Paget's disease of the breast

Paget's disease of the breast is a rare disorder of the nipple-areola complex that is often associated with an underlying in situ or invasive carcinoma. A change in sensation of the nipple-areola, such as itching and burning, is a common presenting symptom. Objectively, eczematoid changes of the nipple-areola complex are common. The later stages of Paget's disease of the breast are characterized by ulceration and destruction of the nipple-areola complex. Eczematoid changes of the nipple-areola complex and persisting soreness or itching, without obvious reason, is a suspicious symptom for Paget's disease of the breast and calls for thorough evaluation, including mammography. Exfoliative cytology with demonstration of Paget's cells may be useful, but a negative finding does not exclude Paget's disease of the breast. Surgical biopsy is the diagnostic standard and therefore the diagnosis should always be confirmed by open (surgical) biopsy. The histogenesis of Paget's disease of the breast continues to be debated. The epidermotropic theory holds that Paget's cells are ductal carcinoma cells that have migrated from the underlying breast parenchyma to the nipple epidermis. According to the in situ transformation theory, the Paget's cells arise as malignant cells in the nipple epidermis independent from any other pathologic process within the breast parenchyma. This theory has been proposed to explain those cases in which there is no underlying mammary carcinoma or when there is a carcinoma remote from the nipple-areola complex. Each of these theories is plausible; however, treatment approaches differ markedly depending on the theory of histogenesis. Mastectomy has been considered the standard of care in the management of patients with Paget's disease of the breast. Nowadays, however, some patients with Paget's disease of the breast are candidates for breast-conserving therapy. Patients must be selected carefully on an individual basis. Until there is a better understanding of the relationship of Paget's disease of the breast to the underlying cancer the surgeon should understand the natural history and behaviour of this lesion and be aware of both the risks of under- and over-treating patients with Paget's disease of the breast.     

Paget's disease of the male breast

Histologically proved Paget's disease of the breast with negative hormonal receptor assay in a 73-year-old man induced a review of the 27 valuable cases of the literature. Our patient is disease-free, eight years after treatment by modified radical mastectomy and adjuvant irradiation. Peak incidence of the disease is between 50 and 70 years of age. The most frequent presenting signs reported are ulcerations and eczematous lesions of the nipple (71.4%) with discharge and bleeding in 39.3% of the cases. Other findings are a palpable mass (42.8%) and involved axillary lymph nodes (53.5%). The treatment of choice is shown to be radical or modified radical mastectomy with adjuvant radiotherapy. To date, no proof exists of the value of hormone receptors assays and routine adjuvant hormone therapy is not practiced.     

Paget's disease of the breast.

Twenty-nine histologically verified cases of Paget's disease of the breast treated at the Hadassah University Hospital in the years 1949-1972 were followed up and analyzed. Dividing this material into two groups according to the presence or absence of a palpable breast tumor revealed significant difference in behavior and survival. Patients with a breast mass (34%) had a 50% axillary lymph node involvement and behaved as with any other ordinary breast cancer, with a 5-year survival rate of 40% and a 10-year survival rate of 33%. Patients with no palpable breast mass (66%) had only a 10.5% lymph node involvement, the 5-year survival rate being 94% and the 10-year survival rate being 91%. Delay in diagnosis seems to play no significant factor in survival rates and outcome. We believe radical mastectomy to be the treatment of choice in all cases of Paget's disease of the breast.     

乳腺Paget's病发病机制的研究进展

乳腺Paget's病是乳腺癌的一种罕见形式,由James Paget's于1874年提出.有关乳腺Paget's病的发病机制一直备受争议,目前最主要的两种理论是嗜表皮理论和转化理论.近年来,随着对乳腺Paget's病发病机制的研究又提出了一些新的假说:因子受体学说、内分泌学说及病毒学说.乳腺Paget's病的治疗方法主要包括改良根治术、单纯乳腺切除术、保乳术等外科手术治疗,根据术后病理辅以放化疗.对于那些有强烈保乳或整形意愿的患者可给予光动力疗法进行新辅助治疗.本文通过对近几年的相关文献的阅读及整理对乳腺Paget's病发病机制的相关理论和假说进行综述.     

Coexistence of carcinoma breast and Paget's disease of bone

We report a case of a patient with carcinoma breast who was incidentally diagnosed to be also suffering from Paget's disease of bone on a routine radionuclide bone scan. CT-guided biopsy and histopathology later confirmed the diagnosis.     

Diagnosis and treatment of extramammary Paget's disease

Extramammary Paget's disease is a malignant tumor with the characteristic bright large atypical cells called Paget's cells, which proliferate within an intraepidermal lesion outside the breast. It occurs most frequently in the external genitalia, followed by perianal and axillary regions. The main clinical symptoms are erythema, erosion, pigmentation and depigmentation. Extramammary Paget's disease is commonly an intraepidermal neoplasm. However, if the tumor cells infiltrate into the dermis and form a clinically manifest nodule, it becomes an invasive carcinoma that can be classified as adnexal adenocarcinoma of the skin. Surgery with wide local excision is the first choice of treatment, and the prognosis is comparatively favorable in the early stages. However, when tumor cells infiltrate into the dermis and advance to Paget's carcinoma, it is referred to as adenocarcinoma of the skin and has a poor prognosis. We report an effective treatment of extramammary Paget's disease in advanced stages' including our case. No standard treatment with a significant effect has yet been established. There are few reports of cases responsive to chemotherapy, and treatment in advanced stages is extremely difficult at present.     

Breast conserving treatment of Paget's disease

Between 1971 and 1984, 13 patients with histologically proven Paget's disease were treated conservatively with radiotherapy only. The disease was clinically confined to the nipple or surrounding skin, without signs of an underlying tumor. With a mean follow-up of 58.6 months (ranging between 15 and 118 months), and a median follow up of 52 months, no recurrences locally or at distance were seen. Therefore in these selected cases a mastectomy could be avoided. The results with this breast conserving management suggest a place for radiotherapy in the treatment of Paget's disease limited to the nipple.     

Paget's disease of the nipple as local recurrence after breast-conservation treatment for early-stage breast cancer

Breast conservation treatment (BCT) for early-stage breast cancer is associated with survival rates comparable with mastectomy but has the risk of ipsilateral breast tumor recurrence, including Paget's disease of the nipple. A small number of cases of Paget's disease presenting as local recurrence following BCT for breast cancer have been previously reported. Between 1977 and 2002, 2181 women with early-stage breast cancer were treated with BCT at the Hospital of the University of Pennsylvania. In this cohort, there were 183 local treatment failures, 4 of which were cases of Paget's disease (2.2%), which are reported herein. These local recurrences developed 1.8, 3.8, 7.3, and 9.7 years after diagnosis of the patients' primary tumors. Three of the 4 primary cancers were invasive ductal carcinomas, with an associated intraductal component, and 1 was ductal carcinoma in situ. All 4 patients were successfully given salvage therapy consisting of mastectomy with or without tamoxifen, with follow-up times of 20.9, 10.6, 3.1, and 3.8 years. Paget's disease as local recurrence after BCT is uncommon and can be treated with salvage therapy if detected early.     

Paget's disease of the breast presenting as a cutaneous horn

A 67-year-old woman developed a cutaneous horn on the nipple of her right breast. Biopsy of the skin underlying the horn disclosed Paget's disease of the breast. An intraductal adenocarcinoma of the same breast was found on mastectomy. High index of suspicion is mandatory in evaluating all nipple lesions.     

Pathogenesis of Paget's disease: epidermal heregulin-alpha, motility factor, and the HER receptor family

BACKGROUND AND METHODS: In Paget's disease of the breast, the epidermis of the nipple is infiltrated by large neoplastic cells of glandular origin. It has been hypothesized that the spread of Paget cells through the nipple epidermis is induced by a motility factor that acts via the HER2/NEU receptor. To test this hypothesis, we characterized and purified a motility factor released by keratinocytes and identified its target receptors in specimens from patients with Paget's disease and in SK-BR-3 breast adenocarcinoma cells, which overexpress HER2/NEU. RESULTS: We isolated the motility factor from keratinocyte-conditioned medium and sequenced tryptic peptides. These sequences were used to identify the motility factor as heregulin-alpha, which is released by skin keratinocytes. Heregulin-alpha induces spreading, motility, and chemotaxis of SK-BR-3 cells, as does motility factor. Motility factor activities of heregulin-alpha are inhibited by monoclonal antibody AB2, directed against the extracellular domain of HER2/NEU, which blocks the binding of heregulin-alpha. We used in situ hybridization to show that normal epidermal cells produce heregulin-alpha messenger RNA and that heregulin receptors, HER3 and/or HER4, as well as their coreceptor HER2/NEU, are expressed by Paget cells. CONCLUSIONS: Heregulin-alpha is a motility factor that is produced and released by normal epidermal keratinocytes and thus plays a key role in the pathogenesis of Paget's disease. Paget cells express heregulin receptors HER2/NEU, as well as HER3 and/or HER4, both of which function as a co-receptor of HER2/NEU. Binding of heregulin-alpha to the receptor complex on Paget cells results in the chemotaxis of these breast cancer cells, which eventually migrate into the overlying nipple epidermis.     

Paget's disease of the breast: a study of 43 cases.

Paget's Disease of the breast is caused by spread of duct carcinoma cells along the mammary ducts to the epidermis of the nipple and areola. This is a study of 43 cases of Paget's Disease of the breast. Though only few patients presented with a lump; a carcinoma, either DCIS or IDC or both were found in all cases. The presence of an underlying breast carcinoma in Paget's Disease of the breast suggests that radical mastectomy is the treatment of choice in this condition.     

Paget's disease of the breast with underlying carcinoma arising in systemic scleroderma

A case is presented of Paget's disease of the breast with underlying infiltrating carcinoma arising in a 35-year-old woman with systemic scleroderma. The tumor arose in an area of the skin affected by the systemic scleroderma 4 years after the onset of her systemic disease. The possibility of a causal relationship between these two processes is discussed and a brief review of the literature is presented.     

Paget's disease of the breast: What the radiologist may expect to find

Paget's disease of the nipple is characterized by the presence of Paget's cells in the epidermis of the nipple or areola. Two case reports of Paget's disease are described and used to highlight unusual features of the disease. The literature on the radiographic and pathologic findings of this disease is reviewed.     

Paget's disease of the male breast: a clinicopathologic study and a collective review

Two cases of Paget's disease of the male breast were detected in a retrospective histopathological review of 27 cases of male breast cancer treated during a period of 13 years from 1966 through 1978. The clinico-pathological data on these two rare cases have been compared with the 23 histologically documented cases of Paget's disease of the male breast from the literature.     

Mammary Paget's disease with acantholytic features and without any detectable breast tumor

Paget's disease is usually associated with an underlying adenocarcinoma of the breast. The initial manifestation is an eczematous or psoriasiform lesion of the nipple, soon extending to the mammary areola and then to the surrounding skin. The histology of the lesions is characterized by the presence, within the epidermal layer, of the so-called Paget's cells, i.e. large cells with vesicular nucleus and clear cytoplasm. The authors report a recent case of Paget's disease of the breast in a 75-year-old woman, unusual both for clinical course and observed histology. As for the clinico-evolutive aspects, although in the case observed the initial skin lesions appeared 20 years before, the different diagnostic procedures repeatedly performed showed no evidence in this patient of an underlying adenocarcinoma. The histologic aspect, on the other hand, was peculiar since the typical characteristics of an acantholytic disease were evident. The presence of intraepidermal cleavages with lost, at times, of the normal contacts among the cells of the Malpighian layer has been described only once in Paget's disease. This fact caused some diagnostic difficulties: however, the typical finding of the Paget cells, their positivity to histochemical methods such as cytokeratin and acid phosphatase allowed the diagnosis. The authors, at last, evaluate the need of a surgical therapy in Paget's disease of the breast without an underlying adenocarcinoma.     

Rarities in breast pathology. Bilateral Paget's disease of the breast--a case report

A case of bilateral Paget's disease of the breast in a 74-year-old woman is reported. The clinicopathological features of the case are presented and the rarity of this clinical entity is reviewed.     

乳房派杰氏病合并浸润性乳腺癌 患者的生存分析

背景与目的:乳房派杰氏病(Paget's disease)是一种很罕见的疾病.文献报道该病患者的生存情况与其下乳房内的病灶的恶性程度相关.该研究旨在探索合并浸润性乳腺癌的乳房派杰氏病的临床病理特征并分析患者的生存率.方法:2002—2007年,共54例在复旦大学附属肿瘤医院接受治疗的合并浸润性乳腺癌的乳房派杰氏病患者纳入该研究.由于乳腺派杰氏病大多数为人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)阳性,研究者随机收集了同期72例HER-2阳性浸润性乳腺癌患者作为对照组,比较两组的生存差异.结果:25例(46.3％)研究组患者没有典型的乳头乳晕派杰氏病皮肤表现,35例(64.8％)研究组患者浸润性癌灶超过2 cm,26例(48.1％)研究组患者腋窝淋巴结有转移.与对照组的患者相比,派杰氏病患者的复发事件更多(5年无复发生存率:76.4％vs 48.5％,P<0.01).对照组复发事件多集中于术后3年内,而派杰氏患者复发风险在术后5年内持续存在.研究组的5年总生存率(61.0％)也低于对照组(80.6％,P=0.01).结论:合并浸润性癌的乳房派杰氏病患者比HER-2阳性乳腺癌患者的预后差.     

Pathogenesis,prevention, diagnosis and treatment of breast cancer

Breast cancer is the most common cancer affecting women worldwide. Prediction models stratify a woman’s risk for developing cancer and can guide screening recommendations based on the presence of known and quantifiable hormonal, environmental, personal, or genetic risk factors. Mammography remains the mainstay breast cancer screening and detection but magnetic resonance imaging and ultrasound have become useful diagnostic adjuncts in select patient populations. The management of breast cancer has seen much refinement with increased specialization and collaboration with multidisciplinary teams that include surgeons, oncologists, radiation oncologists, nurses, geneticist, reconstructive surgeons and patients. Evidence supports a less invasive surgical approach to the staging and management of the axilla in select patients. In the era of patient/tumor specific management, the advent of molecular and genomic profiling is a paradigm shift in the treatment of a biologically heterogenous disease.