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Clinical presentation, diagnosis, and staging of renal

cell carcinoma
AUTHOR: Michael B Atkins, MD
SECTION EDITOR: Jerome P Richie, MD, FACS
DEPUTY EDITOR: Sonali M Shah, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2024.

This topic last updated: Sep 04, 2024.

INTRODUCTION

Malignant neoplasms involving the kidney may be primary or secondary tumors. Secondary
renal neoplasms are usually clinically insignificant and discovered at postmortem
examination.

Renal cell carcinomas (RCCs), which originate within the renal cortex, constitute 80 to 85
percent of primary renal neoplasms. Transitional cell carcinomas of the renal pelvis are the
next most common (approximately 8 percent). Other parenchymal epithelial tumors, such as
oncocytomas, collecting duct tumors, and renal sarcomas, are rare. Nephroblastoma or
Wilms tumor is common in children (5 to 6 percent of all primary renal tumors). (See
"Epidemiology, pathology, and pathogenesis of renal cell carcinoma" and "Malignancies of
the renal pelvis and ureter".)

The clinical presentation, diagnosis, staging, and the methods used for screening of RCC will
be reviewed here. The prognosis and treatment of RCC are discussed separately. (See
"Prognostic factors in patients with renal cell carcinoma".)

CLINICAL PRESENTATION

Patients with RCC can present with a range of symptoms; unfortunately, many patients are
asymptomatic until the disease is advanced. At presentation, approximately 25 percent of
individuals either have distant metastases or advanced locoregional disease [1].
Patients with localized disease can present with a wide array of symptoms and/or laboratory
abnormalities, or they may be diagnosed incidentally. In one review of 309 consecutive
patients with RCC, the most common presenting symptoms were hematuria, abdominal
mass, pain, and weight loss [2]. In contemporary series, fewer patients have the typical
symptoms and there is an increased frequency of incidental diagnosis due to radiologic
procedures performed for other indications [3]. (See "Epidemiology, pathology, and
pathogenesis of renal cell carcinoma", section on 'Epidemiology' and "Diagnostic approach,
differential diagnosis, and management of a small renal mass".)

This shift in pattern of presentation along with improvements in therapy have contributed to
better outcomes in RCC. In a series of 701 patients, those who were diagnosed incidentally
had a significantly better disease-specific survival at five years (76 versus 44 percent in those
with symptoms) [4]. Multivariate analysis showed that the difference was due to the lower
stage and histologic grade at the time of diagnosis. (See "Systemic therapy for advanced and
metastatic clear cell renal carcinoma".)

Symptoms and signs — For patients not diagnosed incidentally, symptoms and signs are
generally related to invasion of adjacent structures or distant metastases.

● The classic triad of RCC (flank pain, hematuria, and a palpable abdominal renal mass)
occurs in at most 9 percent of patients; when present, it strongly suggests locally
advanced disease [2,5].

● Hematuria is observed only with tumor invasion of the collecting system. In an early
series, hematuria was observed in almost 40 percent of patients [6]. When severe, the
bleeding can cause clots and "colicky" discomfort. Clot formation does not occur with
glomerular bleeding; thus, the presence of clots is a significant finding in patients with
otherwise unexplained hematuria. (See "Evaluation of hematuria in adults", section on
'Glomerular versus nonglomerular hematuria'.)

● An abdominal or flank mass, which is associated with lower pole tumors, is more
commonly palpated in the thin adult. The mass is generally firm, homogeneous,
nontender, and moves with respiration.

● Scrotal varicoceles, the majority of which are left sided, are observed in as many as 11
percent of males with RCC [7]. Varicoceles typically fail to empty when the patient is
recumbent. This finding should always arouse suspicion for a kidney tumor that has
obstructed the gonadal vein where it enters the renal vein.

● Inferior vena cava involvement can produce a variety of clinical manifestations,

including lower extremity edema, ascites, hepatic dysfunction (possibly related to a
Budd-Chiari syndrome), and pulmonary emboli.
 ● Among patients with disseminated disease, signs or symptoms may be due to
metastatic tumor; the most common sites of involvement include the lungs, lymph
nodes, bone, liver, adrenal glands, and brain [8]. Thyroid and pancreatic metastases are
typically associated with more indolent tumor biology [8-10]. Gastrointestinal
metastases to the stomach or small bowel are rare but can occur several years after
initial diagnosis [11]. In this setting, the diagnosis is often made by biopsy of an
accessible metastasis in the setting of a renal mass on abdominal computed
tomography (CT). (See "Surveillance for metastatic disease after definitive treatment for
renal cell carcinoma", section on 'Sites of metastasis'.)

Paraneoplastic symptoms — Patients with RCC can present with or subsequently develop
systemic symptoms or paraneoplastic syndromes [12-14]. In some instances, these may be
due to ectopic production of various hormones (eg, erythropoietin, parathyroid hormone-
related protein [PTHrP], gonadotropins, human chorionic somatomammotropin, an
adrenocorticotropic hormone [ACTH]-like substance, renin, glucagon, insulin) [14].

Anemia — Anemia, which can precede the diagnosis of RCC by several months, has been
reported in 29 to 88 percent of patients with advanced disease [7,14-16]. The anemia is often
disproportionately severe, can be either normocytic or microcytic, and is frequently
associated with iron studies typical of those observed with the anemia of chronic disease.
(See "Anemia of chronic disease/anemia of inflammation".)

Hepatic dysfunction — Hepatic dysfunction is an uncommon occurrence in patients with

RCC, which is called Stauffer syndrome when it occurs in the absence of liver metastases [17-
19]. In a series of 365 patients, 21 percent had a paraneoplastic elevation in serum alkaline
phosphatase [19].

When hepatic dysfunction is present, it frequently is associated with fever, weight loss,
fatigue, and a poor prognosis [20]. The dysfunction may result from tumor production of
cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and possibly
interleukin 6 (IL-6) [21-23].

Nephrectomy may result in the amelioration of hepatic dysfunction [17,18]. Recurrent

elevations of liver enzymes in such patients may herald local recurrence or distant metastatic
disease [19].

Fever — Fever, which occurs in up to 20 percent of patients, is usually intermittent and is

frequently accompanied by night sweats, anorexia, weight loss, and fatigue [14,24]. Its origin
is unclear [14].

Hypercalcemia — Hypercalcemia occurs in up to 15 percent of patients with advanced RCC

and can result from a number of different mechanisms:
 ● Lytic bone metastases.

● Overproduction of PTHrP [25-28]. Concurrent production of IL-6 may enhance the

action of PTHrP [29,30].

● Increased production of prostaglandins that promote bone resorption [31,32]. In such

patients, the hypercalcemia can respond to administration of a nonsteroidal anti-
inflammatory drug (NSAID), such as indomethacin [31].

The pathogenesis and management of hypercalcemia in patients with malignancy are

discussed elsewhere. (See "Hypercalcemia of malignancy: Mechanisms" and "Treatment of
hypercalcemia" and "Osteoclast inhibitors for patients with bone metastases from breast,
prostate, and other solid tumors".)

Cachexia — As with other tumors, patients with RCC may suffer from significant cachexia
[14]. (See "Pathogenesis, clinical features, and assessment of cancer cachexia".)

Erythrocytosis — Erythrocytosis occurs in 1 to 5 percent of patients with advanced RCC and

appears to be due to constitutive production of erythropoietin [33]. In addition, since the
mutated von Hippel-Lindau protein is associated with impaired regulation of hypoxia-
induced proteins [34,35], erythrocytosis may be directly related to impaired degradation of
hypoxia-inducible transcription factors under normoxic conditions. (See "Regulation of
erythropoiesis" and "Epidemiology, pathology, and pathogenesis of renal cell carcinoma".)

Secondary (AA) amyloidosis — Secondary (AA) amyloidosis is found in up to 5 percent of

patients [36,37]. This finding reflects a chronic inflammatory response as the amyloid fibrils
are composed of fragments of the acute phase reactant serum amyloid A protein. (See "AA
amyloidosis: Pathogenesis".)

Thrombocytosis — Thrombocytosis is rare in patients with RCC, but its presence is

associated with a poor prognosis [38,39]. The underlying mechanism is not firmly
established but could be related to IL-6 production by the tumor.

Polymyalgia rheumatica — A syndrome resembling polymyalgia rheumatica has been

reported with RCC [40]. In contrast to idiopathic disease, the symptoms do not respond to
prednisone but are often corrected by nephrectomy. (See "Clinical manifestations and
diagnosis of polymyalgia rheumatica".)

DIAGNOSTIC EVALUATION

Patients with unexplained hematuria or other symptoms, signs, or findings suggestive of

possible RCC must undergo imaging evaluation for the presence of a renal mass. In addition,
incidental diagnosis of RCC is becoming more common due to the frequent use of abdominal
computed tomography (CT) and/or ultrasonography for evaluation of an unrelated problem.
(See "Evaluation of hematuria in adults" and "Diagnostic approach, differential diagnosis,
and management of a small renal mass".)

CT or ultrasonography — The usual first test is abdominal computed tomography (CT)

( image 1) or, occasionally, abdominal ultrasound.

Although ultrasonography is less sensitive than CT in detecting a renal mass, it is useful to

distinguish a simple benign cyst from a more complex cyst or a solid tumor. The issues
surrounding the evaluation of an asymptomatic renal mass or a cyst are discussed in detail
separately. (See "Simple and complex kidney cysts in adults" and "Diagnostic approach,
differential diagnosis, and management of a small renal mass".)

Summarized briefly, there are three major criteria that allow a simple cyst to be
differentiated from a tumor or abscess on ultrasonography ( table 1):

● The cyst is round and sharply demarcated with smooth walls

● There are no echoes within the cyst ("anechoic")
● There is a strong posterior wall echo, indicating good transmission through a cyst

If all of these criteria are fulfilled, no further evaluation is necessary since the likelihood of a
malignancy is extremely small. If the criteria for a simple cyst by ultrasonography are not
satisfied, the patient should undergo CT before and after injection of iodinated contrast. On
CT, a simple cyst has a smooth appearance without a clearly delineated wall, has no
enhancement with intravascular contrast, and is the density of water. CT urography allows
imaging of both the renal parenchyma and the collecting system.

By comparison, thickened irregular walls or septa ( image 2) and enhancement after

contrast injection are suggestive of malignancy ( table 1). (See "Simple and complex kidney
cysts in adults", section on 'Bosniak classification of kidney cysts'.)

MRI — Magnetic resonance imaging (MRI) may be useful when ultrasonography and/or CT
are inconclusive or if iodinated contrast cannot be administered because of allergy or poor
renal function ( image 3 and image 4). MRI is particularly helpful in cases where a
neoplasm is diagnosed as it evaluates for tumor growth into the collecting system or the
vessels better than the other modalities. (See "Simple and complex kidney cysts in adults",
section on 'Category IIF' and "Definitive surgical management of renal cell carcinoma".)

MRI with dynamic gadolinium contrast may be useful in distinguishing papillary or clear cell
RCC from other benign and malignant solid renal neoplasms, although the examination does
not obviate the need for tissue for diagnosis. In a meta-analysis, contrast enhancement in
the corticomedullary phase on MRI diagnosed papillary RCC with a pooled sensitivity of 86
percent (95% CI 68-94 percent) and specificity of 92 percent (95% CI 76-98 percent) [41]. In
one large series, clear cell carcinoma was diagnosed with a sensitivity of 85 percent and
specificity of 76 percent [42].

Angiography — Catheter-based renal angiography is rarely necessary. If preoperative

mapping of the vasculature is required prior to possible nephron-sparing surgery, either CT
or MR angiography is preferable.

What is the role of biomarkers (pKIM-1)? — Plasma kidney injury molecule-1 (pKIM-1) is a
biomarker that is expressed by clear cell and papillary RCCs. Observational studies suggest
that pKIM-1 can be used to distinguish between RCC and benign kidney masses and that
higher prenephrectomy levels of pKIM-1 are associated with worsened metastasis-free and
overall survival [43]. However, further studies are necessary prior to incorporating the use of
pKIM-1 into the routine diagnostic and prognostic evaluation of RCC.

TISSUE DIAGNOSIS

For patients with localized disease, nephrectomy or partial nephrectomy is used in most
cases to obtain tissue for diagnosis of RCC. For patients presenting with metastatic disease
who plan to omit or defer cytoreductive nephrectomy, establishing diagnosis via a biopsy of
a metastasis is preferred. After the presumptive diagnosis has been made based upon
imaging studies, the patient must be evaluated for the extent of local involvement and the
presence of metastatic disease prior to surgery. (See 'Staging studies' below.)

In addition to establishing the diagnosis of malignancy, tissue diagnosis provides

information about the histopathologic type of RCC, which may have important implications
for prognosis and treatment. (See "Epidemiology, pathology, and pathogenesis of renal cell
carcinoma", section on 'Pathology'.)

The role of percutaneous biopsy is more limited, although it may be used for a small renal
mass if there is a high index of suspicion for a metastatic lesion to the kidney, lymphoma, or
a focal kidney infection. A biopsy can also be used to confirm a diagnosis of RCC in patients
who are not surgical candidates, although biopsy of a metastatic lesion, if present, is often
preferable. (See "Diagnostic approach, differential diagnosis, and management of a small
renal mass".)

STAGING STUDIES

Abdominal CT — The extent of local and regional involvement is determined primarily by

abdominal computed tomography (CT), which is extremely accurate in staging RCC. In a
retrospective study of 100 RCCs, for example, preoperative CTs were compared with the
findings obtained at surgery [44]. The following results were obtained:
 ● For the detection of renal vein invasion, CT was 78 percent sensitive and 96 percent
specific.

● For the detection of metastatic adenopathy, CT was 83 percent sensitive and 88 percent
specific.

● For the detection of perinephric invasion, CT was only 46 percent sensitive but was 98
percent specific.

● For the detection of adjacent organ invasion, CT was 100 percent specific.

The sensitivity and specificity of CT for detecting nodal metastasis depend upon the size
criterion used to define suspicious nodes. At least some data suggest that approximately 50
percent of patients with radiographically enlarged nodes in the 1 to 2 cm size range do not
harbor metastases [45].

The limitations of imaging for the detection of renal vein or perinephric invasion may result
in upstaging in patients who undergo nephrectomy. In a series of 1448 patients with clinical
T1 lesions, 134 (9 percent) were upstaged to pathologic T3a disease [46]. Patients with
pathologic T3a disease had a worse three-year recurrence-free survival compared with those
with pathologic T1 disease (76 versus 93 percent).

Other imaging studies — Other imaging studies that may be useful for assessing for
distant metastases include bone scan, CT of the chest, magnetic resonance imaging (MRI),
and positron emission tomography (PET)/CT:

● Bone scan – Bone scan is indicated only in patients with bone pain and/or an elevated
serum alkaline phosphatase. In one series, for example, less than 5 percent of such
patients had occult bone metastases [47]. Bone scan can be falsely negative since bone
metastases are frequently osteolytic rather than osteoblastic.

● Chest CT or radiograph – CT of the chest is useful to evaluate for evidence of

pulmonary or mediastinal lymph node metastases. Alternatively, patients with a small
renal mass may be offered a chest radiograph. (See "Diagnostic approach, differential
diagnosis, and management of a small renal mass", section on 'Definition'.)

● MRI – MRI scanning with gadolinium is superior to CT for evaluation of the inferior
vena cava and right atrium when tumor involvement is suspected [48].

● PET/CT – PET scanning has high sensitivity and specificity for the primary lesion.
Although PET/CT may be more sensitive than radionuclide scanning for the detection of
bone metastases, it is expensive and has limited use for routine staging [49-51].

Pathology
 Isolated renal mass — For patients with isolated solid renal masses, resection with either a
partial or complete nephrectomy is preferred over biopsy because it provides the diagnosis,
pathologic tumor (T) and nodal (N) staging ( table 2), and definitive treatment.
Preoperative needle biopsies are usually not used for resectable renal lesions because of
their low specificity [52] and concerns about tumor seeding of the peritoneum.

Although solid renal masses less than 3 cm were once thought to represent benign
adenomas, distinctions based upon size are no longer used, since even small tumors
frequently represent carcinomas that will grow over time [53]. Most solid renal masses
require a histologic diagnosis; in patients with significant comorbidities, "watchful waiting"
might be appropriate. (See "Diagnostic approach, differential diagnosis, and management of
a small renal mass" and "Simple and complex kidney cysts in adults".)

Metastatic disease — When metastatic disease is suspected at initial presentation,

pathologic confirmation is required prior to starting therapy. Biopsy of a metastatic site is
often easier and more informative than biopsy of the primary tumor.

In patients with a previously diagnosed nonrenal malignancy, metastatic disease is more

likely than a new primary RCC. If the renal mass is nonenhancing and there is clinical
evidence of progression of the nonrenal malignancy, biopsy confirmation may be
unnecessary [54].

● Is there a role for upfront cytoreductive nephrectomy in staging? – The role of

upfront cytoreductive nephrectomy is evolving in the era of effective treatments such
as checkpoint inhibitor immunotherapy and antiangiogenic agents for patients with
metastatic RCC ( algorithm 1).

In general, initial cytoreductive nephrectomy may be indicated in select patients with

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)-favorable
or low-intermediate risk features (ie, no or one risk factor) ( table 3). Palliative
cytoreductive nephrectomy may also be indicated in those experiencing symptoms
from the primary tumor (eg, pain, intractable hematuria). Further details on the
approach to cytoreductive nephrectomy and supporting randomized trial data in
patients with metastatic clear cell RCC are discussed separately. (See "Role of surgery in
patients with metastatic renal cell carcinoma", section on 'Cytoreductive nephrectomy'
and "Role of surgery in patients with metastatic renal cell carcinoma", section on
'Palliative nephrectomy'.)

For those with IMDC-high-intermediate or poor risk features (≥2 risk factors)
( table 3), initial systemic therapy is indicated, and a decision about cytoreductive
nephrectomy should be delayed until more information about disease responsiveness
and treatment tolerability is available. (See "Systemic therapy for advanced and
 metastatic clear cell renal carcinoma" and "Antiangiogenic and molecularly targeted
therapy for advanced or metastatic clear cell renal carcinoma".)

TNM STAGING SYSTEM

The eighth (2017) Tumor, Node, Metastasis (TNM) staging system is used for staging all
histologic variants of RCC. This system is supported by both the American Joint Committee
on Cancer (AJCC) and the International Union for Cancer Control (UICC) [55]. These TNM
criteria use the anatomic extent of disease to define prognostic stage groups. (See
"Prognostic factors in patients with renal cell carcinoma".)

The TNM system is shown in the table ( table 2). In this system, tumors limited to the
kidney are classified as T1 or T2 based upon size. T3 tumors extend into the renal vein or
perinephric tissues but not beyond the Gerota fascia, while T4 tumors extend beyond the
Gerota fascia, including direct extension into the ipsilateral adrenal gland. Nodal and distant
metastases are simply classified as absent or present.

SOLID RENAL MASSES

The optimal management of solid renal parenchymal masses is incompletely understood

and relies upon both the ability of imaging studies to identify simple renal cysts and the
likelihood of the lesion to exhibit clinically malignant behavior. The evaluation and initial
management of a patient with a solid renal mass are discussed separately. (See "Diagnostic
approach, differential diagnosis, and management of a small renal mass".)

SCREENING

Screening of asymptomatic individuals is not recommended because of the low prevalence

of RCC in the general population. However, individuals at high risk for the development of
RCC should undergo periodic monitoring with abdominal ultrasonography, computed
tomography (CT), or magnetic resonance imaging (MRI) to detect early disease [56].

Candidates for screening include patients with any of the following conditions:

● Inherited conditions associated with an increased incidence of RCC or other renal

tumors, including Von Hippel-Lindau syndrome and tuberous sclerosis. (See "Clinical
presentation, diagnosis, and surveillance of von Hippel-Lindau disease" and "Kidney
manifestations of tuberous sclerosis complex" and "Tuberous sclerosis complex: Clinical
features".)
 ● End-stage kidney disease, especially younger subjects without serious comorbid
diseases who have been on dialysis for three to five years or more.

● A strong family history of RCC. (See "Hereditary kidney cancer syndromes".)

● Prior kidney irradiation.

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".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

● Beyond the Basics topic (see "Patient education: Renal cell carcinoma (kidney cancer)
(Beyond the Basics)")

SUMMARY

● Clinical manifestations – Patients with renal cell carcinoma (RCC) can present with a
range of symptoms due to the tumor itself (eg, mass, pain), invasion of the urinary tract
(eg, hematuria), paraneoplastic syndromes, or the presence of metastases. In addition,
RCC is more frequently being diagnosed incidentally as a consequence of increased use
of imaging procedures for other reasons. (See 'Clinical presentation' above.)

● Diagnostic evaluation – Patients with symptoms, signs, or other findings suggestive of

RCC should undergo evaluation for the presence of a renal mass. Abdominal computed
 tomography (CT) or ultrasound can confirm the presence of a mass, distinguish RCC
from a benign cyst, and assess the extent of disease. (See 'Diagnostic evaluation'
above.)

● Approach to a solitary small renal mass – In the setting of a solitary small renal mass,
imaging studies cannot reliably distinguish a benign renal tumor from RCC. Thus, it is
generally recommended that lesions other than simple cysts be resected. (See
"Diagnostic approach, differential diagnosis, and management of a small renal mass".)

● Staging – The tumor, node, metastasis (TNM) staging system, which is based upon the
extent of the primary tumor and the presence or absence of regional lymph node
involvement or distant metastases, is used for staging all histologic variants of RCC
( table 2). This staging system correlates with prognosis and provides important
information for patient management. (See 'TNM staging system' above and 'Tissue
diagnosis' above and 'Staging studies' above and "Prognostic factors in patients with
renal cell carcinoma".)

● Screening for individuals at high risk for RCC – Individuals thought to be at increased
risk for the development of RCC should undergo routine screening with abdominal
ultrasound, CT, or magnetic resonance imaging (MRI). (See 'Screening' above.)

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42. Kay FU, Canvasser NE, Xi Y, et al. Diagnostic Performance and Interreader Agreement of
a Standardized MR Imaging Approach in the Prediction of Small Renal Mass Histology.
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43. Xu W, Gaborieau V, Niman SM, et al. Plasma Kidney Injury Molecule-1 for Preoperative
Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With
Clinical Outcomes. J Clin Oncol 2024; 42:2691.
44. Johnson CD, Dunnick NR, Cohan RH, Illescas FF. Renal adenocarcinoma: CT staging of
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45. Studer UE, Scherz S, Scheidegger J, et al. Enlargement of regional lymph nodes in renal
cell carcinoma is often not due to metastases. J Urol 1990; 144:243.
46. Nayak JG, Patel P, Saarela O, et al. Pathological Upstaging of Clinical T1 to Pathological
T3a Renal Cell Carcinoma: A Multi-institutional Analysis of Short-term Outcomes.
Urology 2016; 94:154.
47. Koga S, Tsuda S, Nishikido M, et al. The diagnostic value of bone scan in patients with
renal cell carcinoma. J Urol 2001; 166:2126.
48. Semelka RC, Shoenut JP, Magro CM, et al. Renal cancer staging: comparison of contrast-
enhanced CT and gadolinium-enhanced fat-suppressed spin-echo and gradient-echo MR
imaging. J Magn Reson Imaging 1993; 3:597.
49. Ramdave S, Thomas GW, Berlangieri SU, et al. Clinical role of F-18 fluorodeoxyglucose
positron emission tomography for detection and management of renal cell carcinoma. J
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50. Wu HC, Yen RF, Shen YY, et al. Comparing whole body 18F-2-deoxyglucose positron
emission tomography and technetium-99m methylene diphosphate bone scan to detect
bone metastases in patients with renal cell carcinomas - a preliminary report. J Cancer
Res Clin Oncol 2002; 128:503.
51. Goldberg MA, Mayo-Smith WW, Papanicolaou N, et al. FDG PET characterization of renal
masses: preliminary experience. Clin Radiol 1997; 52:510.
52. Dechet CB, Zincke H, Sebo TJ, et al. Prospective analysis of computerized tomography
and needle biopsy with permanent sectioning to determine the nature of solid renal
 masses in adults. J Urol 2003; 169:71.
53. Bosniak MA, Birnbaum BA, Krinsky GA, Waisman J. Small renal parenchymal neoplasms:
further observations on growth. Radiology 1995; 197:589.

54. Sánchez-Ortiz RF, Madsen LT, Bermejo CE, et al. A renal mass in the setting of a nonrenal
malignancy: When is a renal tumor biopsy appropriate? Cancer 2004; 101:2195.
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n MB (Ed), Springer, New York 2017. p.739.

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Topic 2983 Version 36.0
GRAPHICS

CT image of large clear cell carcinoma of the kidney

Axial contrast-enhanced CT image shows a large enhancing mass in the left kidney with central
necrosis (asterisk). A patent left renal vein (arrow) is noted medially. A low-grade (Fuhrman nuclear
grade 2) clear cell renal cell carcinoma was identified pathologically after nephrectomy.

CT: computed tomography.

Courtesy of Ivan Pedrosa, MD.

Graphic 60352 Version 4.0

Definition of Bosniak classification of cystic kidney masses by CT scanning

Category I – Simple benign cyst with the following features:

 Hairline thin wall.

Density less than 20 Hounsfield units (similar to water).

Does not contain septa, calcification, or solid components.

Does not enhance.

Category II – Cystic lesions with the following features:

A few hairline thin septa.

"Perceived" enhancement may be present. There is no measurable enhancement.

Uniformly high attenuation lesions <3 cm that are well marginated and do not enhance fall into this
category.

Category IIF – Minimally complicated cysts that do not neatly fall into category II.
These lesions are generally well marginated but have some suspicious features that
require follow-up:
Multiple hairline thin septa or minimal smooth thickening of the wall or septa.

"Perceived" enhancement of septa or wall may be present.

Thick and nodular calcification of the wall or septa, but no measurable contrast enhancement is
present.

Totally intrarenal, nonenhancing, high attenuation lesions >3 cm in diameter fall into this category.

Category III – Cystic masses that typically undergo surgical evaluation, although
many lesions are benign. These lesions show the following:
Thickened irregular or smooth walls or septa in which measurable enhancement is present.

Category IV – These mostly malignant lesions have the following features:

All category III criteria.

Enhancing soft-tissue components adjacent to, but independent of, the wall or septum.

CT: computed tomography.

Adapted from Israel GM, Bosniak MA. An update of the Bosniak Renal Cyst Classification System. Urology 2005; 66:484.

Graphic 67087 Version 6.0

CT scan demonstrating cystic renal cell carcinoma

Single axial contrast-enhanced CT scan through the right kidney demonstrates a large, multiloculated
cystic mass containing irregular septations.

CT: computed tomography.

Courtesy of Jonathan Kruskal, MD.

Graphic 77721 Version 4.0

MRI of clear cell carcinoma of the kidney

Coronal T2-weighted single-shot fast spin echo image shows a heterogeneous mass in the right
kidney.

MRI: magnetic resonance imaging.

Courtesy of Ivan Pedrosa, MD.

Graphic 73120 Version 3.0

MRI of clear cell carcinoma of the kidney

Coronal three-dimensional T1-weighted fat-saturated gradient echo image after administration of

gadolinium obtained during the excretory phase confirms the presence of enhancement
(compared with precontrast, not shown) within the mass. After nephrectomy, a low-grade (Fuhrman
nuclear grade 2) clear cell renal cell carcinoma was confirmed.

MRI: magnetic resonance imaging.

Graphic 51129 Version 4.0

Kidney cancer TNM staging AJCC UICC 8 th edition

Primary tumor (T)

T category T criteria

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor ≤7 cm in greatest dimension, limited to the kidney

T1a Tumor ≤4 cm in greatest dimension, limited to the kidney

T1b Tumor >4 cm but ≤7 cm in greatest dimension, limited to the kidney

T2 Tumor >7 cm in greatest dimension, limited to the kidney

T2a Tumor >7 cm but ≤10 cm in greatest dimension, limited to the kidney

T2b Tumor >10 cm, limited to the kidney

T3 Tumor extends into major veins or perinephric tissues, but not into the
ipsilateral adrenal gland and not beyond Gerota's fascia

T3a Tumor extends into the renal vein or its segmental branches, or invades the
pelvicalyceal system, or invades perirenal and/or renal sinus fat but not
beyond Gerota's fascia

T3b Tumor extends into the vena cava below the diaphragm

T3c Tumor extends into the vena cava above the diaphragm or invades the wall
of the vena cava

T4 Tumor invades beyond Gerota's fascia (including contiguous extension into

the ipsilateral adrenal gland)

Regional lymph nodes (N)

N category N criteria

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in regional lymph node(s)

Distant metastasis (M)

M category M criteria

M0 No distant metastasis

M1 Distant metastasis

Prognostic stage groups

When T is... And N is... And M is... Then the stage group
is...

T1 N0 M0 I
 T1 N1 M0 III

T2 N0 M0 II

T2 N1 M0 III

T3 NX, N0 M0 III

T3 N1 M0 III

T4 Any N M0 IV

Any T Any N M1 IV

TNM: Tumor, Node, Metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for
International Cancer Control.

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the
AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Corrected at 4th printing,
2018.

Graphic 110735 Version 11.0

Initial evaluation and treatment of renal cell carcinoma

IVC: inferior vena cava; CT: computed tomography; MRI: magnetic resonance imaging.

* Preliminary diagnosis is based upon characteristic findings on imaging studies (CT/MRI); tissue
diagnosis is generally obtained at time of definitive surgery.

¶ Chest imaging, additional studies as clinically indicated to look for evidence of metastases.

Δ Selection of patients should be done with considerable care so that appropriate patients can
proceed with systemic therapy; important factors include good performance status, ability to perform
adequate debulking, and favorable- or low-intermediate-risk diseases. Refer to UpToDate topic on the
role of surgery in patients with metastatic renal cell carcinoma.

◊ Partial nephrectomy is the preferred approach to confirm the diagnosis and treat a renal mass <4
cm. However, thermal ablation (cryotherapy, radiofrequency ablation) or active surveillance may be
appropriate alternatives for patients who are not surgical candidates. The choice between these
approaches is guided by local expertise and patient preference. Refer to UpToDate topic on the
diagnostic approach, differential diagnosis, and treatment of a small renal mass.

§ Based upon factors including patient preference, age, and comorbidities.

Graphic 109427 Version 4.0
International Metastatic Renal Cell Carcinoma Database Consortium criteria

Karnofsky performance status score <80

Time from original diagnosis to initiation of targeted therapy <1 year

Hemoglobin less than the lower limit of normal

Serum calcium greater than the upper limit of normal

Neutrophil count greater than the upper limit of normal

Platelet count greater than the upper limit of normal

Favorable risk: None of the above risk factors present.

Intermediate risk: 1 or 2 of the above risk factors present.
Poor risk: 3 or more risk factors present.

Adapted from: Heng DYC, Xie W, Regan MM, et al. External validation and comparison with other models of the International
Metastatic Renal Cell Carcinoma Database Consortium prognostic model: A population-based study. Lancet Oncol 2013;
14:141.

Graphic 116130 Version 3.0

Contributor Disclosures
Michael B Atkins, MD Equity Ownership/Stock Options: Pyxis [Immunotherapy]; Werewolf
Therapeutics [Immunotherapy]. Grant/Research/Clinical Trial Support: Agenus [Melanoma, RCC,
Immunotherapy]; Bristol Myers Squibb [Melanoma and RCC]; Merck [Melanoma and RCC].
Consultant/Advisory Boards: 23ANDME [Immunotherapy]; AbbView [Immunotherapy]; Agenus
[Melanoma, RCC, immunotherapy]; Asher Bio [Melanoma, RCC, immunotherapy]; AstraZeneca
[Melanoma, RCC, immunotherapy]; Aveo [Melanoma, RCC, immunotherapy]; Beigene
[Immunotherapy]; Bristol Myers Squibb [Melanoma, RCC, immunotherapy]; Eisai [Melanoma, RCC,
immunotherapy]; Exelixis [Melanoma, RCC, immunotherapy]; Innovent [Immunotherapy]; Jazz
Pharmaceuticals [Immunotherapy]; Merck [Melanoma, RCC, immunotherapy]; Novartis [Melanoma,
RCC, immunotherapy]; Oncorena [RCC]; Pfizer [Melanoma, RCC, immunotherapy]; Pliantrx
[Immunotherapy]; Roche [Melanoma, RCC, immunotherapy]; SAB Bio [Melanoma, RCC,
immunotherapy]; Sanofi [Immunotherapy]; SeaGen [Melanoma, RCC, immunotherapy]; Simcha
[Melanoma, RCC, immunotherapy]; Syncona [Immunotherapy]; Takeda [Melanoma, RCC,
immunotherapy]; Werewolf Therapeutics [Immunotherapy]. All of the relevant financial relationships
listed have been mitigated. Jerome P Richie, MD, FACS No relevant financial relationship(s) with
ineligible companies to disclose. Sonali M Shah, MD No relevant financial relationship(s) with ineligible
companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.

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