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Renal tumours
Current Diagnostic Pathology (2001) 7, 78d80 ^ 2001 Harcourt Publishers Ltd doi:10.1054/cdip.2000.0054, available online at http://www.idealibrary.com on
SELF-ASSESSMENT
Renal tumours Answers Answer 1 The tumour has a disorganised architecture and is composed of cells with eosinophilic cytoplasm and moderate nuclear pleomorphism. The cytoplasm is finely granular while the nuclei contain focally prominent nucleoli and frequent mitoses. Areas of necrosis were identified microscopically (Fig. 7). Neither lymphovascular space nor perineural invasion were identified in multiple sections examined. The diagnosis is renal cell carcinoma, granular cell type, Fuhrman nuclear grade 2/4.1,2,3 Granular renal cell carcinomas constitute approximately 7% of renal neoplasms. Like the majority of renal tumour types, their incidence increases with advancing age and they are often clinically silent until at late stage. They are an aggressive subtype of renalcell carcinoma and local invasion, particularly of the renal vein, is characteristic. Haemorrhage and necrosis within the tumour are more likely to be present than in the commoner clear cell renal parenchymal carcinoma. Ancillary studies are of limited assistance in the diagnosis of granular renal cell carcinoma. Both low molecular weight cytokeratin and vimentin immunohistochemical stains are usually positive while Hale’s colloidal iron stain may show droplet positivity. Electron microscopic examination shows that the tumour cells are rich in mitochondria, rough endoplasmic reticulum and Golgi apparatus. Karyotypic analysis may show a deletion at chromosome 3p13. Granular renal cell carcinomas usually have a high nuclear grade and often show vascular invasion and distant metastases at the time of presentation. Their prognosis, therefore, is generally poor except in cases where they are detected at an early stage.
nucleoli are identified. Focal extension of the tumour through the renal capsule was demonstrated histologically. Extensive sampling of the tumour revealed no evidence of necrosis, papillary differentiation, lymphovascular or perineural invasion. Very few mitoses were identified. The diagnosis is renal cell carcinoma, chromophobe cell type, grade 2/4.1,4 Chromophobe renal cell carcinoma is a distinctive variant of renal cell carcinoma, which may be confused with oncocytoma as well as other renal cell carcinoma variants, such as granular renal cell carcinoma.5,6 These tumours account for approximately 5% of renal neoplasms. An admixture of pale, transparent and eosinophilic granular cells is the typical histological appearance. Electron microscopy demonstrates the presence of numerous microvesicles in the cytoplasm, the presence of which may also be demonstrated using Hale’s colloidal iron stain. The vesicles tend to concentrate around the nucleus, accounting for the aforementioned perivascular halo. Immunohistochemical studies show that the tumour cells are positive with low molecular weight cytokeratins and negative with vimentin. This helps distinguish them from granular renal cell carcinoma, which is usually positive for vimentin. Karyotypic analysis shows a hypodiploid chromosome number. These tumours are said to have a low malignant potential and are usually localised to the kidney at
Answer 2 The tumour is composed of sheets of cells with eosinophilic or clear cytoplasm separated by fine septa. Some cells show clearing of the cytoplasm around the nucleus. The nuclei show mild to moderate pleomorphism (Fuhrman Grade 2/4).2 Occasional
Figure 7
RENAL TUMOURS
79
Figure 8
Figure 9
Table 1 Summary of the features that distinguish eosinophilic renal tumours
Hales colloidal iron Immunohistochemistry low MW cytokeratin vimentin Ultrastructure Behaviour
RCC granular cell type
RCC chromophobe
Oncocytoma
$droplets
#
!
# # Mitochondria, RER, golgi Aggressive
# ! Mitochondria, microvesicles Low malignant potential
# ! Mitochondria Benign
presentation. Their prognosis is, therefore, generally good.
Answer 3 The tumour is composed of cells with abundant eosinophilic cytoplasm arranged in solid and tubular growth patterns. While most of the nuclei show low grade cytological features, scattered nodular proliferations show more pleomorphic cells and multinucleate cells (Fig. 8). Nucleoli are inconspicuous. Other nodules show less mature oncocytes oncoblasts (Fig. 9). Extensive sampling of the tumour revealed no evidence of necrosis, papillary differentiation, lymphovascular or perineural invasion. Very occasional mitoses were seen. Hale’s colloidal iron stain was negative, as was vimentin. Low molecular weight cytokeratins were positive. Electron microscopy showed abundant mitochrondria in the cytoplasm of the tumour cells. This combination of findings is diagnostic of renal oncocytoma.5 Oncocytomas account for approximately 3% of all renal neoplasms. They are now regarded as benign tumours. Previous reports of aggressive behaviour in some oncocytomas are now felt to be due to
misdiagnosis of some granular cell and chromophobe tumours as oncocytomas. Therefore, the distinction between these tumour types (Table 1) is an important one as their outcome is quite different. The most useful distinguishing features include the lack of the following: clear cell areas, significant lesional necrosis and renal vein invasion in oncocytomas. Anaplastic nuclear features such as the presence of numerous mitoses and prominent nucleoli favour a malignant diagnosis. However, some atypical features may be seen in oncocytomas such as the focal nuclear pleomorphism identified in this case as well as perinephric fat involvement and intralesional haemorrhage. Ultrastructural demonstration of welldeveloped organelles other than mitochondria favours a malignant diagnosis in this setting. The prognosis of renal oncocytoma is excellent.
REFERENCES 1. Murphy W M, Beckwith J B, Farrow G M. Tumors of the kidney, bladder and related urinary strictures. In: Atlas of Tumor Pathology, Armed Forces Institute of Pathology, 1994. 2. Fuhrman S A, Lasky L C, Limas S C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982; 6: 655}663.
80 3. Reuter V E. Renal tumours exhibiting granular cytoplasm. Semin Diagn Pathol 1999; 16: 135}145. 4. Akhtar M, Kardar H, Linjewi T, McClintock J, Ashraf Ali M. Chromophobe cell carcinoma of kidney. Am J Surg Path 1995; 19: 1245}1246. 5. Amin M B, Crotty T B, Tickoo S K, Farrow G M. Renal oncocytoma: a reappraisal of morphologic features with clinicopathological findings in 80 cases. Am J Surg Pathol 1997; 21: 1}12. 6. Latham B, Dickerson G R, Oliva E. Subtypes of chromophobe cell renal carcinoma. Am J Surg Pathol 1999; 23: 530}535.
CURRENT DIAGNOSTIC PATHOLOGY This self-assessment was compiled by: M. Leader and C. Muldoon Department of Pathology Beaumont Hospital Dublin 9 Ireland Fax: 00353 1 8370687; E-mail: [email protected]
SELF-ASSESSMENT
Renal tumours Answers Answer 1 The tumour has a disorganised architecture and is composed of cells with eosinophilic cytoplasm and moderate nuclear pleomorphism. The cytoplasm is finely granular while the nuclei contain focally prominent nucleoli and frequent mitoses. Areas of necrosis were identified microscopically (Fig. 7). Neither lymphovascular space nor perineural invasion were identified in multiple sections examined. The diagnosis is renal cell carcinoma, granular cell type, Fuhrman nuclear grade 2/4.1,2,3 Granular renal cell carcinomas constitute approximately 7% of renal neoplasms. Like the majority of renal tumour types, their incidence increases with advancing age and they are often clinically silent until at late stage. They are an aggressive subtype of renalcell carcinoma and local invasion, particularly of the renal vein, is characteristic. Haemorrhage and necrosis within the tumour are more likely to be present than in the commoner clear cell renal parenchymal carcinoma. Ancillary studies are of limited assistance in the diagnosis of granular renal cell carcinoma. Both low molecular weight cytokeratin and vimentin immunohistochemical stains are usually positive while Hale’s colloidal iron stain may show droplet positivity. Electron microscopic examination shows that the tumour cells are rich in mitochondria, rough endoplasmic reticulum and Golgi apparatus. Karyotypic analysis may show a deletion at chromosome 3p13. Granular renal cell carcinomas usually have a high nuclear grade and often show vascular invasion and distant metastases at the time of presentation. Their prognosis, therefore, is generally poor except in cases where they are detected at an early stage.
nucleoli are identified. Focal extension of the tumour through the renal capsule was demonstrated histologically. Extensive sampling of the tumour revealed no evidence of necrosis, papillary differentiation, lymphovascular or perineural invasion. Very few mitoses were identified. The diagnosis is renal cell carcinoma, chromophobe cell type, grade 2/4.1,4 Chromophobe renal cell carcinoma is a distinctive variant of renal cell carcinoma, which may be confused with oncocytoma as well as other renal cell carcinoma variants, such as granular renal cell carcinoma.5,6 These tumours account for approximately 5% of renal neoplasms. An admixture of pale, transparent and eosinophilic granular cells is the typical histological appearance. Electron microscopy demonstrates the presence of numerous microvesicles in the cytoplasm, the presence of which may also be demonstrated using Hale’s colloidal iron stain. The vesicles tend to concentrate around the nucleus, accounting for the aforementioned perivascular halo. Immunohistochemical studies show that the tumour cells are positive with low molecular weight cytokeratins and negative with vimentin. This helps distinguish them from granular renal cell carcinoma, which is usually positive for vimentin. Karyotypic analysis shows a hypodiploid chromosome number. These tumours are said to have a low malignant potential and are usually localised to the kidney at
Answer 2 The tumour is composed of sheets of cells with eosinophilic or clear cytoplasm separated by fine septa. Some cells show clearing of the cytoplasm around the nucleus. The nuclei show mild to moderate pleomorphism (Fuhrman Grade 2/4).2 Occasional
Figure 7
RENAL TUMOURS
79
Figure 8
Figure 9
Table 1 Summary of the features that distinguish eosinophilic renal tumours
Hales colloidal iron Immunohistochemistry low MW cytokeratin vimentin Ultrastructure Behaviour
RCC granular cell type
RCC chromophobe
Oncocytoma
$droplets
#
!
# # Mitochondria, RER, golgi Aggressive
# ! Mitochondria, microvesicles Low malignant potential
# ! Mitochondria Benign
presentation. Their prognosis is, therefore, generally good.
Answer 3 The tumour is composed of cells with abundant eosinophilic cytoplasm arranged in solid and tubular growth patterns. While most of the nuclei show low grade cytological features, scattered nodular proliferations show more pleomorphic cells and multinucleate cells (Fig. 8). Nucleoli are inconspicuous. Other nodules show less mature oncocytes oncoblasts (Fig. 9). Extensive sampling of the tumour revealed no evidence of necrosis, papillary differentiation, lymphovascular or perineural invasion. Very occasional mitoses were seen. Hale’s colloidal iron stain was negative, as was vimentin. Low molecular weight cytokeratins were positive. Electron microscopy showed abundant mitochrondria in the cytoplasm of the tumour cells. This combination of findings is diagnostic of renal oncocytoma.5 Oncocytomas account for approximately 3% of all renal neoplasms. They are now regarded as benign tumours. Previous reports of aggressive behaviour in some oncocytomas are now felt to be due to
misdiagnosis of some granular cell and chromophobe tumours as oncocytomas. Therefore, the distinction between these tumour types (Table 1) is an important one as their outcome is quite different. The most useful distinguishing features include the lack of the following: clear cell areas, significant lesional necrosis and renal vein invasion in oncocytomas. Anaplastic nuclear features such as the presence of numerous mitoses and prominent nucleoli favour a malignant diagnosis. However, some atypical features may be seen in oncocytomas such as the focal nuclear pleomorphism identified in this case as well as perinephric fat involvement and intralesional haemorrhage. Ultrastructural demonstration of welldeveloped organelles other than mitochondria favours a malignant diagnosis in this setting. The prognosis of renal oncocytoma is excellent.
REFERENCES 1. Murphy W M, Beckwith J B, Farrow G M. Tumors of the kidney, bladder and related urinary strictures. In: Atlas of Tumor Pathology, Armed Forces Institute of Pathology, 1994. 2. Fuhrman S A, Lasky L C, Limas S C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 1982; 6: 655}663.
80 3. Reuter V E. Renal tumours exhibiting granular cytoplasm. Semin Diagn Pathol 1999; 16: 135}145. 4. Akhtar M, Kardar H, Linjewi T, McClintock J, Ashraf Ali M. Chromophobe cell carcinoma of kidney. Am J Surg Path 1995; 19: 1245}1246. 5. Amin M B, Crotty T B, Tickoo S K, Farrow G M. Renal oncocytoma: a reappraisal of morphologic features with clinicopathological findings in 80 cases. Am J Surg Pathol 1997; 21: 1}12. 6. Latham B, Dickerson G R, Oliva E. Subtypes of chromophobe cell renal carcinoma. Am J Surg Pathol 1999; 23: 530}535.
CURRENT DIAGNOSTIC PATHOLOGY This self-assessment was compiled by: M. Leader and C. Muldoon Department of Pathology Beaumont Hospital Dublin 9 Ireland Fax: 00353 1 8370687; E-mail: [email protected]