Pathological Complete Response following Neoadjuvant Chemotherapy in Invasive Ductal Carcinoma with Mammary Paget’s Disease: A Case Report

Mammary Paget’s disease is a rare malignancy. Mastectomy or breast-conserving surgery has been considered as the standard treatment, while there have been few reports of neoadjuvant chemotherapy (NAC). A 53-year-old woman with erythema and skin ulceration of the left breast was admitted to our institution. Breast examinations revealed left invasive ductal carcinoma (cT1bN0M0, cStage I), and a punch biopsy of the left mammary erythema indicated Paget’s disease (cTisN0M0, cStage0). The patient received NAC because of multiple lesions. Consequently, the breast tumor clinically disappeared, and the erythema improved. These outcomes made it easier to perform surgery (left mastectomy and sentinel node biopsy). Histopathological examination revealed no residual cancer cells in either the mammary gland or breast skin, and no metastasis was found in the sentinel lymph node. Therefore, NAC may be a useful treatment for mammary Paget’s disease.

Clinicopathological Characteristics and Survival Outcomes in Mammary Paget's Disease: a Retrospective Study Based on a Chinese Population

Background: Mammary Paget's disease (PD) is a rare type of breast cancer. Most cases of PD is presented with underlying ductal carcinoma in situ (DCIS) or invasive breast carcinoma (IDC). This study aimed to investigate the clinicopathological characteristics and survival outcomes of PD patients. Materials and Methods: A total of 406 patients diagnosed with PD with IDC/DCIS at Fudan University Shanghai Cancer Center (FUSCC) were recruited as the PD group, 1218 patients diagnosed with IDC/DCIS alone during the same period were selected as the non-PD group, and the clinicopathological results of these two groups were compared. The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate the clinicopathological features between PD and non-PD patients for validation. Then, a matched group study was performed to compare the survival of PD and non-PD patients.Results: Compared with the non-PD group, the PD group was much more likely to have larger (≥2 cm: 43.1% vs. 35.5%, P<0.001), less hormone receptor (HR)-positive (68.5% vs. 26.6%, P<0.001), more human epidermal growth factor receptor-2 (HER-2)-positive (70.7% vs. 27.5%, P<0.001) and higher Ki-67 proportion (51.5% vs. 42.5%, P<0.001) tumors. The HER-2 overexpression subtype accounted for the largest proportion in the PD-IDC group and the lowest proportion in the non-PD-IDC group (54% vs. 8%, P<0.01). Moreover, the PD group had significantly worse disease-free survival (DFS) than the non-PD group (5-year DFS: 91.8% vs. 97.3%, P=0.001), and the SEER database showed a similar trend. Univariate and multivariate Cox regression analyses demonstrated that PD was an independent poor-risk factor for breast cancer survival. Our matched study showed that the PD group had worse survival than the non-PD group after excluding age, HR, HER-2, tumor size and lymph node status.Conclusions: PD with IDC/DCIS is associated with more aggressive tumor characteristics and worse survival outcomes. More than half of PD breast cancers are of the HER-2 overexpression subtype. PD is an independent poor-risk factor for breast cancer survival.

Not All Cases of Mammary Paget’s Disease are Cytokeratin-7 Positive: A Challenging Diagnosis!

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.

Prevalence of mammary Paget’s disease in urban China in 2016

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.

Hormonal Environment and HER2 Status in Extra-Mammary Paget’s Disease (eMPD): A Systematic Literature Review and Meta-Analysis with Clinical Considerations

Background. Extra-mammary Paget’s disease (EMPD) is a rare neoplasm of epithelial origin, whose precise incidence is not clear. Starting from what is already known, we performed a systematic review and meta-analysis to investigate in male and female patients the immunohistochemical expression of biological markers that could serve as potential prognostic/therapeutic factors, including only human epidermal growth factor receptor 2 (HER2/neu), Estrogen Receptor (ER), Progesterone Receptor (PR), and Androgen Receptor (AR). Methods. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to June 2020. Results. A total of 27 studies with 713 patients assessed the role of HER2/neu, AR, ER, and PR expression in male and female with EMPD. The overall rate of HER2/neu expression was 30%, the expression’s rate for ER and AR was 13% and 40%, respectively, and the overall rate for PR was 8%. The subgroup analysis revealed that there is a different expression of molecular markers between male and female patients. Conclusions. This study revealed that AR status and HER2/neu overexpression/amplification have been shown as two fundamental pathogenetic pathways in both female and male patients affected by EMPD.

Paget’s disease of breast with an unusual presentation of involvement of overlying skin of breast: a case report

Paget’s disease of breast is also known as Paget’s disease of the nipple & mammary Paget’s disease, involving the skin of nipple & areola. It is rare type of cancer with tumors inside the same breast which may be either ductal carcinoma in-situ or invasive breast cancer. We report a case with Paget’s disease of breast which is not only involving the nipple-areola complex but also involving surrounding skin of breast.