Cystic RCC can be unilocular or multilocular, and RCC can develop within the wall of an otherwise benign cyst. The classification of complex renal cysts based on imaging was originally proposed by Bosniak in 1986 to help predict the likelihood of a cystic lesion being malignant [52]. This classification has since been modified. Bosniak originally proposed four categories; more recently, the classification was modified to include a fifth category [55] (Fig. 5.8). The diagnostic clues for the differential diagnosis of cystic renal tumors are CT attenuation on unenhanced CT, the existence of calcification, the number of septa, the irregularity and thickness of walls and septa, the enhancement of walls and septa, and the existence of a solid component.

Category I cysts are simple cysts with thin, noncalcified walls (Fig. 5.8a). These cysts contain simple serous fluid measuring less than 20 HU on CT images. Category II cysts are minimally complicated cysts with either high attenuation lesions (<3 cm) because of an increased protein content or hemorrhage or are multilocular with few septa (Fig. 5.8b) or thin peripheral calcifications. Category II cysts do not show enhancement after the injection of intravenous contrast material and are almost always benign. Category IIF cysts are complex lesions that have a high attenuation (>3 cm) or multiple septa or calcifications and a relatively benign appearance (Fig. 5.8c). Category III cysts are complicated cystic lesions that have some features suggesting malignancy that have multiple septa, thick or irregular rims, or heterogeneity suggesting necrosis (Fig. 5.8d). Category IV cysts contain solid, soft tissue-enhancing elements seen either within the cyst or as part of a complex cystic mass (Fig. 5.8e).

In general, Category I and II lesions are benign and so do not need further evaluation. Category IIF cysts have a less than 25% chance of malignancy and, therefore, may be followed to document stability over time [57, 58]. Concerning the intervals of follow-up examinations, it is recommended to perform the first follow-up after half a year and, if there is no change, to continue the examination annually at least for 5 years [58]. Category III cysts have an approximately 54–84% chance of a cystic RCC [56, 57]. Typically, these lesions are surgically explored. Category IV lesions are almost always cystic RCC and should be treated as such.

While one typically expects Bosniak III or IV lesions to represent cystic RCC, there are a number of benign cystic neoplasms that mimic this diagnosis. These include cystic nephroma (CN) and mixed epithelial and stromal tumor (MEST) of the kidney. In one series, 70% of 22 CN were characterized as Bosniak III lesions, and 70% of 10 MEST had enhanced solid elements [59]. These tumors are much more commonly seen in women or men receiving exogenous hormone treatment.

Biopsies for indeterminate cystic renal masses, such as Category IIF or III, can also be considered. Some studies [60, 61] have reported that a “definitive” diagnosis could be made for 61–88% of lesions, and negative results were supported by interval follow-up.

Solid RCC can show an expansive growth pattern and an infiltrative growth pattern. Renal tumors with an infiltrative growth pattern are almost definitely malignant. On the other hand, the differential diagnosis of benign and malignant lesions is often challenging for renal tumors with an expansive growth pattern. The diagnostic clues for the differential diagnosis of solid renal tumors are CT attenuation on unenhanced CT images, the existence of calcification, the degree of enhancement on the CMP and the enhancement patterns during multiphase CT, the heterogeneity of the tumor, the signal intensity on T2WI images, and the presence or absence of cystic degeneration.

Renal tumors with an expansive growth pattern are well marginated but show various enhancements, depending on the tumor. The major subtypes of RCCs, such as clear cell RCC, papillary RCC, and chromophobe RCC, are included among renal tumors with an expansive growth pattern. This type of tumor also includes almost all benign tumors, such as AML, leiomyoma, or metanephric adenoma. For the diagnosis of renal tumors with an expansive growth pattern, there are three key criteria: the first criterion is that when fat attenuation (attenuations less than −10 HU) is detected in the tumor on an unenhanced CT image, the lesion is a classic AML [28–30, 62] (Fig. 5.9); the second criterion is that when the tumor exhibits marked heterogeneous enhancement almost equal to or greater than that in the renal cortex on the CMP of multiphase CT, the lesion is a clear cell RCC [6, 63] (Fig. 5.10); and the third criterion is that when the tumor appears as a hyperattenuated lesion (>45 HU) on an unenhanced CT image with homogeneous enhancement and T2W hypointensity, the lesion is a benign tumor, such as a fat-poor AML, leiomyoma, or metanephric adenoma [8–10] (Fig. 5.11). For the first criterion, AML with a fat component detectable on imaging is called classic AML. On US, classic AML is almost always markedly hyperechoic relative to the renal parenchyma [4, 5], but RCC can also be hyperechoic. Shadowing is a characteristic finding of AML on US, but this characteristic is only seen in 21–33% of AMLs [4, 5]. Thus, it is often difficult to diagnose a classic AML using US alone, and further CT examination is usually necessary. When evaluating AMLs with CT, the acquisition of thin (1.5–3 mm) sections and the use of attenuation measurements for small ROIs or even pixel values might be necessary to detect small amounts of fat [63, 64]. For the second criterion, no renal tumors other than clear cell RCC exhibit marked enhancement equal to or greater than that of the renal cortex during the CMP. Heterogeneity is caused by intratumoral hemorrhage or necrosis, which is frequently seen in clear cell RCC. For the third criterion, the findings of both hyperattenuation (>45 HU) on unenhanced CT and T2 hypointensity correspond to a smooth muscle component in fat-poor AML and leiomyoma and to psammomatous calcifications in metanephric adenoma [6, 8–10, 65].

Renal tumors with an infiltrative growth pattern are poorly marginated and show relatively decreased and heterogeneous enhancement [66] (Fig. 5.12). The renal contour is maintained, but the involved portion of the kidney is often enlarged. Rare subtypes of renal carcinomas such as collecting duct carcinoma, renal medullary carcinoma, type 2 papillary RCC, transitional cell carcinoma infiltrating the renal parenchyma, and sarcomatoid carcinoma are included in this type. It is often difficult to differentiate these diseases from each other, but most require active management, including surgery. Primary renal non-Hodgkin’s lymphoma (NHL) can also appear as either a focal mass or a lesion with an infiltrative appearance. Lymphoma is typically homogeneous, with less enhancement than the normal renal parenchyma, and is often present as multiple lesions [67]. This disease should be considered when splenomegaly or bulky retroperitoneal or mesenteric lymphadenopathy is present. Perinephric confluent tissue is more suggestive of NHL than RCC. Metastatic disease to the kidneys also appears as multiple, bilateral, poorly marginated solid lesions that can occasionally demonstrate an infiltrative pattern [68, 69]. Metastatic disease to the kidneys is particularly common with lung and breast carcinoma as well as melanoma. Metastases should be considered when infiltrative renal tumor is accompanied by nonrenal tumors. A biopsy should be considered to differentiate from RCC when other imaging findings are suggestive of lymphoma or metastases. It is important to recognize that some nonmalignant conditions can exhibit an infiltrating pattern with decreased enhancement on imaging. Acute pyelonephritis appears as wedge-shaped areas of decreased enhancement that extend from the papilla to the cortex. This appearance should be distinguished from tumor infiltration, especially in patients with a history of fever, flank pain, and pyuria.

Clear cell RCC, the most common type of RCC, originates from the proximal convoluted tubule and accounts for 70–80% of all RCCs. This tumor is seen in patients with von Hippel–Lindau (VHL) disease.

Clear cell RCCs typically show marked heterogeneous enhancement almost equal to that of the renal cortex during the CMP (more than 100 HU) and rapid washout during the NP or EP (80 HU) of multiphase CT (Fig. 5.10). The degree of enhancement is more avid than those of other RCC subtypes because of the deregulated angiogenesis of clear cell RCC (Fig. 4.​2) [6, 7, 70]. Clear cell RCC also usually shows a heterogeneous enhancement because it is often accompanied by intratumoral hemorrhage or necrosis [6]. Cystic degeneration is also more common (15%) in the clear cell subtype than in the other subtypes irrespective of tumor size. On MRI, clear cell RCC is typically isointense on T1-weighted images and isointense to hyperintense on T2-weighted images, compared with the normal renal parenchyma (Fig. 4.​13 ) [71, 72]. Clear cell RCC contains intracellular lipids in the tumor that cannot be detected on conventional fat suppression MR images but can be detected as a signal loss on chemical shift suppression images [72, 73]. This finding can help distinguish clear cell RCC from other RCC subtypes; however, this characteristic is also seen in fat-poor AML (isoattenuating type). The apparent diffusion coefficient calculated from diffusion-weighted images is reportedly lower among high-grade clear cell RCCs than among low-grade clear cell RCCs [74].

Clear cell RCCs tend to be more aggressive than other cell types, and they may directly involve and invade the renal collecting system [75]. Intratumoral necrosis and discontinuity of the capsule are correlated with higher-grade clear cell RCC [76]. Clear cell RCC may contain calcification, but less frequently than that seen in papillary and chromophobe subtypes [77]. Venous invasion is more commonly associated with clear cell RCCs [76].

Papillary RCC comprises 10–15% of all RCCs. An important feature of papillary RCC is that it is more commonly bilateral and multifocal than other RCC subtypes. Papillary RCC occurs in familial papillary RCC syndrome. Papillary RCC has a greater tendency to be of a lower stage and to have a better prognosis than clear cell RCC. There are two different histologic types of papillary RCC: those with small basophilic cells (type 1) and those with eosinophilic cells (type 2) [78]. Type 2 tumors have less distinct margins, are more heterogeneous, generally present at more advanced stages, frequently grow centripetally, and are associated with a poorer outcome [79].

Papillary RCC typically shows mild enhancement less than that of the adjacent cortex during the CMP (50–60 HU) and gradual enhancement during the NP or EP (65–75 HU) of multiphase CT (Fig. 5.13). Type 1 tumors are well marginated and exhibit homogeneous enhancement because they have lower frequencies of intratumoral necrosis and hemorrhage than clear cell RCC [6, 79, 80]. Type 2 tumors are poorly marginated and usually exhibit heterogeneous enhancement, but they can exhibit homogeneous enhancement when they are relatively small [79]. On MRI, papillary RCC can be visualized as a decreased signal intensity on T2-weighted images, compared with the normal renal parenchyma, possibly because of iron-containing hemosiderin, which can be found in the cytoplasm of tumor cells [71]. The imaging findings of type 1 papillary RCC are usually similar to those of metanephric adenoma [6], while the imaging findings of type 2 papillary RCC are similar to those of collecting duct carcinoma, spindle cell carcinoma, and urothelial carcinoma infiltrating the renal parenchyma.

Chromophobe RCC accounts for only 5% of all RCCs. Chromophobe RCC and hybrid oncocytic/chromophobe tumors are associated with Birt–Hogg–Dubé syndrome.

Chromophobe RCC shows a moderate homogeneous enhancement during the CMP and washout during the NP and EP of multiphase CT (Fig. 5.14). The degree of enhancement during the CMP is intermediate between that of clear cell and papillary RCC [6, 81]. This tumor usually exhibits homogeneous enhancement. On MRI, chromophobe RCC is typically isointense on T1-weighted images and isointense to hyperintense on T2-weighted images, compared with normal renal parenchyma. However, this enhancement pattern is also seen in oncocytoma [6, 81]. Thus, differentiating between these two tumors is difficult. One study reported the presence of a spoke-like enhancement pattern with a central stellate form [82]. This pattern can be seen for both chromophobe RCC and oncocytoma and is, therefore, not specific for either tumor. Hale’s colloidal iron stain has been used to differentiate between the two pathologically.

Collecting duct (Bellini duct) carcinomas are uncommon, accounting for 1–2% of renal tumors. Collecting duct carcinoma is an aggressive tumor, with most patients presenting with high-stage disease.

Collecting duct RCC are usually located in the medullary portion or infiltrating the central sinus and have only rarely been reported in the renal cortex [83–85]. They exhibit an infiltrating growth pattern, rather than showing expansile growth, and preserve the reniform shape of the kidney (Fig. 5.12). They are commonly hypovascular with heterogeneous enhancement and may be difficult to differentiate from infiltrating urothelial carcinoma infiltrating the renal parenchyma and sarcomatoid variants of RCC [86]. They have variable signal intensities on T1-weighted images and typically have a low signal intensity on T2-weighted images [86, 87].

Metastases are more common at presentation than with other types of RCC, occurring in 35–40% of patients [84]. When bone metastases occur, they are frequently osteoblastic, unlike metastases from clear cell RCC, which are osteolytic.

Xp11.2/TFE RCC is a rare subtype of RCC characterized by Xp11.2 chromosome translocations and fusion with the transcription factor E3 and is now accepted as a distinct entity according to the 2004 World Health Organization renal tumor classification [88]. It primarily affects children and adolescents. In the adult population, it is associated with a poor prognosis, presenting at an advanced stage and more frequently with lymph node metastasis [88, 89].

Xp11.2/TFE RCC appears as a heterogeneous mass that is frequently accompanied by cystic and necrotic portions. Calcification is frequently seen, especially in younger patients, and is often distributed within the marginal area of the tumor (eggshell calcification). The lesion appears as a hyperattenuation on unenhanced CT and exhibits moderate enhancement during the CMP and gradual enhancement during the NP and EP [90, 91] (Fig. 5.15). The gradual enhancement pattern is similar to that seen for papillary RCC. However, Xp11.2/TFE RCC appears as a hyperattenuation on unenhanced CT, unlike papillary RCC, and has a higher attenuation value during the CMP than papillary RCC. Cystic change, calcification, and lymph node metastasis are more frequent in Xp11.2/TFE RCCs than papillary RCC [91].

Mucinous tubular and spindle cell carcinoma (MTSCC) is a low-grade polymorphic epithelial carcinoma associated with a favorable prognosis.

MTSCC exhibits mild enhancement less than the adjacent cortex during the CMP (50–60 HU) and gradual enhancement during the NP or EP (65–75 HU) of multiphase CT, similar to findings for papillary RCC [92, 93]. Unlike papillary RCC, however, it shows an intermediate to high signal intensity on T2-weighted images corresponding to a mucinous component within the tumor [94]. An enhancement pattern similar to that of papillary RCC but with an intermediate- to high-intensity area on T2WI is suggestive of MTSCC.

Angiomyolipoma is typically a solid tumor composed of varying amounts of three elements: dysmorphic blood vessels, smooth muscle components, and mature adipose tissue. Once thought to be a hamartoma, AMLs are now considered to belong to the family of perivascular epithelioid cell tumors (PEComa) [62]. While 80% of AMLs are sporadic and most of them inconsequential, approximately 20% are associated with tuberous sclerosis complex (TSC).

Because most AMLs contain substantial amounts of adipose tissue, they are usually diagnosed using CT or MRI by identifying the imaging features of fat cells in the mass [28, 29]. Those that can be diagnosed using imaging have been called “classic AMLs” [28–30, 62] (Fig. 5.9). The presence of regions of attenuation less than −10 HU on unenhanced CT or frequency-selective (FS) fat suppression or chemical shift suppression on MRI enables fat to be identified with confidence [28–30, 40, 41]. Intratumoral hemorrhage can occur, particularly in tumors larger than 4 cm; the high attenuation of blood can mask fat, particularly if only a small amount is present, and lead to the misdiagnosis of a classic AML as RCC [95]. On ultrasound, a classic AML is almost always markedly hyperechoic relative to the renal parenchyma and is often as hyperechoic as renal sinus fat [4, 5]. Acoustic shadowing is a characteristic finding of AML but seen only in 21–33% of AMLs smaller than 3 cm [4, 5] (Fig. 5.1). Thus, a confident diagnosis of a classic AML requires the identification of fat using CT or MRI.

Some AMLs, however, have small amounts of fat that cannot be identified preoperatively using unenhanced CT (1.5–3 mm) and rich amounts of smooth muscle component [8]. These subtypes are now collectively referred to as “fat-poor AMLs,” which pathologically contain no more than 25% fat cells [96]. Fat-poor AMLs are divided into mainly two subtypes—hyperattenuating and isoattenuating AMLs—depending on the relationship of the amount of fat cells and their distribution in the mass. Hyperattenuating AMLs represent approximately 4.5% of all AMLs. These lesions are hyperattenuating relative to the renal parenchyma on unenhanced CT (usually more than 45 HU) and T2 hypointese, corresponding to smooth muscle components, and typically show homogeneous enhancement on CT [8, 62] (Fig. 5.11). Pathological examination generally reveals a fat cell content of only 4% (range, 3–10%) and a composition consisting mostly of a smooth muscle component [97]. Signal loss on fat-suppressed pulse sequences and chemical shift suppression are not observed. On ultrasound, they are usually homogeneously isoechoic, similar to smooth muscle components elsewhere [8, 62]. Because only 2% of RCCs show these findings, a percutaneous biopsy is recommended to avoid unnecessary surgery when encountering a renal mass that is hyperattenuating on unenhanced CT, T2 hypointense, and homogeneously enhancing [5, 6, 59, 60]. Isoattenuating AMLs show close attenuation to the renal parenchyma (−10 and 45 HU) on unenhanced CT and slightly hyperechogenicity on US [62]. This type of AML contains diffuse, scattered fat cells (theoretical fat cell content of 10–25%) among the smooth muscle component. Because there are more fat cells than hyperattenuating AMLs, isoattenuating AMLs typically show chemical shift suppression [62, 98]. At the same time, because of the predominance of the smooth muscle component, the lesion exhibits T2 hypointensity [62, 98]. Thus, T2 hypointensity in combination with the signal loss of opposed-phase imaging and homogeneous enhancement is suggestive of an isoattenuating AML, and a percutaneous biopsy is reasonable in such cases.

When calcification is seen in a lesion with no or minimal fat, it is most likely an RCC, and not an AML [99, 100].

Oncocytoma is a common benign renal tumor that accounts for 9% of all renal cell neoplasms. Bilateral and/or multifocal oncocytomas, oncocytosis, and hybrid oncocytic/chromophobe tumors are associated with Birt–Hogg–Dubé syndrome.

Oncocytoma appears as a solid, well-circumscribed tumor with marked or moderate enhancement during CMP and washout during the NP and EP of multiphase CT (Fig. 5.16). The degree of enhancement during the CMP is intermediate between that of clear cell and chromophobe RCC [6, 7]. When the tumor is small in size, there is a homogeneous enhancement pattern with an absence of internal necrosis and hemorrhage [6, 101, 102]. Oncocytoma is typically hypointense to hyperintense on T1-weighted images and isointense to hyperintense on T2-weighted images [103]. When the tumor size is larger, oncocytomas often have a central stellate scar that appears as a low attenuation area during the CMP and an area with delayed enhancement during the NP or EP; such lesions have a low T1 signal and a high T2 signal when observed using MRI [72, 104] (Fig. 5.17). Although this feature is suggestive of oncocytoma, it is nonspecific and can been seen in both chromophobe and clear cell RCCs [101, 102]. Oncocytomas, therefore, present the greatest diagnostic challenge because of the overlap in their appearance with RCC. Recently, the appearance of segmental enhancement inversion during CMP and EP was reported to be a possible characteristic enhancement pattern of small renal oncocytoma when observed using multiphasic CT [105]. This finding consists of two distinct regions of enhancement in which the degree of enhancement reverses during the CMP and EP. The highly enhanced segments during the CMP develop a lower attenuation during the EP (corresponding to the tumor cells), while less-enhanced segments during the CMP develop a higher attenuation during the EP (corresponding to abundant hypocellular hyalinized stroma). Although chromophobe RCC also exhibits this finding, it seems to be more common in oncocytoma and may be helpful for differentiating small oncocytoma from RCC [106, 107].