Metastatic extramammary Paget's disease: dramatic response to combined modality treatment

A case of extramammary Paget's disease is reported. The distinguishing features of the case are: (1) localization of the primary lesion to the scrotum, (2) development of metastases in the absence of a recognizable underlying carcinoma, and (3) response of the systemic disease to a combination of radiation therapy and chemotherapy. The histogenesis, clinical behavior, and treatment of extramammary Paget's disease are reviewed.     

阴囊Paget病的临床和病理研究

目的：探讨阴囊Paget病的临床特点和诊治方法。方法：对14例阴囊Paget病患者的临床、病理资料以及治疗和随访情况进行回顾性研究。结果：14例患者经病理检查证实并行手术治疗，随访2－12年，1例腹股沟淋巴结阳性者1例后死于全身转换，3例死于非癌疾病，3例行腹股沟淋巴结清扫者2例发和皮肤坏死、淋巴瘘等并发症。结论：本病的诊断主要依靠病理学检查，阴囊局部扩大切除是首选治疗方法。预后主要取决于病变浸润的程度，淋巴结有无转换以及是否伴有邻近内脏器官的恶性肿瘤，早期诊断是提高生存率的关键。     

阴囊Paget病79例报告

目的 探讨阴囊Paget病的临床特征、治疗原则和预后因素。方法 回顾性分析我院1993年至2004年收治的经病理证实为阴囊Paget病患者的临床资料。79例患者平均年龄62．3岁,平均病程3年7个月。除1例采用激光治疗外,其余78例均采用局部扩大切除术。7例腹股沟区淋巴结转移者行髂腹股沟淋巴结清扫术。结果 术后局部复发9例,与本病相关死亡3例。结论 阴囊Paget病术后预后良好,治疗的关键是对该病提高警惕,并及早进行组织学检查。     

Vulvar Paget's disease with an underlying sweat gland adenocarcinoma

Vulvar Paget's disease, in contrast to its mammary counterpart, has been found to be associated with an underlying apocrine sweat gland carcinoma in about only 1/4 of the cases. There are two principal theories regarding the pathogenesis of extramammary Paget's disease: (1) intraepidermal origin of the Paget cells occurring independently of, or concomitantly with, an underlying apocrine gland carcinoma, and (2) the migration or metastasis of Paget cells into the epidermis from the underlying apocrine glands and/or ducts. A case of vulvar Paget's disease that, in our opinion, supports the theory of apocrine gland origin of Paget cells is reported herein.     

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.     

乳腺外Paget＇s病五例报告

乳腺外Ｐａｇｅｔ＇ｓ病较罕见。本文报告病检证实的５例，其中男性４例，女性１例。年龄５４～７７岁，平均年龄６９．５岁。１例位于耻骨联合部，１例位于外阴部，３例位于腹股沟阴囊部。作者结合文献对本病的组织发生、临床特点、诊断、治疗和预后作了简要的讨论。     

Pathogenesis and treatment of Paget's disease of the breast

Fifty cases of Paget's disease of the breast treated surgically at The Johns Hopkins Hospital during the past 30 years were studied. Nineteen patients had Paget's disease confined to the nipple and 31 had an associated palpable tumor. An underlying intraductal or infiltrating duct carcinoma of the breast was present in each case. In six cases, the underlying tumor was 2 cm or more from the nipple with no apparent anatomic connection to the Paget lesion, and one case was encountered in whom intradermal Paget's disease develop in the area of a congenitally absent nipple. These findings support the theory of an intradermal origin for the Paget cell. Survival rates of patients with Paget's disease and a palpable breast mass were similar to those of patients with infiltrating duct carcinoma, the presence of axillary node metastases being the most important prognostic factor. Actuarial five- and ten-year survival rates were 22% and 9.9% for patients with positive nodes. The modified radical mastectomy is recommended as primary therapy for this group of patients. In contrast, none of the patients with Paget's disease of the nipple and no evidence of a palpable breast mass developed recurrent carcinoma. A total mastectomy without an axillary node dissection is the treatment of choice in this type of patient.     

外阴Paget's病8例临床分析

背景与目的：外阴Paget's病(Vulvar Paget's disease,VP)是一种罕见疾病,其误诊率较高,且治疗上仍存在争议。本研究的目的是总结外阴Paget's病的临床特点及治疗经验,以提高对该病的认识和治愈率。方法：回顾性分析1964年1月至2001年12月我中心诊治的8例外阴Paget's病患者的临床资料。结果：8例患者的中位年龄66．5岁,起病至确诊的中位时间为5年。病理分类以上皮内Paget's病为主(5／8),其次为浸润性Paget's病(2／8)和Paget's病伴发腺癌(1／8)。8例患者共行10次手术,主要术式为外阴广泛切除术(6／10)。随访中1例Paget's病伴发腺癌患者死于肿瘤,1例上皮内Paget's病患者死于其它病因,5例长期无瘤生存,1例复发。结论：外阴Paget's病治疗以手术为首选,对病变广泛、高龄、随诊条件差者选择外阴广泛切除术,较少出现复发。     

Extramammary Paget's disease of the perineal skin: role of radiotherapy.

We have reviewed our treatment results in 65 patients with extramammary Paget's disease arising in the vulva, perianal area, or scrotum. In 30 patients with primary disease, positive surgical margins were found in 53%, and there was an actuarial local recurrence rate of 40% within 5 years. The median follow-up period for primary extramammary Paget's disease patients treated with surgery alone was 198 months, and none died of this disease. Three patients treated with definitive radiotherapy were without recurrence at 12, 21, and 60 months after 56 Gy of supervoltage x-rays. In 22 patients with extramammary Paget's disease and associated adnexal or rectal adenocarcinoma, nine treated with surgery alone had a 75% local control rate. Three patients treated with surgery and adjuvant radiotherapy all had local control; of two patients treated with radiotherapy alone, one had persistent adenocarcinoma. The median survival for all patients with extramammary Paget's disease and adenocarcinoma was 22 months. We conclude that patients with extramammary Paget's disease have excellent survival but that local recurrence and morbidity from surgery, especially in the elderly, can be high. Radiotherapy greater than 50 Gy as primary treatment for extramammary Paget's disease in those medically unfit for surgery, or as an alternative to further surgery for recurrence after surgery and for anyone wishing to avoid mutilating surgery, is indicated. For those with adenocarcinoma and extramammary Paget's disease, the use of adjuvant postoperative radiotherapy in doses greater than 55 Gy is indicated because of the high risk of local recurrence after surgery alone.     

Extramammary Paget's disease of the vulva. A clinicopathologic study of 13 cases.

The clinicopathologic findings of 13 patients having extramammary Paget's disease of the vulva are discussed with emphasis on its histogenesis and biological behavior. For the purpose of study and assessment of prognosis, these cases were divided into two groups, those with an underlying invasive cutaneous adnexal adenocarcinoma, and those lacking an underlying invasive lesion. Four cases contained invasive cutaneous adnexal adenocarcinoma; in one of these the invasion was superficial. Three of the cases with an invasive lesion and three other cases showed in situ adenocarcinoma of sweat glands. Surgical treatment is mandatory for both groups of patients. The prognosis was excellent for the patients having Paget's disease without an underlying invasive carcinoma. From the literature, the prognosis of those with an underlying invasive carcinoma of the vulva appears to be less favorable. Multiple surgical excisions may be required to control the recurrences and metastases. A frequent association with other internal malignancy was observed. In four cases, second malignancies were found. Of special interest was the demonstration in one case of columns of neoplastic cells extending from involved sweat glands to the surface epithelium via the intradermal sweat duct. Our study leads us to support the concept that the Paget's cells, in a number of cases, are derived from an underlying carcinoma in situ of sweat gland origin.     

Paget's Disease of the Male Breast: A Report of Five Cases and a Collective Review

The literature on Paget's disease of the male breast is reviewedand three additional cases are reported, bringing the totalof recorded cases to 26. Paget's disease of the male breastmay be divided into two subgroups, Paget's carcinoma and Pagetoidcarcinoma. The majority of patients with former had negativelymph nodes in the axilla; accordingly, their prognosis wasbetter. Thirteen of 17 of the latter patients had positive nodesin the axilla; accordingly, their prognosis was worse. The incidence,duration of symptoms, metastasis to axillary lymph nodes, follow-upand pathology in the male were compared with those in the female.Since in the vast majority of patients with Paget's diseaseof the male breast the underlying process was nonspecific infiltrativecarcinoma (25/26 in this collected series), radical mastectomyseems to be the appropriate therapy for this lesion.     

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.     

An autopsy case of Paget's disease of the scrotum with general metastasis

An autopsy case of genital Paget's disease with a widespread metastases is reported. A 69-year-old man with redness, itching and swelling of the scrotum obtained dermatological consultation and underwent tumor resection for Paget's disease. At 8 months after discharge, he suffered from a costal fracture because of carcinomatosis of the bone marrow. In laboratory data the serum level of alkaline phosphatase and carcinoembryonic antigen was shown to be high. Four months later, he died of severe congestive edema of the lung with diffuse micrometastases. An autopsy revealed a widespread metastases in various organs and lymph nodes. The Paget cells were positive in carcinoembryonic antigen.     

Mammary and extramammary Paget's disease. An immunocytochemical and ultrastructural study

Twenty-one cases of Paget's disease have been studied using histochemical, ultrastructural, and immunohistochemical methods. Eight of the tumors involved the nipple, and 13 were extramammary (11 vulvar and two anal). The antibodies used were directed against different classes of cytokeratin proteins, epithelial membrane antigen, carcinoembryonic antigen, gross cystic disease fluid protein-15, and S-100 protein. The findings of this study provide conclusive evidence that Paget's cells, regardless of their location, are adenocarcinoma cells. Intracytoplasmic mucin is scanty in Paget's cells within the nipple, but typically plentiful in the extramammary sites where the cells are frequently signet-ring cells. The common mechanism for the evolution of Paget's disease is extension of cells from an underlying carcinoma, but the possibility that some cases, particularly in the vulva, develop from intraepithelial precursors cannot be excluded.     

Paget's disease of the nipple. Immunohistochemical localization of milk fat globule membrane antigens

The authors have used the indirect immunoperoxidase technique to examine the presence and distribution of milk fat globule membrane antigens in 12 cases of mammary Paget's disease using two monoclonal antibodies, HMFG-1 and HMFG-2. These stain breast epithelial cells but do not stain normal epidermis. The Paget's cells showed a similar pattern of cytoplasmic staining to that seen in the underlying intraduct or invasive carcinoma, therefore confirming them to be malignant ductal cells. To support this one of the cases was stained with the antibody LE 61 which is specific for nonepidermal epithelial cytokeratins. The result was strongly positive in Paget's cells in the epidermis but not in squamous cells.     

Osteosarcoma arising in Paget's disease of the mandible

Although osteosarcoma is a well-known complication of Paget's disease of bone, it uncommonly develops in the jaw bones. We present an osteosarcoma arising in Paget's disease of the mandible with unique features of a normal serum alkaline phosphatase level, and histologic features of telangiectatic change in the osteosarcoma and association with cemento-osseous dysplasia. Sixteen reported cases of osteosarcoma arising in Paget's disease of the jaw bones (OPJ) are also reviewed and compared to osteosarcoma arising in Paget's disease occurring in the entire skeleton (OPS) and osteosarcoma arising de novo in the jaw bones (OJ). Females are more commonly involved in OPJ in contrast to a male predominance in OPS and OJ. OPJ also has a distinctively higher percentage involving blacks compared to OPS. The prognosis of OPJ is poor, with 69% of patients dying within two years after diagnosis. Early recognition, early and aggressive treatment are important to improve the prognosis and are hence emphasized.     

Paget's disease of the nipple: A ten year review including clinical,pathological, and immunohistochemical findings

Thirty-five women with biopsy-proven Paget's disease of the nipple were treated over a 10 year period at the Breast Cancer Unit, Guy's Hospital. Twenty-four (69%) patients had Paget's disease without a palpable mass in the breast; eleven (31%) presented with a palpable mass and Paget's disease of the nipple. Definitive treatment consisted of modified radical mastectomy in 32 patients, radiotherapy only in 2, and one patient had no definitive treatment.All 11 patients with Paget's disease and an associated lump proved to have invasive ductal carcinoma; five also had associated positive axillary nodes. Nine of the 23 patients with nipple changes only, treated by mastectomy, also had invasive carcinoma; three of these had positive axillary nodes. The remaining 14 patients with nipple changes only were found to have in situ ductal carcinoma, which was extensive in the majority of cases.In 13 cases, histological sections of the nipple were examined by immunohistochemical staining which showed that the Paget's cells expressed a keratin phenotype that was specifically characteristic of simple epithelial cells as seen in glandular epithelium. This was quite unrelated to the normal keratin phenotype of the surrounding skin keratinocytes.Clinical, pathological, and immunohistochemical data suggest a mammary origin of the abnormal cells in Paget's disease of the nipple. Mastectomy appears to be the treatment of choice.     

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 anal mucosa in association with carcinoma demonstrating mucoepidermoid features

A case of Paget's disease of the anal mucosa with an underlying carcinoma demonstrating mucoepidermoid features is reported. The histopathologic characteristics of both extramammary Paget's disease and mucoepidermoid carcinoma are noted. Special histochemical staining procedures were consistent with the diagnosis. The actual histogenesis of extramammary Paget's disease and mucoepidermoid carcinomas are controversial topics that are briefly discussed in this paper.