嫌色性肾细胞癌17例临床病理学分析

目的探讨嫌色性肾细胞癌的临床病理特征、诊断与鉴别诊断要点。方法对17例嫌色性肾细胞癌进行组织形态学、免疫组化染色及Hale’s胶样铁染色观察,结合文献对其临床表现、病理形态特点及鉴别诊断进行探讨。结果嫌色性肾细胞癌17例,大体肿瘤直径3-10.5cm。镜下肿瘤由嫌色细胞和嗜酸细胞构成,呈片状、梁状和腺泡状分布。嫌色细胞体积较大,多角形,胞膜清晰,胞质半透明细网状,胞核皱缩,可见核沟及核异型,核仁不明显;而嗜酸细胞胞质嗜酸,可见明显的核周空晕。免疫组化:EMA 100%阳性,CD10 52.9%阳性,Vimentin阴性,CK7 88.2%阳性,P504S29.4%阳性,CD11794.1%阳性。Hale’s胶样铁染色100%阳性。17例中12例随访6个月到3年,仅1例在术后15个月发现肝脏转移,其余均未发现复发及转移。结论嫌色性肾细胞癌是一种少见的肾肿瘤,恶性程度相对较低,预后良好。掌握该肿瘤独特的病理学特征,对鉴别其他肾上皮性肿瘤有重要帮助。     

肾嗜酸细胞瘤的临床病理特征和疗效分析

目的总结肾嗜酸细胞瘤的临床病理特征和治疗方法。方法回顾性分析中国医科大学附属第一医院2013年1月至2020年8月收治的35例肾嗜酸细胞瘤患者的病例资料。男15例, 女20例。平均年龄(59.0±11.3)(35～79)岁。主要症状为腰痛5例, 肉眼血尿3例, 余27例为体检或因其他疾病检查时偶然发现。所有患者均为单侧肿瘤, 左侧22例, 右侧13例。肿瘤位于肾上极7例、中极14例、下极14例。33例行超声检查, 表现为低回声18例, 高回声10例, 等回声3例, 混合回声2例。30例行CT检查, 平扫表现为肿瘤与正常肾实质比较呈等密度或稍低密度影, 增强后肿瘤表现为边界清晰的低强化影, 其中12例有典型的中央星芒状瘢痕征。所有患者均接受手术治疗, 其中肾部分切除术12例, 根治性肾切除术23例;后腹腔镜手术23例, 开放手术12例。结果术后病理检查, 肿瘤平均直径(4.0±2.3)(1.3～14.0)cm, 切面为黄褐色14例, 红褐色19例, 黑色和咖啡色2例。镜下观察, 肿瘤典型特征为瘤细胞呈巢状、腺泡状或管状排列, 细胞呈圆形或多角形, 大小基本一致, 胞质含有丰富的嗜酸颗粒,...     

透明细胞乳头状肾细胞癌的临床病理分析

目的探讨透明细胞乳头状肾细胞癌(clear cell papillary renal cell carcinoma,CCPRCC)的临床病理学特征、免疫表型、鉴别诊断及预后。方法收集2013年至2017年肾细胞癌病理切片,筛选CCPRCC 4例,收集临床资料并研究组织病理学形态及免疫组织化学特征。结果患者年龄在46岁至69岁之间(平均55.3岁),男性1例,女性3例;影像学资料显示,肿瘤平均直径为3.85 cm(1.6～7.0cm),所有肿瘤均为右肾单发肿物。4例均呈大小不等的类圆形单结节,CT显示为低密度,MRI显示为低信号。大体观察肿瘤局限于肾组织内呈单结节状生长,境界清楚,局部似带包膜,切面呈灰红至灰褐色,实性,质地中等,部分区稍韧,局灶伴有出血或囊性变。镜下见肿瘤细胞排列呈囊状、乳头状、管状/腺泡状和实性巢状结构,细胞核形态温和,远离基底膜并朝向腔面,本组病例均为WHO/ISUP分级Ⅰ-Ⅱ级,间质内可见散在数量不等的平滑肌组织。CA-9及CK7免疫组织化学染色阳性,TFE3、vimentin、CD10与AMACR阴性或局灶弱阳性。1例行FISH检测TFE3未见检测出基因相关易位...     

肾嗜酸性细胞瘤的诊治体会（附11例报告）

目的：探讨肾嗜酸细胞瘤的诊断和治疗。方法：回顾分析我院2003．2009年间收治11例肾嗜酸细胞瘤的临床资料,结合文献对肾嗜酸细胞瘤的诊断及治疗进行复习讨论。结果：本组11例患者中,年龄为26—75岁,男性7例,女性4例。合并透明细胞癌者1例,术前误诊为肾上腺肿瘤者1例。7例行根治性肾切除术者,4例行肾部分切除术。术后随访11个月-7年未见肿瘤转移或复发。结论：肾嗜酸细胞瘤倾向于良性肾实质性肿瘤,临床表现无特异性,确诊需临床表现、影像学检查与病理学检查相结合。治疗首选保肾手术,但应注意并发恶性肿瘤的可能,加强随访。     

肾嗜酸性细胞瘤的诊治体会(附11例报告)

目的:探讨肾嗜酸细胞瘤的诊断和治疗。方法:回顾分析我院2003-2009年间收治11例肾嗜酸细胞瘤的临床资料,结合文献对肾嗜酸细胞瘤的诊断及治疗进行复习讨论。结果:本组11例患者中,年龄为26-75岁,男性7例,女性4例。合并透明细胞癌者1例,术前误诊为肾上腺肿瘤者1例。7例行根治性肾切除术者,4例行肾部分切除术。术后随访11个月-7年未见肿瘤转移或复发。结论:肾嗜酸细胞瘤倾向于良性肾实质性肿瘤,临床表现无特异性,确诊需临床表现、影像学检查与病理学检查相结合。治疗首选保肾手术,但应注意并发恶性肿瘤的可能,加强随访。     

肾嗜酸细胞腺瘤的诊疗分析（附47 例报告）

目的:分析肾嗜酸细胞腺瘤的临床特征,指导并提升诊疗水平。方法:回顾性分析47例肾嗜酸细胞腺瘤的临床资料,包括临床特点、影像表现、病理特征、治疗方法及预后等方面。结果:47例患者中43例因查体偶然发现,仅4例表现为患侧腰痛症状。术前影像诊断中1例考虑嗜酸细胞腺瘤,1例考虑腺瘤,2例CT与MRI报告不一致(CT与MRI各有1例诊断良性,具体类型不确定),其余43例均诊断为肾细胞癌(1例囊性肾癌)。27例行肾癌根治性切除术,16例行肾部分切除术,4例行微波或射频消融术。所有患者术后病理均诊断为肾嗜酸细胞腺瘤,随访4～179月,均无转移或复发。结论:肾嗜酸细胞腺瘤作为一种与肾细胞癌难相鉴别的良性肿瘤,因缺乏特异性表现,极易误诊为肾细胞癌,因此对肾肿瘤患者应尽可能选择保肾治疗方案。     

肾上腺皮质嗜酸细胞腺瘤临床病理观察

目的探讨肾上腺皮质嗜酸细胞腺瘤的临床病理特征和诊断要点。方法分析8例肾上腺皮质嗜酸细胞腺瘤的临床资料,观察其组织学形态及免疫表型特征,并复习相关文献。结果 8例患者,3名女性5名男性,6例患者均为体检时偶然发现,无明显临床症状,肾上腺占位术后标本病理检查结果示:镜下肿瘤细胞边界清楚,有明显的包膜,排列呈巢状、梁状或腺泡状,周围包绕纤细的血窦样毛细血管网。肿瘤间质内可见少量成熟淋巴细胞浸润。肿瘤细胞由明显胞浆嗜酸性的大细胞组成,少数肿瘤细胞局部胞浆透亮,富含脂质,有时可见嗜酸性核内假包涵体和脂褐素。局部区域偶见怪异核细胞,核分裂罕见。免疫组织化学表型:CD56及Syn、MelanA、α-inhibin阳性,PCK灶状阳性,CgA、S-100阴性,Ki67增殖指数约为2%;特殊染色:网状纤维染色示肿瘤细胞巢状结构存在。结论肾上腺皮质嗜酸细胞瘤是一种罕见的肾上腺皮质良性肿瘤,大多数表现为无功能的腺瘤。手术切除仍然是主要的治疗方法。这种疾病可以作为良性肿瘤来治疗,SS预后尚可。     

肾嗜酸细胞腺瘤的影像学诊断

目的：探讨螺旋CT和MRI对肾嗜酸性细胞腺瘤的诊断及鉴别诊断的价值。方法：回顾性分析12例肾嗜酸性细胞瘤的CT和／或MRI表现。结果：CT检查12例,平扫8例病灶呈均匀软组织密度影,3例呈不均匀软组织密度影,1例瘤体周边有环状钙化。增强后病灶轻中度强化,6例见星状瘢痕。MRI检查3例,2例T1WI呈等低信号、T2WI呈高信号;1例T1wI呈等信号、T2WI等低信号。结论：多数肾嗜酸细胞腺瘤的影像学表现具有一定特征性。CT结合MRI特别是动态扫描有助于术前做出正确的诊断。     

肾嗜酸细胞腺瘤的影像学诊断

目的:探讨螺旋CT和MRI对肾嗜酸性细胞腺瘤的诊断及鉴别诊断的价值。方法:回顾性分析12例肾嗜酸性细胞瘤的CT和/或MRI表现。结果:CT检查12例,平扫8例病灶呈均匀软组织密度影,3例呈不均匀软组织密度影,1例瘤体周边有环状钙化。增强后病灶轻中度强化,6例见星状瘢痕。MRI检查3例,2例T1WI呈等低信号、T2WI呈高信号;1例T1WI呈等信号、T2WI等低信号。结论:多数肾嗜酸细胞腺瘤的影像学表现具有一定特征性。CT结合MRI特别是动态扫描有助于术前做出正确的诊断。     

前列腺基底细胞癌临床病理特征及文献复习

目的探讨前列腺基底细胞癌(basal cell carcinoma,BCC)的临床特征、病理特点、治疗方法及相关预后,并对相关文献进行复习。方法回顾性分析3例前列腺基底细胞癌的临床特征、病理特点及相关免疫组织化学表型。结果前列腺基底细胞癌男性老年患者多见,临床上常出现尿路梗阻的症状,表现为排尿不尽、尿频、尿急、尿痛等,血清学检查前列腺特异性抗原(prostate specific antigen, PSA)水平在正常范围之内,镜下见肿瘤细胞大多呈巢团状、腺样及腺样囊性结构,外围的瘤细胞可呈栅栏状排列,部分癌巢中心可见坏死,部分腔内可见分泌物。免疫组织化学染色显示,(3/3例)p63、CK5/6及BLC-2大部分细胞呈阳性,但位于最内层的腺腔样细胞阴性,(3/3例)CK7部分细胞阳性,主要是最内层的管腔样细胞阳性,1例行GATA-3、Ber-EP4检测部分肿瘤细胞阳性,(3/3例)肿瘤细胞P504s、PAS、CK20、S-100、CD117阴性,3例Ki-67增殖指数为10%～60%,1例行HER-2检测呈阴性。3例患者均行前列腺电切术,随访6个月至3年,1例患者于术后6个月肿瘤复发死亡...     

Nomograms-based prediction of overall and cancer-specific survivals for patients with chromophobe renal cell carcinoma

This study built and tested two effective nomograms for the purpose of predicting cancer-specific survival and overall survival of chromophobe renal cell carcinoma (chRCC) patients. Multivariate Cox regression analysis was employed to filter independent prognostic factors predictive of cancer-specific survival and overall survival, and the nomograms were built based on a training set incorporating 2901 chRCC patients in a retrospective study (from 2004 to 2015) downloaded from the surveillance, epidemiology, and end results (SEER) database. The nomograms were verified on a validation cohort of 1934 patients, subsequently the performances of the nomograms were examined according to the receiver operating characteristic curve, calibration curves, the concordance (C-index), and decision curve analysis. The results showed that tumor grade, AJCC and N stages, race, marital status, age, histories of chemotherapy, radiotherapy and surgery were the individual prognostic factors for overall survival, and that AJCC, N and SEER stages, histories of surgery, radiotherapy and chemotherapy, age, tumor grade were individual prognostic factors for cancer-specific survival. According to C-indexes, receiver operating characteristic curves, and decision curve analysis outcomes, the nomograms showed a higher accuracy in predicting overall survival and OSS when compared with TNM stage and SEER stage. All the calibration curves were significantly consistent between predictive and validation sets. In this study, the nomograms, which were validated to be highly accurate and applicable, were built to facilitate individualized predictions of the cancer-specific survival and overall survival to patients diagnosed with chRCC between 2004 and 2015.     

Gene expression profiling of chromophobe renal cell carcinomas and renal oncocytomas by Affymetrix GeneChip using pooled and individual tumours

Due to overlapping morphology, malignant chromophobe renal cell carcinomas (RCC) and benign renal oncocytomas (RO) may pose a diagnostic problem. In the present study, we have applied different algorithms to evaluate the data sets obtained by hybridisation of pooled and also individual samples of renal cell tumours (RCT) onto two different gene expression platforms. The two approaches revealed high similarities in the gene expression profiles of chromophobe RCCs and ROs but also some differences. After identifying the differentially expressed genes by statistic analyses, the candidate genes were further selected by a real time and normal RT-PCR and their products were analysed by immunohistochemistry. We have identified CD82 and S100A1 as valuable markers for chromophobe RCC as well as AQP6 for ROs. However, these genes are expressed at the protein level in other types of RCTs as well albeit at a low frequency and low intensity. As none of the selected genes marks exclusively one type of RCTs, for the differential diagnosis of chromophobe RCCs and ROs, a set of markers such as CD82, S100A1 and AQP6 as well as some others would be an option in routine histological laboratories.     

DNA methylation profiling distinguishes histological subtypes of renal cell carcinoma

Renal cell carcinoma (RCC) accounts for around 3% of cancers in the UK, and both incidence and mortality are increasing with the aging population. RCC can be divided into several subtypes: conventional RCC (the most common, comprising 75% of all cases), papillary RCC (15%) and chromophobe RCC (5%). Renal oncocytoma is a benign tumor and accounts for 5% of RCC. Cancer and epigenetics are closely associated, with DNA hypermethylation being widely accepted as a feature of many cancers. In this study the DNA methylation profiles of chromophobe RCC and renal oncocytomas were investigated by utilizing the Infinium HumanMethylation450 BeadChips. Cancer-specific hypermethylation was identified in 9.4% and 5.2% of loci in chromophobe RCC and renal oncocytoma samples, respectively, while the majority of the genome was hypomethylated. Thirty (hypermethylated) and 41 (hypomethylated) genes were identified as differentially methylated between chromophobe RCC and renal oncocytomas (p < 0.05). Pathway analysis identified some of the differentially hypermethylated genes to be involved in Wnt (EN2), MAPK (CACNG7) and TGFβ (AMH) signaling, Hippo pathway (NPHP4), and cell death and apoptosis (SPG20, NKX6-2, PAX3 and BAG2). In addition, we analyzed ccRCC and papillary RCC data available from The Cancer Genome Atlas portal to identify differentially methylated loci in chromophobe RCC and renal oncocytoma in relation to the other histological subtypes, providing insight into the pathology of RCC subtypes and classification of renal tumors.     

Candidate biomarkers in renal cell carcinoma

Although the human genome has been decoded, the knowledge about the pathogenesis of diseases including cancer is still limited. By focusing on renal cell carcinoma (RCC) we here summarize the data of various research groups analyzing the protein/peptide expression profiles of tumor lesions/cell lines or serum obtained from patients and respective controls. Different powerful approaches such as 2-DE, PROTEOMEX/SERPA/SPEARS, and T cell epitope discovery upon elution of MHC class I-bound peptides in combination with MS/LC-MS/MS revealed 500 differentially expressed proteins. The overlap in target recognition limits the pool to 299 unique protein identities, but only few thereof (12%) have been validated. The management, analysis, and interpretation of the distinct data sets derived from 27 publications required bioinformatic restructuring of the results. However, the comprehensive analysis of the results expands the knowledge about the pathophysiology of RCC in particular of the most prominent clear cell subtype by providing information on the differentially expressed proteins, their regulation status in RCC compared to normal kidney epithelium next to additional information on MHC-presented T cell epitopes and on serological targets. Despite the low number of validated differentially expressed proteins some of them might serve as candidate biomarkers for the diagnosis and/or as therapeutic targets.     

Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma

Renal cell carcinoma (RCC) is relatively resistant to conventional chemotherapy and radiotherapy. However, reports of spontaneous regression along with promising results in clinical trials suggest that immunotherapuetic strategies may be of clinical benefit. Few RCC related antigens have been identified to date, and the technical difficulty and time constraints of current antigen identification techniques preclude the screening of large numbers of patients. A comparatively rapid strategy has been used to identify components of tumors that elicit an antibody response in the patient - the serological and proteomic evaluation of antibody responses (SPEAR) approach. This combines two-dimensional polyarylamide gel electrophoresis of tumor and normal kidney samples with immunoblotting using autologous patient sera and protein identification by mass spectrometry. Using the SPEAR approach to screen RCC patients for naturally occurring antitumor antibody responses, a number of candidate immunogens have been identified in patients with high-grade disease and their relative expression levels in tumor tissue compared to normal tissue have been studied. These proteins include annexins I and IV, thymidine phosphorylase (TP), carbonic anhydrase I, Mn-superoxide dismutase and major vault protein (MVP). Downstream analysis of the tissue expression of some of these proteins shows that MVP is up-regulated in 2/4 of RCC tumors but is also expressed in normal kidney whereas TP is up-regulated in 100% (11/11) of RCC cases examined with no or minimal expression in normal kidney, indicating a potential use as a therapeutic target.     

Activity of a short course of interferon α for metastatic renal cell carcinoma — a phase-2 study

Twelve patients with metastatic renal cell carcinoma were entered into a phase-2 study of an 8-week course of interferon (INF) therapy. INF was given subcutaneously at a dose of 3 mu, three times per week. The patients were WHO performance status 0–2. A complete response was obtained in two patients (17% response rate), which has been maintained at 23 and 45 months. One of these patients presented with cranial and lung metastases and received cranial irradiation and decradron concurrent with INF. The toxicity of INF has been low. The optimal duration of INF therapy warrants further evaluation.     

Patient-derived renal cell carcinoma cells fused with allogeneic dendritic cells elicit anti-tumor activity: in vitro results and clinical responses

Renal cell carcinoma (RCC) has been shown to be susceptible to immunotherapeutic treatment strategies. In the present study, patient-derived tumor cells were fused with allogeneic dendritic cells (DC) to elicit anti-tumor activity against RCC. DC from HLA-A2+ healthy donors were fused with primary RCC cells from ten patients. Phenotype of fusion cells were characterized by flow cytometer and confocal microscopy. In vitro, T cell proliferation, IFN-γ secretion and cytotocic T lymphocytes (CTL) activity elicited by allogeneic DC/RCC fusion cells were assessed. Clinically, ten patients were vaccinated with allogeneic DC/RCC fusion vaccine. The adverse effects and toxicity were observed. The clinical response was evaluated by CT scans. After fusion, the created hybrids expressed both tumor associated antigen and DC-derived molecules and could stimulate the proliferation and IFN-γ secretion of T cells as well as elicit strong CTL activity against RCC cells in vitro. In vivo, no serious adverse effects, toxicity, or signs of autoimmune disease were observed after vaccination therapy. Percentage of T lymphocyte subsets in peripheral blood of patients was increased significantly. One of ten patients exhibited a partial response with regression of lung metastases. Six patients showed stable disease with stabilization of previously progressive disease (follow up 1.5 years). The PR and SD responses, exhibited by 7/10 patients who received the allogeneic DC/RCC fusion vaccine treatment, suggest that this approach is safe and can elicit immunological responses in a significant portion of patients with RCC. J. Zhou and D. Weng contributed equally.     

A phase-II study of pegylated interferon alfa-2b for patients with metastatic renal cell carcinoma and removal of the primary tumor

Twenty-two patients with metastatic renal cell carcinoma and removal of the primary tumor were treated with subcutaneous pegylated interferon alfa-2b (PEG-Intron) to evaluate toxicity and efficacy. Start dose was 3.0 g/kg/week, escalated to 6.0 g/kg/week. After 2 months, therapy was extended in case of response or stable disease (SD) until progressive disease (PD) or relapse for a maximum of 2 years. National Cancer Institute common toxicity criteria (NCI-CTC) were monitored every 2–4 weeks. After 2 months, nine patients did not continue (8 PD, 1 SD with grade 4 CTC) and 13 extended treatment [three partial response (PR), 10 SD], of these, 11 progressed. One patient with PR developed a durable complete response later. Overall response rate was 13.6% (3/22). Median overall survival is 13 months (range 3–35 months). Dosage was escalated to 6 g/kg/week in three patients . NCI-CTC grade 2 and 3 required dose attenuation in 12 patients during escalation, and reduction in 10 during the trial. Three patients discontinued because of grade 4 CTC (two fatigue, one hyperglycemia). Fatigue was the major dose-limiting toxicity. These results suggest an efficacy and toxicity of PEG-Intron comparable to standard interferon alfa-2b in patients with mRCC and removal of the primary tumor.Author disclosure declaration: None of the authors has a relationship with pharmaceutical companies, biomedical device manufacturers or other corporations whose products or services are related to the subject matter of the submission, nor do the authors have financial interests such as investments, licensing, or other commercial interest in any drugs, goods, or services in connection with the matter under consideration.