Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.
Department of Pathology & Laboratory Medicine, Henry Ford Health System.
Am J Surg Pathol. 2019 Aug;43(8):1099-1111. doi: 10.1097/PAS.0000000000001288.
We evaluated the clinicopathologic and chromosomal characteristics of a distinct subset of papillary renal tumors and compared them to a control series of papillary renal cell carcinoma types 1 and 2. Of the 18 patients, 9 were women and 9 were men, ranging in age from 46 to 80 years (mean, 64 y; median, 66 y). The tumors ranged in diameter from 0.6 to 3 cm (mean, 1.63 cm; median, 1.4 cm). Fourteen tumors were WHO/ISUP grade 2 and 4 were grade 1. All were stage category pT1. The tumors had branching papillae with thin fibrovascular cores, covered by cuboidal to columnar cells with granular eosinophilic cytoplasm, smooth luminal borders, and mostly regular and apically located nuclei with occasional nuclear clearing and inconspicuous nucleoli. Tubule formation and clear cytoplasmic vacuoles were observed in 5 and 9 tumors, respectively. Ten tumors had pseudocapsules. Psammoma bodies, necrosis, mitotic figures and intracellular hemosiderin are absent from all tumors. In contrast, papillary renal cell carcinoma type 1 consisted of delicate papillae covered by a single layer of cells with scanty pale cytoplasm with nuclei generally located in a single layer on the basement membrane of the papillary cores, while type 2 tumors had broad papillae covered by pseudostratified cells with eosinophilic cytoplasm and more randomly located nuclei. Both had occasional psammoma bodies, foamy macrophages and intracellular hemosiderin. Immunohistochemically, all were positive for pancytokeratin AE1/AE3, epithelial membrane antigen, MUC1, CD10, GATA3, and L1CAM. Cytokeratin 7 was positive in 16 tumors (1 had <5% positivity). CD117 and vimentin were always negative. α-methylacyl-CoA-racemase (AMACR/p504s) showed variable staining (range, 10% to 80%) in 5 tumors. However, all tumors in the control group were negative for GATA3 and positive for AMACR/p504s and vimentin immunostains. Fluorescence in situ hybridization analysis of the study group demonstrated chromosome 7 trisomy in 5 tumors (33%), trisomy 17 in 5 tumors (33%), and trisomy 7 and 17 in 3 tumors (20%). Chromosome Y deletion was found in 1 of 7 male patients and chromosome 3p was present in all tumors. No tumor recurrence or metastasis occurred. In summary, we propose the term papillary renal neoplasm with reverse polarity for this entity.
我们评估了一组独特的乳头状肾肿瘤的临床病理和染色体特征，并将其与乳头状肾细胞癌 1 型和 2 型的对照系列进行了比较。在 18 名患者中，9 名女性，9 名男性，年龄 46 至 80 岁（平均 64 岁；中位数 66 岁）。肿瘤直径 0.6 至 3cm（平均 1.63cm；中位数 1.4cm）。14 个肿瘤为 WHO/ISUP 分级 2 级，4 个为分级 1 级。所有肿瘤均为 pT1 分期。肿瘤有分支状乳头，中心有薄的纤维血管核，被覆颗粒状嗜酸性细胞质的立方柱状细胞，腔面边界光滑，大多数核规则，位于顶端，偶尔可见核空泡和不明显的核仁。5 个肿瘤有肾小管形成，9 个肿瘤有透明细胞质空泡。所有肿瘤均未见假包膜、砂粒体、坏死、有丝分裂象和细胞内含铁血黄素。相比之下，乳头状肾细胞癌 1 型由纤细的乳头组成，被单层细胞覆盖，细胞内有少量淡染的细胞质，核通常位于乳头状核的基膜单层，而 2 型肿瘤有宽阔的乳头，被假复层细胞覆盖，细胞质嗜酸性，核分布更随机。两者均偶尔有砂粒体、泡沫状巨噬细胞和细胞内含铁血黄素。免疫组化染色均为广谱细胞角蛋白 AE1/AE3、上皮膜抗原、MUC1、CD10、GATA3 和 L1CAM 阳性。16 个肿瘤 CK7 阳性（1 个肿瘤阳性率<5%）。CD117 和波形蛋白均为阴性。α-甲基酰基辅酶 A 消旋酶（AMACR/p504s）在 5 个肿瘤中有不同程度的染色（范围 10%至 80%）。然而，对照组所有肿瘤均为 GATA3 阴性，AMACR/p504s 和波形蛋白免疫染色阳性。研究组的荧光原位杂交分析显示，5 个肿瘤（33%）存在 7 号染色体三体，5 个肿瘤（33%）存在 17 号染色体三体，3 个肿瘤（20%）存在 7 号和 17 号染色体三体。7 号染色体 Y 缺失见于 7 名男性患者中的 1 名，3p 染色体均存在于所有肿瘤中。没有肿瘤复发或转移。总之，我们提出了“具有反向极性的乳头状肾肿瘤”这一术语。
