Transcription factor activating enhancer-binding protein 2B expression correlates with invasiveness and prognosis of extramammary Paget's disease.

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.

Pulmonary wedge aspiration cytology for the rapid diagnosis of pulmonary tumor thrombotic microangiopathy: A case report.

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.

Perianal Paget's disease as spread from non-invasive colorectal adenomas.

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.

Weekly docetaxel monotherapy for metastatic extramammary Paget's disease: Retrospective single-institute analysis.

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.

Extramammary Paget Disease: A Review of the Literature-Part I: History, Epidemiology, Pathogenesis, Presentation, Histopathology, and Diagnostic Work-up.

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%.

Vulvar Paget disease: A national retrospective cohort study.

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.