Renal Cell Carcinoma: Histologic Classification with Imaging

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Renal Cell Carcinoma (RCC) is the 7th most common histological type of cancer in the Western World, and it also maintains its increase in the prevalence. [1]
At the same time, Renal Cell Carcinoma (RCC) represents 1% to 3% of all malignant visceral neoplasms.
The cause of death, in approximately 40% of patients with Renal Cell Carcinoma (RCC) is the progression of disease. Therefore, it considered as the most lethal urological malign tumor.
Currently, many Renal Cell Carcinomas are diagnosed incidentally by imaging techniques, irrespective of whether there is a urological symptom.
For this malignancy, there is a clear-cut predominance of men, representing as two third of cases.

For more information about the etiology of Renal Cell Carcinoma, you can read:
Renal Cell Carcinoma: Etiology

Imaging classification of Renal Cell Carcinoma (RCC) is extremely important. Because histological subtypes have extremely important implications on both prognosis and treatment. [2]

As it is known, with recent advances in immunohistochemical techniques, minimally invasive imaging-guided biopsy has come to an important workup in determining the histological character, in the preoperative stage. [3]
However, because of the risk and limitations, percutaneous biopsy is indicated only in cases where the tumor cannot be radiologically characterized or in specific clinical situations.

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In this sense, the radiological characterization of subtypes of Renal Cell Carcinoma may be of great importance depending on the clinical situation, whether supplemented by percutaneous biopsy or not.

Such a procedure may be particularly useful in patients whose clinical status is not suitable for surgery, in metastatic diseases, in patients with a solitary kidney, and in tumors that are difficult to treat with conservative surgery. [4]

According to the current World Health Organization (WHO) classification published in 2004, Renal Cell Carcinoma has histological subtypes such as clear cell, papillary, chromophobe, cystic-solid, collecting ducts (Bellini), medullary, Xp11 translocation, mucinous tubular and spindle cell, associated with neuroblastoma, and non-classified.

For more information about the classification of Renal Cell Carcinoma, you can read:
Renal Cell Carcinoma: Histological Classification and Correlation with Imaging Findings

The subtypes of clear cell, papillary, and chromophobe are representing more than 90% of all Renal Cell Carcinomas. [5]

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1.Clear Cell Carcinoma

Clear Cell Carcinoma is the most common subtype in the imaging classification of Renal Cell Carcinoma. It represents between 70% and 75% of all cases of Renal Cell Carcinoma. [6]

Most of the clear cell carcinomas are sporadic as 95%, and the rest of them are associated with hereditary syndrome such as von Hippel-Lindau syndrome, tuberous sclerosis.


The clear cell type of Renal Cell Carcinomas is originated from the proximal part of the convoluted tubules epithelium, which is in the renal cortex. It usually has a predominantly expansile type of growth pattern.

Macroscopic examination

In the content of macroscopic examination, clear cell carcinoma has a solid, yellowish appearance with the variable levels of the cystic degeneration, hemorrhage, calcification and necrosis. These finding usually present in the fast growing and large volumed tumors.

Histologic examination

In the histological manner, these lesions have clear cell, because of their cytoplasmic content which is rich from the lipid and glycogen. [7]
In addition, these tumors may also have eosinophil granules in their cytoplasm.

Imaging findings

Imaging findings usually show heterogenous lesions because of necrosis, hemorrhage, calcifications and cysts. Also, hypervascularization is prominent in the imaging modalities.

In the larger lesions such as >4cm, necrosis may be in the foreground. Also, the degree and existence of the necrosis is associated with the high-grade tumors. [8]

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  • CT scan: In the CT scan of these tumors, it usually presents with contrast uptake in the corticomedullary phase and washout typically in the in the nephrographic phase. It may also have hypo-dense pseudo capsule in the corticomedullary phase.
  • MRI scan: In MRI scan, the intensity of the clear cell tumor signal is similar to the renal cortex at T1-weighted images and hypersignal at T2-weighted images. Like CT scan, it may have hypo signal pseudo capsule at the T1- and T2-weighted sequences. [9]

    In the radiological differentiation of the clear cell carcinoma and papillary cell carcinoma, the intensity of the lesion signal in contrast enhanced MRI at corticomedullary phase is very important. [10]
  • Diffusion-weighted MRI scan: The usage of Diffusion-weighted MRI in the classification of clear cell carcinoma is controversial, but still it may give some useful information. [11]

Metastasis and prognosis

The one of the common findings of clear cell carcinomas is the extension to the perirenal fat and renal sinus fat, even into the renal vein and inferior vena cava. If the venous invasion is present, perirenal collateral venous circulation become more prominent, usually.

Besides, hematogenous metastases that principally affects the lungs, liver and bones are relatively common. Also, lymph nodes metastasis can be seen as approximately 15% of cases.
As a rule, the prognosis of clear cell carcinoma accepted worse than the papillary and chromophobe renal cell carcinoma, which are the other most common types.

2. Papillary Carcinoma

The second most common histological subtype in the imaging classification of Renal Cell Carcinoma is papillary variant. It represents approximately 10% of all cases. [12]
Likewise, papillary carcinoma also may occur sporadically or in a manner of familial condition.

Differently, papillary carcinoma also has two histological subtypes based on appearance and biological behavior, which the prognosis of them very different from each other. But these subtypes cannot be differentiated in pre-operative stage, with the imaging techniques. [13]

The type of 1 the papillary carcinoma is generally detected earlier and in low-grades than type 2. For these reason, type 1 has better prognosis. Type 2 generally diagnosed in high-grade levels and frequently with the ganglial metastasis, even in venous invasion.

Macroscopic examination

For most part, papillary types of the Renal Cell Carcinoma are solid, slow-growing and well-defined lesions. Also, they may be multifocal and bilateral. Also, they may be associated with the chronic renal diseases. [14]

Histological examination

The histologic appearance of papillary carcinoma has organized cells in a pattern of spindle-shape. Also, there may be some areas of internal hemorrhage and cystic degenerations, depending on the size of the lesion. [5]

  • Type 1: This is the basophilic type of the papillary carcinoma. It has single layer of basophilic cells surrounding the basal membrane. These basophilic cells have cytoplasm which has a clear appearance and also a hyperchromatic nucleus.
  • Type 2: This is the eosinophilic type of the papillary carcinoma. These cells have a papillae which is surrounded by very wide granular eosinophilic cytoplasm. Also, these cells have prominent nuclei, but this time generally with the necrosis areas.

Imaging findings

In the imaging tests, these tumors usually appeared as more homogenous than clear cell carcinoma. Also, in contrast to the adjacent renal parenchyma, they tend to be hypo vascular. [15]

Lesions of papillary carcinoma that in >4 cm diameter, may have features such as hemorrhage, necrosis or calcification.

Signal loss can be observed in case of if tumor have internal focus of macroscopic fat or intracytoplasmic fat. But this is a very rare condition.

  • CT scan: In the contrast enhanced CT scan, these tumors tend to have an appearance with mean density in both corticomedullary and nephrographic phases.
  • MRI scan: In T2-weighted MRI scans, papillary carcinomas usually appear as peripheral lesions with hypo signal intense. This feature most probably assumed due to the intra tumoral content of hemosiderin. [16]

3. Chromophobe Renal Cell Carcinoma

Chromophobe carcinoma represents approximately 5% of all tumors in the imaging classification of Renal Cell Carcinoma.

It is most frequent in the 6th decade of life and at the same time it is less aggressive than the other subtypes. It has the pest prognosis among all malignant epithelial tumors. [17]

Metastasis rates of chromophobe carcinoma is about 7%.

Histological examination

In pathological examination these tumors represent as the large pale cells. These cells have perinuclear halos and reticulated cytoplasm.

If sarcomatoid transformation is present, then tumor become more aggressive and because of that it has worse prognosis. [18]

In the literature, there are some publishing that says oncocytomas and chromophobe variants are in very close relationship. Both of them originate from the collecting ducts of the intercalated cells and also can be associated with Birt-Hogg-Dubé syndrome. [19]

Imaging findings

These lesions are representing as more homogenous carcinomas than the clear cell variant. [14]

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  • CT scan: Such tumors are mostly present with the moderate contrast uptake in corticomedullary phase at CT scan. In addition, it more intense than papillary variant and less intense than the clear cell variant.
    Also, they are hypo vascular in appearance when compared to the renal cortex. However, chromophobe carcinomas can appear as homogenous and hyper vascularized lesion in the corticomedullary phase.
  • MRI scan: In T2-weighted MRI scan modalities, these tumors present with the slight hypo signal or intermediate signal intensity. Also, tumor can have appearance of a central scar. But the important point in here, oncytomas, which are the benign tumors that originated from the intercalated type B cells, can also have the appearance of central scar.

4. Collecting Duct Carcinoma (Bellini Duct Carcinoma)

This is a very rare variant in the imaging classification of the Renal Cell Carcinoma. It represents less than 1% of all malignant tumors of the kidney. Still, it is very important because of its aggressive progression. [20]

Approximately 30% of the collecting duct carcinoma patients, diagnosed with metastasis and 60 to 70% of them lose their lives within 2 year. So, prognosis is really unfavorable.

In these tumors, which usually present after the age of 50, male predominance is more prominent.

Histological examination

This tumor is mostly characterized by the cells which have features of the irregularity and infiltrative. They arrange in walls of the collecting ducts and show remarkable desmoplasia. [21]

Imaging findings

In imaging studies collecting duct carcinoma mostly seen as heterogenous lesions with the features of hemorrhage, necrosis, cystic component and calcification. For this reason, these tumors generally have extremely variable intensities in T2-weighted MRI studies.

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While larger tumors may invade the cortex of the kidney, most of them originate in the medulla. Because of all of these, differential diagnosis with the transitional cell carcinoma become very important. [22]

Most of these tumors are solid, but there may be also complex lesions.

5. Multilocular Cystic Renal Cell Carcinoma

This is a very rare histological subtype of all Renal Cell Carcinomas which has incidence of approximately 1-4%. It generally presents with a fibrous capsule and multiseptated cysts.

The one of the most important part of these lesions is, they have the best prognosis and can be completely cured. There are not any described metastasis or recurrence.

Histological examination

In histological analysis of these lesions, there are serous or gelatinous cysts with hemorrhagic areas. These cysts are also lined by single layer of epithelial cells which have clear cytoplasm.

There are no solid nodule development multilocular cystic carcinoma. This differentiates it from the collecting duct carcinoma. [23]

Imaging findings

In both CT and MRI scans, they present as complex cysts. These cysts classified according to the Bosniak system, from II-F to IV categories. [9]

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6. Medullary Renal Cell Carcinoma

This histological subtype is firstly described by Davis in 1995. It has very aggressive progression. In addition, medullary cell carcinomas originate from the distal nephrons.

One of most important features of this tumor is that it has an association with the sickle cell disease. Because of that association medullary cell carcinoma typically affects young patients, such as second or third decades of lives.

Imaging findings

At all of the imaging studies such as CT or MRI scan, this tumor present itself as infiltrating lesions. With these features it causes calyceal obstruction and dilatation. 

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Besides, medullary cell carcinoma is a hypo vascular tumor and usually associated with locoregional adenopathy. [24]

7. Renal Cell Carcinoma Associated with Chromosome’s Short Arm Translocation

This is the most recent described subtype in the imaging classification of Renal Cell Carcinoma. Renal Cell Carcinoma associated with chromosome’s short arm translocation is very rare neoplasm and it involves the TFE3 gene and 11 Xp11.2 chromosome’s short arm translocation. [12]

This lesion mostly seen in children and young adults. It is mostly present with localized mass with pseudo capsule. With this feature it resembles the clear cell carcinoma. However, it also presents with papillary projections and also with these features it resembles the papillary cell carcinoma.

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Besides, it has more indolent prognosis when it compared to the clear cell carcinoma. [25]

In imaging studies, renal mucinous tubular and spindle cell carcinoma is seen as heterogenous and hyper vascular lesion. Apart from that there is no characteristic finding.

8. Renal Cell Carcinoma Associated with Neuroblastoma

Renal cell carcinoma which associated with neuroblastoma also is very rare class in the imaging classification of Renal Cell Carcinoma. There are only a few case reports that described children who developed Renal Cell Carcinoma after the treatment of neuroblastoma. [26]

It can be both unilateral o bilateral and usually affects the young patients such as age of 13.

In some rare cases, this tumor is described as well delimited, hypo vascular lesion with indolent behavior. [25]

9. Unclassified Renal Cell Carcinoma

Still in the imaging classification of Renal Cell Carcinoma, there are 4% to 6% of tumors are unclassified. [3]

The tumors which have worst prognosis among all of the subtypes, in this category.

Tumors in these categories usually have the features of heterogeneousity and high-grade.

There some features to describe and identify these unclassified lesions, as follows; [27]

  • Sarcomatoid component without any recognized epithelial elements
  • Mucin production
  • Mixed stromal and epithelial elements
  • Non-recognized cell types


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