Hayes Malcolm, Peckova Kvetoslava, Martinek Petr, Hora Milan, Kalusova Kristyna, Straka Lubomir, Daum Ondrej, Kokoskova Bohuslava, Rotterova Pavla, Pivovarčikova Kristyna, Branzovsky Jindrich, Dubova Magdalena, Vesela Pavla, Michal Michal, Hes Ondrej
Department of Pathology, BC Cancer Agency and Clinical Professor of Pathology, University of British Columbia, Vancouver, Canada.
Virchows Arch. 2015 Mar;466(3):313-22. doi: 10.1007/s00428-014-1702-7. Epub 2014 Dec 28.
Xp11.2-translocation renal carcinoma (TRCC) is suspected when a renal carcinoma occurs in young patients, patients with a prior history of exposure to chemotherapy and when the neoplasm has morphological features suggestive of that entity. We retrieved 20 renal tumours (from 17,500 archival cases) of which morphology arose suspicion for TRCC. In nine cases, TFE3 translocation was confirmed by fluorescence in situ hybridisation analysis. In 9 of the remaining 11 TRCC-like cases (7 male, 4 female, aged 22-84 years), material was available for further study. The morphological spectrum was diverse. Six tumours showed a mixture of cells with eosinophilic or clear cytoplasm in tubular, acinar and papillary architecture. One case was high grade with epithelioid, spindle cell and sarcomatoid areas. Another showed tubular, solid, and papillary areas and foci containing spindle cells reminiscent of mucinous tubular and spindle cell carcinoma. The third showed dyscohesive nests of large epithelioid and histiocytoid cells in a background of dense lymphoplasmacytic infiltrate. By immunohistochemistry, keratin AE1/AE3 was diffusely positive in three tumours, while CK7 strongly stained one tumour and another focally and weakly. CD10 and Pax8 were expressed by eight, AMACR and vimentin by seven, CA-IX by four and TFE3 and cathepsin K by two tumours. Of the two TFE3-positive tumours, one showed polysomy of chromosome 7 and the other of 17; they were VHL normal and diagnosed as unclassifiable RCC. Of the seven TFE3-negative tumours, three showed polysomy of 7/17 and VHL abnormality and were diagnosed as combined clear cell RCC/papillary RCC. One TFE3-negative tumour with normal 7/17 but LOH 3p (VHL abnormality) was diagnosed as clear cell RCC. One TFE3-negative tumour with polysomy 7/17 but normal VHL was diagnosed as papillary RCC, and two with normal chromosomes 7/17 and VHL gene were considered unclassifiable. As morphological features and IHC are heterogeneous, TRCC-like renal tumours can only be sub-classified accurately by multi-parameter molecular-genetic analysis.
当年轻患者、有化疗史的患者发生肾癌，且肿瘤具有提示该实体的形态学特征时，应怀疑为Xp11.2易位性肾癌（TRCC）。我们从17500例存档病例中检索出20例形态学上怀疑为TRCC的肾肿瘤。9例通过荧光原位杂交分析证实存在TFE3易位。在其余11例TRCC样病例中的9例（7例男性，4例女性，年龄22 - 84岁），有材料可用于进一步研究。形态学谱多样。6例肿瘤表现为管状、腺泡状和乳头状结构中嗜酸性或透明细胞质细胞的混合。1例为高级别，具有上皮样、梭形细胞和肉瘤样区域。另一例显示管状、实性和乳头状区域以及含有梭形细胞的灶性区域，让人联想到黏液性管状和梭形细胞癌。第三例在密集的淋巴浆细胞浸润背景下显示大上皮样和组织细胞样细胞的离散巢状结构。免疫组化显示，角蛋白AE1/AE3在3例肿瘤中弥漫性阳性，CK7在1例肿瘤中强阳性，在另一例中局灶性弱阳性。8例表达CD10和Pax8，7例表达AMACR和波形蛋白，4例表达CA - IX，2例表达TFE3和组织蛋白酶K。在2例TFE3阳性肿瘤中，1例显示7号染色体多体性，另1例显示17号染色体多体性；它们的VHL正常，诊断为无法分类的肾细胞癌。在7例TFE3阴性肿瘤中，3例显示7/17多体性和VHL异常，诊断为透明细胞肾细胞癌/乳头状肾细胞癌合并。1例TFE3阴性肿瘤7/17正常但3p杂合性缺失（VHL异常），诊断为透明细胞肾细胞癌。1例TFE3阴性肿瘤7/17多体性但VHL正常，诊断为乳头状肾细胞癌，2例7/17染色体和VHL基因正常的肿瘤被认为无法分类。由于形态学特征和免疫组化结果具有异质性，TRCC样肾肿瘤只能通过多参数分子遗传学分析进行准确的亚分类。
