Perianal Paget's disease / Doença de Paget perianal

ABSTRACT Paget's disease most commonly affects the breast. Extramammary involvement is rare, and the most commonly affected sites are the vulva, anus, perianal region, and axilla. The disease may progress to invasive adenocarcinoma or synchronous cancers. Due to the lack of distinctive features and nonspecific presenting symptoms, Paget's disease may be misdiagnosed as other conditions, thus delaying the correct diagnosis. We report a case of extramammary Paget's disease in the perianal region that initially presented as an irregular, circumferential, scaling lesion with eczematous eruptions. Immunology and immunohistochemistry confirmed the diagnosis. Although surgery is the standard treatment, the patient opted for pelvic radiotherapy associated with radiosensitizing chemotherapy.

RESUMO A doença de Paget acomete mais comumente a mama. Os focos extramamários são raros e os locais mais habitualmente acometidos são vulva, ânus, região perianal e axila. A patologia envolve a evolução da doença para adenocarcinoma invasivo ou neoplasias sincrônicas. Devido à singularidade e sua aparência inespecífica, a doença pode ser confundida com outras comorbidades, retardando o diagnóstico. O objetivo foi relatar um caso de doença de Paget extramamária na região perianal, a qual inicialmente apresentou lesão circunferencial com erupção eczematosa, descamativa e irregular. A confirmação diagnóstica foi por meio de exames imuno-histoquímico e imunológico. O tratamento padrão da doença é cirúrgico, porém optou-se por radioterapia pélvica associada à quimioterapia radiossensibilizante.

A case of chronic and relapsing paget disease of the vulva

Abstract Extramammary Paget disease is a rare neoplastic condition that more commonly affects postmenopausal Caucasian women. Although the vulvar area is the most frequently affected location, it corresponds solely to 1 to 2% of all vulvar malignancies. A 72-year-old female patient was observed in our outpatient clinic with a 2-year history of an erythematous and pruritic plaque on the vulva. Histopathology and immunohistochemistry studies were compatible with extramammary Paget disease of the vulva. Associated neoplastic conditions were excluded. Due to multiple relapses, the patient was submitted to three surgical interventions, including a total vulvectomy, and to external radiotherapy. The present case illustrates the chronic and recurrent nature of extramammary Paget disease despite aggressive procedures as well as the challenge in obtaining tumor-free resection margins.

Pigmented extramammary Paget's disease accompanied with condyloma acuminatum: a case report / 北京大学学报(医学版)

Pigmented extramammary Paget's disease (PEMPD) is an uncommon intraepithelial adenocarcinoma and a rare variant of Paget's disease, characterized as a superficial pigmented scaly macule clinically and an increased number of melanocytes scattered between the Paget's cells histologically. So it may be confused clinically and histologically with melanocytic tumors, dermatitis and other dermatoses. Different therapeutic attitudes are required in this case of adenocarcinoma in situ as opposed to melanoma and dermatitis. Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papilloma virus infection, which is also called as genital warts. In this article, we first reported a case of a 65-year-old Chinese man who had pigmented extramammary Paget's disease complicated with CA. This patient presented with verrucous papules on the scrotum for 3.5 years, infiltrative erythema with itch on the mons pubis for 3 years, and scrotum and penis involved gradually for 4 months. Physical examination showed a 8 cm×10 cm dark red patch on the upper part of the scrotum, penis and mons pubis, as well as few maculopapules and nodules. Histopathologic examination of the lesion on the scrotum revealed a focus of Paget's disease, characterized by the presence of large round cells with abundant pale or granular/dusty cytoplasm, pleomorphic vesicular nuclei and prominent nucleoli (Paget's cells), while the histology of the verrucous lesion was consistent with CA. Immunohistochemistry was performed, which showed diffuse positive staining with CK, CEA, PAS, CK20, EMA, CK7, and Ki-67 (40%), HER2 in Paget's cells and negative with P53, P16, CK5/6, S100, MelanA, HMB45, estrogen receptor, progesterone receptor, and gross cystic disease flid protein 15 (GCDFP15). Human papillomavirus-11 (HPV-11) was positive by genotyping using gene amplification in the lesion of scrotum. According to clinical features and laboratory findings, a diagnosis of PEMPD complicated with CA was made. Local excision of the lesion was performed and sent for histological examination, with all margins clear of tumor. Both aforementioned diseases often occur in the vulva. Even so, it has been rarely reported coexisting of the above two diseases, of which the clinical significance and association are also unclear. In this article, we also reviewed the literature relating to PEMPD, and on this basis, the profile of this disease is discussed including its pathogenesis, clinical manifestation, diagnosis, treatment and advances. Due to PEMPD occasionally accompanied with an underlying carcinoma, it's essential to make an accurate diagnosis. Besides, review of the literature reveals that pigmented variant of Paget's disease could be initially misdiagnosed as melanocytic tumors and other dermatoses unless the entity is considered in the differential diagnosis and additional confirmatory studies are performed.

Enfermedad de Paget extramamaria de la vulva: a propósito de un caso clínico / Extramammary Paget's disease of the vulva: apropos of a clinical case

La Enfermedad de Paget extramamaria de la vulva es una neoplasia poco frecuente que representa solo el 1% de los cánceres de vulva. Clínicamente, se caracteriza por una placa eritematosa, bien definida, con erosiones y ulceraciones. El síntoma más frecuente es el prurito. Esta clínica tan inespecífica puede retrasar el diagnóstico, además de inducir a tratamientos inadecuados. El diagnóstico se realiza con estudio histopatológico e inmunohistoquímica, la cual orienta si es primario de piel o metástasis de otro cáncer, usualmente genitourinario o gastrointestinal subyacente. Actualmente no hay guías clínicas de tratamiento, pero dentro de las opciones la más aceptada es la cirugía de Mohs. Otros tratamientos incluyen uso de imiquimod, láser CO2, quimioterapia tópica o local, radioterapia o terapia fotodinámica. Cuando se trata de una enfermedad de Paget extramamaria primaria, el pronóstico es excelente y la mayoría de los pacientes fallece por otra condición. En cuanto a la enfermedad invasora, tiene una mortalidad de 13-18% con sobrevida a 5 años de 72% (1)

Extramammary Paget Disease of the Vulva - Case Report / Relato de Caso: Doença de Paget Extramamária da Vulva

Abstract Extramammary Paget disease (EPD) is a rare malign neoplasm that may affect the vulva and has manifestations common to benign diseases such as itching, pain and eczema. This leads to delay in diagnosis and consequent worse prognosis. The definitive diagnosis is obtained by biopsy of the vulva, which shows Paget cells. The treatment of choice is wide excision with margins, which leads to sequelae, functional and aesthetic. Recurrence is common. This article reports the case of a 48-year-old female patient with history of vulvar itching for the past 2 years, who had been submitted to various treatments for benign pathologies. The patient was biopsied and was diagnosed with extensive EPD, being submitted to vulvectomy. This article aims to draw attention to the need for biopsy of pruritic vulvar lesions that do not respond to usual treatment.

Resumo A doença de Paget extramamária (DPEM) é uma neoplasia maligna incomum que pode acometer a vulva, e que tem manifestações comuns a doenças benignas como prurido, dor e eczema. Isto leva a atraso no diagnóstico e, consequente, piora do prognóstico. O diagnóstico de certeza se dá pela biópsia de vulva que evidencia células de Paget. O tratamento de escolha é a excisão com margens amplas, que leva a sequela funcional e estética. A recidiva é frequente. Este artigo relata o caso de uma paciente do sexo feminino, de 48 anos, com história de prurido vulvar há 2 anos com diversos tratamentos para patologias benignas. A biopsia da paciente confirmou diagnóstico de DPEM extensa sendo submetida a vulvectomia. Este artigo visa chamar a atenção para a necessidade de biópsia das lesões vulvares pruriginosas que não respondem ao tratamento habitual.

Mammary and extramammary Paget's disease

Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent.

Extramammary Paget's disease: Analysis of 17 Chinese cases.

Background/Objective: Extramammary Paget’s Disease (EMPD) seems to be more common in Caucasians than Chinese. We report the clinical manifestations, management, and prognostic characteristics in 17 Chinese patients. Methods: Medical records and biopsies of 17 patients who had been treated at a large university hospital in China between March 2005 and January 2012 were reviewed. Results: Of the 17 patients, 14 were men. They had lesions on the scrotum and the penis. Of the three women, two had vulvar and one had inguinal lesions. All patients underwent Mohs micrographic surgery (MMS). Three men had metastasis to the inguinal lymph nodes and underwent an extensive local excision with inguinal lymphadenectomy. Eight patients who had positive excision margins received additional radiation therapy. The mean follow-up duration was 54 months (4-85 months). One patient had two recurrences. Three had metastasis to the inguinal lymph node. One had metastasis to the bone and concomitant prostate cancer. Two patients died of the disease. Conclusion: A striking difference in presentation of EMPD in Chinese compared with Caucasians is the male predominance and location on the penis and scrotum. Mohs micrographic surgery followed by radiotherapy is an effective treatment. Long-term follow-up suggests that the disease has a good prognosis when it does not metastasise.

Enfermedad de Paget extramamaria: reporte de caso / Extramammary Paget's disease: case report

Se presenta el caso de una mujer de 67 años de edad, sin antecedentes de importancia, con un tiempo de enfermedad de un año. La paciente refiere una lesión tipo placa amarronada con áreas eritematosas y de bordes definidos, localizada en la región púbica izquierda, con extensión a la región inguinal, asociada a intenso prurito. Se le diagnosticó eccema y recibió tratamiento con corticoides tópicos, sin mostrar mejoría. Al momento de la evaluación, el examen físico no reveló adenopatías y los exámenes de laboratorio resultaron normales. El diagnóstico fue inmunohistopatológico, mediante el hallazgo de células de Paget y la tinción positiva para CK-7 y panqueratina, compatible con una enfermedad de Paget extramamaria, debida a diseminación intraepidérmica de un tumor primario de glándulas sudoríparas tipo adenocarcinoma in situ. La paciente fue sometida a una evaluación general para descartar una diseminación a distancia, pero no se encontró evidencia alguna. Se la trató exitosamente con cirugía escisional estándar con bordes libres y cursó favorablemente sin recurrencias cinco meses después.

A 67-year-old woman presented with a history of one year of pruriginous well defined brownish-reddish patch lesion on pubic area, which extended to inguinal area. An external diagnosis of eccema was made and the patient initiated treatment with topical corticosteroids for several months, without results. At present time, physical examination and laboratory evaluation did not reveal major alteration. A biopsy was taken and immunohistochemistry analysis was made, which revealed the presence of Paget's cells positive to CK-7 and pan Keratin. The results were compatible with extramammary Paget's disease secondary to intraepidermal dissemination of primary apocrine sweat glands adenocarcinoma. The patient underwent further evaluation to rule out distant metastases and was treated successfully with surgical excision alone with free margins. At follow-up five months later was still free of recurrences.

Case for diagnosis / Caso para diagnostico

An 83 year-old man was observed for an 8 year-long pruritic, erythematous plaque of the left axilla. He had been continuously medicated with topical antifungals and steroids with occasional symptomatic relief, but with disease progression. After a clinical and histological diagnosis of Extramammary Paget's Disease, a total excision with wide margins was performed. He remains disease-free 12 months after surgery. We report this rare presentation of Extramammary Paget's Disease on a male patient.

Um homem de 83 anos foi observado por placa eritematosa pruriginosa da axila esquerda com 8 anos de evolução. Estivera continuamente medicado com antifúngicos e corticóides tópicos com alívio sintomático ocasional, contudo com progressão da doença. Após diagnóstico clínico e histológico de Doença de Paget Extramamária, foi feita excisão total com margens largas. Mantém-se sem evidência de doença aos 12 meses após cirurgia. Salientamos esta apresentação rara de Doença de Paget Extramamária num paciente do sexo masculino.

Extramammary Paget's disease: presenting in an unusual site

Extramammary Paget's disease [EMPD] is a rare neoplasm with only a limited number of reported cases in literature. It is mainly composed of intraepidermal Paget cells and possesses variable clinical behaviour and histological appearance leading to difficulty in diagnosis. We here report a case of primary EMPD in a 71-year-old male who presented with gradually progressive, pruritic, eczematous lesion in suprapubic region, not responding to topical medications. Histological assessment showed Paget cells infiltration throughout the epidermis with dermal invasion. Using immunohistochemistry, the expression of CK7, carcinoembryonic antigen [CEA] was examined to elucidate cellular differentiation of the carcinoma

Enfermedad de paget perianal / Extra mammary paget disease: report of one case

Extra mammary Paget disease is rare and mostly affects perianal and vulvar zones, in patients of both sexes and from the sixth decade of life. We report a 66 years old woman with a vulvar Paget disease, subjected to a vulvectomy. Two years later, a pruriginous and erythematous plaque appeared in the perianal region. The pathological study informed an extra mammary Paget disease. The patient was subjected to a perianal excision and the correction of the surgical defect in a second intervention. After one year of follow up, there is no evidence of disease relapse.

La enfermedad de Paget de localización extramamaria (EPEM) es una patología infrecuente que afecta preferentemente a zonas perianal y vulvar en pacientes de ambos sexos y desde la sexta década de vida. Presentamos un caso clínico tratado en conjunto por los Servicios de Cirugía General, Cirugía Plástica, Ginecología y Anatomía Patológica del Hospital Universitario de Getafe.

Extramammary Paget's disease.

Two patients with extramammary Paget's disease are being reported. The first case was a 60-year-old male who presented with gradually progressive pruritic ulcerated lesion over perianal region not responding to various topical medications. Dermatological examination revealed a large erythematous sharply marginated scaly plaque in the perianal region extending into the anal canal, covered with grayish crusts and shallow erosions. Skin biopsy from the lesion was suggestive of Paget's disease. The second patient, a 60-year-old male, with a three year long history, presented with similar lesions and findings. Skin biopsy in this case was also consistent with Paget's disease. These two cases of extramammary Paget's disease involving the perianal region are being reported because of their rarity and also to stress the fact that a high degree of suspicion is needed for the diagnosis of this uncommon disease entity.

Enfermedad de Paget mamaria y extramamaria: dos entidades diferentes bajo un mismo nombre / Extramammary and mammary Paget's disease: two different clinical entities

La enfermedad de Paget mamaria es una neoplasia de carácter maligno, desarrollada principalmente en la areola mamaria y pezón, que se diagnostica por sus características histológicas específicas. Se considera una manifestación cutánea de un carcinoma subyacente, ya que en casi todos los casos se detecta una neoplasia maligna mamaria. La enfermedad de Paget extramamaria es una neoplasia intraepidérmica que se ubica en zonas donde existen glándulas apocrinas. Esta entidad se diferencia de la enfermedad de Paget mamaria en cuanto a su histogénesis, características tintoriales y frecuencia relativa de carcinomas subyacentes. En este artículo se describen las características más importantes de ambas entidades.

Paget's disease of the breast, diagnosed by specific histologic characteristics, is a malignant neoplasm that develops mainly in the areola and nipple. It is considered a cutaneous manifestation of an underlying carcinoma because a malignant neoplasm is almost always detected. Paget's extramammary disease is an intraepidermal neoplasm that is located in apocrine gland regions. This entity differs from Paget's mammary disease with respect to its histogenesis, staining qualities and relative frequency of underlying carcinomas. In this article we describe the most important characteristics of the both entities.

Doença de Paget extramamária em região períneo-ínguino-escrotal / Extramamary Paget's disease in perineo-inguinoscrotal region

A doença de Paget extramamária constutui-se numa patologia rara. Existe uma estreita correlação com carcinoma anorretal quando a doença é perianal. Também está associada com malignidades internas e mau prognóstico. Os autores relatam um caso de Doença de Paget extramamária em região períneo-ínguino-escrotal, num homem branco de 59 anos, que apresentava uma lesão de aproximadamente 6 cm de diâmetro, hiperpigmentada e pruriginosa, lesão esta que aumentou de tamanho e que vinha apresentando mínimo sangramento. Os exames de estadiamento foram normais, sem evidência de metástases. O exame anátomopatológico da lesão revelou aspecto compatível com Doença de Paget extramamária. A conduta então foi a excisão ampliada da lesão e enxerto de pele fina. São discutidos os aspectos referentes à epidemiologia, patologia, estadiamento, prognóstico e tratamento desta neoplasia.

Enfermedad de Paget recurrente de la vulva: presentación de 2 casos tratados con radioterapia / Pagetïs disease of the vulva recurrence: 2 cases treated with radiotherapy

Se presenta dos pacientes con enfermedad de Paget de la vulva con múltiples recurrencias. La evaluación histológica confirmó el diagnóstico y descartó la posibilidad de adenocarcinoma subyacente. Después de varias resecciones quirúrgicas, ambas pacientes fueron tratadas con radioterapia. Los resultados estéticos así como también la tolerancia y toxicidad durante y después del tratamiento, fueron aceptables. Ambos casos han completado al menos 1 año de seguimiento sin recurrencia clínica demostrable por vulvoscopia

Extramammary Paget's disease with aggressive behavior: a report of two cases

Extramammary Paget's disease (EMPD) is an intraepithelial neoplastic disorder which is included as a rare malignant condition. However, it sometimes shows aggressive behavior of local recurrence and coexisting malignancy. We had experienced nine cases of EMPD involving the scrotum for seven years. Two cases of them presented metastasis. The first case presented extensive inguinal lymph node metastasis with underlying adnexal adenocarcinoma one year after wide local excision. The second case initially presented multiple metastasis to the liver and in the lymph node. The latter, showing fulminant progression with liver metastasis, may be only the second case reported in English literature. EMPD is considered as a malignant neoplasm with aggressive behavior from initial presentation. Because wide local excision of the lesion alone may be occasionally insufficient, a careful follow-up must be done to detect recurrence or internal malignancy.

Enfermedad de Paget extramamaria y mamaria, anaplásica y acantolíca: presentación de 7 casos y revisión de la literatura / Paget disease, extrammamary and mammary, anaplastic, acantholytic: a report of 7 cases and review of the literature

La enfermedad de Paget extramamaria anaplásica y acantolítica (EPeMAA) y la enfermedad de paget mamaria anaplásica y acantolítica (EPMAA), son formas raras de la EP; no se sabe en el momento actual su frecuencia real. Se presentaron por arriba de la cuarta decada, en 4 mujeres y 3 hombres. Su evolución fué crónica, clínicamente fueron placas verrugosas, ulceradas, facilmente sangrantes, bien limitadas. Clínica e histológicamente se confundieron con enfermedad de Bowen y con el pénfigo vegetante. Microscópicamente se observó en todo el espesor de la epidermis células anaplásicas pequeñas, con núcleo ovoide, cromatina fina sin disqueratosis, escaso citoplasma; la acantólisis fué acentuada con formaciones vegetantes. Se observaron células clásicas de Peget en forma alterna; todos exhibieron ulceración y en la periferia la imagen típica de EP. En la base de la neoplásia hubo infiltrado linfocitario en banda "patrón liquenoide". En 4 de los casos se identificó neoplásia maligna sincrónica en la profundidad (1 caso Ca de conductos mamarios, 2 casos Ca de conductos de glándulas apócrina y 1 caso de Ca. de conductos de glándulas ecrina de tipo esclerosante) fueron positivos al antígeno carcinoembrionario (ACE) 5/5, al antígeno de membrana epitelial (AMA) 5/5, y a la citoqueratina de bajo peso molecular (Cqbpm) 5/5. Hay que hacer el diagnóstico diferencial con la enfermedad de Bowen (EB), melanoma de diseminación superficial (MMDS) y con el pénfigo vegete. No hay diferencias en pronóstico entre la EP mamaria y extramamaria clásica y la EPeMAA u EPMAA