RCC After Kidney Transplantation From Live Donor

A 42-year-old woman presented for her regular checkup 3 years after receiving a kidney from a related live donor.

The woman had been diagnosed with end-stage renal disease related to chronic glomerulonephritis, and had been receiving programmed hemodialysis for 3 years prior to the transplant. She had not previously had any blood transfusions.

Clinicians had initiated immunosuppression with basiliximab, followed by tacrolimus (starting dose 0.1 mg/kg), mycophenolate, and a steroid to maintain immunosuppression. Surgery and recovery had proceeded without any unexpected events.

At her checkup, clinicians performed a routine sonogram of her abdomen, which revealed the presence of a solid mass in the transplanted kidney. This was confirmed with MRI. A biopsy of the renal allograft was sent to pathology for assessment.

The pathology report showed evidence of chronic inflammation and chronic graft rejection. Assessment of the tumor tissue suggested the possibility that the tumor was an oncocytoma; thus, differentiation from chromophobe renal cell carcinoma (RCC) was required.

Clinicians biopsied the graft, but it was not possible to determine the tumor subtype. A PET-CT was conducted to identify neoplasms of other localizations or metastases. This imaging revealed metabolically active growth in the transplanted kidney. However, there was no evidence of regional or distant metastases (Figure).

Clinicians determined that the graft was not functioning fully; diuresis decreased to 800 mL per day and creatinine level increased to 250 mkmol/L (normal range 53-97 mkmol/L). Thus, it was determined that open surgery was needed to allow for biopsy of the graft at several sites. The intraoperative repeated biopsy revealed an eosinophilic variant of chromophobe RCC.

Clinicians performed a graft resection, and reinstated the patient's hemodialysis. Three months later, another PET scan found no evidence of neoplasms. Follow-up 2 years after graftectomy also found that the patient had not developed any new or metastatic tumors.

Discussion

Clinicians reporting on this case of a patient who developed a rare eosinophilic variant of chromophobe RCC in a transplanted kidney noted that the "incidence of this form of carcinoma in kidney transplant is unclear because fewer than 10 cases have been described in the world literature."

This subtype of kidney malignancy, first described in 1985, accounts for less than 10% of all types of RCC overall, the authors noted; originally it was considered a form of papillary RCC, and was subsequently reclassified as a separate morphological type.

"RCC is one of the most lethal urologic malignancies and accounts for 90% of adult renal cancer," they wrote. Subtypes of RCC include clear cell (70%), papillary (10-15%), and chromophobe (5%).

Of the two subtypes of chromophobe RCC, classical and eosinophilic, the latter is seen less often, and can be distinguished from the classical type by its characteristic localized neoplastic cells and cell cytoplasm density, the authors explained. The pronounced cytoplasmic eosinophilia of this form of chromophobe RCC makes it challenging to differentiate from oncocytoma, they added.

Mortality from chromophobe RCC is less than 10%, making it less deadly than clear cell RCC, the group noted, although the prognosis worsens in the presence of large tumor size and the disintegration of the malignancy.

For patients with end-stage renal disease, "transplantation is the best treatment option," the authors wrote, despite the need for lifelong immunosuppression, which is accompanied by an increased risk of cancer, which, in turn, is a leading cause of death following kidney transplantation.

The risk of developing RCC in transplant recipients' native kidneys is 15 times higher than in the general population, and the development of RCC in the graft occurs in 0.22-0.25% of cases, the authors noted.

Transplant patients who develop chromophobe RCC in the renal allograft have several treatment options, depending on the tumor size: transplantectomy, cryoablation, and radiofrequency ablation.

"In our clinical observation, the size of the tumor in the graft exceeded 2 cm," the case authors wrote. Whether the tumor was oncocytoma or the eosinophilic variant of chromophobe RCC was not clear from the biopsy results. These factors, in addition to the reduced graft function and increased creatinine levels, necessitated the patient's transplantectomy.

RCC typically involves infiltration of the tumor mass and surrounding vessels with various immune cells, such as CD4 and CD8 T cells, B cells, antigen-presenting cells, and natural killer cells, they said.

While immunosuppression is necessary to prevent host rejection of the graft, agents currently used "target the adaptive component of host immunity," the authors wrote, referencing the concept of "danger theory," which suggests that an innate immune response may be triggered by any extracellular or intracellular disruption. Thus, development of a malignancy may give rise to rejection of an allograft.

Little is known about the eosinophilic form of chromophobe RCC due to its rarity and similarity to the classical form of chromophobe RCC and oncocytoma, the authors noted.

Based on their review of the data, "sex is not a risk factor for de novo RCC in allografts," they wrote, although there were reports of chromophobe RCC occurring 11 and 13 years after kidney transplantation and at older ages (67 and 73 years).

The duration of time between transplantation and development of an allograft tumor depends on various risk factors, they added. The development of their patient's tumor only 36 months after transplantation suggests it may have been derived from the donor kidney.

RCC often causes no symptoms and is rarely diagnosed in its early stages. Of reported instances of graft tumors in the literature, the authors noted that only two out of four patients developed symptoms that caused them to go to the emergency department, including fever, vomiting, diarrhea, weakness, and abdominal pain; the rest were identified during a routine follow-up assessment, as was the case with this patient. The authors suggested that routine post-transplant assessments, including ultrasound examination of the graft, can help detect neoplasms in transplanted and native kidneys.

"Differential diagnosis of a solid mass in the kidney remains a challenging issue," they wrote. Identifying the type of RCC typically relies on imaging with ultrasound, CT, or MRI.

National guidelines in Kazakhstan, where the patient lived, recommend that transplant recipients be monitored with ultrasound of the graft monthly for the first 6 months, and every 3 months thereafter, they noted.

They also suggested that MRI is a more effective diagnostic option to differentiate between benign and malignant solid kidney tumors, with a specificity of 89%. Thus, they recommend MRI as the best option for differential diagnosis.

"Regular examinations of kidney recipients, especially the combination of ultrasound and MRI, should be carried out regardless of graft function," they concluded.

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