Paget disease of the nipple is a rare presentation of breast cancer. It is sometimes mistaken for a benign skin condition of the nipple and surrounding areola, which can significantly delay the diagnosis and treatment. In over 90% of cases there is an underlying carcinoma, either ductal carcinoma in situ (DCIS) or invasive breast cancer. We present a rare case of Paget disease of the nipple without the typical characteristics, detected by simple nipple scraping technique. A 62-year-old woman presented with a small fissure on the left nipple with scant clear nipple discharge. There were no other changes to the nipple-areola complex. The mammography and ultrasound were unremarkable. However, nipple scraping provided the immediate cytological diagnosis of Paget disease. Breast MRI with core biopsy showed high grade ductal carcinoma in situ with suggestion of microinvasion, confirmed histologically after mastectomy. Nipple scraping is a simple and inexpensive technique, which can be used in the office without anesthesia and with minimal discomfort to the patient. It could allow for significantly earlier cancer detection and treatment at the earliest stage of breast cancer. However, if the results are negative, full thickness biopsy may be needed if clinically indicated.

A 25-year-old woman presented to our dermatology unit with progressive diffuse thickening of the both areolas. A skin biopsy was taken from the right areola showing irregular filiform acanthosis with elongation and anastomosis of rete ridges, irregular orthokeratotic hyperkeratosis, pseudocyst formation, and hyperpigmentation of the basal layer. The cause of nevoid hyperkeratosis of the nipple and areola is unknown. Eighty percent of cases occur in women and are often manifested during puberty or pregnancy. The disease may also occur in men receiving hormonal therapy. There is no uniformly effective treatment. Dermatologists, gynecologists, and general practitioners have an important part to play in recognizing this condition that may be underdiagnosed because of lack of awareness.

Paget disease of the breast is an uncommon tumor ofthe nipple-areola complex that usually presents as anerythematous and erosive lesion. We report the caseof a 61-year-old man that presented with a three-yearhistory of an erythematous lesion of the right areola,first treated with topical corticosteroids withoutbenefit. He was then referred to our dermatologydepartment and the clinical suspicion of Paget diseasewas considered. The diagnosis was later confirmed bybiopsy. This case report highlights the importanceof clinical recognition of this entity along with otherdiseases that mimic these skin changes in order toallow earlier diagnosis and proper follow-up.

In 1874, Sir James Paget first described Paget disease of the nipple, also known as mammary Paget disease. In 1889, extramammary Paget disease (EMPD) of the scrotum and penis was identified. Although mammary and extramammary Paget disease are both characterized by epidermal Paget cells and share a similar clinical presentation, their uniqueness lies in anatomical location and histogenesis. EMPD presents as an erythematous plaque on apocrine gland bearing areas (i.e. vulva, perineum, perianal region, scrotum, and penis) in older men and women. It can be a focal, multifocal, or an ectopic process. Immunohistochemical staining allows for differentiation between primary and secondary EMPD in addition to the many other disease entities that clinically resemble this malignancy. When diagnosing a patient with EMPD, a full history and physical should be performed given the possibility of an underlying malignancy. Surgical excision currently is first line therapy and the prognosis is often favorable. Recent advances within the field have examined the expression of chemokine receptors within tumors, which may be applicable in determining prognosis. This review addresses the history, epidemiology, pathogenesis, clinical presentation, histopathology, differential diagnosis, diagnosis, management, and new observations with respect to extramammary Paget disease.

Molluscum contagiosum is a common cutaneous infection caused by a double-stranded DNA poxvirus. Skin lesions classically present as small, flesh-colored papules with central umbilication. Lesions are frequently seen on the face, trunk, and extremities of children, or on the genitals of young adults as a sexually transmitted infection. Molluscum contagiosum on the nipple or areola has only been previously described in 4 women. We describe a woman with molluscum contagiosum on the left areola and review the clinical characteristics and histological findings of patients who developed molluscum contagiosum of the nipple or areola.

Erosive and oozing lesions of the nipple, especially when unilateral, should raise suspicion about malignant neoplasms. Herein we report a patient with typical clinical and histopathological features of erosive adenomatosis of the nipple (EAN). It is an uncommon, benign proliferative process of lactiferous ducts of the nipple. Clinically, EAN is characterized by erosion, serous discharge, edema, itching, and erythema of one of the nipples. Complete excision of the tumor yields excellent results. Although EAN is a rare disease, clinicians must be aware of this benign neoplasm in patients with erosive lesions of the nipple. The main concern is the need to rule out malignant proliferations in the differential diagnosis. Histology is the gold standard for diagnosis. The coexistence of nipple adenoma and breast cancer is well-reported in the literature. Thus, it is necessary to encourage patients with a history of EAN to maintain regular breast screening.

Clear cell acanthoma (CCA) is a rare, benign cutaneous condition most often seen on the lower extremities. Lesions are of variable morphology and have been described as polypoid, pigmented, giant, and cystic lesions. Although no racial or gender predilection has been reported, CCA on the breast is a very rare finding that has been observed mainly in young Korean women. Herein, we describe a case of CCA of the areola in an elderly woman with metastatic renal cell carcinoma. Physical exam revealed a pink plaque with central erosions on the left areola. Given the concern for cutaneous metastasis, excisional biopsy was performed, which showed pale glycogenated epithelium consistent with CCA. No evidence of recurrence or new lesions was observed after 6 months of follow-up. Our case exemplifies that clinicians should consider CCA in the differential diagnosis for a new eczematous lesion involving the breast, even in the setting of malignancy.

Background: Nipple-areolar complex (NAC) conditions affect reproductive-age women, yet it is not known how care of NAC complaints is distributed among medical specialties. There is a need to characterize all NAC conditions, including their treatment and the care team involved in their clinical management, of nonlactating and lactating patients to determine care gaps. Materials and Methods: This was a retrospective cohort study of reproductive-age females who presented to a large tertiary health system with an NAC complaint between 2015 and 2020. Data about the symptoms, diagnosis, specialty providing care, diagnostic considerations, and treatments were collected. Results: Nipple pain, dermatitis, and thrush were the most common diagnoses among 407 encounters (215 patients). Lactating patients represented half (204, 50%) of the study sample. Benign breast conditions like obstructed ductal openings, accessory nipples, nipple growth, inverted nipples, and chronic and bacterial infections represented a third of all encounters. Primary care physicians (167, 41%) and obstetricians (105, 26%) provided most of the care and referred a third and quarter of patients, respectively, to another provider. Conclusion: The care of patients with NAC complaints is not limited to obstetricians. Internal medicine, family medicine, emergency medicine, and obstetrician-gynecology, dermatology, and surgery resident physicians should receive training in benign breast conditions and clinical lactation.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways - including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.