Imaging Analysis

Renal cell carcinoma: A correlation of radiological and pathological findings

A 49-year-old female with a history of nephrolithiasis and renal cysts underwent routine imaging and was found to have an incidental left renal mass.

She was clinically asymptomatic and denied any hematuria, abdominal pain or any other systemic symptoms.

A renal ultrasound showed an isoechoic lesion in the lateral aspect of the left interpolar region measuring 2.5 cm × 2.5 cm, consistent with a solid renal mass. MRI of the abdomen confirmed a well-defined lesion measuring 2.9 cm × 2 cm in the mid-lower left kidney. The dynamic study indicated enhancement with a differential diagnosis of renal cell carcinoma with hemorrhagic component.

Figure 1
Figure 1. Noncontrast CT of the abdomen demonstrates a focal mass (arrow) in the lateral aspect of the mid-level of the left kidney. This homogenous focal mass demonstrates slightly higher attenuation, though not significantly, measuring approximately 28 Hounsfield units (HU). The remaining uninvolved portions of the kidney demonstrate approximately 22 HU attenuation.

Images courtesy of M. Ghesani, MD, reprinted with permission

She underwent left radical nephrectomy. The gross pathology specimen showed a 2.8 cm × 2.4 cm × 2 cm, well-circumscribed, golden-yellow, round mass. The mass was unifocal, and histological analysis showed a 2.8-cm papillary renal cell carcinoma showing type 1 tubulopapillary pattern.

The surgical margins were free of tumor with no evidence of lymphatic or venous invasion. She was surgically staged I. She did well postoperatively with no complications. Her routine follow-up scans showed no evidence of recurrent disease.

Figure 2
Figure 2. Ultrasound of the kidney demonstrates a probable sold left renal mass, which measured approximately 2.5 cm × 2.5 cm.

Discussion

Renal cell carcinoma (RCC) includes 80% to 85% of all primary renal neoplasms. They originate primarily from the renal cortex.

Primary renal medullary carcinoma is a rare form of RCC seen in patients with sickle cell trait. An estimated 61,000 cases of RCC were diagnosed in the United States in 2011, with about 13,000 deaths.

The prognosis is dependent upon the stage at presentation, with 5-year survival varying from 90% for localized disease to less than 10% for metastatic disease.

Different histological subtypes of RCC have been identified, and they differ in their prognosis and genetic alterations. Overall, clear cell subtype accounts for 75% to 85% of all renal cell carcinomas. The next most common is papillary subtype (10% to 15%), followed by chromophobic (5% to 10%), oncocytic and collecting duct tumors.

In a 2006 study in RadioGraphics, Prasad and colleagues described various radiographic findings in different histological subtypes. Clear cell RCC are hypervascular secondary to inactivation of von Hippel-Lindau gene with subsequent activation of various growth factor genes involved in angiogenesis and metastasis. The degree of enhancement seen on a contrast study can be useful in distinguishing clear cell RCC from nonclear variants.

Figure 3aFigure 3bFigure 3c
Figure 3. MRI of the abdomen, high-resolution SPGR pulse sequence (FAME sequence), dynamic gadolinium-contrast kidney imaging. This study demonstrates a mid-left homogenous kidney mass, which appears iso-intense on noncontrast imaging (Figure 3a). Additionally, this left renal lesion shows enhancement in the cortico-medullary (Figure 3b) and nephrogenic phases (Figure 3c). These findings are consistent with a renal cell carcinoma. The mass does enhance; however, the mass does not enhance avidly upon gadolinium administration. In fact, measurements show it only enhances approximately 50% when compared with the level of enhancement of the surrounding uninvolved renal parenchyma.

These tumors also can demonstrate areas of hemorrhage and necrosis that can be visible on the imaging studies. The papillary variant, however, is more homogeneous and hypovascular than the clear cell. These tumors frequently are multifocal and bilateral, and they commonly present as small tumors. Rarely, macroscopic fat deposits on CT have been described in papillary tumors. These are related to the presence of foamy macrophages with cholesterol necrosis, a pathological finding very suggestive of papillary cell carcinoma.

Chromophobe variant and oncocytomas originate from the intercalated cells of the collecting system, and they demonstrate similar genetic alteration and imaging features. These are hyperechoic on ultrasonography and appear homogeneous on contrast enhanced studies. They often are well circumscribed and are relatively hypovascular. Collecting duct tumors and renal medullary carcinoma are aggressive tumors and present with infiltrating features on imaging. These usually are heterogeneous with areas of hemorrhage, necrosis and calcifications.

Papillary RCC is readily distinguished from clear cell RCC based on microscopic findings. Papillary RCC is characterized by a complex papillary architecture and is subtyped into two groups depending on the histological findings.

In type 1, a single layer of cells with scanty cytoplasm lines the papillae. Additional, the stroma may be infiltrated by neutrophils or foamy macrophages, and psammoma bodies are commonly present. In type 2, a pseudostratified epithelium composed of cells with abundant acidophilic cytoplasm line the papillae.

4a4b
Figure 4. A low-power hematoxylin and eosin (H&E) slide demonstrates a well-circumscribed tumor with a complex tubulopapillary pattern and compressed surrounding renal parenchyma (Figure 4a). A high-power H&E slide depicts papillae lined by a single layer of cells with scanty cytoplasm (Figure 4b).

Regardless of morphologic appearance, the clinical outcome is similar. Although clear cell RCC may have a papillary architecture, the cells should contain cytoplasm in contrast to the acidophilic cytoplasm seen in papillary RCC.

Papillary RCC also can be distinguished from clear cell RCC based on cytogenetics. Papillary RCC present with trisomies of chromosomes 3q, 7, 8, 12, 16, 17 and 20, and loss of Y chromosome, and it does not show loss of 3p, which often is present in clear cell RCC.

Thus, these renal cell carcinomas include several distinct subtypes characterized by different radiological and pathological findings. With the development of new targeted agents, it also is important to recognize these different subtypes, as these can show different response to treatment. For example, sorafenib (Nexavar, Bayer HealthCare) and sunitinib (Sutent, Pfizer) are shown to be active in clear cell carcinoma. Everolimus (Afinitor, Novartis) and a new multitargeted tyrosine kinase inhibitor, cabozantinib (Exelixis), have shown to have some activity in papillary tumors. The radiological features can provide important information in the pretreatment diagnosis of these tumors.

References:

  • Lesavre A. AJR Am J Roentgenol. 2003;181:143-145.
  • Prasad SR. Radiographics. 2006;26:1795-1806.
  • Rosai J. Rosai and Ackerman’s Surgical Pathology. 10th ed. St. Louis: Mosby; 2011.
  • Siegel R. CA Cancer J Clin. 2011;61:212-236.

For more information:

  • Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons, and a HemOnc Today section editor. Matthew Teng, MD, is a resident in radiology at St Luke’s-Roosevelt Hospital Center. Sumit Talwar, MD, is a fellow in hematology/oncology at St. Luke’s-Roosevelt Hospital Center. Darren Buonocore, MD, is a postdoctoral residency fellow in pathology at St. Luke’s-Roosevelt Hospital Center. Peerapod Chiowanich, MD, is an assistant attending radiologist at St. Luke’s-Roosevelt Hospital Center. Disclosure: Drs. Ghesani, Teng, Talwar, Buonocore and Chiowanich report no relevant financial disclosures.

A 49-year-old female with a history of nephrolithiasis and renal cysts underwent routine imaging and was found to have an incidental left renal mass.

She was clinically asymptomatic and denied any hematuria, abdominal pain or any other systemic symptoms.

A renal ultrasound showed an isoechoic lesion in the lateral aspect of the left interpolar region measuring 2.5 cm × 2.5 cm, consistent with a solid renal mass. MRI of the abdomen confirmed a well-defined lesion measuring 2.9 cm × 2 cm in the mid-lower left kidney. The dynamic study indicated enhancement with a differential diagnosis of renal cell carcinoma with hemorrhagic component.

Figure 1
Figure 1. Noncontrast CT of the abdomen demonstrates a focal mass (arrow) in the lateral aspect of the mid-level of the left kidney. This homogenous focal mass demonstrates slightly higher attenuation, though not significantly, measuring approximately 28 Hounsfield units (HU). The remaining uninvolved portions of the kidney demonstrate approximately 22 HU attenuation.

Images courtesy of M. Ghesani, MD, reprinted with permission

She underwent left radical nephrectomy. The gross pathology specimen showed a 2.8 cm × 2.4 cm × 2 cm, well-circumscribed, golden-yellow, round mass. The mass was unifocal, and histological analysis showed a 2.8-cm papillary renal cell carcinoma showing type 1 tubulopapillary pattern.

The surgical margins were free of tumor with no evidence of lymphatic or venous invasion. She was surgically staged I. She did well postoperatively with no complications. Her routine follow-up scans showed no evidence of recurrent disease.

Figure 2
Figure 2. Ultrasound of the kidney demonstrates a probable sold left renal mass, which measured approximately 2.5 cm × 2.5 cm.

Discussion

Renal cell carcinoma (RCC) includes 80% to 85% of all primary renal neoplasms. They originate primarily from the renal cortex.

Primary renal medullary carcinoma is a rare form of RCC seen in patients with sickle cell trait. An estimated 61,000 cases of RCC were diagnosed in the United States in 2011, with about 13,000 deaths.

The prognosis is dependent upon the stage at presentation, with 5-year survival varying from 90% for localized disease to less than 10% for metastatic disease.

Different histological subtypes of RCC have been identified, and they differ in their prognosis and genetic alterations. Overall, clear cell subtype accounts for 75% to 85% of all renal cell carcinomas. The next most common is papillary subtype (10% to 15%), followed by chromophobic (5% to 10%), oncocytic and collecting duct tumors.

In a 2006 study in RadioGraphics, Prasad and colleagues described various radiographic findings in different histological subtypes. Clear cell RCC are hypervascular secondary to inactivation of von Hippel-Lindau gene with subsequent activation of various growth factor genes involved in angiogenesis and metastasis. The degree of enhancement seen on a contrast study can be useful in distinguishing clear cell RCC from nonclear variants.

Figure 3aFigure 3bFigure 3c
Figure 3. MRI of the abdomen, high-resolution SPGR pulse sequence (FAME sequence), dynamic gadolinium-contrast kidney imaging. This study demonstrates a mid-left homogenous kidney mass, which appears iso-intense on noncontrast imaging (Figure 3a). Additionally, this left renal lesion shows enhancement in the cortico-medullary (Figure 3b) and nephrogenic phases (Figure 3c). These findings are consistent with a renal cell carcinoma. The mass does enhance; however, the mass does not enhance avidly upon gadolinium administration. In fact, measurements show it only enhances approximately 50% when compared with the level of enhancement of the surrounding uninvolved renal parenchyma.

These tumors also can demonstrate areas of hemorrhage and necrosis that can be visible on the imaging studies. The papillary variant, however, is more homogeneous and hypovascular than the clear cell. These tumors frequently are multifocal and bilateral, and they commonly present as small tumors. Rarely, macroscopic fat deposits on CT have been described in papillary tumors. These are related to the presence of foamy macrophages with cholesterol necrosis, a pathological finding very suggestive of papillary cell carcinoma.

Chromophobe variant and oncocytomas originate from the intercalated cells of the collecting system, and they demonstrate similar genetic alteration and imaging features. These are hyperechoic on ultrasonography and appear homogeneous on contrast enhanced studies. They often are well circumscribed and are relatively hypovascular. Collecting duct tumors and renal medullary carcinoma are aggressive tumors and present with infiltrating features on imaging. These usually are heterogeneous with areas of hemorrhage, necrosis and calcifications.

Papillary RCC is readily distinguished from clear cell RCC based on microscopic findings. Papillary RCC is characterized by a complex papillary architecture and is subtyped into two groups depending on the histological findings.

In type 1, a single layer of cells with scanty cytoplasm lines the papillae. Additional, the stroma may be infiltrated by neutrophils or foamy macrophages, and psammoma bodies are commonly present. In type 2, a pseudostratified epithelium composed of cells with abundant acidophilic cytoplasm line the papillae.

4a4b
Figure 4. A low-power hematoxylin and eosin (H&E) slide demonstrates a well-circumscribed tumor with a complex tubulopapillary pattern and compressed surrounding renal parenchyma (Figure 4a). A high-power H&E slide depicts papillae lined by a single layer of cells with scanty cytoplasm (Figure 4b).

Regardless of morphologic appearance, the clinical outcome is similar. Although clear cell RCC may have a papillary architecture, the cells should contain cytoplasm in contrast to the acidophilic cytoplasm seen in papillary RCC.

Papillary RCC also can be distinguished from clear cell RCC based on cytogenetics. Papillary RCC present with trisomies of chromosomes 3q, 7, 8, 12, 16, 17 and 20, and loss of Y chromosome, and it does not show loss of 3p, which often is present in clear cell RCC.

Thus, these renal cell carcinomas include several distinct subtypes characterized by different radiological and pathological findings. With the development of new targeted agents, it also is important to recognize these different subtypes, as these can show different response to treatment. For example, sorafenib (Nexavar, Bayer HealthCare) and sunitinib (Sutent, Pfizer) are shown to be active in clear cell carcinoma. Everolimus (Afinitor, Novartis) and a new multitargeted tyrosine kinase inhibitor, cabozantinib (Exelixis), have shown to have some activity in papillary tumors. The radiological features can provide important information in the pretreatment diagnosis of these tumors.

References:

  • Lesavre A. AJR Am J Roentgenol. 2003;181:143-145.
  • Prasad SR. Radiographics. 2006;26:1795-1806.
  • Rosai J. Rosai and Ackerman’s Surgical Pathology. 10th ed. St. Louis: Mosby; 2011.
  • Siegel R. CA Cancer J Clin. 2011;61:212-236.

For more information:

  • Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons, and a HemOnc Today section editor. Matthew Teng, MD, is a resident in radiology at St Luke’s-Roosevelt Hospital Center. Sumit Talwar, MD, is a fellow in hematology/oncology at St. Luke’s-Roosevelt Hospital Center. Darren Buonocore, MD, is a postdoctoral residency fellow in pathology at St. Luke’s-Roosevelt Hospital Center. Peerapod Chiowanich, MD, is an assistant attending radiologist at St. Luke’s-Roosevelt Hospital Center. Disclosure: Drs. Ghesani, Teng, Talwar, Buonocore and Chiowanich report no relevant financial disclosures.