Clear cell-papillary renal cell carcinoma (CC-Pap RCC) is a recently described renal tumor initially reported in the setting of end-stage renal disease (ESRD). It has unique morphologic and immunohistochemical features that differentiate it from the more common clear cell RCC and papillary RCC. Recently, these tumors have also been described in a sporadic setting. We studied 64 cases of CC-Pap RCC not associated with ESRD (57 CC-Pap RCCs and 7 cases with features of renal angiomyoadenomatous tumors [RAT] including 5 initially diagnosed as such). The morphologic features of all cases and the immunohistochemical profile of 59 cases were studied along with the clinical and molecular features of 30 and 12 cases, respectively. All the tumors were well circumscribed with a mean tumor size of 2.6 cm and showed a wide array of architectural patterns, usually mixed, including tubular (77%), papillary (62%), tubulocystic (52%), and compact nested (21%). Seventy-three percent of the cases showed areas in which the tumor nuclei had a distinct orientation away from the basement membrane. Ninety-two percent of the cases had a low Fuhrman nuclear grade (nuclear grade 2%-86%, and nuclear grade 1%-6%); however, 8% cases showed foci of Fuhrman nuclear grade 3. In 4 cases, epithelial tumor comprised <5% of the tumor; >95% of the tumor was cystic or hyalinized. The stroma varied from being minimal to occasionally prominent myxoid to hyalinized and rarely with organized amianthoid fibers or well-defined smooth muscle bundles. Pathologic stage was reliably assigned in 60 cases, of which 93.3% (56 cases) were pT1, 3.3% (2 cases) were pT2, and 3.3% (2 cases) were pT3a with extension into the perinephric fat. One case had coagulative necrosis; sarcomatoid change and vascular invasion was not identified. The tumors showed a fairly typical immunoprofile characterized by positivity for CK7 (100%), HMCK (96%), CAIX (94%), and vimentin (100%) with negativity for AMACR, RCC, and TFE3; CD10 was positive in 24%. None of the cases tested showed recurrent chromosomal imbalances by virtual karyotyping, fluorescence in situ hybridization, or 3p loss of heterozygosity analysis. VHL gene mutations were, however, noted in 3 cases (2 in exon 1 and 1 in exon 3). Clinical follow-up information was available in 47% of the patients, with a mean and median follow-up of 47 and 37 months, respectively (range, 18 to 108 mo). One case occurred in the setting of VHL syndrome and multiple benign cysts. None of the cases showed local recurrence, metastasis, or death due to disease. Morphology, immunophenotype, and molecular studies did not vary between typical cases, those with prominent smooth muscle (so-called RAT), and historically published data on cases occurring in ESRD. Our analysis confirms that CC-Pap RCC is a unique subtype of adult renal epithelial neoplasia in which tumors are frequently small, are of low nuclear grade and pathologic stage, and have extremely favorable short to intermediate range prognosis. Tumors occurring sporadically, with prominent smooth muscle stroma (so-called RAT), and occurring in ESRD are in the spectrum of the same category of tumors.
透明细胞乳头状肾细胞癌(CC-Pap RCC)是新近被描述的一种肾肿瘤，最初报道发生于终末期肾病(ESRD)。 它有独特的形态学和免疫组化特征，区别于：更常见的透明细胞RCC和乳头状RCC。最近，也有散发病例的描述。
我们研究了64例不伴ESRD的CC-Pap RCC（57例CC-Pap RCCs，7例具有肾血管肌腺瘤样肿瘤（RAT）特征，其中有5例最初被诊断为RAT）。研究分析所有病例的形态学特征、59例的免疫组化特点、30例的临床特征以及12例的分子特征。所有肿瘤均边界清楚，肿瘤平均大小2.6厘米，排列结构多样，通常混合性存在，呈管状(77%)、 乳头状 (62%)、管囊状(52%)以及致密巢状(21%)。
73%的病例显示部分区域内肿瘤细胞核明显远离基底膜分布。92%的病例Fuhrman核级低(核级2的为86%，核级1的为6%)。8%的病例显示局灶Fuhrman核级3级。有4例肿瘤中上皮性肿瘤成分<5%，而囊性及透明变性成分>95%。间质的量多少不等，可以是轻微到偶尔显著的黏液样或透明变性，很少见有序的石棉样纤维或界清的平滑肌束。60例有可靠的病理分期，93.3% (56例)是pT1期，3.3% (2 例)是pT2期，3.3%(2例)是pT3期，浸润到肾周脂肪。1例见凝固性坏死，未见肉瘤变及血管侵犯。
肿瘤显示相当典型的免疫组化特点，阳性：CK7(100%)、HMCK(96%)、CAIX(94%)、vimentin (100%)，阴性：AMACR、 RCC和TFE3。CD10只有24%阳性。用可视化核型分析、FISH或3p杂合性缺失分析检测，12例均无周期性染色体不平衡。但是，有3例VHL基因突变(2例在1号外显子，1例在3号外显子)。47%的病人有临床随访资料，随访（18-108个月）平均时间47个月，中位数37个月。1例发生于VHL综合征及多发良性囊肿中。均无局部复发、转移或因病死亡。
本文的CC-Pap RCC病例、伴明显平滑肌成分的病例（所谓的RAT）、过去文献发表发生于ESRD的CC-Pap RCC病例，其形态学、免疫组化和分子研究没有差异。我们的分析证实CC-Pap RCC是成人肾上皮性肿瘤的一种独特亚型，肿瘤常常体积小，核级低，病理分期早，预后非常好。散发的CC-Pap RCC、伴显著平滑肌间质成分（所谓的RAT）的CC-Pap RCC以及发生于ESRD的CC-Pap RCC均属同一肿瘤类别范畴。