Computed tomography and magnetic resonance imaging characteristics of renal cell carcinoma: Differences between subtypes and clinical evaluation

Included studies

Original research articles examining the CT and MRI features of RCC subtypes were included in the screening process. These studies included detailed reviews of histopathological and imaging findings of different RCC subtypes. The publication dates of the studies were limited to a 15-year period (2009–2024).

Excluded studies

Small case series, studies with limited sample sizes, systematic reviews, and studies that did not provide sufficient histopathological information on RCC subtypes or focused only on invasive methods such as biopsy were excluded from the screening [Figure 1].

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Figure 1:

PRISMA flow diagram.

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ccRCC

Known as the most common type of RCC and originating from the proximal tubule, these tumors are characterized by intense contrast enhancement in the corticomedullary phase and rapid wash-out in the nephrogenic phase. The tumor usually has irregular borders and is markedly hypervascular.^[9] In particular, patients with localized RCC lesions without surrounding invasion or distant metastasis had a significantly higher 5-year survival rate (91.7%), highlighting the critical importance of early diagnosis in improving patient survival^[10] [Figure 2].

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Figure 2:

(a) A 65-year-old woman with a mass in the left kidney observed on CT in the portal phase, (b) On MRI, the mass appears heterogeneously hyperintense on T2-weighted and fat-suppressed T2-weighted images,(c) while areas within the mass demonstrate focal diffusion restriction on diffusion-weighted imaging (DWI) (d) and apparent diffusion coefficient (ADC) maps.

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CcRCC usually presents as heterogeneous iso-hypodense lesions compared to normal renal parenchyma on CT. The characteristic feature of ccRCC on IV contrast-enhanced CT is rapid wash-in and wash-out. The tumor shows rapid and intense contrast enhancement in the corticomedullary phase, while in the nephrogenic phase, the density of the lesion, which shows rapid contrast washout, decreases rapidly and becomes lower than the surrounding renal parenchyma. In addition, more heterogeneous enhancement is seen in ccRCC.^[11]

In the study conducted by Wang et al., it was reported that CT had 88% sensitivity and 82% specificity in detecting ccRCC.^[9] Depending on the level of vascularity, tumors may show homogeneous or heterogeneous enhancement, which helps distinguish ccRCC from other renal tumors.^[10] Zhu et al. and Gentili et al. compared RCC subtypes with imaging findings, emphasizing the importance of contrast patterns in distinguishing ccRCC from oncocytoma (ONC).^[12,13]

pRCC

Known as the second most common type of RCC and originating from the proximal tubule, these tumors are prominent with their hypovascular characteristics and exhibit lower contrast enhancement after Intravenous (IV) contrast injection. This tumor, which does not show significant contrast enhancement in the corticomedullary phase on dynamic CT examination, reaches peak enhancement level in the nephrogenic phase. Compared to ccRCC, pRCC usually has more homogeneous and regular borders^[14] [Figure 3].

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Figure 3:

A 54-year-old man with a localized exophytic mass lesion in the left kidney, showing no significant contrast enhancement (a) on the pre-contrast phase, (b) corticomedullary phase, (c) nephrogenic phase images (Papillary renal cell carcinoma).

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It is known that pRCC shows less contrast enhancement than ccRCC.^[15] This difference in contrast enhancement is related to the microvascular density within the tumor. Calcification is more common in pRCC than in ccRCC on non-contrast CT. However, the presence of calcification is not significant in distinguishing these two tumors.^[16]

There are two types of pRCC. Type 1 consists of small cells with basophilic cytoplasm and uniform small round nuclei, while type 2 consists of large cells with eosinophilic cytoplasm and large spherical-shaped nuclei.^[17] Murugan et al.’s (2022) study examined the long-term follow-up results of 199 pRCC cases and revealed that type 1 pRCC has a better prognosis.^[16]

The study by Delahunt et al. shows that type 1 and type 2 pRCC are morphologically defined for the 1^st time. It is emphasized that type 2 pRCC has a larger tumor size and higher nuclear grade. This suggests that type 2 pRCC may follow a more aggressive course and is also invasive on CT imaging.^[18] The study by Klatte et al. shows that type 1 pRCC tends to show a more limited growth and invasion pattern on CT imaging.^[19]

The study by Sukov et al. showed that larger tumors and cases with lymphovascular invasion had a more aggressive and widespread appearance on CT. These findings support the general understanding that type 2 pRCC generally has a worse prognosis and is more obvious on imaging.^[20]

Type 1 pRCC generally has a better prognosis and a more limited pattern of invasion, which may be associated with less aggressive findings on CT and MRI, while type 2 pRCC may have a more aggressive and invasive course. This information provides important clues on how to interpret imaging findings in the diagnosis and treatment of pRCC.^[21]

chRCC

This subtype of RCC, which is the third most common and originates from the collecting duct, shows a homogeneous structure. The tumor, which can show different contrast enhancement patterns in IV contrast-enhanced CT examinations, most often shows moderate contrast enhancement in the corticomedullary phase. While no significant vascularity is observed in dynamic CT images of this type, it tends to have less contrast enhancement than ccRCC^[22] [Figure 4].

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Figure 4:

A 53-year-old woman with a mass lesion in the upper pole of the left kidney, displaying macrolobulated contours and minimal contrast enhancement in the portal phase on (a) axial and (b) coronal planes on CT (Chromophobe renal cell carcinoma).

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Studies on chRCC show that these tumors generally have a better prognosis and that imaging findings are typically well-circumscribed, hypodense lesions. Amin et al. emphasize that chRCC has lower metastasis rates than other subtypes, while these tumors have higher long-term survival rates.^[23,24] It has also been found that tumor size, small vessel invasion, and necrosis are associated with poor prognosis.^[25]

mRCC

It is one of the aggressive types of RCC and has an irregular and invasive appearance on CT. It is usually hypovascular and does not show significant contrast enhancement in the late phase.^[26] The known features are the tendency to involve the right kidney, caliectasis, intratumoral necrosis, and accompanying lymphadenopathy.^[27]

In the 2024 study by Lebenthal et al., a distinction was made between mRCC with SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) deficiency and RCCU-MP (RCC, medullary phenotype), the subtype of RCC with a medullary phenotype. The study emphasizes that mRCC often presents with hematuria and usually metastasizes to retroperitoneal lymph nodes.^[28]

MRCC is a rare and aggressive tumor that is usually seen in young patients with sickle cell disease, especially in African individuals, and imaging findings provide important clinical clues. Studies emphasize that these tumors are usually diagnosed at an advanced stage and have a heterogeneous structure with no clear borders on imaging.^[29]

Lebenthal et al. study demonstrates the current management approaches and improved survival with response to treatment. This study examines the differences between mRCC and RCCU-MP (RCC, medullary phenotype) associated with SMARCB1 deficiency and indicates that current imaging techniques are important in better characterizing tumor spread. In addition, retroperitoneal lymph node metastases are frequently observed in these tumors and methods such as CT and MRI play a critical role in the diagnosis of metastases.^[28]

Collecting duct RCC (cdRCC)

This rare subtype, which is located in the medullary region and has a very aggressive course, has invasive and irregular borders on CT. As the tumor size increases, it can extend from the medulla to the renal pelvis and cortex, hemorrhage, and necrosis areas and cystic components are also noted within the tumor.^[30] A heterogeneous uptake is observed after IV contrast injection.

In the study by Karakiewicz et al., it was stated that the prognosis of cdRCC is quite poor and is mostly metastatic at the time of diagnosis. On imaging, it was determined that these tumors usually invade the renal sinus.^[31]

In the study by Gupta et al., mRCC and cdRCC were compared clinically and histopathologically. The study revealed that although there were some similarities between the two tumor types, mRCC had a worse prognosis.^[26] CdRCC has been shown to be medullary, poorly contrasting, and frequently cystic.^[32,33]

mcRCC

A multiloculated cystic tumor with a fibrous capsule containing cystic areas of different sizes separated by septa on CT may show different degrees of contrast enhancement in the septa after IV contrast.^[34] Calcification can be observed in the walls and septa in approximately 20% of tumors.

McRCC radiologically contains well-defined cystic structures and is a cystic mass separated by septa with minimal or no solid components within the tumor. In CT and MRI, these cystic structures usually have thin, regular septa, and mild contrast enhancement is observed in the septa after contrast injection.^[34,35] These tumors are usually located in the renal cortex and contain distinct cystic structures.^[34]

In two recent studies, methods such as contrast-enhanced ultrasound (CEUS), contrast-enhanced computed tomography (CECT), and lipid-to-carbohydrate ratio (L/C) ratio provided effective measurements in distinguishing RCC subtypes.^[36,37] These studies support the importance of imaging features in the diagnosis of subtypes of RCC [Table 1].

ccRCC

The most common type of all RCC and ccRCC is 95% sporadic. However, it can also be encountered rarely with familial and Von Hippel–Lindau disease. The vast majority of cases are associated with 3p deletion.^[40] It is more symptomatic than other types and is often encountered as advanced stage and metastatic disease.^[23] On MRI, it appears iso-hypointense with renal parenchyma on T1WI and hyperintense on T2WI. These characteristic signal features are important in distinguishing it from other types.^[41,42] Necrosis, hemorrhage, and cysts may create variable signals. Necrotic areas are typically observed with high signal on T2WI but not stained on contrast-enhanced series. In dynamic contrast-enhanced MRI, intense contrast enhancement is observed in the corticomedullary phase, while a rapid wash-out is noted in the nephrogenic phase.^[43] In addition, a hypointense rim or pseudocapsule formed by tumor growth and compression of adjacent renal parenchyma can be observed on both T1WI and T2WI [Figure 5].

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Figure 5:

A 60-year-old woman with a lesion observed as hypointense compared to the renal parenchyma in precontrast fat-suppressed T1-weighted imaging, containing a hyperintense area suggestive of focal hemorrhage. The mass shows contrast enhancement except for the central cystic areas in the corticomedullary phase and nephrogenic phase on dynamic MR examination, displayed sequentially in the images (Clear cell renal cell carcinoma).

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The high vascularity of this type can be clearly assessed with MRI. In particular, ccRCC tumors show contrast enhancement patterns due to their vascular structure. This allows us to better understand the extent of the tumor’s blood supply and its relationship with surrounding tissues. The MRI features of ccRCC play a critical role not only in the diagnostic process but also in determining the tumor’s prognosis and optimizing the treatment plan.^[14]

Beek et al. reported that MiT-RCC is characterized by well-defined pseudocapsules and lobulated morphology.^[44]

MRI-based apparent diffusion coefficient (ADC) and contrast pattern analyses have been reported to be important in distinguishing RCC subtypes.^[45] It has also been stated that ccRCC and its other subtypes can be accurately classified using the clear cell likelihood score (ccLS) system.^[46,47] It has contrast enhancement, and the ccLS 4–5 score is effective in identifying ccRCC with 78% sensitivity and 80% specificity.^[48]

pRCC

It often tends to grow slowly and presents as well-circumscribed fibrous-encapsulated solid masses. It is usually recognized by hypointense appearance and low contrast enhancement on T2WI on MRI [Figures 6 and 7].^[49] Due to its hypovascular characteristics, it shows minimal contrast enhancement in the corticomedullary phase, while it is hypointense compared to the renal parenchyma in the nephrogenic phase. There are studies indicating that the most effective examination in differentiating from ccRCC is the corticomedullary phase.^[50] As the lesion size increases, heterogeneity secondary to necrosis, hemorrhage, and calcifications may be observed. It may show also sarcomatous differentiation at a rate of 5%. Type 2 pRCC has been determined to have higher invasiveness than type 1 and to have a more heterogeneous appearance on CT. Similarly, type 2 tumors have been seen to have more frequent infiltrative edges and calcifications on MRI.^[51] In addition, the presence of intratumoral hemorrhage on MRI of pRCC stands out as an important feature that can distinguish such tumors from fat-poor angiomyolipomas (AMLs).^[6] It has been shown that using quantitative tissue analysis on MRI can differentiate between type 1 and type 2 pRCC, and these analyses can improve model accuracy.^[52]

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Figure 6:

A 54-year-old man with a lesion observed as hypointense in T2-weighted imaging on axial (a) and coronal (b) planes on MRI, hyperintense on DWI (c), and showing diffusion restriction suggestive of malignancy on ADC (d) (Papillary renal cell carcinoma).

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Figure 7:

A 54-year-old man with a lesion observed as hypointense in precontrast fat-suppressed T1-weighted imaging (a), showing no significant contrast enhancement in the corticomedullary phase (b) and nephrogenic phase (c), with the subtraction image (d) confirming the absence of contrast enhancement (Papillary renal cell carcinoma).

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chRCC

This tumor, which is most commonly seen in the 6^th decade and has a similar distribution between men and women, is the 3^rd most common type of RCC. This tumor, which usually shows a solid growth pattern, is cytogenetically associated with multiple monosomies (1 and 2) and hypodiploidy.^[53] It has the best prognosis among RCC types, with a 5-year surveillance of around 78–92%.^[24] Often shows high signal intensity on T2A and low homogeneous enhancement after contrast injection.^[54] The enhancement patterns of chRCCs show intermediate signal changes compared with other RCC subtypes. For example, the signal intensity change of chRCCs in the corticomedullary phase is lower than that of ccRCC but higher than that of pRCC. ChRCCs show intermediate enhancement in the arterial and venous phases and washout in the late phase [Figure 8].^[50]

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Figure 8:

A 53-year-old woman with a mass that is iso-hypointense compared to the renal parenchyma in T2-weighted imaging on axial (a) and coronal (b) planes on MRI, with focal hyperintense areas noted sporadically. The mass is observed to be hyperintense on DWI (c) and shows diffusion restriction suggestive of malignancy on ADC (d) (Chromofobe renal cell carcinoma).

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ChRCC and ONCs may present similar imaging findings due to their similar histological and ontogeny features. ONCs originate from intercalated cells in the collecting ducts and may show central scarring and wheel-like contrast enhancement like chRCC.^[55] Among hypovascular tumors, chRCC, which comes after pRCC, can reach large sizes but shows relatively homogeneous contrast enhancement compared to pRCC.

mRCC

This aggressive tumor originates from the medullary collecting ducts and occurs at a young age. It has low signal on T1WI and T2WI in MRI and has invasive features. Heterogeneous contrast enhancement is noted in IV contrast-enhanced MRI.^[56] MRCC is often located in the medulla region of the kidney and is observed as a heterogeneous mass with ill-defined borders. The tumor can usually reach large sizes and is often necrotic. MRCC usually has an aggressive course and tends to spread to surrounding tissues, especially caliectasis and retroperitoneal lymph node enlargement. These distinctive features identified on MRI are important in supporting the diagnosis of mRCC, especially in young patients with sickle cell anemia.^[57]

Studies have reported that while cdRCC and mcRCC have aggressive biological behaviors and tendencies toward widespread metastasis, mRCC has a better prognosis.^[26,58]

cdRCC

This tumor, which is seen in <1%, is a very aggressive subtype of RCC. The average age of onset is 55.^[59] On MRI, they appear as masses localized in the medulla, with ill-defined borders, isointense on T1WI, low signal on T2WI, invasive in the medullary region, and showing heterogeneous contrast enhancement.^[60] These tumors often appear as heterogeneous complex masses consisting of solid or solid-cystic components.^[32] The enhancement patterns are different from other renal tumors. cdRCC shows low contrast enhancement compared to the cortex and medulla; limited enhancement in the corticomedullary phase and no significant washout in the late phases. This weak and heterogeneous enhancement stands out as an important distinguishing feature in diagnosis.^[33] It often shows infiltrative growth and tends to spread to the renal pelvis. Invasion of these tumors into surrounding tissues and lymph nodes is common, so the rate of metastasis is high. Perinephric stranding and vascular invasion are often observed on MRI.

mcRCC

This type, encountered as cystic masses separated by septa, may show asymmetric wall thickening. The average age of onset is 51, and the female–male ratio is 1/3. In T2WI on MRI, cystic foci appear hyperintense, while septa appear hypointense. In IV contrast-enhanced MRI, septa become apparent with contrast enhancement.^[58] It usually presents as a multi-chambered cystic mass with well-defined, thin septa. In addition, in some cases, small nodular structures or calcifications may be seen on the septa.^[61]

De Silva et al. and Dunn et al. emphasized that ADC values and enhancement patterns present significant differences among RCC subtypes.^[62,63] Wang et al. showed that low ADC values were associated with increased cellular density and aggressive pathologies.^[56] These studies provide important data to more clearly distinguish the imaging findings of different RCC subtypes.