Giunchi Francesca, Franceschini Tania, Gruppioni Elisa, Altimari Annalisa, Capizzi Elisa, Massari Francesco, Schiavina Riccardo, Brunelli Matteo, Martignoni Guido, Fiorentino Michelangelo
Department of Pathology, University of Bologna, 40138 Bologna, Italy.
Department of Oncology, University of Bologna, 40138 Bologna, Italy.
Diagnostics (Basel). 2020 Feb 23;10(2):123. doi: 10.3390/diagnostics10020123.
Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC).
We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade.
All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting resultsAmong the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected mutations; two (33%) harbored pathogenic mutations in the or the genes; and one (16%) was wild type.
We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least mutations.
透明细胞管状乳头状肾细胞癌（cctpRCC）以透明细胞形态为特征，但因其惰性的临床行为和遗传背景与传统透明细胞癌（ccRCC）不同。两者的鉴别诊断基于组织学和免疫组化（IHC）。
我们通过下一代测序（NGS）进行了对比病例对照组织学、免疫组化和基因分析，以指出10例cctpRCC与6例低分期和低分级ccRCC对照之间的差异。
所有16例病例均显示出与每种肿瘤类型组织学特征相符的细胞角蛋白7、消旋酶和碳酸酐酶IX免疫组化图谱。相比之下，覆盖50个癌基因或肿瘤抑制基因的207个扩增子的NGS突变分析得出了相互矛盾的结果。在10例cctpRCC病例中，8例（80%）所有检测基因均为野生型，而2例（20%）携带ccRCC典型突变。6例ccRCC对照病例中有3例（50%）显示出预期突变；2例（33%）在特定基因中携带致病性突变；1例（16%）为野生型。
我们可以认为组织学和免疫组化不足以明确诊断cctpRCC或ccRCC。尽管检测了50个基因，但我们发现80%的cctpRCC在基因上无异常，这表明这些肿瘤具有惰性生物学行为。对于选择最佳治疗策略而言，ccptRCC和ccRCC之间的鉴别诊断可能需要综合评估组织学、免疫组化以及至少某些突变情况。
