Papillary renal cell carcinoma with sarcomatoid differentiation in a native kidney of transplant recipient: A case report and review of literature
Satish K Ranjan1, Ankur Mittal1, Sunil Kumar1, Sanjeev Kishore2, Tushar A Narain1, Kim J Mammen1
1 Department of Urology, AIIMS, Rishikesh, Uttarakhand, India
2 Department of Pathology, AIIMS, Rishikesh, Uttarakhand, India
|Date of Submission||26-May-2020|
|Date of Acceptance||18-Aug-2020|
|Date of Web Publication||16-Feb-2021|
Department of Urology, AIIMS, Rishikesh, Uttarakhand
Source of Support: None, Conflict of Interest: None
Renal cell carcinoma (RCC) developing in a transplant recipient is about 5–20 times higher than the general population. It is more common in native kidneys than graft kidney, and incidence varies between 0.3% and 4.8%. Clear cell and papillary types are more frequently reported. Most RCC of allograft recipient is usually low-grade with favorable prognosis. We present a case of papillary RCC with sarcomatoid differentiation (SD) in a native kidney of renal transplant (RT) recipient. The coexistence of sarcomatoid variant with papillary RCC, as in our case, makes it a high grade (WHO/ISUP grade 4) and portends a poor prognosis. Relative aggressiveness and rarity of this variant histology in transplant recipients prompted us to report this case and carry out an extensive search of the available literature.
Keywords: Renal cell carcinoma, renal transplantation, sarcomatoid differentiation
|How to cite this URL:|
Ranjan SK, Mittal A, Kumar S, Kishore S, Narain TA, Mammen KJ. Papillary renal cell carcinoma with sarcomatoid differentiation in a native kidney of transplant recipient: A case report and review of literature. Indian J Nephrol [Epub ahead of print] [cited 2021 Jun 20]. Available from: https://www.indianjnephrol.org/preprintarticle.asp?id=309552
| Introduction|| |
Renal cell carcinoma (RCC) is the third most common malignancy after skin and hematopoietic cells in the renal transplant recipient. Papillary RCC is more commonly reported than clear cell carcinoma in native kidneys, and are usually low-grade with a favorable prognosis. Although sarcomatoid differentiation rarely coexists, its presence makes papillary RCC a highly aggressive disease with a propensity for distant metastasis (70-80%). Sarcomatoid differentiation (SD) is not a distinct histological subtype; rather it arises from epithelial-mesenchyme transition. Recently, the International Society of Urological Pathology (ISUP/WHO 2016) recognized this as a grade 4 RCC (validated for clear cell and papillary), which consists of extreme nuclear pleomorphic, multinucleated giant cells, and/or rhabdoid and/or sarcomatoid differentiation. These features are found in 5-8% of clear cells, 8-9% of chromophobe, and 2-3% of papillary RCC., Current case report reinforces the role of regular screening of not only the transplant kidney but also the native kidneys, which is usually missed.
| Case Details|| |
A 45-year-old, known diabetic and hypertensive male was incidentally diagnosed with a solid–cystic mass, around 5 cms in size, in the right native kidney on ultrasonography of abdomen. He had a history of right renal transplantation ten years (2009) back, followed by left transplant four years (2015) ago [Figure 1]a. He was on triple immunosuppression drugs i.e., Tacrolimus, Mycophenolate mofetil, and Prednisolone for ten years. Although he was on regular ultrasound screening for graft kidney, yet screening of native kidneys were somehow missed. Considering his comorbidity and low creatinine clearance (Crcl) of <45 ml/minute, he underwent noncontrast MRI of abdomen and pelvis for further characterization of incidentally detected right native kidney mass. MRI revealed bilaterally small native kidneys with few subcentimetric renal cortical cyst and a well-defined solid exophytic lesion from upper and middle pole of right side approximately 5.1 × 5.4 × 4.9 cm in size. The lesion was hypointense on T1WI and iso-hyperintense on T2WI images, highly suggestive of RCC [Figure 1]b. HRCT thorax showed no evidence of metastasis. Patient underwent robot-assisted right radical nephrectomy [Figure 2]a and [Figure 2]b. Histopathology showed papillary RCC with sarcomatoid differentiation (PRCCs) of 10-15%, WHO/ISUP grade 4(pT1N0Mx) [Figure 2]c and [Figure 2]d. Because of the high propensity for metastasis and poor prognosis of sarcomatoid differentiation, bone scan was done, and it showed subtle osteoblastic active suspicious lesion involving right 9th rib and right iliac bone, which was mildly FDG avid (SUV 3.2) on PET CT. Role of adjuvant therapy, i.e., tyrosine kinase inhibitors and immune check inhibitors were discussed in multidisciplinary tumor board. In view of the limited proven role and risks of the development of acute rejection, an informed decision was made to keep him on close surveillance. He continues with the same triple immunosuppressive therapy as before.
|Figure 1: (a) Right (red arrow) and left (green arrow) graft kidney in iliac fossa, (b) Exophytic mass arising from the right native kidney (yellow arrow)|
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|Figure 2: (a) Right radical nephrectomy specimen, (b) cut section showed well-defined mass arising from the upper pole, (c) papillary RCC with sarcomatoid differentiation (100X), (d) Sarcomatoid differentiation (400X)|
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| Discussion|| |
Malignancy after transplantation is not a rare occurrence. The meantime of occurrence for lymphomas, skin, and endocrine cancers, and respiratory tract malignancies were six and eight years respectively. However, for leukemia, breast and genitourinary cancers, and the cancers of the alimentary tract it was nine and 10 years post-transplantation. It was difficult to comment on the time of occurrence in our case as he was routinely screened for cancer in the graft kidneys only and was incidentally diagnosed with right native kidney mass, approximately 9–10 years of first renal transplantation. More than 90% of patients are diagnosed incidentally, only a handful of patients present with haematuria, flank pain, and lump abdomen., Thus, active screening of both native and graft kidney for early detection and management is warranted.
An immunocompromised status, deficient immune surveillance against malignant cells, susceptibility for oncogenic viruses, and chronic urinary tract infection are hypothesized to play a significant role in genitourinary cancers in these patients., Male sex, African- American race, pre-transplant dialysis interval >4.6 years, age of recipient >65 yrs, age of donor >50 years and allograft rejection within 1 year of transplantation were independent predictors of RCC in transplant recipients in a study by Hurst FP et al. Renal cysts, congenital (polycystic disease) or acquired renal cystic disease (ARCD) during dialysis were also identified as risk factors but often within 6 months of transplantation., Several researchers have specified risk factors for specific histological subtypes. They have shown an increased risk for papillary RCC among blacks, dialysis vintage and patients with hypertensive nephrosclerosis and vascular diseases.
The most common variant in a transplant recipient is clear cell, but the incidence of papillary type is more common than in nontransplant. True incidence and prognosis of RCC with SD in a transplant recipient is still not known. In a large series of RCC of 101 patient in nontransplant patients, SD was found in about 8%. Long term prognosis of even localized disease of SD is very poor, reported overall survival is only 50% at 2 years and recurrence of about 77%. Hence, patients even with the localized disease with sarcomatoid variant should be advised strict surveillance for disease progression.
Limited studies have been reported in the literature on RCC with SD in the native kidney of transplant recipients. Kitajima et al. reported the sarcomatoid clear cell RCC in a 60-year-old male in the left native kidney, about 12 years after renal transplantation. The patient had multiple lung metastasis at the presentation, and he also had a long history of dialysis (16 years) with the acquired renal cystic disease before transplantation. So the author concluded that long term dialysis and immunosuppression may be considered as risk factors. In another retrospective series of 43 RCC in the native kidney by Vegso et al., only one patient (2.4%) had SD, highlights the rarity of this variant. The exact nature of the disease in the transplant recipient is least understood, and most of the data is extrapolated from the sarcomatoid variant from the non-transplant population.
Regular follow up and imaging of native kidneys along with graft kidney is probably the key to diagnose RCC in the native kidney as well as in the graft. Although there is no good evidence that mortality is reduced, several United States, European, and Asian centers are doing regular screening for renal cell carcinoma after transplant. Most of the international guideline recommendations are based on retrospective studies, observational cohort studies, registry-based studies, or modeling analyses. The European renal association-European dialysis and transplant association-2002 (ERA-EDTA) recommends yearly ultrasonography of graft and native kidneys, after the first year. The KDIGO guideline (2020) recommends screening for RCC in high-risk patients, i.e., patients with a family history of RCC, long duration of hemodialysis before transplantation (>3 years), history of the acquired renal cystic disease and analgesic nephropathy. In a follow-up study with annual ultrasonography by Chiang et al. of 326 transplant recipient, abnormal USG (benign as well as malignant disease) were found in 105 patients in native and 45 patients in graft kidneys. With this brief review of the literature we suggest annual USG screening of graft as well as native kidneys after the first year of transplantation and further cross-sectional imaging if any suspicious lesion (complex cyst, renal mass with calcification, rapid increase in size of existing cyst) is found in USG.
Radical nephrectomy is the standard of care for the patient with a papillary carcinoma with sarcomatoid variant and no metastases. There are limited studies on Immune checkpoint inhibitor (ICI) and Tyrosine kinase inhibitors (TKIS) as adjuvant therapies in non-clear cell RCC with anecdotal results. A study on ICI has shown that tumoral PD-L1 and PD-1 expression was higher in RCC with SD than pure RCC in 54% and 96% versus 17% and 62%, respectively. These findings suggest that blockade of the PD-1/PD-L1 axis could be an attractive therapeutic approach in the SD of RCC. Other studies have shown risks of the development of acute rejection with ICI. Similarly, TKIs have shown modest response rate in RCC, whereas metastatic sarcomatoid-variant RCC responds poorly to systemic therapy. Thus safety and efficacy of these drugs in immunosuppressed patients either in adjuvant or palliative setting need further larger prospective study. Trials with tyrosine kinase inhibitors and immune checkpoint inhibitors are the need of the hour to answer questions revolving around the appropriate management of such patients.
| Conclusion|| |
Papillary RCC with sarcomatoid differentiation is a rare clinicopathological finding in transplant recipients and has a poorer prognosis than pure RCC. We hereby suggest a regular annual screening by ultrasonography of both native and graft kidneys post-transplantation that could be beneficial in early detection of renal cell carcinomas.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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