Correlation analysis between androgen receptor and the clinicopathological features and prognosis of mammary Paget's disease.

PURPOSE: Little is known about the prognostic value of androgen receptor (AR) status in mammary Paget's disease (MPD). The purpose of this study was to explore AR status and the distribution of molecular subtypes in MPD as well as the relationship between AR expression and clinicopathological factors and to evaluate its prognostic value. METHODS: We analyzed 170 MPD patients of varying subtypes. AR expression was verified by immunohistochemical staining, and the correlations between AR expression and clinicopathological characteristics and survival status were analyzed. We further investigated 91 MPD patients with invasive ductal carcinoma (MPD-IDC). RESULTS: AR was expressed in 55.3% of overall MPD patients, and 78.2% had the human epidermal growth factor receptor 2 (HER2) overexpression subtype. AR positivity was significantly correlated with BMI (P = 0.037) and pathological N stage (P = 0.023). Multivariate analysis indicated that pathological T stage and pathological N stage were independent prognostic factors for overall survival (OS). The positive AR group was significantly associated with better OS (P = 0.014). Among 91 MPD-IDC patients, AR was expressed in 56.0%, and 80.0% had the HER2 overexpression subtype. AR positivity was significantly correlated with pathological N stage (P = 0.033). Multivariate analysis indicated that AR and pathological T stage were independent prognostic factors for OS. Furthermore, AR positivity was significantly related to better OS (P = 0.005) in MPD-IDC patients as well as in patients with the HER2 overexpression subtype (P = 0.029). CONCLUSION: Our results confirmed that AR is a potential biomarker for evaluating the prognosis of patients.

Molecular subtyping of mammary Paget's disease using immunohistochemistry.

OBJECTIVE: To evaluate the molecular subtypes of Mammary Paget's disease (MPD) and the associated breast carcinomas. METHODS: This retrospective study was carried out at King Khalid University Hospital and King Faisal Specialist Hospital, Riyadh, Saudi Arabia. Data from MPD patient cases from January 2010 to June 2016 were reviewed. The molecular subtypes were determined based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression with immunohistochemical staining. The relative frequencies of the luminal A and B, HER2-enriched and basal-like molecular subtypes were calculated and compared for MPD and the associated breast carcinomas. Results: Among 22 patients with MPD, HER2-enriched was the most frequently occurring molecular subtype and was observed in 11 (50%) patients. Mammary Paget's disease was classified as basal-like in 5 (22.7%) patients, and luminal A and B were each detected in 3 (13.6%) patients. The molecular subtype of MPD corresponded with the subtype of the associated breast carcinoma in 18 out of 20 patients (90%). CONCLUSIONS: The HER2-enriched subtype is the most frequently occurring molecular subtype in MPD. The molecular subtype of the associated breast carcinoma is usually similar to that of MPD. The molecular subtypes vary between MPD associated breast carcinoma and overall breast carcinoma. The HER2-enriched subtype is the most frequently occurring subtype of MPD associated breast carcinoma, while luminal subtypes are more common in overall breast carcinoma.

Paget's disease of the male breast: case report and a point of view from actual literature.

INTRODUCTION: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer. CASE DESCRIPTION: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications. CONCLUSIONS: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.

[Paget's disease of ectopic breast]. / Maladie de Paget sur sein surnuméraire.

BACKGROUND: Paget's disease of the breast is rare, even more so when it occurs in a supernumerary breast since diagnosis is delayed due to lack of exploration and ignorance of the pathology of ectopic breast. Based on an original clinical case, we provide a clinical update concerning ectopic breast and ectopic carcinoma, including Paget's disease. PATIENTS AND METHODS: A 44-year-old woman had complained of pain in the area of her supernumerary breast for several months. The ultrasound examination was normal but the unexplained symptoms led to performance of an excision biopsy of the lesion. This showed strictly intra-epidermal Paget's disease measuring 2mm, without any underlying carcinoma. A wider excision was performed. Follow-up at one year showed no recurrence. DISCUSSION: An ectopic breast, present in 6 % of the population, is often ignored, despite being subject to the same diseases as anatomical breasts: it is at the origin of 0.6 % of breast cancers. Paget's disease is a rare in situ adenocarcinoma comprising fewer than 3 % of cases of breast cancer. It is extremely rare in ectopic breast. Ours is only the fourth reported case in the literature. This case is original because of the lack of objective clinical signs. Subjective symptoms such as pain, tingling, burning sensation and pruritus related to the supernumerary breast must be taken into consideration in order to enable early diagnosis of Paget's disease. Exploration by ultrasound and mammography generally appears flawed. Breast MRI may be useful but is not performed routinely. A promising future approach may consist of confocal microscopy screening of all ectopic breasts with areola or nipple patches, since this method enables the visualization of Paget cells and their organization.

Surgical treatment in Paget's disease with invasive ductal carcinoma: an observational study based on SEER.

The aim is to analyse the clinical presentation, treatment and outcomes in patients with Paget's disease with invasive ductal carcinoma (PD-IDC), with special emphasis on the role of surgical treatment. Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2013, we investigated the differences in characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM) between patients with PD-IDC and those with invasive ductal carcinoma (IDC). Compared with IDC group, patients with PD-IDC had a better prognosis and lower mortality in adjusted analyses. In the multivariate analysis of cases with PD-IDC, history of ALND was significantly associated with OS while Her2 status were associated with BCSM. Further, subgroup analysis demonstrated no difference between surgical treatment subgroups for either OS or BCSM. The results demonstrated that PD-IDC appears to alter the association between prognosis and Her2 status. Meanwhile, breast-conserving surgery with radiotherapy may be a feasible treatment alternative and sentinel lymph node biopsy should be considered as an appropriate treatment for patients with PD-IDC.

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.

Successful use of rFVIIa for major breast surgery prophylaxis in congenital factor VII deficiency: a case report.

INTRODUCTION: Factor VII deficiency is a rare cause of haemorrhagic syndrome. The Authors describe a case of a 46 years old patient with congenital factor VII deficiency that successfully underwent breast surgery after treatment with Novoseven® before the procedure. MATERIALS AND METHODS: The AA used the schedule reported below to value the levels of PT and aPTT in the patient. Blood Collection: Venous blood from patient and control was collected in glass tubes for routine serum preparation and into plastic tubes (0.129 M sodium citrate, Becton-Dickinson Vacutainer Systems) in a ratio of blood to anticoagulant of 9:1. Platelet Poor Plasma (PPP) was obtained by centrifugation at 4.000 x g for 15 minutes at room temperature. The plasma was recentrifuged for another 10 min at 12000 g to fully eliminate platelet concentration. A normal control plasma pool was prepared by mixing equal volumes of platelet-free plasma obtained from at least 50 normal volunteers. Prothrombin time (PT) was measured with Recombiplastin (IL, Milano Italy). Activated partial thromboplastin times (APTT) was measured with APTT-SP (IL, Milano Italy). They were performed on the coagulation analyzer ACL 1000 (IL, Milano Italy). RESULTS: The results were interpreted from the ratio of the patient times to the normal control times (Table I). CONCLUSION: The infusion of Novoseven solved the clotting problems enabling the surgical procedure, without risks for the patient.

Successful use of rFVIIa for major breast surgery prophylaxis in congenital factor VII deficiency.

INTRODUCTION: Factor VII deficiency is a rare cause of haemorrhagic syndrome. The Authors describe a case of a 46 years old patient with congenital factor VII deficiency that successfully underwent breast surgery after treatment with Novoseven® before the procedure. MATERIALS AND METHODS: The AA used the schedule reported below to value the levels of PT and aPTT in the patient. Blood Collection: Venous blood from patient and control was collected in glass tubes for routine serum preparation and into plastic tubes (0.129 M sodium citrate, Becton-Dickinson Vacutainer Systems) in a ratio of blood to anticoagulant of 9:1. Platelet Poor Plasma (PPP) was obtained by centrifugation at 4.000 x g for 15 minutes at room temperature. The plasma was recentrifuged for another 10 min at 12000 g to fully eliminate platelet concentration. A normal control plasma pool was prepared by mixing equal volumes of platelet-free plasma obtained from at least 50 normal volunteers. Prothrombin time (PT) was measured with Recombiplastin (IL, Milano Italy). Activated partial thromboplastin times (APTT) was measured with APTT-SP (IL, Milano Italy). They were performed on the coagulation analyzer ACL 1000 (IL, Milano Italy). RESULTS: The results were interpreted from the ratio of the patient times to the normal control times (Table I). CONCLUSION: The infusion of Novoseven solved the clotting problems enabling the surgical procedure, without risks for the patient. KEY WORDS: Breast cancer, Factor VII deficiency, Major surgery, Recombinant fVIIa.

Mammary Paget disease in Darier disease: beware the wolf in sheep's clothing.

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.

An unusual presentation of breast cancer in a very young woman.

A healthy 27-year-old woman presented to an outside institution with unilateral nipple pruritus and a slight brown discolouration. When her symptoms failed to respond to topical therapy, nipple biopsy revealed Paget's disease of the nipple. The patient sought further evaluation and care at our institution. Further investigation revealed multifocal breast cancer and the patient underwent bilateral mastectomies with sentinel lymph node biopsy followed by adjuvant systemic therapy. She is currently more than 4 years out from surgery and chemotherapy and has had no evidence of breast cancer recurrence.

[Brownish coloration of the left nipple in a 60-year-old woman]. / Bräunliche Verfärbung der linken Brustwarze bei einer 60-jährigen Patientin.

Pigmented Paget disease of the nipple is a rare disease. We report on a 60-year-old woman in whom this diagnosis was made based on clinical findings, dermoscopy, histology and immunohistology. Circumscribed pigmentation of the nipple includes a wide spectrum of benign and malignant differential diagnostic considerations. Dermoscopy can enhance the clinical diagnosis. Biopsies should always be performed on unclear pigmentation of the nipple in both women and men. On histology, rare melanocytic tumors must be differentiated from pigmented Paget disease and pigmented Bowen disease. Pagetoid intraepithelial cells of a melanocytic tumor are positive for S100, HMB45 or melan A, but not for cytokeratins. Intraepithelial tumor cells of Paget disease are positive for cytokeratin 7. The clear cells in Bowen diseases are usually not positive for cytokeratin 7 and are also negative for all melanocytic markers.

Different panels of markers should be used to predict mammary Paget's disease associated with in situ or invasive ductal carcinoma of the breast.

Mammary Paget's disease (MPD) is a rare manifestation of breast carcinoma involving the nipple. Our objective was to identify molecular markers and molecular subtypes that may predict patients at high risk of developing MPD. Immunohistochemical (IHC) analyses were performed with antibodies to estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), HER2, epidermal growth factor receptor (EGFR), and several cytokeratins (CK5/6, CK14, CK17, CK8, CK18) on representative sections of 121 cases of ductal carcinoma of the breast, including 28 cases with MPD, 81 cases with neither MPD nor nipple involvement, and 12 cases of non-MPD with nipple involvement. The rates of receptor expression and subtype distributions of 3 IHC-based molecular classifications were compared among these groups. The results showed that: (1) MPD is more likely to be associated with ER- and PR-negative ductal carcinoma in situ (DCIS), but not invasive ductal carcinoma (IDC); (2) MPD is more likely to be associated with HER2-over expression subtype DCIS, but not IDC; and (3) carcinomas with non-MPD nipple involvement differ from those with MPD, since they are more likely to be ER- and PR-positive, HER2-negative, and luminal A subtype. In summary, different panels of markers should be used to predict MPD associated with different underlying lesions; for DCIS, the ER-negative, PR-negative, and HER2-subtype and not basal-like subtype is most predictive of MPD; for IDC, the luminal B-subtype is most predictive of MPD.

Paget's disease of the breast in a woman with neurofibromatosis.

Paget's disease of the breast is a rare and specific type of breast carcinoma in the nipple or areola. On the other hand, neurofibromatosis (NF) is also a rare neurocutaneous disease, which is inherited and affects mainly the skin and the nervous system. In addition, NF is rarely associated with malignant tumors. We present a case of Paget's disease concomitant with NF type 1 in a 66-year-old woman.