Mammary Paget's Disease Research Articles

Mammary Paget's Disease Mimicking Benign and Malignant Dermatological Conditions: Clinical Challenges and Diagnostic Considerations.

Mammary Paget's disease (MPD) or Paget's disease of the breast is a rare dermatological malignancy of the nipple-areolar complex that manifests with a spectrum of symptoms spanning from itching and redness to more severe indications such as breast lump, nipple-areolar complex destruction, or nipple discharge. It is predominantly associated with an underlying ductal carcinoma in situ or invasive ductal carcinoma. MPDoften masquerades as other benign and malignant dermatological conditions, including eczema, atopic dermatitis, psoriasis, and squamous and basal cell carcinomas, leading to delayed diagnosis and inappropriate treatment. Only one-third of the patients present with a palpable lump; therefore, advanced age with chronic and unilateral lesions should raise concern for MPD. Our review article presents case reports of MPD imitating other skin conditions and underscores the key findings of clinical features and diagnostic workup to help differentiate the condition. A literature review revealed that studies emphasize caution regarding the sole use of mammography and ultrasound in diagnosing MPD, particularly in cases lacking a palpable lump. This highlights the MRI as a superior and more accurate imaging tool. However, any suspicious lesion must be biopsied to allow histopathological and immunohistochemical examination, since there are some cases where MRI findings were negative in the presence of a biopsy-proven MPD. This highlights the need for clinicians to investigate any suspicious lesion of the nipple or breast using the complete triple assessment approach to exclude an underlying malignancy. It is imperative to establish therapeutic guidelines to approach any nipple lesion to minimize the risk of misdiagnosing any underlying cancer, which can be potentially fatal if left alone.

Mammary Paget disease

Mammary Paget disease

Novel Androgen Receptor Splice Variant 7 in Gynecologic Tumors.

Androgen receptor splicing variant 7 (AR-V7) is a truncated variant of the AR mRNA that may be a predictive biomarker for AR-targeted therapy. AR-V7 has been described in prostate, breast, salivary duct, and hepatocellular carcinomas as well as mammary and extra-mammary Paget disease. We report 2 gynecologic cancers occurring in the lower uterine segment and ovary and both harboring AR-V7 by targeted RNA sequencing. The uterine tumor was an undifferentiated carcinoma consisting of epithelioid cells and focally spindled cells arranged in sheets, nests, and cords associated with brisk mitotic activity and tumor necrosis. The ovarian tumor consisted of glands with cribriform and solid architecture and uniform cytologic atypia. ER and PR were positive in the ovarian tumor and negative in the uterine tumor. Both were positive for AR and negative for HER2, GATA3, and NKX3.1. DNA methylation profiling showed epigenetic similarity of the AR-V7-positive gynecologic cancers to AR-V7-positive breast cancers rather than to prostate cancers. AR-V7 may underpin rare gynecologic carcinomas with undifferentiated histology or cribriform growth reminiscent of prostatic adenocarcinoma and breast invasive ductal carcinoma.

Histopathological analysis of skin adnexal tumors: An experience at a tertiary center.

Skin appendage tumors (SATs) are benign and malignant neoplasms. Although there are many studies on their clinical features and epidemiology in the literature, most of these studies have a small number of patients and are not classified according to the WHO 2018 classification. This study aimed to reveal the clinical and histopathological features of the SATs and compare the pre-diagnosis. Cases diagnosed with SATs in the last 7 years in the Pathology Department were re-evaluated according to the WHO 2018 classification. Patients' ages and genders, as well as the location and pre-diagnosis of the lesion, were all recorded. A total of 437 patients, 198 (45.3%) male and 239 (54.7%) female, were included in the study. Of 437 patients, 399 (91.3%) were diagnosed with benign SATs and 38 (8.7%) were diagnosed with malignant SATs. Most of the cases were benign tumors with follicular differentiation. Malignant SATs were seen in patients significantly older than benign ones. The majority of SATs were in head and neck localization. Mammary Paget's disease was the most common malignant SAT (n = 14, 36.8% of patients diagnosed with malignant SATs). It was noted that clinicians were less likely to consider a specific diagnosis of SAT before excision. SAT, a diagnosis that can be seen at any age and is difficult to predict clinically, may be malignant, especially in elderly patients. Histopathology is the gold standard in diagnosing SATs, and immunohistochemical staining may be useful in diagnosing tumors with uncertain histopathological features.

Dermoscopy to differentiate clinically similar inflammatory and neoplastic skin lesions.

Over the few last decades, dermoscopy has become an invaluable and popular imaging technique that complements the diagnostic armamentarium of dermatologists, being employed for both tumors and inflammatory diseases. Whereas distinction between neoplastic and inflammatory lesions is often straightforward based on clinical data, there are some scenarios that may be troublesome, e.g., solitary inflammatory lesions or tumors superimposed to a widespread inflammatory condition that may share macroscopic morphological findings. We reviewed the literature to identify dermoscopic clues to support the differential diagnosis of clinically similar inflammatory and neoplastic skin lesions, also providing the histological background of such dermoscopic points of differentiation. Dermoscopic differentiating features were identified for 12 relatively common challenging scenarios, including Bowen's disease and basal cell carcinoma vs. psoriasis and dermatitis, erythroplasia of Queyrat vs. inflammatory balanitis, mammary and extramammary Paget's disease vs. inflammatory mimickers, actinic keratoses vs. discoid lupus erythematosus, squamous cell carcinoma vs. hypertrophic lichen planus and lichen simplex chronicus, actinic cheilitis vs. inflammatory cheilitis, keratoacanthomas vs. prurigo nodularis, nodular lymphomas vs. pseudolymphomas and inflammatory mimickers, mycosis fungoides vs. parapsoriasis and inflammatory mimickers, angiosarcoma vs granuloma faciale, and Kaposi sarcoma vs pseudo-Kaposi. Dermoscopy may be of aid in differentiating clinically similar inflammatory and neoplastic skin lesions.

Primary melanoma of the nipple: Report of 10 cases including coexistence with Paget’s disease

Primary melanoma of the nipple (PMN) is exceedingly rare, with only single cases reported to date. We identified 10 patients with PMN: 5 females, 5 males, median age 55.5 years (range 29–66) at diagnosis of melanoma in situ (4 cases) or invasive melanoma (6 cases, Breslow depth 0.2 mm to 3.5 mm). Follow-up was available for all 10 patients (median 19 months, range 1–183). Nine patients had no evidence of disease; one patient died of disease (13.5 months) after presenting with a nodal metastasis. One case was exceptional, because the patient presented with a pigmented lesion that histopathologically exhibited co-existence of melanoma in situ and Paget disease, a challenging differential diagnosis due to immunohistochemical pitfalls in distinction between melanoma in situ and the pigmented variant of mammary Paget disease. Here we report the second largest series of PMN including a case of PMN colliding with mammary Paget disease, to raise awareness of these rare malignancies.

Invasive Paget disease of the breast: two unique cases with diagnostic conundrum

Abstract Introduction/Objective Invasive Paget disease of the breast is a rare entity with diagnostic challenges. It has been reported in 4-8% of cases of mammary Paget disease, while Paget disease itself represents only 1-4% of all breast carcinomas. The pigmented variant of this entity brings even greater diagnostic challenge. Herein, we present two patients with Paget disease of the breast with dermal invasion, one case with associated ulceration and another with pigmentation. Methods/Case Report Patient 1 is a 47-year-old female with a 9 mm right breast mass with a lobulated margins and calcifications. Simple mastectomy was grossly notable for nipple ulceration. Patient 2 is a 54-year-old female with a cm irregular mass in the right breast. Grossly, the nipple appeared blackened and mildly everted. Results (if a Case Study enter NA) Histopathologic evaluation of the nipple sections from patient 1 show invasive Paget disease with associated ulceration, with a depth of invasion of 4.5 mm. The breast biomarkers on the nipple section show tumor cells are negative for ER (0%) and PR (0%), and positive for HER2/neu (3+). Additionally, there was a separate 1.5 cm invasive ductal carcinoma, combined Nottingham histologic grade 3, pathologic stage of pT1c. The nipple sections from patient 2 show pigmented, invasive Paget disease, with a 1.5 mm depth of invasion. The tumor cells are positive for CK7 (weak), ER and PR, and negative for HER2/neu (1+). HMB45 and MART1 show increased reactivity in melanocytes. She also had a separate 2.5 cm invasive ductal carcinoma, combined Nottingham histologic grade 3, pathologic stage of pT2. Conclusion We present two unique cases of breast invasive Paget disease: one with associated ulceration, which brings challenges with tumor staging; and another one with pigmentation, which can be mistaken as melanoma. Invasive Paget disease must be distinguished from locally advanced breast cancer presenting as satellite skin nodules or skin ulceration, as it can lead to erroneous tumor over-staging as pT4b. It is important to recognize these two variations of invasive Paget disease so as to avoid over-staging or misdiagnosis, respectively, and to be cognizant of the fact that the treatment and prognosis differ.

A Pictorial Exploration of Mammary Paget Disease: Insights and Perspectives

Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple–areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed.

Time for detailed clinical management of Paget's disease of the breast.

Time for detailed clinical management of Paget's disease of the breast.

Expression of MSI1 and HER2 in mammary Paget's disease and their correlation with clinicopathological features and prognosis

Objective: To investigate the expression of MSI1 and HER2 in mammary Paget's disease, and the correlation between the expression levels of MSI1 and HER2 and the clinicopathologic characteristics and prognosis of the patients. Methods: Clinical data and paraffin-embedded specimens of 34 pairs of mammary Paget's disease and underlying breast cancer were collected at the Department of Pathology, Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University from March 2011 to December 2019. Immunohistochemistry was used to detect the expression of MSI1 and HER2 in mammary Paget's disease and the accompanying breast cancer, and to analyze the correlation between the expression levels of MSI1 and HER2 and their clinicopathologic features, as well as their influence on prognosis. Results: In mammary Paget's disease, the positive rate of MSI1 was 91.2% (31/34) and the positive rate of HER2 was 88.2% (30/34); the expression of MSI1 and HER2 was positively correlated (P=0.001, r=0.530). The expression of MSI1 was positively correlated with menopausal status (r=0.372, P=0.030) and lymph node metastasis (r=0.450, P=0.008). HER2 expression was positively correlated with menopausal status (r=0.436, P=0.010), and negatively correlated with ER expression (r=-0.365, P=0.034). The co-expression of MSI1 and HER2 was positively correlated with age (r=0.347, P=0.044) and menopausal status (r=0.496, P=0.003), and negatively correlated with ER expression (r=-0.461, P=0.006). Conclusions: MSI1 and HER2 are highly expressed in mammary Paget's disease and their expression levels are positively correlated. The correlation analysis between clinicopathological features and prognosis suggests that both of them may be involved in the occurrence and development of mammary Paget's disease and are potential therapeutic targets for mammary Paget's disease.

A Clinicopathological and Immunohistochemical Profile of Primary Extra Mammary Paget's Disease in Skin of Colour: A Case Series.

Extramammary Paget's disease is an intraepithelial neoplasm, usually found in areas rich in apocrine gland concentration. The clinical features, histopathology, immunohistochemistry and management details of five patients (F = 3, M = 2) have been described here. While a well-defined persistent plaque with crusting and erosion was the most common presentation, hyperpigmentation, hypopigmentation and depigmentation were also observed in two patients. Characteristic Paget's cells with cytokeratin 7 and EMA positivity were seen on histopathology examination. Authors conclude that pigmentary alterations may be under-reported in extra mammary Paget's disease in the skin of colour.

Claudin-4 Expression in the Distinction of Mammary and Extramammary Paget Disease From Morphologic Mimics: Diagnostic Utility and Pitfalls.

Claudin-4 Expression in the Distinction of Mammary and Extramammary Paget Disease From Morphologic Mimics: Diagnostic Utility and Pitfalls.

Cover Image

The cover image is based on the Original Article Immunohistochemical expression of TRPS1 in mammary Paget disease, extramammary Paget disease, and their close histopathologic mimics by Woo Cheal Cho et al., https://doi.org/10.1111/cup.14414. image

Immunohistochemical expression of TRPS1 in mammary Paget disease, extramammary Paget disease, and their close histopathologic mimics.

Trichorhinophalangeal syndrome type 1 (TPRS1) expression has been found to be highly sensitive and specific for breast carcinomas. The frequency of TRPS1 expression in cutaneous neoplasms such as mammary Paget disease (MPD) and extramammary PD (EMPD) is currently unknown. We assessed the utility of TRPS1 immunohistochemistry (IHC) in the evaluation of MPD, EMPD, and their histopathologic mimics, squamous cell carcinoma in situ (SCCIS) and melanoma in situ (MIS). Twenty-four MPDs, 19 EMPDs, 13 SCCISs, and 9 MISs were subjected to immunohistochemical analysis using anti-TRPS1 antibody. The intensity (none, 0; weak, 1+ ; moderate, 2+ ; strong, 3+ ) and proportion (<1%, absent; 1%-25%, focal; 26%-75%, patchy; >75%, diffuse) of TRPS1 expression were recorded. Relevant clinical data were documented. TPRS1 expression was present in 100% (24/24) of MPDs, with 88% (21/24) of MPDs exhibiting strong, diffuse immunoreactivity. Sixty-eight percent (13/19) of EMPDs showed TRPS1 expression. Intriguingly, EMPDs lacking TRPS1 expression were consistently of perianal origin. TRPS1 expression was seen in 92% (12/13) of SCCISs but was absent in all MISs. TRPS1 may be useful to distinguish MPDs/EMPDs from MISs, but its utility is limited in distinguishing them from other pagetoid intraepidermal neoplasms such as SCCISs.

The effects of clinicopathological and imaging findings on recurrence and survival in mammary Paget's disease.

Mammary Paget's disease (MPD) is a rare presentation type of breast cancer. The aim of this study was to evaluate the clinicopathological and imaging features affecting the invasive component, loco-regional recurrence, prognosis, and survival of MPD. Patients who had undergone surgery due to MPD in a 10-year period were included. Parameters including mammography and magnetic resonance imaging (MRI) findings, tumor stage, molecular subtype, axillary involvement, presence of invasive carcinoma, loco-regional recurrence, overall survival (OS), and disease-free survival (DFS) were recorded and statistically analyzed. P<0.05 was determined as statistically significant. The study group consisted of 49 women with a mean age of 67.05±14.43 (range: 23-90) years. There was a significant association between the presence of invasive carcinoma and a mass lesion in the MRI (p=0.002). The frequency of sentinel lymph node (SLN) metastasis was significantly higher in patients with multicentric tumors (p=0.029; p<0.05). Locoregional recurrence and distant metastasis were significantly more frequent in patients with axillary involvement (p=0.0336; p<0.05). The mean DFS was 115.02±7.28 months, while the mean OS was 119.29±6.57 months. The presence of a mass lesion on MRI was determined to be significant in recognizing invasive carcinoma in MPD. The rate of SLN metastasis was higher in patients with multicentric tumors than in patients with unifocal tumors. Axillary involvement was associated with impaired DFS.

Mammary Paget's Disease of Young Females: Case Reports and Comparison With Middle-Aged and Elderly Patients.

Mammary Paget's disease (PD) in young women has seldom been reported. The aim of this study was to improve the knowledge of the clinicopathological characteristics in young patients with PD to provide a basis for the precise treatment of young patients. The medical records and pathological slides of 8 young patients (younger than 40 years old) with PD were reviewed. The data of 20 patients over 40 years old within the same period were used as controls. The average age was 32.00 ± 3.96 years for the young patient group, with the youngest aged 27 years. The first symptom, physical examination, Paget cell morphology, and immunohistochemical marks were the same in different age groups. But young patients have varied tumor distribution patterns, fewer interstitial inflammatory cells, and advanced pathological local lymphatic metastasis than older patients in the same period. PD in young women has unique histopathological features. These manifestations seem to provide personalized treatment for PD treatment in young patients. More research is needed to clarify the significance of this research.

Pathoanatomical algorithm for differential diagnosis of Paget's disease of the breast

Paget's disease of the breast is a rare type of cancer that affects the skin of the nipple and usually the areola. At the same time, most patients also have one or more tumors in the immediate vicinity of the focus of mammary Paget's disease. This tumor must be distinguished from normal or atypical Toker cells, and also differentiated from diseases such as Bowen's disease of the nipple and melanocytic lesions of the nipple and areola region, including nipple melanoma and BAP1-inactivated nevus (Wiesner nevus). Currently, there is no routine pathological diagnostic algorithm for these conditions. The aim of the work is to formulate a clear clinical and morphological algorithm for diagnosing Paget's disease of the breast and Toker cells, Bowen's disease of the nipple and areola, as well as melanoma and BAP1-inactivated nevi of the above localizations. Surgical material obtained from patients with Paget's disease of the breast (18), Toker cells of the nipple (2), Bowen's disease of the nipple (6), melanoma of the nipple (1), BAP1-inactivated nevus (1) was studied. The material was examined histologically with hematoxylin and eosin staining, Alcian blue and PAS reaction, as well as immunohistochemically with the following panel of antibodies: CD138, p53, CK8, CK7, HER2/neu, EMA, HMB-45, Melan A, S-100, p63, p16 and BAP1. An easy-to-learn pathoanatomical algorithm for diagnosing Paget's cancer has been developed, which will be especially useful for pathologists who encounter pathology of the nipple and areola in their work.

Insights into Mammary Paget's disease: A Dermoscopic Description of 8 Cases

Insights into Mammary Paget's disease: A Dermoscopic Description of 8 Cases

Is prediction of local recurrence possible in Paget’s disease of the breast?

Objective: Mammary Paget disease of the breast is a rare form of breast cancer. The study aimed to predict the patients prone to local recurrence, and to find out the answer to the question of who should be a candidate for breast conserving surgery. Material and Methods: Between January 2007 and February 2022, 83 patients who underwent surgery and pathology report diagnosed as Paget’s disease, were analyzed retrospectively. As factors that may affect local recurrence; age, presence of nipple symptoms, mass detection in radiological imaging, type of the surgery, stage, pathological findings of the tumor (histological type, multicentricity, ER, PR, HER2, Ki 67 proliferative index, molecular subtype) were evaluated. Results: Among 83 patients, 32 (38.6%) had ductal carcinoma in situ, and 50 patients (60.2%) had invasive ductal carcinoma, and others had pure Paget disease. Number of the patients who underwent breast-conserving surgery and mastectomy was 19 and 64, respectively. Patients were followed-up for a median time of 73 months. Recurrence was developed in 12 patients (14.5%), 7 of them with local recurrence. Type of the surgery (p=0.001) and young age (p=0.02) were the factor influencing local recurrence. Subgroup analysis was performed among patients undergoing breast-conserving surgery, and age (p=0.07) and absence of nipple symptoms (p=0.07) were found to affect local recurrence. Conclusion: Although the number of patients is small, it should be kept in mind that local recurrence may be high when breast-conserving surgery is performed in patients with young age

Young mammary Paget's disease patients with underlying breast invasive ductal carcinoma: clinicopathological features and prognosis

Objective: To investigate the clinicopathological factors and prognostic status of young Mammary Paget's disease (MPD) patients with invasive ductal carcinoma (IDC). Methods: In this study, we defined the age at diagnosis below 40 years old as young patients, and retrospectively analyzed data from 123 MPD-IDC patients who were admitted at the Cancer Hospital Chinese Academy of Medical Sciences from June 2002 to February 2019. Patients were divided into the young group (≤40 years old, 15 cases) and the old group (>40 years old, 108 cases) according to the age of onset, and the clinicopathological characteristics and prognosis of the two groups were compared. Cox regression model analysis was used to analyze the prognosis influencing factors. Results: The proportions of patients in the young group with non-menopausal, axillary lymph node metastasis, and Ki-67 index ≥15% were 93.3% (14/15), 73.3% (11/15), and 86.7% (13/15), respectively, which were higher than those in the old group [45.4% (49/108), 39.8%(43/108), and 60.2% (65/108), respectively] , with statistically significant differences (P<0.05). At an average follow-up of 63.2 months, patients in the young group had a significantly shorter disease-free survival (DFS) compared with that of the old group (P=0.012), while the difference in overall survival (OS) between the two groups was not statistically significant (P=0.161). Multifactorial Cox regression analysis showed that axillary lymph node status was an independent influencing factor on OS (HR=3.339, 95% CI: 1.121-9.943) in patients with MPD-IDC, while age was not. Conclusion: Compared with the old group, young patients with MPD-IDC have a higher incidence of axillary lymph node metastasis, high Ki-67 expression, and a shorter DFS, but age is not an independent influencing factor on DFS or OS in patients with MPD-IDC.