Asunto(s)
Paclitaxel , Enfermedad de Paget Extramamaria , Trastuzumab , Humanos , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Enfermedad de Paget Extramamaria/patología , Enfermedad de Paget Extramamaria/secundario , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Trastuzumab/uso terapéutico , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Persona de Mediana EdadRESUMEN
BACKGROUND: Extramammary Paget's disease (EMPD) is a slowly advancing malignancy that sometimes progresses to the invasion of the dermis, systemic metastases, and death. Although there have been reports that dermal invasion is associated with poor prognosis, no molecular markers of this invasion have been identified thus far. The aim of this study was to identify key molecules for predicting the risk of EMPD dermis invasion. METHOD: We performed microarray screening for three cases of in-situ EMPDs, three cases of invasive EMPDs, and three cases of normal epidermis. We identified a molecule that exhibited a stepwise increase in expression. Further, we analyzed 47 cases of EMPD using immunohistochemical staining (IHC) and examined the correlated clinicopathological findings, including prognosis. RESULT: We examined molecules that showed stepwise differences with invasion. We focused on transcription factor activating enhancer-binding protein 2 B (TFAP2B). Of the 47 EMPD patients, 38 (80.9 %) and 9 (19.1 %) had low and high TFAP2B expression, respectively. TFAP2B expression was significantly correlated with invasion into the dermis, mass formation, and preoperative lymph node metastasis (p = 0.001, 0.042, and 0.033, respectively). The cumulative postoperative recurrence-free rate in the TFAP2B-high expression group was significantly lower than that in the TFAP2B-low expression group (P < 0.001). In univariate analysis of recurrence-free survival, TFAP2B expression was found to be a significant factor (p = 0.006). CONCLUSION: The expression of TFAP2B, which was comprehensively found by microarray screening, may correlate with the invasiveness of EMPD and may be an unfavorable prognostic factor.
Asunto(s)
Enfermedad de Paget Extramamaria , Neoplasias Cutáneas , Factor de Transcripción AP-2 , Humanos , Metástasis Linfática , Enfermedad de Paget Extramamaria/metabolismo , Enfermedad de Paget Extramamaria/patología , Enfermedad de Paget Extramamaria/secundario , Pronóstico , Neoplasias Cutáneas/patología , Coloración y Etiquetado , Factor de Transcripción AP-2/metabolismoRESUMEN
Pulmonary tumor thrombotic microangiopathy (PTTM) is a cancer-related pulmonary complication characterized by rapid progression of dyspnea and pulmonary hypertension, occasionally causing sudden death. Given the condition of patients with dyspnea, lung biopsies are limited because of their invasiveness. A 72-year-old man presented with chronic atrial fibrillation and a high right heart load, as determined using ultrasonography. He had previously undergone resection of the left axillary skin secondary to extramammary Paget's disease (EMPD). Clinically, PTTM was suspected and pulmonary wedge aspiration cytology, collected from the pulmonary artery during catherization, was performed. Cytologically, the tumor demonstrated three-dimensional cell clusters with good cohesion and molding by the blood vessel lumen. Additionally, endothelial-like cells were observed at the periphery of the tumor clusters; fibrin was evident in the clusters. The tumor cells were large, round, and had high nuclear/cytoplasmic ratios. The nuclei demonstrated a variety of sizes and were irregularly shaped, with prominent nucleoli; cells undergoing mitosis were evident. The tumor cells were suspected of being poorly differentiated adenocarcinoma cells, consistent with PTTM. Two days after the aspiration cytology, the patient died and a pathological autopsy was performed. Histologically, the PTTM was determined to have caused the pulmonary hypertension and the primary PTTM site was apparently derived from the EMPD. For rapid diagnoses, an understanding of the tumor's cytological features is important and should contribute to early treatment intervention. Aspiration cytology, using pulmonary artery blood samples, during catherization is a useful tool for diagnosing PTTM.
Asunto(s)
Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/secundario , Enfermedad de Paget Extramamaria/secundario , Microangiopatías Trombóticas/etiología , Anciano , Biopsia con Aguja , Citodiagnóstico , Humanos , MasculinoRESUMEN
AIMS: Paget's disease of the perianal skin is a rare form of extramammary Paget's disease, and may be a primary intraepithelial adnexal neoplasm or secondary due to spread from an underlying colorectal lesion, nearly always colorectal adenocarcinoma. Secondary perianal Paget's disease associated with non-invasive colorectal adenomas is exceedingly uncommon, with only a few reported cases. METHODS AND RESULTS: Herein, we present the clinical and pathological features of the largest series of secondary perianal Paget's disease arising in association with colorectal adenomas. There was gender parity and the median age was 72 years (range = 68-76 years). In all cases, perianal Paget's disease was associated with colorectal adenomas, including three (75%) conventional tubular adenomas and one (25%) tubulovillous adenoma with serrated foci. All adenomas had high-grade dysplasia and one had intramucosal adenocarcinoma (lamina propria invasion; Tis), but all lacked submucosal invasion. The intraepithelial Paget's cells showed a colorectal phenotype by immunohistochemistry in all cases. At follow-up, two patients had no evidence of disease at 6 and 87 months, one had residual perianal Paget's disease at 8 months and one developed invasive adenocarcinoma of the perianal tissue at 36 months. CONCLUSIONS: Similar to its mammary analogue, secondary perianal Paget's disease may arise in association with invasive and/or in-situ colorectal lesions. Although the latter is an uncommon presentation of a recognised rare disease, knowledge of this phenomenon is important to forestall overdiagnosis of invasion and potential overtreatment. The clinical course is variable, such that close follow-up is required.
Asunto(s)
Enfermedad de Paget Extramamaria , Adenocarcinoma/complicaciones , Adenocarcinoma/patología , Adenoma/complicaciones , Adenoma/patología , Anciano , Canal Anal/patología , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/etiología , Neoplasias del Ano/patología , Neoplasias del Ano/secundario , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/etiología , Enfermedad de Paget Extramamaria/patología , Enfermedad de Paget Extramamaria/secundarioAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Docetaxel/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Enfermedad de Paget Extramamaria/secundario , Supervivencia sin Progresión , Estudios Retrospectivos , Terapia Recuperativa , Neoplasias Cutáneas/patología , Tasa de Supervivencia , Tegafur/administración & dosificaciónAsunto(s)
Neoplasias Encefálicas/mortalidad , Recurrencia Local de Neoplasia/epidemiología , Enfermedad de Paget Extramamaria/mortalidad , Neoplasias Cutáneas/mortalidad , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Quimioradioterapia/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Enfermedad de Paget Extramamaria/secundario , Enfermedad de Paget Extramamaria/terapia , Pronóstico , Radiocirugia , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Neoplasias Óseas/secundario , Neoplasias de los Genitales Femeninos/patología , Neoplasias de los Genitales Masculinos/patología , Neoplasias Infratentoriales/diagnóstico , Enfermedad de Paget Extramamaria/diagnóstico , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Femenino , Estudios de Seguimiento , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/terapia , Neoplasias de los Genitales Masculinos/mortalidad , Neoplasias de los Genitales Masculinos/terapia , Humanos , Neoplasias Infratentoriales/mortalidad , Neoplasias Infratentoriales/secundario , Neoplasias Infratentoriales/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Enfermedad de Paget Extramamaria/mortalidad , Enfermedad de Paget Extramamaria/secundario , Enfermedad de Paget Extramamaria/terapia , PronósticoAsunto(s)
Neoplasias de los Genitales Masculinos/patología , Células Neoplásicas Circulantes/patología , Enfermedad de Paget Extramamaria/complicaciones , Embolia Pulmonar/etiología , Angiografía por Tomografía Computarizada , Resultado Fatal , Vena Femoral/diagnóstico por imagen , Vena Femoral/patología , Humanos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico por imagen , Invasividad Neoplásica/patología , Enfermedad de Paget Extramamaria/secundario , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/patología , Embolia Pulmonar/diagnósticoRESUMEN
Monthly docetaxel (DTX) monotherapy is the first-line regimen that is preferably used for metastatic extramammary Paget's disease (EMPD). However, the high-dose DTX regimen frequently causes severe hematological adverse events (AE). To overcome such safety concerns, a weekly low-dose DTX monotherapy has been proposed for use in the treatment of various cancer types. In this study, we aimed to evaluate the feasibility and efficacy of weekly DTX (25 mg/m2 ) monotherapy for metastatic EMPD by retrospectively analyzing the clinical courses of 14 patients treated with this regimen. Weekly DTX monotherapy was well tolerated and all patients completed the treatment schedule without treatment withdrawal, dose reduction or treatment-related death. While five cases (35.7%) experienced hematological AE, their severity was mild. The response rate was 35.7% (5/14 cases), which included five partial responses. The mean progression-free survival (PFS) and overall survival were 7.1 (95% confidence interval [CI], 5.1-9.1) and 26.4 months (95% CI, 16.7-36.1), respectively. Furthermore, the median PFS was 7.3 months (95% CI, 4.5-10.0) in patients aged 65 years and younger and 7.1 months (95% CI, 4.4-9.9) in patients older than 65 years. These results suggest that weekly DTX monotherapy may be a useful regimen that has a high treatment continuation rate with low levels of hematological toxicity, regardless of the patient's age for metastatic EMPD.
Asunto(s)
Antineoplásicos/administración & dosificación , Docetaxel/administración & dosificación , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Docetaxel/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Paget Extramamaria/mortalidad , Enfermedad de Paget Extramamaria/secundario , Supervivencia sin Progresión , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Extramammary Paget disease (EMPD) is a rare malignancy with unclear pathophysiology that occurs predominantly on apocrine rich skin. Surgery is the treatment of choice; however, procedures tend to be extensive and associated with a high rate of recurrence. OBJECTIVE: To review the current literature on EMPD regarding epidemiology, pathogenesis, clinical presentation, histology, diagnostic work-up, treatment, and prognosis. MATERIALS AND METHODS: Literature review using PubMed search for articles related to EMPD. RESULTS: Extramammary Paget disease classically presents as a slowly growing red plaque, which often mimics an inflammatory condition leading to significant delay in diagnosis. Diagnosis requires histopathologic examination and is often supported by immunohistochemical analysis. Once a diagnosis of EMPD is made, the patient must be risk-stratified and evaluated for an underlying malignancy. CONCLUSION: Standard of treatment is surgery, with data suggesting that Mohs micrographic surgery may have superior clinical outcomes and lower recurrence rates. Alternatives such as photodynamic therapy and topicals have been explored and may be appropriate in certain situations. Patients with EMPD generally have a good prognosis with a 5-year overall survival rate of 75% to 95%.
Asunto(s)
Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/secundario , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Humanos , Metástasis Linfática , Estadificación de Neoplasias , Enfermedad de Paget Extramamaria/epidemiología , Enfermedad de Paget Extramamaria/etiología , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiologíaAsunto(s)
Antineoplásicos/administración & dosificación , Biosimilares Farmacéuticos/administración & dosificación , Docetaxel/administración & dosificación , Ácido Oxónico/administración & dosificación , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Tegafur/administración & dosificación , Trastuzumab/administración & dosificación , Anciano , Diagnóstico Tardío , Combinación de Medicamentos , Quimioterapia Combinada , Humanos , Masculino , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/secundario , Pronóstico , Neoplasias Cutáneas/diagnósticoAsunto(s)
Neoplasias Óseas/secundario , Neoplasias de los Genitales Femeninos/patología , Carcinomatosis Meníngea/secundario , Enfermedad de Paget Extramamaria/secundario , Anciano , Antineoplásicos/administración & dosificación , Neoplasias Óseas/líquido cefalorraquídeo , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/terapia , Irradiación Craneana , Docetaxel/administración & dosificación , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Metástasis Linfática , Imagen por Resonancia Magnética , Carcinomatosis Meníngea/líquido cefalorraquídeo , Carcinomatosis Meníngea/diagnóstico por imagen , Carcinomatosis Meníngea/terapia , Enfermedad de Paget Extramamaria/líquido cefalorraquídeo , Enfermedad de Paget Extramamaria/diagnóstico por imagen , Enfermedad de Paget Extramamaria/terapia , Punción Espinal , Resultado del TratamientoAsunto(s)
Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Enfermedad de Paget Extramamaria/diagnóstico por imagen , Cuidados Preoperatorios/métodos , Neoplasias Cutáneas/patología , Biopsia , Genitales/patología , Genitales/cirugía , Ingle , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Enfermedad de Paget Extramamaria/secundario , Enfermedad de Paget Extramamaria/cirugía , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/instrumentación , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/cirugía , Ultrasonografía/instrumentación , Ultrasonografía/métodosAsunto(s)
Carcinoma/diagnóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Hipofaríngeas/patología , Enfermedad de Paget Extramamaria/diagnóstico , Biopsia , Carcinoma/secundario , Carcinoma/cirugía , Mucosa Esofágica/diagnóstico por imagen , Mucosa Esofágica/patología , Neoplasias Esofágicas/secundario , Neoplasias Esofágicas/cirugía , Esofagectomía , Esofagoscopía , Humanos , Hipofaringe/patología , Masculino , Persona de Mediana Edad , Enfermedad de Paget Extramamaria/secundario , Enfermedad de Paget Extramamaria/cirugíaRESUMEN
BACKGROUND: Vulvar Paget disease (VPD) is a rare skin disorder that is considered premalignant. OBJECTIVE: To assess the clinical course, treatment schedules, and effect of invasion and treatment on recurrence and survival in patients with VPD. METHODS: Data on women with VPD were retrieved from the medical files and pathology reports in all Dutch tertiary university medical centers. Disease-free survival and 5-year disease-specific survival were estimated by using Kaplan-Meier curves. RESULTS: Data on 113 patients whose VPD was diagnosed between 1991 and 2016 were analyzed; 77% had noninvasive VPD. Most of the women (65%) underwent a surgical procedure. Recurrences were reported in 40%. Of the women with noninvasive VPD, 8% developed invasion. There were no disease-specific deaths reported in the women with noninvasive VPD. The 5-year disease-specific survival rate was greater than 98% in noninvasive and microinvasive VPD, but significantly worse in invasive VPD (50% [P < .0005]). LIMITATIONS: The main limitations of this study are its retrospective character and the fact that original pathology samples were not available for reassessment. CONCLUSIONS: VPD is extremely rare, and the recurrence rates are high. Most patients have noninvasive VPD, which does not affect survival and should be considered a chronic disorder with limited invasive potential. In cases of invasive disease, survival decreases significantly.