Pediatric with localized renal cell carcinoma (RCC)

Abstract

Renal cell carcinoma (RCC) is an extremely rare cancer in pediatric, accounting for 0.1% to 0.3% of all pediatric malignancies. Due to its low incidence in this age group, literature on pediatric RCC is limited. We present a case of localized RCC in pediatric patient treated with nephroureterectomy and lymphadenectomy. A 14-year-old girl with a 2-year history of red urine, blood clots, and left flank pain underwent physical examination, revealing left flank tenderness. Laboratory results showed anemia, leukocytosis, elevated LDH, and erythrocytes in urine. Imaging revealed a hyperechoic area in the left kidney's lower pole (4.0 × 2.8 cm). Contrast abdominal CT scan indicated a solid mass (5.4 × 3.8 × 3.2 cm) in left renal pelvis extending to the minor calyx and severe hydronephrosis. The patient was diagnosed with suspected cT3N0M0 left upper tract urothelial carcinoma and underwent cystoscopy, bladder cuff excision, and left radical nephroureterectomy with paraaortic lymph node dissection. Pathological analysis revealed clear cell type renal cell carcinoma, WHO ISUP grade IV, extending to the perirenal fat, with tumor-free ureteral resection margins, and no paraaortic lymph node metastasis. Follow-up on postoperative period showed a satisfactory outcome. In cases of pediatric localized RCC, surgical therapy, including radical nephrectomy or nephron-sparing surgery (NSS), can be a preferred treatment for small tumor volumes. This approach preserves kidney function and is generally considered safe for achieving tumor-free margins.

Introduction

Renal cell carcinoma (RCC) originates from the epithelium of the kidney tubules. RCC is the most common type of kidney cancer, consisting of several subtypes, with clear cell carcinoma being the most common subtype [1]. According to GLOBOCAN 2020 data, 431,288 new cases of kidney cancer were globally found in 2020. In pediatric, it is very rare, accounting for 0.1%-0.3% of all malignancies in pediatrics. The incidence of RCC in pediatrics is 2% of all kidney malignancies in pediatrics, ranking second after Wilm's tumor or nephroblastoma [2,3]. The manifestations of RCC are highly heterogeneous and can even be asymptomatic in some cases, leading to delays in diagnosis [4]. The most reported symptoms in pediatric RCC cases are hematuria, back pain, and a mass in the flank [5].

Currently, surgical therapy with radical nephrectomy for localized RCC is the most effective surgical option. Nephron-sparing surgery (NSS) may be chosen for small tumor volumes, offering the advantage of preserving kidney function and is generally considered safe for obtaining tumor-free margins [6]. The benefits of lymphadenectomy in RCC are still controversial, but patients at high risk of lymph node involvement may benefit from LND [7]. Evidence suggesting the benefits of LND includes patients with locally advanced disease (T3-T4) and/or clinically unfavorable and pathological characteristics (high Fuhrman grade, large tumors, presence of sarcomatous features, or coagulative necrotic tumors) [8].

RCC is not a common malignancy in pediatric, and the published literature on this topic is still limited. In this paper, we report a case of localized RCC in pediatric who underwent surgical therapy, specifically nephroureterectomy with lymph node dissection.

Cases description

A 14-year-old girl presented to the emergency department of Dr. Soetomo Regional Hospital with complaints of red urine accompanied by blood clots and intermittent left flank pain for the past 2 years. A general examination showed normal vital signs, Karnofsky Score 90, no palpable mass in the left flank but pain upon percussion was observed in the left flank. The patient denied any history of malignant disease in herself or her family.

A 22 Fr 3-way catheter was inserted, irrigated with normal saline, and initial urine showed red color with blood clots. Laboratory investigations revealed anemia (Hb 9.6 g/dL), leukocytosis (WBC 12,980/uL), normal kidney function (BUN 9.4 mg/dL, serum creatinine 0.63 mg/dL), elevated LDH (218 U/L), and erythrocytes in urine dipstick analysis (3+). Urine cytology showed no signs of malignancy.

Abdominal ultrasound revealed a hyperechoic area in the lower pole of the left kidney (4.0 × 2.8 cm), severe hydronephrosis, hydroureter (+), mass (+), stone (-). It also revealed a blood clot in the bladder (6.5 × 4.5 × 5.2 cm) while no mass or stone was observed (Fig. 1).

Fig. 1.

Abdominal ultrasound. (A, B) Kidney View. White arrow: hyperechoic area in the lower pole of the left kidney (4.0 × 2.8 cm). (C) Bladder View. White arrow: blood clot in the bladder (6.5 × 4.5 × 5.2 cm).

Contrast abdominal CT scan indicated solid mass with partial unclear border, irregular sized 3.2 × 3.8 × 5.4 cm at pelvis renalis trough calyx minor, contrast enhancement (97 HU), expanding to proximal left ureter, causing severe hydronephrosis, infiltrating lower pole, adjacent to left renal artery, not infiltrating fascia gerota (Fig. 2).

Fig. 2.

Contrast abdominal CT scan. (Red line: solid mass with partial unclear border size 3.2 × 3.8 × 5.4 cm accompanied by severe hydronephrosis in left renal).

Patient was diagnosed with suspected left upper tract urothelial carcinoma (UTUC) stage cT3N0M0. Subsequent procedures included cystoscopy, blood clot evacuation from the bladder, left ureterorenoscopy, and washing biopsy with barbotage technique. Cystoscopy revealed a blood clot in the bladder, which was evacuated. Ureterorenoscopy revealed a mass from the proximal 1/3 of the ureter to the ureteropelvic junction. Washing biopsy results were inconclusive due to inadequate specimens. Further interventions included cystoscopy for blood clot evacuation, bladder cuff excision, and left radical nephroureterectomy. During surgery, a tumor was found protruding into the renal pelvis, measuring 3 × 1.5 × 1 cm, and enlarged paraaortic lymph nodes, leading to nephroureterectomy and paraaortic lymph node dissection (Fig. 3).

Fig. 3.

Intraoperative of left ren.

Histopathological examination of the renal specimen revealed a tumor growth composed of lobules, some papillary and forming an alveolar pattern, and some pseudopapillary. The tumor consisted of anaplastic cell proliferation with round nuclei, coarse chromatin, prominent nuclei, abundant clear cytoplasm, eosinophilic, with well-defined cell membrane boundaries. Some bizarre cells were observed, some with multinucleated giant cells. No necrotic areas were observed. Mitosis was noted at a rate of 16 per 10 high-power fields (HPF). No lymphangioinvasion or perineural invasion was observed. The tumor grew invasively into the perirenal fat layer. The para-aortic lymph nodes showed a reactive pattern but no tumor infiltration. The ureter showed no abnormalities. The conclusion includes clear cell type renal cell carcinoma, WHO ISUP grade IV with size 3 × 1.5 × 1 cm. The tumor extended to the perirenal fat, and the ureteral resection margins were tumor-free. No lymphangioinvasion, perineural invasion, or metastasis was found in the paraaortic lymph nodes. The patient didn't undergo immunohistochemical studied on mentioned specimen. The patient's postoperative condition is good clinical outcome with hemodynamically stable.

Discussion

Kidney malignancy in pediatric most commonly occurs as Wilm's Tumor of Nephroblastoma. Meanwhile, renal cell carcinoma (RCC) is a rare kidney malignancy in pediatric. The incidence of RCC increases with age, peaking between the ages of 9 and 15 years, while Wilm's Tumor reaches its peak incidence at the age of 3 years [9]. Although RCC in pediatric is uncommon, its incidence is approximately 2%-6% of all kidney cancers, accounting for about 0.1%-0.3% of all malignancies in pediatrics. The youngest reported patient was 1 year old [3]. In contrast to the pediatric population, RCC is the most common kidney malignancy in adults, accounting for approximately 90% of all kidney cancers and around 2%-3% of all cancers worldwide, with 30% of patients experiencing metastasis [10]. We report a 14-year-old girl with renal cell carcinoma.

Literature of RCC in pediatric has increased in recent years; however, it is still often based on knowledge derived from RCC in adults. Thus, recommendations are often based on retrospective case series with small samples or extrapolated from RCC guidelines for adults. Moreover, pathogenesis of RCC still a developing field. Genetic translocations play a crucial role in the occurrence of RCC in pediatrics, while in adults, smoking, obesity, and high blood pressure increase the risk of RCC [11].

The establishment of RCC in pediatric were based on clinical manifestations, histopathological examination, complemented with immunohistochemical studies, and genetic analysis if available [12]. Most commonly encountered clinical features are flank pain (57%), hematuria (45%), and mass in the flank (38%). The classical triad is only found in 6% of cases, primarily in advanced-stage cases [9,13]. Radiological examinations have limited diagnostic value as it is challenging to differentiate RCC from other kidney malignancies [12]. Our patient showed red urine accompanied by blood clots and intermittent left flank pain for the past 2 years. Abdominal ultrasound revealed a hyperechoic area in the lower pole of the left kidney. Contrast abdominal CT scan indicated severe hydronephrosis and an ill-defined solid mass (5.4 × 3.8 × 3.2 cm) in the left kidney, irregular borders, infiltrating the lower pole, extending to the proximal ureter, adjacent to the renal artery.

Currently, surgical therapy is the most effective treatment, as RCC is resistant to chemotherapy and radiotherapy [14]. Radical nephrectomy for localized RCC is the most effective surgical option. Nephron-sparing surgery (NSS) can be considered for small tumor volumes, as it has the advantage of preserving kidney function and is generally considered safe for obtaining tumor-free margins [14]. At present, radical nephrectomy is the most effective treatment option for RCC. He et al. showed indicates that patients with tumors measuring less than or equal to 4 cm can undergo NSS with satisfactory short-term and long-term outcomes similar to adult patients. The therapeutic value of retroperitoneal lymph node dissection is still considered controversial. However, several studies suggest that retroperitoneal lymph node dissection can improve patient survival and provide accurate pathological staging [3]. Both chemotherapy and radiotherapy do not yield significant results in patients, whether pediatrics or adults, with residual or metastatic RCC, regardless of histopathological findings. Therefore, adjuvant therapy is not recommended for pediatric RCC patients [12]. The therapeutic options for metastatic RCC have rapidly evolved in the last decade, with targeted immunotherapy emerging as a new cornerstone, especially tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors (ICIs) [15,16]. For unresectable and metastatic RCC, the available therapy options are suboptimal due to the lack of guidelines and relatively low overall survival [17]. Our patient was diagnosed with suspected cT3N0M0 upper tract urothelial carcinoma and underwent cystoscopy, bladder cuff excision, and left radical nephroureterectomy with paraaortic lymph node dissection.

RCC in pediatric patients must be differentiated from Wilm's tumor/nephroblastoma, as they require different therapeutic approaches. Wilm's tumor may necessitate chemotherapy and radiotherapy, whereas it is less recommended for RCC. To differentiate between them, an assessment based on the patient's age is crucial; Wilm's tumor/nephroblastoma is most prevalent at the age of 3-4 years, while RCC is most common at the age of 9-15 years. Additionally, distinguishing between the 2 should be based on histopathological examination, immunohistochemistry, and genetic analysis if available.

The prognosis of RCC in pediatrics is similar to that in adults. Several factors influencing prognosis include tumor size, patient's age, the approach of complete excision, the presence or absence of vascular invasion, as well as clinical and pathological staging [9].

Conclusions

RCC is a rare kidney tumor in pediatrics. Surgical therapy is the most effective option, with radical nephrectomy or nephron-sparing surgery (NSS) being suitable for localized RCC. NSS is particularly considered for small tumor volumes, offering the advantage of preserving kidney function and tends to be safe for obtaining tumor-free margins. Further research or reports are strongly recommended for determining more accurate methods of diagnosis, therapy, and prognosis in managing these cases.

Patient consent

Informed consent for patient information to be published in this article was obtained. Appropriate informed consent was obtained for the publication of this case report and accompanying images. This report has been approved by the ethical committee of Dr. Soetomo General-Academic Hospital.