Diagnostic approach, differential diagnosis, and management of a small renal mass

INTRODUCTION — Small renal masses (SRMs; <4 cm) suspicious for clinical stage T1a renal cell carcinoma (RCC) are among the most common kidney tumors encountered in clinical practice (table 1) [1,2].

The detection of SRMs has increased due to the increased use of imaging tests, such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), performed for unrelated indications [3,4]. Despite the high incidence of such masses, mortality rates from RCC have remained stable or decreased slightly in developed countries.

SRMs of indeterminate significance represent a heterogeneous group of lesions that range from benign masses and cysts to indolent and aggressive malignancies. SRMs and complex cystic masses (typically with a solid enhancing component) are more likely to be malignant and warrant further evaluation. (See 'Differential diagnosis' below.)

The initial evaluation, differential diagnosis, diagnostic approach, and treatment of SRMs suspicious for malignancy will be reviewed here. The approach outlined in this topic is consistent with guidelines from the American Urological Association (AUA) [5,6].

The evaluation of RCC in general and kidney cysts are discussed separately. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma" and "Simple and complex kidney cysts in adults".)

DEFINITION — An SRM suspicious for malignancy is defined as a kidney lesion <4 cm in largest dimension on high-quality, multiphase, cross-sectional abdominal imaging with and without contrast enhancement [5,6]. These lesions are classified as either solid (image 1) or complex cystic (Bosniak class III or IV (table 2)) (image 2) based on their imaging appearance. (See 'Dedicated kidney imaging' below and "Simple and complex kidney cysts in adults".)

Dedicated kidney imaging — Optimal imaging to assess an incidental kidney lesion utilizes dedicated kidney computed tomography (CT) or magnetic resonance imaging (MRI), without and then with intravenous contrast administration.

CT versus MRI — Data suggest that both CT and MRI have similar diagnostic accuracy [7]. SRMs with a cystic component present on the original imaging evaluation can be evaluated using either a dedicated kidney CT scan or MRI. If a CT scan is obtained, the lesion can be characterized using the Bosniak criteria (table 2), which were originally based upon CT findings. If an MRI is obtained, MRI-based criteria for the classification of complex kidney cysts are also available [8].

Ultimately, the choice between CT and MRI for the workup of a complicated cystic or solid kidney mass should be based upon the locally available scanner, managing clinician preference, radiologist expertise, potential contraindications to the various contrast agents, and costs. Other factors that may influence the choice of imaging procedure include the following:

●Features favoring the use of CT

•Rapid image acquisition, which may be a consideration for patients with claustrophobia or other factors that preclude lying still for an MRI, which usually takes 20 to 30 minutes.

•Compatibility with metallic medical implants (eg, pacemakers and orthopedic prostheses), which may preclude MRI.

•Ability to obtain a high-resolution quantitative assessment of enhancement using Hounsfield unit measurements, which can be done with CT but not MRI.

•Dual-energy CT with material attenuation analysis, if available, may be preferred for SRMs, as it decreases false positive rates [9].

●Features favoring the use of MRI

•No exposure to radiation, which may be a particular consideration for younger patients.

•MRI may be better for characterization of SRMs, especially those <2 cm in diameter.

•Use of gadolinium contrast, which has a much lower risk of an allergic reaction and contrast nephropathy compared with intravenous contrast used with CT.

Additionally, most centers allow patients with severe chronic kidney disease or end-stage kidney disease to proceed with dedicated MRI of the kidneys, which is consistent with recommendations from the American College of Radiology [10]. MRI was previously restricted for patients with estimated glomerular filtration rate (GFR) <30 mL/min per 1.73 m² due to concern about nephrogenic systemic fibrosis. However, with the use of next-generation gadolinium-based contrast agents (table 3), which prevent the release of gadolinium from chelating agents, nephrogenic systemic fibrosis is extremely uncommon [11]. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging", section on 'Approach to preventing nephrogenic systemic fibrosis' and "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease", section on 'Prevention'.)

●Other imaging procedures

•Emerging data indicate that contrast-enhanced (microbubble-based) ultrasound may offer another imaging option for patients with severely compromised kidney function.

•While multiphase contrast-enhanced MRI can differentiate the various types of renal cell carcinoma (RCC; eg, clear cell, papillary, or chromophobe) with excellent reader agreement, it is not able to differentiate between clear cell RCCs and oncocytomas [12]. Technetium-99m sestamibi single-photon emission computed tomography (SPECT)/CT imaging has demonstrated promising results in distinguishing renal oncocytoma and hybrid oncocytic/chromophobe tumors, which tend to be very indolent, from clear cell RCC, although these data await large-scale validation [13].

Imaging characteristics — The following imaging-based characteristics are used to describe kidney masses:

●Presence of fat – The presence of fat on CT is characterized as a density measured by Hounsfield units that is less than water or soft tissue (ie, ≤10 Hounsfield units) (image 3). A distinct area with less than -20 Hounsfield units in a kidney mass is diagnostic for angiomyolipoma, which is a benign kidney neoplasm. It can also be detected on MRI by a loss of high T1 signal on fat-suppression sequences [14]. (See "Renal angiomyolipomas (AMLs): Management".)

●Enhancement – Enhancement is characterized on CT as an increase in signal >15 to 20 Hounsfield units after intravenous contrast administration [15]. Enhancement can also be assessed qualitatively on MRI by subtracting the signal intensity on postcontrast images from that on the precontrast images [16]. Absence of enhancement suggests that the lesion is more likely benign, while enhancement suggests a greater risk of malignancy. However, benign oncocytomas often demonstrate enhancement patterns similar to clear cell RCC.

●Characteristics of a cystic component – Cystic lesions are characterized by the Bosniak criteria, which are defined based upon CT findings [17]. Although not yet validated for reader agreement or generalizability [18], these criteria have been widely adopted to classify kidney cysts as definitely benign (type I and II), likely benign (type IIF), or likely malignant (type III and IV). (See "Simple and complex kidney cysts in adults", section on 'Bosniak classification of kidney cysts'.)

●Tumor complexity – In general, tumor complexity describes the size and approximation of the kidney mass to the central or hilar structures of the kidney. A number of objective systems exist to classify complexity, including the RENAL nephrometry score, the Padua Prediction Score, and the C-index. Categorization as low or high complexity may be useful for selection of type of surgery and surgical approach and may also provide an estimate for risk of surgical complications [19-21].

RISK OF MALIGNANCY — SRMs with contrast enhancement or a complex cystic structure are important because of the risk of malignancy. The majority of these lesions are malignant, but a significant proportion are benign and only a small proportion are aggressive malignancies.

Increasing tumor size and male sex are the best predictors of malignancy, higher tumor grade, and higher pathologic stage [22]. For contrast-enhancing SRMs <2 cm, 20 to 40 percent are benign tumors, less than 10 percent are high-grade renal cell carcinoma (RCC), and less than 1 percent will present with or develop metastatic RCC (table 4) [23-25]. By contrast, for kidney masses ≥4 cm, only 5 to 10 percent are benign, and upwards of 20 to 30 percent are high-grade or advanced RCC [25-27].

Females have an approximately two- to threefold increased likelihood of benign pathology compared with males with comparably sized tumors, although the majority of contrast-enhancing SRMs in females are malignant [28]. Central tumor location may also indicate a higher risk of malignancy or aggressive behavior, but this finding has not been rigorously established [29]. Put in context, a female with a peripherally located kidney mass <3 cm has only a 65 percent chance of having RCC and a less than 10 percent risk of harboring unfavorable pathology; a male with a centrally located kidney mass 3 to 4 cm has a 90 percent risk of RCC and a 35 percent risk of unfavorable pathology [30].

While male sex, tumor size, and tumor location have implications for diagnosis, tumor histology, and pathology, there are no clinical or radiographic features of solid or complex cystic masses that accurately predict biologic behavior.

NATURAL HISTORY — The natural history of most contrast-enhancing SRMs is one of very slow progression. A meta-analysis that incorporated retrospective data from 234 SRMs suspicious for malignancy in 11 series demonstrated an average growth rate of only 0.28 cm per year on observation [31]. Prospective active surveillance programs confirm slow growth rates (on the order of 0.1 cm per year) and exceedingly low rates of metastatic progression (<1 percent in two to three years) [32,33].

However, these favorable outcomes likely reflect a selection bias for small tumors and comorbid patients and represent limited follow-up in most series (mean 30 months). In such tumors, long-term local and metastatic recurrence-free survival rates are likely excellent, regardless of the management strategy selected [5,6,34]. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of SRMs that are suspicious for malignancy includes a biologically heterogeneous group ranging from benign tumors to cancers that can be indolent or aggressive [24,35].

Renal cell carcinoma — The majority of contrast-enhancing SRMs are renal cell carcinoma (RCC) [25,36]. The major subclassifications of RCC include, but are not limited to, clear cell, papillary, and chromophobe; each subtype has distinct morphologic appearance, clinical characteristics, and prognostic significance [37]. Clear cell RCC is the most common histology (approximately 55 percent of SRMs), followed by papillary (20 percent) and chromophobe (5 percent) RCC. Clear cell RCCs have a variable prognosis, determined by stage and grade. Papillary and chromophobe RCCs <4 cm generally demonstrate an indolent course and have a better prognosis than clear cell tumors [32,33,35]. (See "Epidemiology, pathology, and pathogenesis of renal cell carcinoma", section on 'Pathology'.)

Benign kidney tumors — Even with a suspicious appearance on initial evaluation, contrast-enhancing SRMs can be benign kidney lesions, and benign lesions are more common in females and with smaller tumors. In a single-institution experience, 311 of 2675 surgically resected tumors were benign [23]. These included oncocytoma (75 percent), angiomyolipoma (11 percent), and metanephric adenoma (3 percent).

Oncocytoma — Oncocytoma typically appears on computed tomography (CT) or magnetic resonance imaging (MRI) as a homogeneous, well-circumscribed solid mass, often containing a central scar [38]. However, these features are not sufficiently specific to exclude RCC. (See "Epidemiology, pathology, and pathogenesis of renal cell carcinoma", section on 'Oncocytomas'.)

Angiomyolipoma — Angiomyolipomas can be reliably distinguished on imaging as an enhancing mass that contains macroscopic fat and no calcifications (image 3). RCC, particularly the clear cell subtype, can contain microscopic fat, but this can be reliably distinguished from macroscopic fat, as seen in most angiomyolipomas. Small angiomyolipomas with minimal fat, designated fat poor, are difficult to characterize on imaging and generally require further evaluation [39,40]. (See "Renal angiomyolipomas (AMLs): Management".)

When renal angiomyolipomas are bilateral, patients have an 80 to 90 percent chance of having tuberous sclerosis. Patients with tuberous sclerosis also have an increased frequency of RCC, as approximately 1 to 2 percent will develop this malignancy; hence, surveillance for RCC should be considered in this population. Kidney imaging in this setting is also needed to follow the progress of the angiomyolipomas, which are at a low but increased risk for hemorrhage as they grow [41]. Kidney manifestations of tuberous sclerosis are complex and their management, including their relationship to RCC, are discussed separately. (See "Renal manifestations of tuberous sclerosis complex".)

Metanephric adenoma — Metanephric adenomas are rare benign lesions that are more common in females than males [42,43]. Although many cases are initially identified incidentally, some patients present with pain, hematuria, or a palpable mass. Metanephric adenomas are defined by a characteristic histology but may be difficult to distinguish from papillary RCC or epithelial predominant Wilms tumor [44]. Approximately 90 percent of metanephric adenomas contain a BRAF V600 mutation [45].

Metastatic disease — If a lesion in the kidney is suspected to be a metastasis and if knowledge of the histology of the kidney lesion could affect management, kidney mass biopsy should be considered. This may be particularly important in patients undergoing surveillance after previous definitive treatment for another malignancy who have a solitary lesion in the kidney or in patients presenting with oligometastatic disease and a suspected metastatic lesion in the kidney. More typically, metastases to the kidney present with multiple kidney lesions with borderline enhancement and widespread metastatic disease.

However, in patients with a history of a cancer that is not RCC, a solitary lesion in the kidney may represent either metastatic disease or a primary kidney tumor. In a series of 2340 patients with a primary cancer other than RCC, 36 (1.5 percent) had a kidney lesion concomitantly diagnosed [46]. Of these, 21 (58 percent) were due to metastatic disease to the kidney; in the remaining 15 (42 percent), there was a concomitant RCC.

Lymphoma — When hematologic malignancy involvement of the kidney is a possibility and the histopathology of the kidney lesion may affect management, percutaneous biopsy should be considered to obtain a pathologic diagnosis.

Kidney involvement with hematologic malignancies is found at autopsy in approximately 34 percent of patients dying of progressive lymphoma or leukemia, but it is uncommon in clinical practice as kidney involvement is often silent and a late manifestation of systemic disease [47]. Kidney lymphoma should be suspected in patients with massive retroperitoneal lymphadenopathy, splenomegaly, or lymphadenopathy in other regions of the body or in atypical regions within the retroperitoneum.

Kidney abscess or focal pyelonephritis — A variety of inflammatory and infectious conditions can mimic RCC and can pose a significant diagnostic challenge [48]. These include acute and chronic pyelonephritis and abscess. Perirenal inflammatory changes are common on axial imaging, and careful interpretation of clinical symptoms (ie, chills, fever, flank pain, pyuria) can aid in the diagnosis [49]. Kidney mass biopsy or aspiration with drain placement can also be utilized in this setting, or patients can be followed with serial imaging that should demonstrate resolution of the suspected mass with appropriate antibiotic therapy. (See "Renal and perinephric abscess".)

MANAGEMENT APPROACH — There is no single approach to the management of SRMs, and management decisions require consideration of all of the patient- and tumor-specific features in an individual case. The primary management options include surgery (generally nephron-sparing surgery), thermal ablation, and active surveillance. Each management strategy has a unique profile of advantages and potential serious harms and risks, including potential deterioration of kidney function.

Initial evaluation — Once an SRM has been characterized as suspicious for malignancy based upon dedicated imaging, multiple factors need to be considered and discussed with the patient when planning the diagnostic and therapeutic approach. This process should be led by a urologist experienced in dealing with kidney masses and should include a multidisciplinary team as indicated. Such a team may include (but is not limited to) nephrology, diagnostic and interventional radiology, pathology, medical oncology, and genetics (table 5 and table 6) [5,6].

●Tumor biology – SRMs suspicious for malignancy often are slow growing, and the risk of metastasis is low even if malignancy is present in the early phases of their natural history.

A comprehensive metabolic panel and complete blood count are indicated as part of the initial evaluation for a possible associated paraneoplastic syndrome, and chest imaging to evaluate for metastatic disease is indicated if malignancy is suspected. While these SRMs are unlikely to develop metastatic disease, a small percentage of patients will present with a small primary lesion and metastatic disease. (See "Clinical manifestations, evaluation, and staging of renal cell carcinoma", section on 'Paraneoplastic symptoms' and "Clinical manifestations, evaluation, and staging of renal cell carcinoma", section on 'Other imaging studies'.)

●Tumor-specific factors – The initial imaging may provide important information regarding the probability of malignancy and the likelihood that malignancy, if present, will be aggressive. For patients who have had a biopsy, histology may provide information about the potential aggressiveness of the tumor.

Factors to consider that are associated with a higher risk of malignancy or with aggressive tumor behavior include the size of the lesion (3 to 4 versus <3 cm), a rapid growth rate of the mass (>5 mm/year, if multiple time points are available), imaging characteristics (infiltrative versus noninfiltrative), and the location of the lesion within the kidney and its accessibility for surgical resection.

•Lesions <1 cm – An incidental lesion <1 cm is unlikely to be further characterized by additional imaging or biopsy, and these patients should be offered surveillance. This size cutoff is accepted by most radiologists and urologists because lesions this small cannot be biopsied and generally have high rates of benign histology. Even for lesions <1 cm that are malignant, almost all will demonstrate indolent tumor biology, with low rates of metastatic progression and slow linear growth rates on active surveillance [24,25,32,33]. Hence, surveillance is the most reasonable course of action for such lesions. (See 'Dedicated kidney imaging' above.)

●Patient-specific factors – Factors such as older age, shorter life expectancy, significant comorbidity or frailty, or increased operative risk may lead to a patient preference for active surveillance or thermal ablation rather than nephron-sparing surgery. Male sex is more likely to be associated with malignancy, although even in females the majority of suspicious SRMs are malignant.

●Complications of treatment – The potential morbidities of each treatment approach need to be discussed with the patient. As examples:

For patients opting for active surveillance, regular follow-up imaging is required, which may lead to the eventual need for therapeutic intervention, as well as the risk for subsequent development of metastases.

For thermal ablation, the patient should be aware of the increased risk of local recurrence, the need for more frequent imaging after treatment, and the potential need for treatment of recurrent disease.

For surgery, both the immediate operative risks as well as the potential late effects on kidney function should be taken into account. As an example, partial nephrectomy is associated with the highest rates of clinically significant bleeding and urologic complications (ie, urine leak) compared with other treatments, although such events are still generally uncommon. Radical nephrectomy is also associated with the highest rates of nonurologic complications (likely related to patient comorbidities) and the greatest changes in kidney function.

●Kidney function – Factors to consider include the risk of future progression to chronic kidney disease, as well as the potential short-term need for dialysis, associated with surgery or thermal ablation. Impaired kidney function or risk factors for chronic kidney disease may lead to a preference for active surveillance or thermal ablation. (See "Definition and staging of chronic kidney disease in adults".)

Kidney function should be assessed for assignment of chronic kidney disease stage if necessary. Serum creatinine and urinalysis will allow for estimation of glomerular filtration rate (GFR) and evaluate for proteinuria. Patients with a positive dipstick test for proteinuria (1 or greater) should undergo confirmation by a quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio) as part of a focused medical workup for kidney dysfunction [50]. Nephrology consultation should be considered for patients with marginal or impaired kidney function.

These factors need to be integrated with the patient's personal preferences and values in determining the therapeutic approach and deciding whether or not to proceed with a kidney mass biopsy.

Examples of how these factors may influence patient decision making include:

●Partial nephrectomy is often preferred for young patients with substantial life expectancy and without significant comorbidity or risk for kidney function impairment who desire definitive treatment. Imaging and/or histologic findings (if a biopsy is performed) may provide additional guidance. Nonetheless, active surveillance may be an appropriate alternative for those wishing to avoid surgery. (See 'Partial nephrectomy' below and 'Active surveillance' below.)

●Older patients and those with significant comorbidity or frailty are more likely to favor active surveillance over immediate therapeutic intervention, particularly if the SRM is <3 cm. Thermal ablation (cryotherapy, radiofrequency ablation) is an alternative that has a lower risk of complications than surgical excision, but it can be associated with increased local recurrence rates. (See 'Active surveillance' below and 'Ablative techniques' below.)

Genetic counseling — Genetic counseling to assess for a hereditary kidney cancer syndrome (table 7) is recommended for the following clinical scenarios:

●All patients with kidney cancer ≤46 years of age.

●Multifocal or bilateral lesions.

●A personal or family history suggesting an inherited kidney cancer syndrome.

●A first- or second-degree relative with a history of kidney cancer or a known clinical or genetic diagnosis of a hereditary kidney cancer syndrome (even if kidney cancer has not been observed).

●If the patient's pathology demonstrates histologic findings suggestive of a hereditary kidney cancer syndrome.

The presence of an inherited kidney cancer syndrome may be associated with other tumor types or clinical conditions. Some inherited kidney cancer syndromes are associated with an increased risk of a second kidney primary tumor; therefore, early diagnosis is important for maintaining as much kidney function as possible. Hereditary kidney cancer also has clinical implications for the patient's family members. Further details on hereditary kidney cancer syndromes are discussed separately. (See "Hereditary kidney cancer syndromes".)

Kidney mass biopsy — A percutaneous needle biopsy of a suspicious SRM can provide important information about the nature of the kidney lesion in many cases, which can influence counseling and management [5,6,51]. However, biopsy is not required in all cases, depending on the potential therapeutic approaches under consideration (table 8).

Biopsy is usually performed as an outpatient procedure under computed tomography (CT) or ultrasound guidance with conscious sedation and/or local anesthesia. Percutaneous biopsy is generally safe with a low risk of complications such as hematoma, pain, gross hematuria, pneumothorax, and hemorrhage [52]. Seeding of the needle tract with malignant cells has also been described during kidney mass biopsies but is relatively uncommon [53].

A biopsy may help distinguish the histologic subtype and aggressiveness of a tumor and, thus, help guide management. In the absence of a definitive diagnosis, the mass should be managed as a renal cell carcinoma (RCC).

Biopsy is indicated:

●Whenever the pathology of the kidney lesion is unclear and ascertainment of the etiology of the mass will influence subsequent management. This includes but is not limited to situations where the SRM is suspected to be a metastatic lesion, a manifestation of lymphoma (image 4), or of infectious or inflammatory origin rather than a primary kidney tumor.

●For patients who will be managed with thermal ablation, ideally as a separate procedure, to provide a pathologic diagnosis and to assist in guiding subsequent surveillance.

●In patients who are surgical candidates when confirmation of malignancy is desired by the patient or the surgeon prior to the procedure or if further information may help in the decision-making process.

Biopsy is generally not indicated as part of the initial evaluation:

●In young and healthy patients who are not willing to accept the potential uncertainties associated with a false-negative result on kidney mass biopsy and who will choose surgery even if the biopsy is negative for cancer.

●For older or frail individuals who will initially be managed with surveillance rather than surgery or thermal ablation regardless of the outcome of a kidney mass biopsy.

●For SRMs <1 cm and cystic kidney masses, the nondiagnostic rates are significantly higher than for larger solid masses, and the rates of aggressive malignancy are much lower, limiting the utility of kidney mass biopsy in these patients.

In a systematic review of the literature that included data from 2979 patients, kidney mass biopsy had an excellent specificity (96.2 percent), sensitivity (97.5 percent), and positive predictive value (99.8 percent), indicating that a diagnosis of cancer is highly reliable [52].

However the clinical utility of kidney mass biopsy is limited by a significant nondiagnostic rate (14 to 15 percent), significant negative predictive value (63 percent, indicating that a benign biopsy does not always indicate the absence of cancer), and poor grade concordance for high-grade disease. In addition, many kidney mass biopsy specimens are read as an "oncocytic renal neoplasm," which is somewhat indeterminate. When surgery is performed for such lesions, most prove to be benign oncocytoma or low-grade, indolent variants of kidney cancer [5,6].

A biopsy can render a definitive diagnosis for RCC and benign masses, including angiomyolipoma, metanephric adenoma, or focal infection. However, a diagnosis of oncocytoma, while reassuring, should be viewed with caution, as chromophobe RCC can result in a similar appearance on needle biopsy [54]. If the biopsy yields a nondiagnostic or nonspecific result, a repeat biopsy is a reasonable option. Core needle specimens are preferred and have demonstrated superior diagnostic rates compared with fine needle aspiration [52]. Biopsy or aspiration of complex cystic masses is generally discouraged due to the risk of spillage [5,6,52].

MANAGEMENT OPTIONS — There is no single approach to the management of SRMs, and management decisions should be made in conjunction with patient counseling based on patient-specific assessment of the oncologic risk of the SRM, the general health and comorbidities, and the efficacy and risk of each intervention, taking into special consideration kidney function (table 5) [5,6]. (See 'Management approach' above.)

Partial nephrectomy — Surgical removal of the tumor with preservation of normal kidney parenchyma (nephron-sparing surgery) is the preferred management strategy for SRMs suspicious for malignancy in patients who are candidates for definitive treatment (table 9) [5,6]. (See "Definitive surgical management of renal cell carcinoma".)

Partial nephrectomy is associated with favorable oncologic outcomes and minimizes the risk of chronic kidney disease or progressive chronic kidney disease [55]. Partial nephrectomy has the highest risk of perioperative bleeding (approximately 1 to 2 percent incidence) or urinoma formation (approximately 3 to 5 percent incidence) compared with other management options, although the absolute rates are relatively low when performed at experienced centers. Such complications are almost always manageable with conservative measures and typically are associated with good outcomes [5,6].

Surgical removal of the entire kidney (ie, radical nephrectomy) is an acceptable option for the management of an SRM when tumor size, kidney mass biopsy, or imaging characteristics (eg, infiltrative appearance) indicate increased oncologic potential. In this setting, radical nephrectomy is preferred if all of the following criteria are also met [5,6] (table 9):

●High tumor complexity such that a partial nephrectomy would be technically challenging (even in experienced hands).

●No preexisting chronic kidney disease or proteinuria.

●Normal contralateral kidney and new baseline glomerular filtration rate (GFR) will likely be >45 mL/min/1.73 m² even if radical nephrectomy is performed.

Patients who do not meet all these criteria should alternatively be evaluated for partial nephrectomy unless there are overriding concerns about the safety and oncologic efficacy of partial nephrectomy.

A randomized study demonstrated no difference in oncologic outcomes and small differences in kidney function in over 500 patients randomized to partial and radical nephrectomy with tumors 5 cm or smaller [56,57]. Importantly, patients in this study were in good general health with excellent preoperative kidney function.

Systematic reviews of the surgical literature consistently report lower estimated glomerular filtration rates (eGFRs) and higher rates of stage 3 or worse chronic kidney disease in patients undergoing radical nephrectomy [34,55]. In general, radical nephrectomy should be avoided for SRMs, but it may be needed in a small minority of patients with masses involving a more central position in the kidney (eg, hilar location) or infiltrative features on imaging. (See "Definitive surgical management of renal cell carcinoma", section on 'Radical versus partial nephrectomy'.)

Ablative techniques — Thermal ablation (cryotherapy or radiofrequency ablation) is an alternative to partial nephrectomy for patients who do not want or are not able to tolerate definitive surgery and who have an SRM <3 cm (table 10). (See "Radiofrequency ablation, cryoablation, and other ablative techniques for renal cell carcinoma".)

Ablation of a kidney mass can be accomplished by either freezing (cryoablation) or heating (radiofrequency ablation). A needle biopsy of the kidney mass prior to or concomitant with thermal ablation is strongly encouraged to determine diagnosis and guide surveillance [5,6]. Laparoscopic or percutaneous approaches are feasible, although the favorable perioperative outcomes associated with thermal ablation are likely driven by the percutaneous approach.

Percutaneous thermal ablation is typically carried out as an outpatient procedure under conscious sedation and requires a needle applicator to be placed under imaging guidance. After ablation, all patients with malignancy should undergo surveillance to assess for residual or recurrent tumor that would require additional therapy. Thermal ablation is most efficacious in masses <3 cm, where oncologic outcomes are best and complications are less common [5,6].

A systematic review of the literature demonstrates a higher rate of local recurrence or persistence with thermal ablation, so in general, partial nephrectomy is preferred when intervention is elected. With thermal ablation, the five-year lesion recurrence-free rate was 93.5 percent. However, recurrence/persistence after thermal ablation can often be managed with repeat ablation, and when this is taken into account, the outcomes approach those achieved with surgery [34,58,59]. Overall, the five-year lesion recurrence-free rate for thermal ablation is approximately 94 percent. The most common complication is ureteral injury [5,6].

A number of extracorporeal ablative modalities are also being studied, including stereotactic body radiation therapy (SBRT), microwave treatment, and electroporation, but the data regarding these modalities are preliminary, and they are still best considered investigational [60]. Additional experience will be required to determine the role of these approaches compared with other ablative techniques.

Active surveillance — For patients with an SRM <1 cm, we suggest active surveillance rather than immediate treatment.

For patients with an SRM between 1 and 4 cm, active surveillance is an alternative management approach, particularly for those with masses that are thought to be lower risk (eg, <2 cm or those that are predominantly cystic, which tend to be nonaggressive). This option is suitable for such patients who prefer to avoid treatment-induced complications and would tolerate regular imaging studies. Active surveillance is preferred whenever the risks associated with intervention or the competing risks of death outweigh the potential oncologic benefits of active treatment (table 11).

Given the indolent biology of most contrast-enhancing SRMs, active surveillance is now considered an acceptable initial management strategy for any patient (regardless of age or comorbidity) with an SRM <2 cm [61], and after evaluating age, comorbidities, suitability for surgery, and patient preferences, it is an option for patients with an SRM up to 4 cm [5,6].

While active surveillance protocols have yet to be validated, recommendations for surveillance include initial high-quality axial imaging and baseline metastatic evaluation (labs and chest imaging). Serial imaging (computed tomography [CT], magnetic resonance imaging [MRI], or ultrasound) of the kidney lesion every three to six months is used to establish an acceptable linear growth rate (less than 0.5 cm per year); annual imaging is then recommended every 6 to 12 months after the initial two years of surveillance. Although rare in SRMs, imaging findings that suggest tumor infiltration (eg, invasion of the renal sinus, collecting system, or a branch vein) would also warrant further evaluation for treatment.

A meta-analysis of retrospective data and prospective active surveillance programs demonstrated slow linear growth rates (0.1 cm per year on average), low rates of surgical intervention (10 to 15 percent), and exceedingly low rates of metastatic progression in appropriately selected patients with SRMs [32]. Other observational studies also confirm these findings and report average linear growth rates of approximately 0.1 to 0.3 cm per year [62-66].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cancer of the kidney and ureters".)

SUMMARY AND RECOMMENDATIONS

●Definition of small renal mass – A solid, enhancing kidney lesion less than 4 cm in largest dimension on high-quality, multiphase, cross-sectional abdominal imaging with and without contrast enhancement meets criteria for a small renal mass (SRM) suspicious for clinical T1a renal cell carcinoma (RCC) (table 1), as does a Bosniak class III/IV cystic lesion (table 2). (See 'Definition' above.)

●Differential diagnosis – The majority of such SRMs are RCCs. However, a significant number of such lesions are benign, and other processes (metastases, inflammation, infection) can also present in this fashion. (See 'Differential diagnosis' above.)

●Initial evaluation

•Imaging – The initial evaluation should include dedicated kidney imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) in addition to a baseline assessment for metastatic disease and kidney function (table 6). (See 'Dedicated kidney imaging' above.)

•Indications for biopsy – Percutaneous kidney mass biopsy may be indicated when there is uncertainty about the diagnosis or when knowledge of histology may influence subsequent management; in addition, such a biopsy can often provide additional information about the histology of a primary kidney tumor (table 8). (See 'Kidney mass biopsy' above.)

●Management – Multiple factors need to be considered when planning the diagnostic and therapeutic approach for an individual patient, and these factors should be integrated with the patient's personal preferences and values (table 5). These include tumor-specific factors, patient-specific factors, potential complications of treatment, and kidney function, as well as the natural history of T1a RCCs. (See 'Initial evaluation' above.)

This multidisciplinary process should be led by a urologist experienced in dealing with kidney masses and should take into account the oncologic risks, functional considerations, risk of death from competing causes, comparative harms of intervention, and patient preferences (table 5 and table 9 and table 10 and table 11).

●Small renal mass <1 cm – For patients with an SRM <1 cm, we suggest active surveillance rather than immediate treatment (Grade 2C). (See 'Active surveillance' above.)

●Small renal mass between 1 and 4 cm

•Partial nephrectomy – For otherwise healthy patients with an SRM between 1 and 4 cm, we suggest partial nephrectomy rather than ablation or active surveillance (Grade 2C). (See 'Partial nephrectomy' above.)

However, in the setting of limited data and given the overall good prognosis regardless of management strategy, patients may reasonably opt for one of the alternatives such as:

-Active surveillance – Some patients may opt for active surveillance, particularly for those with masses thought to be a lower risk (eg, <2 cm or predominantly cystic). This option is suitable for such patients who prefer to avoid treatment-induced complications and would tolerate regular imaging studies (table 11). (See 'Active surveillance' above.)

-Ablation – Patients with an SRM <3 cm may reasonably opt for ablation over partial nephrectomy if they prefer a lower complication rate and would tolerate the possibility of needing repeat intervention. (See 'Ablative techniques' above.)

●Patients with limited life expectancy or comorbidities – For patients with a limited life expectancy or comorbidities, we generally pursue active surveillance, although ablation may be an option for some such patients with tumors <3 cm. (See 'Active surveillance' above and 'Ablative techniques' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Shauna Duigenan, MD, FRCPC, and Susanna Lee, MD, PhD, who contributed to an earlier version of this topic review.