The incidence of renal cell carcinoma (RCC) in renal allograft in transplant recipients is 0.22–0.25%. De novo clear cell, papillary, and chromophobe RCCs and RCCs with sarcomatoid differentiation originating in renal allograft have been reported. Routine surveillance for graft tumours is not routinely practiced and these tumours are commonly asymptomatic and incidentally discovered. We describe a case of incidental, eosinophilic chromophobe RCC in a 31-year-old, long-term renal transplant male recipient, who presented with acute gastroenteritis 11 years after transplantation. The graft was nonfunctional at the time of presentation. Abdominal ultrasound and computed tomography scan demonstrated 1.8 cm well-defined, round enhancing lesion, confined to the renal allograft and suspicious for malignancy. Pathological examination of graft nephrectomy specimen showed gross, histopathological, and immunohistochemical features of eosinophilic chromophobe RCC. Fifty-five months after surgery, the patient was alive and free of malignancy. To the best of our knowledge, only five chromophobe RCCs originating in a renal allograft were previously described in English literature. We suggest that chromophobe RCC should be considered in the differential diagnosis of renal allograft mass, including eosinophilic tumours, and emphasise the importance of periodic screening of renal allograft in all renal transplant recipients.
Patients with end stage renal disease (ESRD), particularly those with a history of chronic haemodialysis and subsequent acquired cystic kidney disease, have a high incidence of native kidney epithelial neoplasms [
A 31-year-old man underwent living nonrelated kidney transplantation at age of 16 years for ESRD secondary to biopsy-proved immune-complex mediated membranoproliferative glomerulonephritis. The patient was maintained on cyclosporine A, prednisone, and azathioprine immunosuppression regimen. His early posttransplant course was complicated with lymphocele, which was percutaneously drained and
(a) Computed tomography scan coronal section demonstrates an enhancing, round lesion, suspicious for malignancy in the mid renal zone (arrow). (b) Embolization of the renal artery of the renal allograft was performed before graft nephrectomy.
Gross examination of the graft nephrectomy specimen showed well-defined, solitary, round, mahogany corticomedullary tumour in the mid zone of the renal allograft, measuring 1.6 cm in maximum dimension. No tumour central scar, haemorrhage, or necrosis was seen. The tumour was confined to the kidney and showed no extracapsular extension. Sections from the tumour were fixed in 10% buffered formalin, paraffin-embedded, sectioned at 5
Primary antibodies used for IHC, their clone, dilution, and source.
Antibody | Clone | Dilution | Source |
---|---|---|---|
Pan CK | AE1/AE3 | 1/100 | Cell Marque, CA, USA |
CK8/18 | TSIFB5 | RTU | Ventana, AZ, USA |
CK7 | OV-TL12/30 | 1 : 50 | Cell Marque |
EMA | E29 | 1 : 50 | Cell Marque |
E-Cadherin | NCH-38 | 1 : 50 | Cell Marque |
RCC | SPM314 | 1 : 20 | Dako, Denmark |
Vimentin | V9 | 1 : 300 | Dako |
CD10 | 56C6 | RTU | Ventana |
CD117 (C-KIT) | YR145 | 1 : 400 | Cell Marque |
CK, cytokeratin; RTU, Ready to Use; EMA, epithelial membrane antigen; RCC, renal cell carcinoma.
Histopathological examination showed well-circumscribed eosinophilic variant of ChRCC. The tumour consisted of medium to large, round, and polygonal neoplastic cells that exhibited mild degree of nuclear pleomorphism and arranged predominantly in variably sized nests, cords, and poorly formed acini and had hyperchromatic nuclei, indistinct nucleoli, irregular “raisinoid” or round nuclear cell membranes, abundant amount of dense eosinophilic cytoplasm, and poorly defined cell membranes (Figures
(a) Histopathological examination of the renal allograft tumour showed eosinophilic chromophobe renal cell carcinoma. The tumour consisted of medium to large round and polygonal neoplastic cells arranged in variably sized nests and cords and poorly formed acini [H&E ×200]. (b) Tumour cells exhibited hyperchromatic nuclei, irregular “raisinoid” nuclear membranes (arrows) and voluminous, and dense eosinophilic cytoplasm [H&E ×400]. (c) Tumour cells “raisinoid,” wrinkled nuclear membranes, and perinuclear cytoplasmic clearing (arrows) [H&E ×600]. Immunophenotypically, the tumour cells exhibited positive immune reaction to pancytokeratin (CK) (d), low-molecular weight CK (e), CK7 (diffuse and strong staining, (f)), and E-cadherin (g), while staining for renal cell carcinoma (h), CD10 (i), and CD117 (j) antibodies was negative [(d–j) ×200].
The patient had an uneventful postoperative clinical course. On follow-up, the patient remains clinically stable on haemodialysis and without clinical or radiological evidence of locoregional recurrence or distant metastasis at 55 months after graft nephrectomy.
Renal cell carcinoma of the native kidneys affects 1–3% of all renal transplant recipients with 5.6 years’ estimated median interval time between renal transplantation and the occurrence of RCC [
Various histological types of renal allograft de novo RCC were reported. In most reported series of cases, papillary RCC was the most common type, followed by clear cell (conventional) RCC [
Clinicopathological features of reported chromophobe renal cell carcinoma in renal allograft.
Reference | Age at RCC diagnosis (yr)/sex | Primary kidney disease | Interval before RCC |
Treatment | Tumour location | Tumour size (cm) & histological variant | Clinical follow-up |
---|---|---|---|---|---|---|---|
Greco et al. [ |
13.5/M | Juvenile nephronophthisis | 5 | Graft nephrectomy | Near the hilum | 2.1, classical | N/A |
Ploussard et al. [ |
58/M | Polycystic kidney | 8 | Graft nephrectomy | Upper pole | 0.5, classical | Alive, NED at 96 mo |
Ajabnoor et al. [ |
52/F | N/A | 15 | Graft nephrectomy | Mid renal | 8, classical | N/A |
Troxell and Higgins [ |
27/M | N/A | 9 | Partial graft nephrectomy | Unknown | 3.5, classical | Graft failed at 5 yr; NED at 6 yr, died of unrelated cause |
Althaf et al. [ |
20/F | Unknown | 5 | Graft nephrectomy | Renal pelvis | 3.5, classical | N/A |
Current case | 31/M | IC-MPGN | 11 | Graft nephrectomy | Mid renal | 1.6, eosinophilic | Alive, NED at 55 mo |
Chromophobe RCC is uncommon distinct type of RCC that is derived from the intercalated cells in the collecting ducts and accounts of approximately 5% of all native renal neoplasms. Morphologically it is classified into two main variants: classical and eosinophilic [
The histopathological differential diagnosis of eosinophilic ChRCC includes eosinophilic variant of conventional RCC, oncocytoma, and hybrid oncocytic/chromophobe tumour/renal cell carcinoma (HOCT). The latter two entities can be very difficult to distinguish even for an experienced urological pathologist. Several histological, histochemical, and immunohistochemical features distinguish ChRCC from other mimicking entities. In the current case the absence of typical tumour vascular component and the immunophenotypical features of the tumour easily excluded eosinophilic variant of conventional RCC, and the presence of readily identified irregular, raisinoid nuclear contour and cytoplasmic perinuclear clearing and strong diffuse immunohistochemical positivity for CK7 favour ChRCC over oncocytoma (CK7 tends to be negative or only focally positive in oncocytoma). Hybrid oncocytoma/chromophobe tumour/renal cell carcinoma is rare kidney tumour, which can be associated with renal oncocytosis and Birt-Hogg-Dube syndrome; rare sporadic HOCT were also described. These tumours exhibit histopathological features of both renal oncocytoma and ChRCC and can be extremely difficult to classify [
In general, ChRCC tends to be low-grade and has better prognosis compared to conventional (clear) RCC with a mortality rate < 10% [
Renal cell carcinoma can be silent and has insidious biological behavior, which result in a large tumour size. Similar to the current case, all reported ChRCC were discovered incidentally by radiological investigations for other clinical indications [
Renal allograft tumours can be treated by different treatment modalities that include graft nephrectomy, nephron-sparing surgery, cryoablation, and radiofrequency ablation [
In summary, ChRCC is extremely rare in renal allograft. We described a case of incidentally discovered, de novo eosinophilic variant of ChRCC, originating in a nonfunctional renal allograft 11 years after transplantation, which was treated by graft nephrectomy. This is the first case of eosinophilic ChRCC, which expands the spectrum of morphological variants of renal allograft RCC. Early detection of renal allograft tumours by annual radiological screening should be implemented regardless of the graft functionality throughout recipient’s lifetime.
The authors disclose no financial interest in the products or companies described in this article.
Dr. A. Alharbi performed gross examination of the graft nephrectomy specimen and participated in histopathological analysis and writing the manuscript. Miss M. S. Al Turki performed literature review and obtained histopathological images. Dr. N. Aloudah performed diagnostic histopathological analysis of the pathology specimen. Dr. K. O. Alsaad performed diagnostic histopathological analysis of the pathology specimen and wrote the manuscript.