Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cellq possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.     

乳头状肾细胞癌32例临床病理分析

目的：探讨乳头状肾细胞癌( papillary renal cell carcinoma, PRCC)的临床病理特征、免疫表型、鉴别诊断和预后。方法回顾性分析32例PRCC患者的临床和病理资料,采用免疫组化EnVision法染色,并对患者进行随访。其中21例行根治性肾切除术,11例行肾部分切除术。结果770例肾上皮性肿瘤中32例为PRCC(4.2%)。镜下见PRCC主要由多少不等的乳头状和管状结构组成,被覆单层立方或多层柱状肿瘤细胞,乳头轴心及间质内可见泡沫细胞、砂砾体沉积,部分肿瘤细胞胞质内可见含铁血黄素。Ⅰ型18例,细胞呈立方形,胞质少,嗜碱性,淡染,Fuhrman分级低级别16例;Ⅱ型14例,细胞呈高柱状,胞质丰富,嗜酸性,Fuhrman分级高级别12例。Ⅰ型和Ⅱ型PRCC不同程度地表达vimentin、EMA、CK(AE1/AE3)、CK7、CD10和AMACR,均不表达CK(34βE12)和TFE-3。31例患者获得随访,1例术后肝、肺转移,4个月后死亡,3例术后1年分别出现骨、肺、肝等处转移,2年后死亡;死亡患者中Ⅱ型3例、Ⅰ型1例。其余27例均无瘤生存。高核分级、血管内癌栓、淋巴结转移、高临床分期提示患者预后较差。结论 PRCC国内少见,具有独特的病理形态特征,Ⅱ型PRCC较Ⅰ型患者预后差。 PRCC细胞核分级高、出现肉瘤样成分或有透明细胞癌结构可能提示肿瘤具有侵袭性,预后不良。诊断时需结合病理组织学特征、免疫表型和细胞遗传学分析。     

Chromophobe cell carcinoma and renal cell neoplasms with mucin-like changes

Hale's colloidal iron staining of 8 chromophobe cell carcinomas (CCC) was compared with that of non-chromophobe renal cell carcinomas (RCC), renal oncocytomas, and renal adenomas. Six non-chromophobe RCC showing diffuse and moderate cytoplasmic staining contained extensive areas with translucent cytoplasm as observed in CCC. Seventeen of 25 conventional RCC of the clear cell variant (randomly chosen from 130 cases), 21 of 26 RCC with areas of chromophilic cytoplasm, and 16 of 20 papillary RCC, 7 of 14 adenomas and 14 of 16 oncocytomas displayed focal areas with mild to moderate staining of the cytoplasm. Hale's colloidal iron staining was partially reduced by digestion with neuramidase but not with hyaluronidase. This positive staining demonstrated glycoproteins containing sialylated glycoconjugates, probably a type of acid epithelial mucin. We suggest that there is a spectrum of mucin-like changes in typical CCC representing RCC with extensive and marked "mucin-like changes". The eosinophilic variant of CCC and some RCC with extensive chromophobe cell features represent renal neoplasms with moderate changes. The other RCC, oncocytomas and papillary renal neoplasms with mild to moderate staining with Hale's colloidal iron represent renal neoplasms with focal mucin-like changes. RCC with extensive chromophobe cell features may pose a differential diagnostic problem with CCC.     

甲状腺样滤泡性肾细胞癌的临床病理特点

甲状腺样滤泡性肾细胞癌(thyroid-like follicular renal cell carcinoma,TLFRCC)是一种非常少见的肾原发性恶性上皮性肿瘤,确诊主要依靠病理组织学及免疫组织化学,外科手术切除是最好的治疗方法,预后好.通过对郑州人民医院2014年收治的1例TLFRCC患者的临床资料、大体特征、组织病理学及免疫表型等进行分析,并结合文献报道的28例,进一步探讨TLFRCC的临床病理特点、免疫表型、诊断与鉴别诊断及遗传学特点.     

Chromophobe renal cell carcinoma with extensive calcification and ossification

A 39-year-old woman presenting with microscopic hematuria was found to have an extensively calcified mass in the upper pole of the right kidney. Gross and histologic examination of the nephrectomy specimen revealed a 9.3-cm renal tumor composed of solid trabecular sheets of polygonal epithelial cells with clear cytoplasm and distinct cell borders characteristic of a chromophobe renal cell carcinoma. Electron microscopy showed the presence of numerous intracytoplasmic microvesicles, thereby confirming the diagnosis. However, the unique additional feature of this tumor included the presence of dense calcification and ossification throughout the tumor. To our knowledge, we report the first case of chromophobe renal cell carcinoma with the concomitant presence of extensive calcification and ossification. A literature review on chromophobe renal cell carcinoma with either calcification or ossification is performed.     

Chromophobe renal cell carcinoma: a comparative study of histological, immunohistochemical and ultrastructural features using high throughput tissue microarray

AIMS: In some cases distinction between chromophobe renal cell carcinoma (CRCC), oncocytoma and clear cell (conventional) renal cell carcinoma (eosinophilic variant) using routine light microscopy remains problematic. The present study investigates the level of agreement in the diagnosis of CRCC, as well as the histological features most frequently used for this diagnosis by two pathologists with a special interest in renal neoplasia. The sensitivity and specificity of immunohistochemical markers in cases with overlapping histological features in the diagnosis of CRCC were also studied. Electron microscopy was performed, as a diagnostic gold standard, on all of the cases. METHODS AND RESULTS: Thirty-two renal tumours with predominantly eosinophilic cytoplasm were reviewed in a blinded fashion by two pathologists. The diagnosis and morphological features used to render each diagnosis were tabulated. Validation of the utility of keratin 7 and 20, epithelial membrane antigen (EMA), vimentin, CD10, parvalbumin, RCC antigen, antimitochondrial antibody and Hale's colloidal iron was performed by the construction of a tissue microarray (TMA) master block. Based on histological criteria alone, overall agreement on the diagnosis of these tumours was reached in 69% of the cases, while there was total disagreement in 12%. In 59% of the cases, total agreement was reached in classifying the case as a CRCC based on histology alone. Kappa statistics for interobserver variability were calculated as only slight agreement (kappa = 0.3). The histological features most frequently associated with a diagnosis of CRCC were accentuated cell borders (87%) and a combination of hyperchromatic wrinkled nuclei (79%) and perinuclear halos (74%). The most sensitive and specific marker for CRCC was parvalbumin (sensitivity 0.91; specificity 1.0). The immunohistochemical profile of EMA+/ vimentin- was useful but had low specificity (sensitivity 0.75; specificity 0.4). CD10 had the highest sensitivity (1.0) but worst specificity (0.25) for CRCC. Keratin 7 had high sensitivity (0.83) but fairly low specificity (0.37) for CRCC. Hale's colloidal iron and the RCC antigen marker were not contributory. Finally, the antimitochondrial antibody was found to be fairly sensitive (0.83) for excluding CRCC. CONCLUSIONS: A small but significant proportion of renal tumours with cells having eosinophilic cytoplasm cannot be classified, even by experienced pathologists, based on histology alone. In these cases it is imperative to use markers with known sensitivity and specificity for the diagnosis of CRCC.     

子宫颈鳞状移行细胞癌临床病理分析

目的 分析子宫颈鳞状移行细胞癌（squamotransitional cell carcinoma,STCC）的临床、病理及免疫组化表达特征,探讨STCC的诊断和鉴别诊断及细胞分化。方法 参照2003年WHO子宫颈肿瘤组织学分类,对8例STCC进行临床病理形态学观察和免疫组化检测。结果 患者平均年龄37．1岁（28～54岁）,临床表现为接触性阴道出血,部分病例白带有异味,病程1个月～5年。子宫颈肥大呈粗颗粒状或微绒状,部分病例（2／8）见息肉或菜花样新生物。所有病例均见乳头状结构,乳头由多层异型鳞状细胞样或移行细胞样上皮覆盖,细胞无挖空特征,乳头内为纤维血管中心柱;大部分乳头为非浸润性,2例为浸润性,2例子宫颈壁有深部浸润的表面乳头中见厚壁血管。所有病例均见程度不等的子宫颈间质浸润（0．1cm至全层）,HE切片下判断4例有脉管内浸润,1例盆腔淋巴结有转移。免疫组化染色显示p16均呈强阳性表达,CK7、CK14、CK19呈不同程度阳性表达,CK20仅在2例见局灶阳性,在D2-40标记下发现6例有淋巴管浸润。结论 STCC是一种具有独立形态学特征的子宫颈恶性肿瘤,有别于子宫颈普通鳞癌及其他呈乳头状生长的恶性肿瘤如疣性癌、疣状癌等;尽管大部分乳头为非浸润性,STCC易向子宫颈壁浸润的特点提示深部活检明确诊断的必要性,乳头内厚壁血管可能与深部浸润有关;免疫组化结果提示STCC属鳞状细胞癌,不支持有真正的移行细胞分化。STCC与高危型HPV感染有关,易经淋巴道转移。     

嗅神经母细胞瘤的临床病理学特征及其与小细胞癌的鉴别诊断

目的 观察嗅神经母细胞瘤(ONB)的临床病理学特点,为其鉴别诊断及预后判断提供依据.方法 对22例ONB进行了形态学和免疫组化观察,并与小细胞癌(SCC)进行比较.结果 22例ONB中,组织学分级G1、G2、G,和G4者分别为1、11、8和2例,部分表达神经内分泌标志物和vimentin.ONB中CK8和CK18的阳性率分别为41%和46%,阳性细胞呈灶状分布,多表现为核旁点状阳性;而SCC组中,96%的病变呈CK18阳性,且多表现为弥漫性阳性.两种病变中EMA阳性率分别为41%和91%.ONB中神经丝蛋白(NF)的阳性率为64%;检查过的SCC病变均为NF阴性.有完整随访资料的12例ONB中,无瘤生存8例,复发4例,其中2例带瘤生存,2例死亡.4例ONB复发病例中,3例(75%)CK8及CK18阳性.结论 NF免疫组化染色可以用于ONB与SCC之间的鉴别;CK或EMA阳性不能完全除外ONB,且CK阳性产物的分布及亚细胞定位有助于ONB与SCC之间的鉴别;表达CK的ONB病变可能预后较差.     

Chromophobe renal cell carcinoma: clinical, pathological and molecular biological aspects

Chromophobe renal cell carcinoma (RCC), a newly established subtype of renal neoplasm, is composed of tumor cells with characteristically cloudy, weakly eosinophilic and reticular cytoplasm. The tumor should be distinguished from the common clear cell RCC, because of the unique clinicopathological and molecular biological features. The tumor does not show gender bias. Patient ages are similar to those of clear cell RCC, but might occur in the 20- to 40-year-old age group. Grossly, the tumor tends to be beige in color, which is different from the yellowish color of common RCC. Electron microscopy and immunohistochemistry indicate the intercalated cell of the collecting duct as the cellular origin. Cytogenetic study shows non-random multiple chromosome loss, with mitochondrial DNA rearrangement. Alteration of the von Hippel-Lindau (VHL) gene, a cancer suppressor gene relating with clear cell RCC, has not yet been observed. In order to adopt the most appropriate treatment, including gene therapy, recognition and correct pathological diagnosis of chromophobe RCC are extremely important.     

Chromophobe renal cell carcinoma with neuroendocrine differentiation

Chromophobe renal cell carcinoma was described by Thoenes et al. in 1986, and associations with carcinoma of collecting ducts, conventional renal cell carcinoma and sarcomatoid renal cell carcinoma have been described. We report a case of chromophobe renal cell carcinoma which showed neuroendocrine differentiation. This is the first known case to be clearly identified as such. The patient was a 56‐year‐old man with constant right flank pain and hematuria; CT scan revealed an 8.5 cm non‐homogeneous mass involving the right kidney. Right radical nephrectomy was performed. The tumor showed a mixture of classical and eosinophilic patterns of chromophobe cell carcinoma. Additionally, it showed insular, glandular and rosetoid‐like formations embedded in a dense eosinophilic hyaline stroma. The cells were cuboid or cylindrical with well‐defined boundaries, finely stippled chromatin and a small nucleolus. The appearance of the cytoplasm varied from faintly eosinophilic to coarsely granular eosinophilic. Immunohistochemically, the neuroendocrine areas were reactive for C‐kit, epithelial membrane antigen, cytokeratin, cytokeratin 7, chromogranin A, neuron‐specific enolase, CD56 and S‐100 protein. Our case represents a typical chromophobe carcinoma with neuroendocrine differentiation. Additionally, the immunohistochemical profile in both types of lesion suggests a common origin from renal tubular cells.     

涎腺腺泡细胞癌临床病理分析并文献复习

目的：探讨涎腺腺泡细胞癌的临床病理学特点及诊断要点。方法：对1例涎腺腺泡细胞癌进行临床资料、病理形态学及免疫组织化学观察,并结合文献对其诊断及鉴别诊断进行探讨。结果：镜下瘤细胞胞体宽大,胞浆嗜碱性呈细颗粒状,核圆形瘤细胞生长呈腺泡状或实性片状生长,部分区域呈乳头状改变,免疫组化显示AE1/AE3(+)、CK8/18(+)、CK7(+)、AAT(+)、S-100(+)。结论：涎腺腺泡细胞癌发病率低,但根据其常见的发病部位及特征性的组织形态,结合免疫组织化学方法,有助于其诊断及鉴别诊断。     

喉大细胞神经内分泌癌

目的：探讨喉大细胞神经内分泌癌的临床及病理特征。方法：复习2例患者的临床病史，肿瘤组织的病理形态和免疫表型及相关文献。结果：2例患者均为男性，以声音嘶哑、喉部不适为主要表现；病变均位于声门上，以具有丰富嗜酸性胞质，巢状排列为肿瘤细胞的形态特征，免疫组化表达神经内分泌肿瘤标志物。2例均因短期内发生肿瘤广泛转移而死亡，结论：喉大细胞神经内分泌癌属于高度恶性的肿瘤。形态上需与低分化鳞癌，甲状腺样癌，肺神经内分泌癌，副神经节瘤和无色素性黑色素瘤等相鉴别。     

Spindle cell/sclerosing rhabdomyosarcoma: case series from a single institution emphasizing morphology,immunohistochemistry and follow-up

Spindle cell/sclerosing rhabdomyosarcoma is a rare skeletal-muscle tumor with distinctive clinicopathologic characteristics. 10 cases (6 cases of spindle cell rhabdomyosarcoma and 4 cases of scleroisng rhabdomyosarcoma) were composed of 6 males and 4 females aging from 5 months to 57 years, with median age 33 years, most of who represented a painless solid mass. Histologically, the tumors were composed of fascicles of spindle cells or primitive round cells embed in sclerotic matrix with presence of rhabdomyoblasts in varying proportion. Immunohistochemically, the tumor cells expressed MyoD1 (10/10), Desmin (10/10), myogenin (6/10), AE1/AE3 (2/10), EMA (2/10), but were negative for SMA, caldesmon, S-100. All of the patients underwent a complete surgical resection without or with chemotherapy (2/10) or radiotherapy (1/10). During the follow-up period (1 to 24 months), 1 patient was succumbed, and 2 cases showed in situ recurrence with 1 of them adopting metastasis. Our cases further demonstrate there do present some clincopathologic relations between spindle cells rhabdomyosarcoma and sclerosing rhabdomyosarcoma, but the latter seems to have a better prognosis. Exact grading and staging contribute to predict the outcome.     

Intratumor heterogeneity in clear cell renal cell carcinoma: a review for the practicing pathologist

Intertumor heterogeneity, defined as the spectrum of morphological differences found in similar tumors in different patients, is a well‐known event for pathologists. However, recent molecular studies have pointed to intratumor heterogeneity as one of the most important issues in human neoplasia in the next years. Clear cell renal cell carcinoma is an example of an intrinsically heterogeneous neoplasm, and some of the most salient advances in the knowledge of intratumor heterogeneity have been developed on it. This review intends to analyze this phenomenon in this tumor from the practicing pathologist's point of view. A careful study of the surgical specimen and an exhaustive tumor sampling are mandatory to keep relevant information. Currently accepted protocols designed for renal tumor sampling may be insufficient. As a result, a different approach to tumor sampling is advisable to ascertain that intratumor heterogeneity, if present, will be well represented in the selected material.     

多囊性肾细胞癌1例报道及文献复习

目的：阐明多囊性肾细胞癌的病理形态学特征及鉴别诊断要点。方法：报道1例多囊性肾细胞癌,结合文献对本病的临床病理特征进行探讨。结果：肿瘤由厚的假纤维被膜环绕,瘤体全部由大小不等的囊腔及无膨胀性实性结节的薄的间隔构成,囊腔被覆透明细胞,异形性小,间隔内含聚集的透明细胞上皮巢,结论：多囊性肾细胞癌是一种罕见的有低度恶性倾向的肿瘤,术前影像学,细胞学检查及术后的肉眼特征均与囊性肾瘤,囊性部分分化性肾母细胞瘤相似,最重要的是本瘤缺乏肉眼所见的膨胀性实性结节,显微镜下的关键特征是间隔内可见聚集的透明细胞巢。