To screen or not to screen renal cell cancer in a kidney transplant patient

CASE REPORT

Hippokratia 2023, 27(2): 69-71

Kaynar K1, Alizade L2, Uyar Ö2, Mungan S3, Rashidzade K2

1Department of Nephrology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
2Department of Internal Medicine, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
3Department of Pathology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

Abstract

Background: The prevalence of malignancies is higher among kidney transplant recipients (KTR) than general population. Although the incidence of renal cell cancer (RCC) after KTR was reported as 0.6 % with a high mortality rate of 13.9 %, none of the guidelines except the European Best Practice Guideline (EBPG) recommends RCC screening based on cost-effectiveness and lack of solid evidence. The EBPG recommends RCC screening in native kidneys (not the allograft) by ultrasonography (USG) every 1-3 years.

Case description: A 55-year-old male patient who had a kidney transplant from a living donor 14 years before, presented with sudden onset uncontrolled hypertension (180/110 mmHg) and rapid deterioration in graft functions (increase in serum creatinine to two-times baseline). Evaluations revealed RCC in the allograft. Abdominal pain, hematuria, fever, weight loss, flu-like syndrome, recurrent urinary tract infections, weakness, hypertension, and allograft dysfunction are reported as the main complaints and signs of RCC in KTR patients. Our patient’s findings were hypertension and allograft dysfunction.

Conclusion: It is essential to follow EBPG for KTR and not to forget the annual USG for screening of RCC both in native kidneys and allograft. HIPPOKRATIA 2023, 27 (2):69-71.

Keywords:  Kidney transplantation, carcinoma, renal cell, ultrasonography

Corresponding author: Prof. Dr. Kubra Kaynar, Karadeniz Teknik Üniversitesi, Tıp Fakültesi, Nefroloji Bilim Dalı, 61080 Trabzon, Turkey, tel: +905422415879, fax: +904623252270, e-mail: kkaynar@yahoo.com

Introduction

The prevalence of malignancies is higher (two fold) among kidney transplant recipients (KTR) than general population (GP)1. Also, the most prevalent cancer types differ between KTR and GP. For example, renal cell carcinoma (RCC) was reported in 5 % and 3 % of all malignancies in men and women, respectively, among the GP2. However, it was detected in 10.7 % of posttransplant malignancies3. Although the incidence of RCC after KTR was reported as 0.6 % with a high mortality rate of 13.9 %, none of the guidelines except the European Best Practice Guideline (EBPG) recommends RCC screening based on cost-effectiveness and lack of solid evidence1,4. The EBPG recommends RCC screening in native kidneys (not the allografts) by ultrasonography (USG) every 1-3 years4.

Case presentation

A 55-year-old male patient who had kidney transplantation from a living donor 14 years before presented with sudden onset uncontrolled hypertension (180/110 mmHg) and rapid deterioration in graft functions (increase in serum creatinine to two-times baseline) nearly two years after his last control visit. He was taking cyclosporine (75 mg twice daily), prednisolone (5 mg daily), mycophenolate mofetil (750 mg twice daily), lansoprazole (30 mg daily), and lercanidipine (20 mg daily). He had no hematuria, malnutrition, or anemia (Figure 1). The patient had no documented coronavirus infection and received five doses of Sinovac coronavirus vaccines. Abdominal ultrasonography, which was normal four years before, revealed a centrally located (interpolar region) complex (solid and cystic) mass (45 × 26 mm in size) with internal vascularity in the allograft. This mass (36 × 38 mm in size) had both thin and thickened septa, mural nodules, and enhancement with intravascular contrast without renal vein invasion, metastatic adenopathy, perinephric invasion, or adjacent organ invasion on magnetic resonance imaging (MRI) (Figure 2). Metastasis was not detected by screening thorax and abdominal computed tomographies. Radical allograft nephrectomy was preferred as the preliminary diagnosis was centrally located RCC, stage one (T1, N0, M0) based on the American Joint Committee on Cancer (AJCC) Staging Manual, Eighth Edition5. Pathological evaluations of the resected specimens (30 × 28 × 40 mm in size) revealed grade two clear cell RCC, with weak positive for paired box protein 8 (PAX8) and positive for epithelial membrane antigen (EMA), renal cell carcinoma marker (RCC-Ma), CD10, vimentin, and carbonic anhydrase IX (CA IX) (Figure 3). No adjuvant therapy for RCC was required, autogenous radial-cephalic arteriovenous fistula in the non-dominant arm was created, and since then, the patient has been receiving hemodialysis treatment.

Figure 1: Histogram demonstrating the transplanted patient’s clinical course and the graft function’s rapid deterioration.

Figure 2: The axial magnetic resonance imaging section through the patient’s abdomen showing the mass in the graft with thin and thickened septa, mural nodules, and enhancement with intravascular contrast (red arrow).

Figure 3: Images of the pathological examination of the resected specimen showing: a) neoplastic renal tubular epithelial cells with clear cytoplasms under the kidney capsule (Hematoxylin-Eosin stain, × 100); b) at higher magnification, neoplastic epithelial cells with clear cytoplasms and vascular structure between these cells (Hematoxylin-Eosin stain, × 400); c) the immune expression of carbonic anhydrase (CA) in neoplastic renal cells (immunohistochemical staining of CA IX, × 200); d) the immune expression of renal cell carcinoma marker (RCC-Ma) in neoplastic renal cells (RCC-Ma, × 200).

Discussion

The 2-6 fold increased risk of RCC incidence among KTR is mainly due to immunosuppressive treatments given to prevent rejection, previous renal stone diseases, chronic infections, and oncogenic viruses. In contrast, risk factors for RCC in GP are male sex, older age, African descent, obesity, smoking, and hypertension1-3,6,7. In addition, the malignant transformation or degenerative changes of cysts in the kidneys and regular use of nonaspirin nonsteroidal anti-inflammatory drugs have higher risk of RCC incidence8. The reported and well-known risk factors for RCC in native kidneys are chronic dialysis, acquired cystic kidney diseases, and end-stage kidney disease. The  risk factors for RCC in allograft are increased donor and recipient age, duration of graft, smoking, obesity, hypertension, and environmental risk factors9. The increase of RCC risk in KTR patients was also reported to be due to detection and surveillance biases6. For example, USG is a cheap and non-invasive method for screening, but, on the other hand, it has low sensitivity in detecting small lesions or cancer development in multi-cystic kidney diseases. The RCCs in these patients occur mainly in the native kidneys (90 %) rather than in the donor kidney (10 %), and the most common histology was reported as clear cell RCC in the native kidneys. In contrast, the most common histology was papillary RCC in allograft tumors7,10,11. The presentation of RCC in KTR patients is usually non-specific and asymptomatic in 80 % of the cases. Allograft RCCs were mostly diagnosed incidentally during a routine follow-up for other co-morbidities. Main complaints and signs of RCC in KTR patients were abdominal pain, hematuria,  fever, weight loss, flu-like syndrome, recurrent urinary tract infections, weakness,  hypertension, and allograft dysfunction. Our patient’s findings were hypertension and allograft dysfunction12.

Although the evidence for a standard approach to treat RCC in allograft remains weak, nephron-sparing surgery (radiofrequency ablation, cryoablation, microwave ablation, high-intensity focused ultrasound, irreversible electroporation, and partial nephrectomy) and graftectomy are performed in selected patients. Transplantectomy is generally recommended for patients with irreversible allograft failure, sarcomatoid type RCC, multi-focal papillary type RCC, RCC greater than seven cm in maximal diameter (AJCC stage II), locally invasive or metastatic RCC. Cryoablation has recently been considered for centrally located lesions, as in the reported case12. Center experiences for these approaches are also critical in decision-making.

In conclusion, RCC in the allograft of our patient was presented with hypertension and deterioration in graft functions. We detected the mass in allograft by USG and confirmed the preliminary diagnosis by MRI with contrast. The risk factors for tumor genesis in our case were immunosuppressive treatments of 14 years (all the trough drug levels were in target limits), hypertension, and male gender. Total graftectomy was performed due to the central location of the cancer and lack of experience and evidence for other treatment options. Based on the reported patient’s clinical course and a well-known RCC risk in KTR, which is relatively younger and has a longer life expectancy than dialysis patients, we prefer regular screening by annual USG in KTR.

Conflict of Interests

All co-authors have agreed with the contents of our manuscript and declare no conflict of interest. 

Acknowledgment

Written informed consent regarding the publishment of this manuscript was obtained from the patient.

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