Extramammary Paget’s Disease Manifested by Intraepithelial Adenocarcinoma of the Vulva and Anus Combined with Invasive Adenocarcinoma of the Ampullary Part of the Rectum

The Object of the Study: The author of the given paper describes an unusual combination of two diseases: extramammary Paget’s disease manifested by intraepithelial adenocarcinoma of the vulva and anus combined with invasive adenocarcinoma of the ampullary part of the rectum and describes the atypical manifestations of these diseases. The Content: The content of this research paper includes a description of the patient, an analysis of the clinical picture, diagnostic methods and therapeutic interventions used, a report of the following disease, and the result of the presented case. The Result of the Research Work: The result of the research work is the analysis of a clinical case with two different tumors, where such a combination of tumors is rarely described in the literature. Moreover, no large specific sample with this combination of diseases is available. Patient Characteristics: The given case report describes a patient of the Palliative Care Unit of the Gerontology Clinic with a primary diagnosis of C20-rectal adenocarcinoma in the background of the anal canal, perineal skin Paget’s disease, stage IV. The presented complications of the patient’s primary diagnosis are multiple metastases in the liver;status post palliative chemotherapy;hepatomegaly;metastases to abdominal lymph nodes, inguinal lymph nodes;metastases at Th12, L4 level;pain syndrome. The presented above combination of diagnosed diseases is very rare. Applied Diagnostics: In October 2021, it was performed diagnostic manipulation: biopsy and the pathologist have provided a microscopic description. The first tissue fragment had a pronounced electrothermal lesion and the epithelial structures were not valuable. The second skin tissue fragment was covered with hyperplastic and acanthotic epithelium;its basal and middle layers contained multiple large cells proliferates extending into the medial epidermis, and the cytoplasm of these cells reacted positively with PAS (Periodic Acid Schiff reaction). It needs to be noted that the patient had previously had several years of biopsies from the perineal and anal epidermis, where Paget’s disease had also been diagnosed. The performed immunohistochemistry showed these cells to be CK20 positive, CK7 rare positive and p16 negative. The following pathohistological findings were made: morphological and immunohistochemical picture is consistent with Paget’s disease. According to the ICD-10, the patient was diagnosed with C51 malignant neoplasm of the female external genitalia. Using imaging diagnostics, it became clear that the patient’s rectal adenocarcinoma had progressed to metastatic stage with distant liver metastases in the background of anal canal, perineal skin Paget’s disease. Therapeutic Plan of the Patient: Based on the patient’s main diagnoses, the complications of the principal diagnosis, the patient’s overall severe condition, pain syndrome, age and comorbidities, palliative chemotherapy was approved as a therapeutic option in council of doctors. Monitoring and Outcome of the Patient: The patient’s general condition was becoming worse over time, and she was diagnosed with exitus latalis in December 2022. At that time, the patient was discharged from hospital and was on palliative care at home under the control of her family physician.

Development a survival prediction model for patients with Paget disease of the breast based on the SEER database

Background:We explored the risk factors that affect the prognosis of patients with Paget disease of the breast(PD)and constructed a survival prediction model.Methods:The data of PD patients from 2004 to 2014 were collected through the SEER database.The factors affecting the prognosis of PD patients were analysed by a single factor,and the prediction model of the independent risk factor transformation model diagram that affected their 1-,3-,and 5-year survival rates was screened by multivariate Cox proportional hazard regression analysis coefficients.The consistency index was used to evaluate its predictive value,and its predictive performance was tested by the 1000 bootstrap method.Then,the calibration curve was used to verify the predictive performance of the model,and the receiver operating characteristic curve and decision curve analysis were used to assess the sensitivity and practicability of the model compared to the American Cancer Commission staging(AJCC)staging system.Results:The consistency index of the model was 0.795(95%confidence interval 0.773–0.818).The calibration curve shows good consistency,while the receiver operating characteristic curve shows the sensitivity of the model to predict the survival rate of PD at 1,3,and 5 years.Decision curve analysis confirmed that the nomogram can predict the survival rate of PD patients at 1,3,and 5 years instead of the traditional AJCC system.Conclusion:Regarding the independent prognostic factors of age,marital status,AJCC classification,surgery,radiotherapy,chemotherapy and marital status conversion in PD patients,the nomogram established in sequence has higher accuracy and clinical value than the traditional AJCC system.

Extramammary Paget’s disease: Updates in the workup and management

Objective:Extramammary Paget’s disease(EMPD)is a rare cutaneous malignant disease.Due to its rarity,there is a paucity of data regarding best treatment strategy.EMPD primarily affects apocrine gland-bearing skin areas such as the vulva,scrotum,and penis.Our objective was to provide a present-day rationale for diagnosis,pathogenesis,and treatment of EMPD with a focus on recent progress in workup and management of the disease.Methods:Literature on EMPD until February 2022 was assessed through PubMed,MEDLINE databases,and Google scholar.A narrative review of the most relevant articles was provided.Results:EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ.The foundation of EMPD treatment centers around prompt and accurate diagnosis,wide local or Mohs micrographic surgical excision with proper management towards the margin status,and careful consideration for lymphadenectomy in patients with regionally positive disease.Conventional chemotherapies are alternative treatments modality for patients with distant metastases;however,they sometimes have suboptimal efficacy.At present,there is no agreement regarding adjuvant or systemic therapies,although recent studies have shown several insights into the molecular pathogenesis,tumor biology,and genomics of the development and advancement of EMPD,which may lead to novel and targeted treatment approaches for metastatic EMPD in the future.Conclusion:Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling.These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression.Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors,and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

Photodynamic Therapy for Extramammary Paget's Disease:5 Cases Report

Objective： To study the therapeutic effect of photodynamic therapy for extramammary Paget＇s disease. Methods： DIOMED 630 nm diode laser was used as light source and photofrin as photosensitizer. The patient＇s lesion was irradiated for 24-72 h after administrating of photofrin. The power density was 100-150 mW/cm^2 and energy density was 150-300J/cm^2. Dosage of photofrin was 2 mg/kg. Results： Lesion darkened 24 h after irradiation and formed a scar 96-120 h after irradiation. One patient＇s lesion disappeared, three patients＇ lesion diminished apparently and one patient＇s lesion was not controlled 3 months later. Conclusion： Photodynamic therapy is an effective modality for extramammary Paget＇s disease.

An autopsy case of metastatic extramammary Paget’s disease treated with multimodality treatment including anti-HER2 therapy: What is the clinical and pathological significance of trastuzumab to the patient?

Advanced Extramammary Paget’s disease (AEMPD) shows a poor prognosis despite multimodality therapy. In recent years, it is suggested that anti-HER2 therapy may be promising for HER2-positive AEMPD. We herein present an autopsy case of a patient with AEMPD treated with multimodality treatment including anti-HER2 therapy. A 78-year-old man who diagnosed with AEMPD died after surgery and systemic chemotherapy including anti-HER2 therapy (trastuzumab). The metastatic skin lesions were immnohistologically HER2-positive. While the patients were administrated trastuzumab plus taxan (docetaxel, and paclitaxel) regimen, the metastatic skin lesion decreased, however, brain metastases were found in his brain and trastuzumab is discontinued. The skin metastasis rapidly spread over his body, leading to weakness, and he eventually died. At autopsy, the lesions of EMPD were extended distant organs including brain, although each metastasis was small and asymptomatic. The wide lesion of skin metastasis was exacerbated after discontinuation of trastuzumab, and transudate was observed due to the extensive necrosis and erosion. Our autopsy findings showed one progressive pattern of AEMPD, and indicated what is the clinical and pathological significance of anti HER2 therapy for HER2-positive AEMPD.

Extramammary Paget’s Disease Covered the Left Nipple and Areola

We present a case of a 71-year-old woman suffering from mammary Paget,s disease and having a 10-years history of an irregular, widespread erosion accompanied by itching and burning on the skin of her left chest, extending to the breast. The erosion had steadily enlarged and had become increasingly tender. The nipple and areola of the left breast disappeared and could not be recognized. No abnormality of the right nipple, areola, and covering skin and no supernumerary nipple were seen. Mammography and ultrasonography could not be performed because of severe pain and erosive wetness. Histopathology of a surgical biopsy specimen showed epidermal infiltration by large, round, clear atypical cells scattered individually or in small clusters and distributed horizontally throughout the epidermis. The cytoplasm of these large cells was pale and vacuolated and was equivalent to that in nipple cells in Paget,s disease, and a diagnosis of mammary Paget,s disease was made. We performed total mastectomy of the left breast with wide excision of the Paget lesion of the left chest and axillary lymph node sampling. Histological examination of the specimen showed typical distribution of Paget,s cells;however no ductal carcinoma in situ was found in the mammary ducts and invasive growth was not recognized beyond the basal membrane of the lesion. From this evidences, we established a diagnosis of large, irregulaly shaped unusual mammary Paget,s disease, not of breast cancer origin, covering the left breast, areola, and nipple.

The Disturbance of Melanogenesis and Melanosome Transfer in the Leukoderma Lesions of Extramammary Paget’s Disease

We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructural analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complexes were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.

CLINICAL ANALYSIS AND TREATMENT OF 14 CASES OF EXTRAMAMMARY PAGET'S DISEASE

Objective To diffrentiate extramammary Paget’s disease (EPD) clinically and histologically from other skin diseases. Methods Clinical analysis and excisional treatment of 14 patients with EPD were reviewed from 1987 to 1997. Results of 14 patients, 12 involved scrotum and penis, one in the groin and the other one in the syrianal region. All were positive for cytokeratin and negative for S-100 protein. Follow-up showed 3 recurrences who had positive surgical margin biopsy. One died of other diSease. Conclusion Surgery is the first choice for treatment of EPD. Negative margin must he achieved to prevent local recurrence.

TRPS1在原发性乳腺外Paget病中的表达及其诊断价值

目的分析TRPS1在原发性乳腺外Paget病(EMPD)中的表达情况,探讨TRPS1在原发性EMPD诊断中的价值。方法收集宿迁市第一人民医院病理科2015年7月至2023年12月诊断的39例原发性EMPD、6例继发性EMPD、15例黑色素瘤和11例鳞状细胞原位癌病历资料,采用免疫组织化学En Vision法检测TRPS1的表达情况。结果原发性EMPD患者39例,男性29例,女性10例;年龄53~81岁(平均年龄68岁,中位年龄71岁)。继发性EMPD患者6例,男性4例,女性2例;年龄45~76岁(平均年龄59岁,中位年龄62.5岁)。39例原发性EMPD中,35例(35/39)显示TRPS1强和弥漫的细胞核表达,阳性率为89.7%,且4例阴性病例均位于肛周;而在6例继发性EMPD中均为阴性。TRPS1在15例黑色素瘤中也呈阴性,在90.9%(10/11)的鳞状细胞原位癌中表现为弥漫强阳性。本组病例中,TRPS1诊断原发性EMPD的敏感性和特异性分别为89.7%和68.8%。结论TPRS1在原发性EMPD中的表达具有高敏感性,有助于与继发性EMPD和黑色素瘤进行鉴别,但在原发性EMPD与鳞状细胞原位癌的鉴别中作用有限。

Retrospective analysis of perianal Paget's disease with underlying anorectal carcinoma

AIM:To analyze clinical and pathological characteristics of an aggressive subtype of perianal Paget's disease(PPD) and explore its rational treatment modalities.METHODS:PPD patients were retrospectively collected in the institutional colorectal database of the Fudan University Shanghai Cancer Center.Detailed patient histories of past medical condition,diagnosis,treatment,and pathological findings were reviewed.Surgical specimen from diagnosis and surgery were reviewed by two independent pathologists for confirmation of diagnoses.Follow up was accomplished by clinical interview by cellphone.RESULTS:In total,eight cases of PPD were analyzed.All patients had underlying anorectal adenocarcinoma,including seven with synchronous lesions and one with metachronous lesions.Moreover,all anorectal lesions had a mucin-producing component.The median age at diagnosis was 65(range 29-81 years),and the male/female ratio was 7:1.The Median follow-up time of all patients was 61.5 mo(range 10-204 mo).One patient treated with abdominoperineal resection(APR) died from lung metastases 10 mo after the APR operation.The other patients are still free of disease at the time of this analysis.CONCLUSION:PPD is a rare malignancy and is easily misdiagnosed.Underlying anorectal cancer was not unusual and was a significant prognostic factor.Rational treatment of both anorectal cancer and PPD lesion is essential for long-term survival.

Paget’s disease of bone: Report of 11 cases

BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

Total knee arthroplasty in patients with Paget's disease of bone: A systematic review

AIM To determine the functional outcomes, complications and revision rates following total knee arthroplasty(TKA) in patients with Paget's disease of bone(PDB). METHODS A systematic review of the literature was performed. Four studies with a total of 54 TKAs were included for analysis. Functional outcomes, pain scores, complications and revision rates were assessed. The mean age was 72.0 years and the mean follow-up was 7.5 years.RESULTS All studies reported significant improvement in knee function and pain scores following TKA. There were 2 cases of aseptic loosening, with one patient requiring revision of the femoral component 10 years after the index procedure. Malalignment, bone loss, soft tissue contractures were the most commonly reported intraoperative challenges. There were five cases(9%) that were complicated by intra-operative patellar tendon avulsion.CONCLUSION The findings support the use of TKA in patients with PDB. The post-operative functional outcomes are largely similar to other patients, however there are specific perioperative challenges that have been highlighted, in particular the high risk for patellar tendon avulsion.

Total hip arthroplasty in patients with Paget's disease of bone: A systematic review

AIM To investigate the clinical and functional outcomes following total hip arthroplasty(THA) in patients with Paget's disease.METHODS We carried out a systematic review of the literature to determine the functional outcome, complications and revision rates of THA in patients with Paget's disease. Eight studies involving 358 hips were reviewed. The mean age was 70.4 years and follow-up was 8.3 years. There were 247 cemented THAs(69%), 105 uncemented THAs(29%) and 6 hybrid THAs(2%). RESULTS All studies reported significant improvement in hip function following THA. There were 19 cases of aseptic loosening(5%) at a mean of 8.6 years. Three cases occurred in the uncemented cohort(3%) at a mean of 15.3 years and 16 cases developed in the cemented group(6%) at a mean of 7.5 years(P = 0.2052). There were 27 revisions in the 358 cases(8%) occurring at a mean of 7 years. Six revisions occurred in the uncemented cohort(6%) at a mean of 8.6 years and 21 in the cemented cohort(9%) at a mean of 6.5 years(P = 0.5117). CONCLUSION The findings support the use of THA in patients with Paget's disease hip arthropathy. The post-operative functional outcome is largely similar to other patients; however, the revision rate is higher with aseptic loosening being the most common reason for revision. Uncemented implants appear to be associated with a lower failure rate, however, there were no modern stem designs fixed using current generation cementing techniques used in the reported studies, and as such, caution is advised when drawing any conclusions.

A Case of Thoracic Spinal Stenosis Secondary to Paget's Disease

PAGET＇S disease, also called osteitis deformans, is a metabolic bone disorder. It is characterized by increased bone resorption and the compensatory formation of new bones. The increased bone conversion and remodeling lead to the incrustation of woven bones and lamellar bones and finally result in the expansion, loosening, and excessive vascularization of the affected bones, rendering them susceptible to deformity and fracture. Paget＇s disease occurs much more commonly in Anglo-Saxons than in Asians and Africans.

Clinical characteristics and survival outcomes of perianal Paget’s disease:A SEER population-based study

Objective The aim of the study was to analyze the clinical features of patients with perianal Paget’s disease(PPD)and investigate prognosis risk factors.Methods The SEER*Stat software was used to identify 116 PPD patients from 1975 to 2015 in the SEER research database.The Kaplan-Meier method was used to conduct a univariate analysis for PPD patients.The differences in survival rates were evaluated using the log-rank test.The differences in the clinicopathological features of PPD patients with or without anorectal carcinoma were compared using the chi-square test.Results The median survival time of PPD patients was 44 months.The median age of onset was 73 years old.The 43.10%of the patients were alive at the end of follow up,and only 12.93%of the patients died of PPD.Elderly(age>70 years;χ^2=9.453,P=0.002),poor differentiation(χ^2=46.557,P=0.000)and abdominal perineal resection(APR;χ^2=46.557,P=0.000)were unfavorable risk factors of prognosis.Nearly 50%of PPD had combined with other malignancies,and over 22.41%of those had multiple primary neoplasms(3 or more).PPDs predisposed concurrent malignancy,and 48.21%of PPD patients with other malignancies combined with anorectal carcinoma in the study.Stage(χ^2=10.127,P=0.018),and surgical method(χ^2=12.245,P=0.007)were statistically significant in the PPD patients with or without anorectal carcinoma.The 16.07%of patients had multiple lesions of Paget’s.Conclusion Patients with PPD have a favorable survival,while the disease-specific mortality is low.Diagnosed age,differentiation,and surgical methods were the influence factors of prognosis in PPD patients.PPDs with anorectal carcinoma is of most important in further investigation.

HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL STUDY OF EXTRAMAMMARY PACET'S DISEASE

The histogensis of extramammary Paget's disease has not been solved and remained controversial. Eight cases of extramammary Paget's disease of geni-tocrural region were investigated by alcian blue and PAS stain and immunoreaction of anti-CEA and anti-keratin. It was found that the pattern and intensity of alcian blue, PAS staining were identical for Paget cells and secretory cells of apocrine sweat gland; and CEA immunoreactivity was uniformly observed in both Paget cells and eccrine sweat gland. The keratin immunoreaction was positive in keratinocytes, apocrine and eccrine sweat gland, whereas Paget cells were negative. These results suggested that Paget cells of extramammary Paget's disease could be derived from multipotential epidermal germ cells.

Paget's Disease is Associated with Eleven Cancerous Regions:a Case Report and Therapeutic Strategy

Paget＇s disease of the breast is an uncommon disorder that accounts＇for 1% to 3% of all mammary tumors. The incidence of underlying carcinoma associated with Paget＇s disease has been reported in 82% to 100% of cases. The finding of underlying carcinoma reaches almost 100% when a palpable lump is also present. In this rare case, we described a patient presenting with Paget＇s disease but no palpable lump. However, we found 11 independent regions which were all invasive ductal carcinoma after the operation. Considering this patient, we should pay more attention to a multifocal and multicentric breast carcinoma associated with Paget＇s disease. Furthermore, we believe the mammography examination and a modified radical mastectomy are the most appropriate treatments for this population in clinical practice.

A case report of breast Paget’s disease and related literature

Paget’s disease is a relatively rare disease that occurs in the nipple and areola areas,and the early symptoms are not typical.In this study,we notified a case of a patient with Paget’s disease complicated with breast cancer.The tumor found in the postoperative pathological specimen has no blood flow signal,and its tissue density is similar to that of the surrounding glandular tissue,and there is no calcification point.This situation is rare through an extensive literature review.Our research can provide experience for clinical diagnosis and treatment of Paget’s disease with breast cancer.

中医情志综合护理对光动力治疗乳房外Paget病患者的影响

目的:探讨中医情志等综合护理方法对光动力治疗(photodynamic therapy,PDT)乳房外Paget病患者护理满意度、疼痛程度及生存质量的影响。方法:将52例乳房外Paget病确诊患者随机分为对照组和观察组各26例,对照组给予常规护理,观察组在常规护理基础上给予中医情志等综合护理。比较两组患者护理满意度、疼痛程度和生活质量。结果:观察组疼痛程度改善、护理满意度均高于对照组,差异具有统计学意义(P<0.05),观察组在生活质量的症状感知、日常生活、娱乐活动、工作学习及个人活动等方面得分均低于对照组,差异具有统计学意义(P<0.05)。结论:在PDT乳房外Paget病的治疗过程中应用中医情志综合护理措施,可减轻疼痛,提高患者满意度和生活质量。

改良Mohs显微描记手术在原发性乳房外Paget病中的应用

目的:研究探讨改良莫氏显微描记手术(modified Mohs microsurgery,mMMS)在原发性乳房外Paget病(extramammary Paget s disease,EMPD)中的应用。方法:对2021年8月至2022年12月我院收治的8例原发性乳房外Paget病手术病例进行回顾性分析。结果:8例患者术前均行光动力判断肿瘤边缘,其中2例患者行传统扩大切除治疗(wide local excision,WLE),3例患者行周围组织的快Mohs手术(rapid peripheral MMS,rpMMS),3例患者行周围组织的慢Mohs手术(slow peripheral MMS,spMMS)。1例WLE治疗患者冰冻切片术后常规组织病理复核出现假阴性切缘,予以局部放射治疗,其余WLE、rpMMS治疗患者未出现假阴性切缘。结论:周围组织的MMS(pMMS)治疗原发性EMDP,可在保证肿瘤切净率的同时提高手术效率,spMMS可有效规避EMPD冰冻切片的不准确性及大面积创面暴露的感染、出血风险。