Renal Mass

Etiology

The causes of renal mass are multifactorial. Specifically, studies have found that smoking increases RCC's risk in a dose-dependent fashion with renal cell carcinoma. Other classical precipitation agents such as benzene, herbicides, and vinyl are commonly known to increase carcinoma risk. Furthermore, medications have also been implicated. Results from a prospective study by Cho et al showed that non-steroidal anti-inflammatory drugs correlate with the increased risk of cancer.[3] However, this is the first kind of such study, and further evaluation and validation are needed.

Genetics plays a role in the formation of renal masses as well. The most common example is polycystic kidney disease. In this condition, there are autosomal dominant and autosomal recessive forms. The recessive form is more aggressive and often fatal. Both of these have a high potential for aggressive, malignant kidney masses. Other examples of disorders associated with the development of renal masses include Von Hippel-Lindau and Birth-Hogg Dube syndromes. Interestingly, medical pathologies such as hepatitis C and kidney stones are also associated with RCC.[4][5]

Epidemiology

Kidney and renal pelvic cancers are the 12th most common cancer in the United States (US), with more men affected than women. Mid-age White and Black individuals are equally affected, with Asians being the least affected. US Census found that there were around 7400 cases in 2019. There are approximately 15,000 deaths yearly, with RCC accounting for approximately 80% of those deaths. Overall, renal masses have increased in the past decades because of improved sensitivity and usage frequency of advanced imaging modalities such as MRIs and CTs. Therefore, it is not surprising to find such renal mass in healthy individuals. On the other hand, new malignant kidney mass cases have been holding steady from 2008 to 2016, with the 5-year survival rate steadily improving due to advancements in detection and intervention.

History and Physical

Renal masses are frequently found incidentally without signs or symptoms. The triad of hematuria, flank pain, and flank mass is seen infrequently in modern medicine because they, more likely than not, have already been detected by imaging before symptomatology. The classic triad is observed in approximately 15% of cases, and most of those are in advanced stages. However, if these findings are present, then it warrants further evaluation. New hypertension, unintentional weight loss, and night sweats are nonspecific but essential in elucidating the differential diagnosis. Laboratory findings for anemia, polycythemia, or hypercalcemia are useful in this case. Physical examination should evaluate for varicoceles in the setting of tumor invasion.

History taking should be thorough and explore information such as smoking history, eating habits, exercise status, comorbidities, and exposures to known cancer-causing agents. Literature suggests that obesity, hypertension, and smoking are present in up to 50% of cases.[6] Furthermore, high body mass index, triglyceride, and blood glucose seem to increase RCC risks.[7] Occupation exposures to dye-containing hydrocarbons have long been thought to cause RCC, but recent literature is still inconclusive, requiring further assessment. Family history and comorbidities are significant if positive. Research has linked conditions such as end-stage renal disease to RCC because of the tendency to induce the kidney's cystic formation, leading to aberrant cell formation. Also, patients with a family history of genetic conditions such as polycystic kidney disease are at a higher risk, requiring close monitoring.

Evaluation

Evaluation of renal mass is diverse, depending on the patient's presentation, demographic, and symptomatology. Patients with symptoms and signs such as hematuria, palpable flank mass, or flank pain should be further evaluated. Patients should undergo laboratory tests and advanced imaging such as CT, MRI, and ultrasound. The decision to use CT or MRI depends on the tumor and the patient's clinical characteristics. It is better to use CT when fast imaging acquisition is preferred or there is a contraindication to MRI, such as with patients with metallic implants. In contrast, MRI is preferred for smaller renal lesions' characterization with the benefits of no radiation exposure.

It is essential to evaluate asymptomatic patients with incidental findings of renal mass. Most renal masses are benign, but there is a significant concern for carcinoma. Some signs are notable on advanced imaging to differentiate benign from malignancy. For instance, on a CT scan, fat is less dense than water and soft tissues. Therefore, Hounsfield units of less than -10 to - 20 have more fat content and likely indicate an angiolipoma, a benign tumor.[8] In contrast, a strong enhancement characteristic indicates that the tumor is lipid-poor with a much higher malignancy potential.

If there is a suspicion of renal cell carcinoma, metastasis needs to be evaluated. The most common sites for metastatic RCC are the lung (75%), followed by soft tissues, bone, liver, and brain. It is helpful to evaluate such patients with advanced imaging such as CT chest, CT brain, and bone scan. Laboratory workups include urinalysis, complete blood count, liver function test, calcium, and comprehensive metabolic panel; all are helpful in the examination. A para-neoplastic syndrome is frequently found in RCC; therefore, hyperkalemia and elevated ESR are useful markers in this setting. 

Also, tumor size is an essential consideration in the evaluation. In general, less than 3-4 cm tumor size has lower malignant potential than larger tumors. Up to 40% of 2 cm renal masses are benign, and only a small percentage, 10%, are high-grade RCC.[9][10] In contrast, up to 30% of 4 cm or larger renal masses are high-grade cancer.[11] There is a lower threshold for further evaluation with larger renal masses due to higher malignancy potential.

Treatment / Management

Renal mass management varies depending on multiple factors, including patient size, shape, and renal tumor pathology. Different interventions include close monitoring, biopsy, surgical resection, and thermal ablation. The decision to choose one over another depends on balancing the risks and benefits. As with many other interventions, it is essential to take the age, comorbidities, risk factors, and ESRD status of a patient into consideration. For example, it is beneficial to offer patients a short life expectancy of either surveillance or ablation, depending on tumor characteristics. They are more likely to succumb to their comorbidities or surgery than from the complications of the tumor.

A renal biopsy is indicated when the renal mass characteristic is unrevealing. Significant non-diagnostic results (15%) after a renal biopsy require patients to undergo additional biopsies.[12] There are also risks of hematoma, renal failure, and other complications. Due to its limitation, a biopsy is only indicated in certain situations. Biopsies are commonly performed when a patient is a surgical candidate, and the biopsy results help guide management. Biopsies are also of value to provide tumor pathology. Biopsies are not indicated if the result would not impact management. One typical example of when a biopsy would not be justified is when the mass is less than 1 cm. Please see Renal Biopsy by Michael Young and Stephen Leslie, published via StatPearls, for further discussion. 

Thermal ablation is indicated in patients who are not surgical candidates. It is most useful for a tumor with a size of less than 3 cm. Ablations are less invasive than surgery; however, this increases the risk of recurrence of cancer, the need for close and active surveillance, and the potential for further treatment. Percutaneous Biopsy is recommended for post-procedural surveillance. Surgery is the most definitive intervention for malignant renal masses. The two most common approaches are partial and radical nephrectomy. Partial nephrectomy is preferred as it preserves kidney function compared to radical nephrectomy, especially in patients with chronic kidney disease stage 3 or worse.[13] However, there is an increase in the risk of bleeding in partial nephrectomy. Total nephrectomy should be considered when a tumor has unfavorable pathology or is larger than 5cm.[14](A1)

Active surveillance is indicated in many situations, especially in small masses with benign characteristics. When a tumor is less than 1cm with a gradual growth rate, further imaging and biopsy are not beneficial due to minimal malignant transformation risks. These patients should be offered active surveillance instead. Surveillance should also be offered to patients who are not surgical candidates. An elderly patient with a short life expectancy with a less than 4 cm tumor size is a suitable candidate for active surveillance. Although there is no unified guideline for the frequency of active surveillance, consensus indicates that renal ultrasound, CT, or MRI can be used for monitoring renal mass every 3 to 6 months for the first year. It can be spaced out depending on the renal pathology and progression.[15]

Differential Diagnosis

Whenever there is a renal mass, it is always important to rule out infection and abscess, as antibiotics are required for such treatment. When an infection is ruled out, further investigation is needed for malignant etiologies such as renal cell carcinoma, metastasis, or lymphoma. While investigating malignancies, it is crucial to identify benign tumors such as oncocytoma, angiomyolipoma, or adenoma. These usually require active surveillance, with no interventions needed.

Prognosis

The prognosis for renal mass depends on the tumor identified. RCC accounts for about 15,000 deaths or 80% of kidney and renal pelvic cancers. As with most other cancers, the survival rate improves with early diagnosis and treatment. According to the American Cancer Society, the localized disease in stages 1 and 2 has an above 90% survival rate, while distant metastasis, such as in stage 4, has a 13% 5-year survival rate. In stage 3, the survival rate for patients who underwent nephrectomy is up to 70%. However, invasion into the renal vein indicates a poorer prognosis.[16]

For other types of tumors, classical variant angiomyolipomas have a prolonged growth rate. In one case report, 90% of tumors with a size of less than 1.5 cm have no growth over the 5-year follow-up.[17] The epithelioid variants, however, have a small but significant potential for malignant transformation. A small case series indicates that out of 40 participants, about 9 (26%) have malignant transformation.[18]

Oncocytoma is mostly benign and well organized compared to RCC. They are encapsulated and not invasive. However, RCC can be seen in up to 30% of patients who have oncocytoma. As a result, they should be closely monitored for renal malignancy. A metanephric adenoma is mostly benign; however, it can present similarly to RCC in symptomatology. Patients can present with the classical triad of flank pain, hematuria, and a palpable mass. The critical difference is that they present more frequently in females than males, unlike their RCC counterparts. Histology is the primary way to diagnose this type of mass. Up to 90% of the adenoma have a BRAF V600 mutation.[19] Due to the tumor pathology, there is no surgical indication since it is benign.

Complications

It is vital to balance the risks and benefits of intervention versus surveillance. When surgery is indicated, it is essential to evaluate the risk of infection, bleeding, and renal failure. Therefore, it is essential to assess patients before undergoing invasive procedures. When a patient is not a candidate for surgery, ablation is an option. Although there are fewer complications than surgery, the risk for recurrent, requiring multiple treatment sessions, is higher in the ablation group. Providers must inform patients about the risks and benefits before undergoing interventions.