically by eczema-like changes of the nipple and areola. Variants with different histological, immunohistological, and clinical features are observed in nonclassical forms of Paget's disease, such as isolated Paget's disease of the nipple, anaplastic Paget's disease, Paget's disease with invasion, and pigmented Paget's disease of the nipple. In the differential diagnosis of Paget's disease, benign changes have to be considered, including Toker cell hyperplasia, nipple eczema, and rare dermatoses.

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.

Background: The aim of this study was to present several cases of benign and malignant nipple lesions and contribute to diagnosis and differential diagnosis. Methods: A retrospective study was conducted on 13 patients. All of the patients were evaluated by ultrasonography, and 11 of them had pathological results. We analyzed the clinical and sonographic features. Results: There were 3 malignant lesions, 7 benign lesions, and 3 congenital nipple dysplasia, listed as follows: Malignant lesions (n = 3, 23%): Paget's disease (PD, n = 3, 23%). All of the patients with PD showed unilateral nipple erosion, discharge, and pain. The ultrasound showed abundant blood flow (n = 3, 23%); 2 patients (n = 2, 15%) had microcalcifications. Benign lesions (n = 7, 54%): Adenoma of the nipple (n = 2, 15%). One patient (n = 1, 8%) had nipple erosion and discharge. Two patients (n = 2, 15%) had a palpable nodule in the nipple. The ultrasound of both patients (n = 2, 15%) showed regular-shaped, clear border nodule with abundant blood flow (n = 2, 15%). Leiomyoma of the nipple (n = 1, 8%): This male patient was characterized by unilateral nipple enlargement and pain. The ultrasound showed a regular nodule with absent blood flow. Plasma cell mastitis (n = 2, 15%): Two patients showed unilateral nipple inversion and pain. One patient (n = 1, 8%) showed swollen and redness. The 2 patients showed a lesion in the gland around the nipple present as an irregular shape and unclear boundary hypoechoic mass. Nipple wart (n = 2, 15%): Two patients showed a unilateral soft exogenous neoplasm. Both of the patients showed a hypoechoic wart; the echo was similar to the nipple, the border was clear, and had no blood flow in the wart. Nipple Dysplasia (n = 3, 23%): Accessory nipple (n = 3, 23%). Two patients (n = 2, 15%) had accessory nipples in the subcoastal area, 1 patient (n = 1, 8%) in the areolar. All of the patients’ sonographic features were the same as the nipple. The positive predict value (PPV) of the clinical symptoms: Erosion and discharge are both 75% (P

Paget’s disease of the breast is a rare intraepithelial malignancy involving the nipple–areola complex, often associated with an underlying in-situ or invasive carcinoma in the breast parenchyma. Most of the cases disease is usually limited to nipple–areola or surrounding periareolar skin. We are reporting a case of extensive Paget’s disease, involving entire breast skin and even part of abdominal wall skin without any underlining breast pathology, which is a rare presentation.

Paget's disease (PD) denotes an initially intra-epidermal adenocarcinoma that can later invade the dermis and metastasise. Among the extramammary forms of PD (EMPD), penoscrotal presentations are rarer than the vulvar and perianal forms. Once diagnosis has been confirmed by histopathological examination, a search for associated neoplasia must be conducted, although penoscrotal EMPD is less frequently associated with underlying neoplasia than mammary PD (MPD). The associated cancer most often involves a neighbouring organ, with prostate cancer being the most common, or in some cases consists of underlying cutaneous adnexal tumours. First-line therapy consists of surgical excision. Alternatives to surgery (imiquimod, CO2 laser vaporisation, dynamic phototherapy) may be considered in certain cases.

Context.— Paget disease of the breast, in most cases, represents intraepidermal spread of ductal carcinoma in situ. Molecular subtypes of invasive carcinoma of the breast have prognostic and therapeutic significance and show characteristic distribution. Little is known about the distribution of molecular subtypes in Paget disease of the breast. Objectives.— To examine the distribution of molecular subtypes in Paget disease of the breast and to compare them to concurrent invasive carcinoma of the breast, if present. Design.— We examined 48 cases of Paget disease of the breast with immunohistochemistry and antibodies against estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as HER2 chromogenic in situ hybridization, to classify the cases into molecular subtypes. Then, we compared the results to the molecular subtypes of associated invasive carcinoma of the breast, if present. Results.— The HER2 subtype was the most common found in Paget disease of the breast, followed by the luminal B subtype and 2 cases of the triple-negative subtype. The associated invasive carcinoma cases were most often of the luminal B subtype, followed by the HER2 subtype and the triple-negative subtype. The molecular subtype of Paget disease and invasive carcinoma was congruent in most of the cases. Conclusions.— Molecular subtypes of invasive carcinoma of the breast can already be detected in Paget disease. The distribution of molecular subtypes of Paget disease and of Paget disease–associated invasive carcinoma differs from invasive carcinoma without associated Paget disease, with the HER2 subtype overrepresented in Paget disease and associated invasive carcinoma and the luminal and triple-negative subtypes underrepresented.

The objective of this study was to investigate the clinicopathological characteristics and survival outcomes of Paget disease (PD), Paget disease concomitant infiltrating duct carcinoma (PD‐IDC), and Paget disease concomitant intraductal carcinoma (PD‐DCIS). We identified 501,631 female patients from 2000 to 2013 in the Surveillance, Epidemiology, and End Results (SEER) database. These identified patients included patients with PD (n = 469), patients with PD‐IDC (n = 1832), and patients with PD‐DCIS (n = 1130) and infiltrating ductal carcinoma (IDC) (n = 498,076). Then, we compared the clinical characteristics of these patients with those who were diagnosed with IDC during the same period. The outcomes of these subtypes of breast carcinoma were different. Based on the overall survival, the patients with PD‐IDC had the worst prognosis (5‐year survival rate = 84.1%). The PD‐DCIS had the best prognosis (5‐year survival rate = 97.5%). Besides, among patients with Paget disease, the one who was married had a better prognosis than who were not. And, according to our research, the marital status was associated with the hormone receptor status in patients with PD‐IDC. Among three subtypes of Paget disease, patients with PD‐IDC had the worst prognosis. Besides, patients who were unmarried had worse outcomes. And the marital status of patients with PD‐IDC is associated with hormone status. The observation underscores the importance of individualized treatment.

We report a case of invasive solid papillary carcinoma (SPC) of the nipple with Pagetoid extension to the skin and lymph node metastasis. SPC is an uncommon primary breast cancer accounting for less than 1% of all breast cancers. Only 2 cases occurring in the nipple have been reported. However, both cases were without Pagetoid extension or lymph node metastasis. The presently reported tumor consisted of irregularly shaped solid cell nests with delicate fibrovascular cores. The tumor cells had round nuclei with low-grade atypia and eosinophilic cytoplasm. Neuroendocrine differentiation was confirmed by immunohistochemical positivity for CD56, synaptophysin, and chromogranin A. Immunohistochemistry also confirmed the absence of myoepithelial cells around the tumor cell nests. Therefore, a diagnosis of invasive SPC was made. Additionally, tumor cell deposits in the intramammary and axillary lymph nodes were identified, and these deposits had the same histological characteristics as the invasive SPC of the nipple. The invasiveness of SPC can be difficult to determine. However, the tumor cell nests in the current case exhibited a retraction artifact, which is known to be associated with invasive carcinoma and a poor prognosis, as well as morphological patterns that have been previously identified as characteristic of invasive SPC. Although SPC is widely recognized as having a favorable outcome, the existence of exceptionally aggressive cases occurring in the nipple must be recognized. Additional cases of invasive SPC of the nipple are needed to analyze the clinicopathological correlation.

Paget disease, Bowen disease, and malignant melanoma in situ are intraepidermal neoplasms, characterized by the presence of pagetoid scatter of atypical cells in the epidermis. This study reviewed the frequency of select histologic criteria to validate their usefulness in the histologic distinction between these entities.One hundred forty-four specimens with the diagnosis of Bowen disease, 144 specimens with Paget disease (mammary and extramammary), and 144 specimens with malignant melanoma in situ were examined microscopically to define frequencies of select histologic criteria present in each disease.Comparison between mammary Paget and extramammary Paget disease showed no significant differences in the features studied. Crushing of basal keratinocytes, presence of atypical cells in the corneum, and presence of large cells with amphophilic cytoplasm were significantly noted in Paget disease. Transition between the atypical clear cells and surrounding keratinocytes was absent in all cases of melanoma in situ and in 87 (60.4%) cases of Paget disease, but it was significantly associated with Bowen disease (98.6%). Dyskeratotic cells were significantly associated with Bowen disease cases.Our study demonstrated a practical histologic approach to differentiate between intraepidermal pagetoid neoplasms. Careful histologic study of the proposed criteria may reduce reliance on immunohistochemical stains.

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.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.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).Her2 positive tumors have distinct epidemiologic, clinical, and treatment characteristics.