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Renal oncocytoma with a novel chromosomal rearrangement, der(13)t(13;16)(p11;p11), associated with a renal cell carcinoma
  1. X Leroy1,
  2. E Leteurtre1,
  3. P H Mahe1,
  4. B Gosselin1,
  5. B Delobel2,
  6. M F Croquette2
  1. 1Service d'Anatomie et de Cytologie Pathologiques, Faculté de Médecine, Pôle Recherche, Rue Polonovski, CHRU, 59045 Lille Cedex, France; x-leroy{at}chru-lille.fr
  2. 2Laboratory of Cytogenetics, Saint-Antoine Hospital, Lille, France

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    Oncocytoma is a benign epithelial tumour that makes up approximately 5–7% of primary renal neoplasms.1 This tumour can be bilateral or multifocal and in 10% of cases there is an association between oncocytoma and renal cell carcinoma.2 We report the case of a renal oncocytoma associated with a necrotic and cystic clear cell carcinoma. A cytogenetic study of the oncocytoma showed a new chromosomal rearrangement, namely: der(13)t(13;16)(p11;p11).

    A 75 year old man with an unremarkable medical history presented with abdominal pain. Echotomography and an abdominal computed tomography scan showed two solid tumours in the right kidney. The first tumour measured 4.5 cm, was located at the lower pole of the kidney, and appeared to be necrotic. The second tumour measured 3 cm, was homogeneous, and was located in the periphery of the first tumour. A radical right nephrectomy was performed.

    Gross examination showed two tumours at the lower pole of the kidney. The first tumour measured 4.5 cm in its largest diameter. It was partially cystic and largely necrotic. The second tumour measured 3 cm. It was solid, homogeneous, and had a brown to mahogany colour.

    Fresh samples of the tumours were immersed in RPMI for short term culturing. Failure of the culture was observed for the large necrotic tumour.

    The kidney was immersed in 10% buffered formalin and routinely processed for paraffin wax embedding; 4 μm sections were cut and stained with haematoxylin and eosin and saffron. Histochemical study was performed using the Hale's colloidal iron staining (Mowry's method). Sections from paraffin wax embedded material were stained with a panel of antibodies using the streptavidin–biotin–peroxidase complex technique. The antibodies used were: pancytokeratin (KL1; Immunotech, Marseille, France; 1/150 dilution), anticytokeratin 7 (Dako, Trappes, France; 1/150 dilution), and antivimentin (Dako; 1/100 dilution).

    Cytogenetic analysis was performed on RHG (R bands obtained by heating and Giemsa) banding metaphases according to conventional procedures. Multitarget fluorescence in situ hybridisation (M-FISH) techniques were also performed on metaphase spreads to confirm the cytogenetic abnormality (Spectra Vysion DNA probe; Vysis, Downers Grove, USA). The M-FISH result was confirmed by specific chromosome painting (Oncor, Qbiogene, Illkinch, France). Specific telomeric probes (Cytocell, Banbury, UK) of this chromosome defined which arm was implicated in the translocation.

    On microscopic examination, the first tumour was largely necrotic and a few sheets of tumour cells were identified (fig 1). The tumour cell cytoplasm was large and clear. The nuclei were round to oval, with a central nucleolus (Furhman's nuclear grade II). No granular cells were found. Immunohistochemical staining of the clear cell tumour showed positivity with antibodies to pancytokeratin and vimentin, and negativity for cytokeratin 7.

    The second lesion was entirely composed of nests and tubulocystic structures of large eosinophilic and granular cells (fig 2). The nuclei were round or oval with minimal atypia. A small nucleolus was frequently seen. No necrosis or areas of clear cells were observed. The mitotic count was low (one mitotic figure/20 high power fields).

    Hale's colloidal iron staining was negative. Oncocytic cells were positive with antibody to pancytokeratin but staining for vimentin and cytokeratin 7 was negative.

    Karyotyping of oncocytic cells showed a lost of the Y chromosome and a translocation of a piece of an autosome on chromosome 13 (fig 3). M-FISH analyses identified the addition to chromosome 13 to be a partial chromosome 16 translocation (fig 4) (confirmed by 16 specific whole chromosome painting). After FISH studies, the result of this karyotype was: 45, X, add(13)(p11.ish der(13))t(13;16)(p11;p11) (wcp16+),inv(16qh). This unbalanced 16 translocation induces a complete 16p trisomy.

    Renal oncocytoma is a benign epithelial neoplasm which is now well defined.1 Histological criteria are: tumour composed of an exclusive or predominant component of granular eosinophilic cells arranged in nests or tubulocystic structures. Areas of clear cells, pronounced necrosis, and papillary formations are lacking by definition.1 Dechet et al reported bilaterality and multicentricity in 5% of cases and an association with renal cell carcinoma in 10%.2 The main differential diagnosis for oncocytoma is chromophobe renal cell carcinoma. Cytological features (wrinkled nuclei, perinuclear halos, binucleation), histochemical staining (positivity of Hale's iron staining), and ultrastructural study (intracytoplasmic microvesicules) are helpful for the diagnosis of chromophobe cell carcinoma.3 Cytogenetic studies showed different profiles. In chromophobe renal cell carcinoma, the most common karyotypic abnormalities are: loss of chromosomes 1, 2, 6, 10, 13, 17, and 21.4 Cytogenetic studies of oncocytomas have reported several clonal abnormalities but no recurrent aberration. The most common are loss of chromosome Y or 1.5 Translocations affecting chromosome 11 have also been described, namely: t(9;11)(p23;q23)6 and t(5;11)(q35;13).7,8 Other rare chromosome rearrangements have been reported, such as: t(1;12)(p36;q13),9 loss of chromosome 14,10 and gain of chromosome 12.5 In a recent study, Tickoo et al reported 14 cases of diffuse renal involvement by numerous oncocytic nodules with features of oncocytoma and chromophobe renal cell carcinoma.11 These authors proposed the term renal oncocytosis. They also suggested that these lesions may constitute a morphological spectrum of oncocytic tumours. Dijkhuizen et al proposed that renal oncocytoma characterised by loss of chromosomes 1 and Y may progress to chromophobe renal cell carcinoma with subsequent losses of chromosomes 2, 6, 10, 13, 17, and 21.12 Here, we describe an additional new chromosomal rearrangement, der(13)t(13;16)(p11;p11), in a morphologically typical oncocytoma.

    Figure 1

    Necrotic and haemorrhagic tumour with sheets of large clear cells.

    Figure 2

    Typical oncocytoma composed of large granular cells arranged in tubulocystic structures.

    Figure 3

    Complete karyotype of one metaphase cell showing: 45, X, add(13)(p11).

    Figure 4

    Multitarget fluorescence in situ hybridisation study showing p16 trisomy by unbalanced 16 translocation (arrow).

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