|Year : 2012 | Volume
| Issue : 3 | Page : 178-180
Clear cell renal carcinoma with areas of chromophobe renal cell carcinoma
Rekha Thodavadi Subbanna, Nandini Nandish Manoli
Department of Pathology, JSS Medical College, Constituent College of JSS University, Mysore, India
|Date of Web Publication||26-Dec-2012|
Rekha Thodavadi Subbanna
818, 13th Main, 4th Stage, T. K. Extension, Mysore - 570 009
Source of Support: None, Conflict of Interest: None
The classification of renal cell carcinoma (RCC) is based upon various histological features which aids in determining the treatment and prognosis. We report a unique case of RCC displaying features of predominantly clear cell RCC with areas of chromophobe RCC in an unusual edematous background. The tumor cells from chromophobe RCC were positive for Hales colloidal iron stain. On Immunohistochemistry majority of them were positive for vimentin and CD10, the markers of clear cell RCC with scattered cells positive for cytokeratin 7, marker of chromophobe RCC. It was grade 4 malignant tumor according to Fuhrman nuclear grading.
Keywords: Renal cell carcinoma, chromophobe renal cell carcinoma, clear cell renal cell carcinoma, hales colloidal iron stain
|How to cite this article:|
Subbanna RT, Manoli NN. Clear cell renal carcinoma with areas of chromophobe renal cell carcinoma. Int J Health Allied Sci 2012;1:178-80
|How to cite this URL:|
Subbanna RT, Manoli NN. Clear cell renal carcinoma with areas of chromophobe renal cell carcinoma. Int J Health Allied Sci [serial online] 2012 [cited 2019 Sep 20];1:178-80. Available from: http://www.ijhas.in/text.asp?2012/1/3/178/105082
| Introduction|| |
Renal cell carcinoma accounts for 3% of all malignancies. The incidence of clear cell RCC is 80% and chromophobe RCC is 5%, based on 2004-WHO classification of adult renal tumors.  The clear cell RCC is known to have unfavorable prognosis and has a few difficulties to diagnose on histopathological study, whereas chromophobe RCC has favorable prognosis. The cell of origin, genetic etiology and immunohistochemistry are different in these two subtypes. The present rare case displayed both features the cause of diagnostic ambiguity.
| Case Report|| |
Fifty seven year old man presented with mass per abdomen. He had hematuria, elevated levels of blood urea of 44 mg/ dl and serum creatinine of 1.8 mg/dl. Computerized tomography (CT) abdomen showed a mass measuring 6×3 cm in the upper pole of left kidney. Grossly, the outer surface of left nephrectomy was smooth and the cut section revealed a well circumscribed grey-brown tumor measuring 4×3cm in the upper pole with areas of hemorrhage and cystic change. Capsule was easily stripped off. Histopathology displayed a well defined tumor, with tumor cells arranged in nests, cords and tubules in an edematous stroma [Figure 1]a Individual tumor cells at some places showed eosinophilic large polygonal cells with hyperchromatic, pleomorphic nuclei with good number of binucleated and multinucleated cells [Figure 1]b. At other areas the tumor cells had abundant eosinophilic cytoplasm with raisinoid, vesicular nuclei, prominent nucleoli and perinuclear halo [Figure 2]a. Hale's colloidal iron stain showed diffuse, cytoplasmic positivity [Figure 2]b in the chromophobe RCC component. On IHC scattered cells expressed CK7, while rest of the tumor was positive for vimentin and CD10. A final diagnosis of clear cell RCC with areas of chromophobe RCC was achieved. The "Fuhrman nuclear grading" was grade four.
|Figure 1: (a) RCC – Islands of pleomorphic tumor cells in edematous stroma (H and E, ×10). (b) RCC – Clear cell type with binucleated and multinucleated cells, Fuhrman grade 4 (H and E, 15;40)|
Click here to view
|Figure 2: (a) Chromophobe RCC showing binucleation, rasinoid nucleus with perinuclear halo (H and E, ×40). (b) Chromophobe RCC showing diffuse fine cytoplasmic reaction with Hale's colloidal iron stain (H and E, ×40)|
Click here to view
| Discussion|| |
Earlier RCC was considered as a single entity. Since it was resistant to chemotherapy and radiotherapy total nephrectomy was considered as treatment of choice. Later based on morphology RCCs were classified in which 70-80% of them belonged to clear cell RCC and the treatment continued to be total nephrectomy. But now 2004-WHO classification is based on cell of origin, histomorphology, IHC and ultrastructural features  which has been found to have variation in the prognosis of different subtypes. Clear cell RCC has poor prognosis compared to non-clear cell RCC. Among non-clear cell RCC, chromophobe RCC has a better prognosis.  It has become essential to know the precise histological subtype since the therapeutic options varies. The anti-Vascular Endothelial Growth Factor, , Platelet Derived Growth Factor receptor inhibitor  in clear cell RCC and tyrosine kinase inhibitors,  mTOR inhibitors , in chromophobe RCC has shown promising results.
In the present case grossly the presence of hemorrhage and cystic change rules out benign tumor. On microscopy the tumor cells had eosinophilc cytoplasm; therefore the differential diagnoses include type 2 papillary RCC, granular variant of conventional RCC and chromophobe RCC. In type 2 papillary RCC, the cells are arranged in a papillary pattern having fibrovascular core with aggregates of foamy macrophages, calcified concretions and frequent hemosiderin granules  which were absent in the present case.
The clear cell RCC is the commonest subtype of RCC. The cell of origin is the lining cells of proximal convoluted tubule. The tumor cells are arranged as solid sheets or tubules or trabacular pattern separated by delicate branching vasculature. They have clear to granular cytoplasm. The term "granular cell" indicates RCC with acidophilic cytoplasm, a specific tumor category in the 1998 WHO classification. RCCs with this morphology are now included among the clear cell type based on the absence of genetic and clinical differences between both types. 
Chromophobe RCC was first reported in 1985 and the name is derived due to the presence of eosinophilic cytoplasm. In chromophobe RCC, the cell of origin is intercalated cells of collecting duct system. Unlike the usual solid growth pattern of chromophobe RCC, the present case had tumor cells arranged in nests, cords and tubules in an edematous stroma which is similar to that of oncocytoma.  A few cases of chromophobe RCC with oncocytoma-like pattern are reported and authors have attributed the cause to, the same cell of origin in both chromophobe RCC and oncocytoma.  Renal oncocytosis, oncocytoma and chromophobe RCC are suggested to represent the various phases of the morphological spectrum. 
The routine Hematoxylin and Eosin stain is sufficient to histopathologically subtype RCC, but several authors have experienced difficulty, whenever the tumor cells have eosinophilic cytoplasm, to differentiate between oncocytoma, chromophobe RCC and clear cell RCC. Ancillary techniques utilized by various authors include vimentin ,, glutathione S?transferase -transferase α parvalbumin , c-kit  CD 10 ,,, CK 7 ,, CK8  CK18  CK19  CK20  EMA  CD 117  epithelial cell adhesion molecule  alpha-methyl-acyl-CoA racemase  RCC marker , Hales colloidal iron stain , and ultrastructural features  are necessary to arrive at the correct diagnosis.
Geramizadeh et al, has found in Chromophobe RCC: Vimentin, CD10 and RCC marker - negative, CK 7 and diffuse fine reticular cytoplasmic pattern of Hale's colloidal iron positive; Oncocytoma: Vimentin, CK 7, RCC marker, CD10 and Hale's colloidal iron - negative; Clear cell RCC: CK 7 and Hale's colloidal iron - negative, Vimentin, CD10 and RCC marker - positive.
In the present case due to the presence of edematous stroma, focal delicate branching vasculature and positive Hales colloidal iron stain a diagnosis of chromophobe RCC was in consideration. Because of usnusual morphological features IHC was requested where scattered cells expressed CK7, while rest of the tumor was positive for vimentin and CD10 and an impression of clear cell RCC with areas of chromophobe RCC was obtained.
According to Pradhan et al.,  the diagnostic discordance in majority of cases [12/28] is between clear cell and chromophobe RCC similar to our case. The ancillary techniques aided to categories into one of the RCC subtype. But unusually the present case had features of both RCC subtypes. Clinically the treatment and prognosis varies between the two and it is important to distinguish the two entities. The present case, two years after nephrectomy is doing well.
Electron microscopy and fluorescence in situ hybridization can be suggested depending upon availability and affordability.
| Acknowledgment|| |
Dr. G. V. Manjunath, Prof. and HOD of Department of Pathology, JSS Medical College, Constituent college of JSS University, Mysore.
| References|| |
|1.||Ebele JN, Sauter G, Epstein JI, Sesterhenn IA. Genetics of Tumors of the Urinary system and Male Genital Organs. In: World Health Organization Classification of Tumors. Lyon: IARC; 2004. p. 2-3. |
|2.||Bitting RL, Madden J, Armstrong AJ. Therapy for non-clear cell histologies in renal cancer. Curr Clin Pharmacol 2011;6:169-80. |
|3.||Michalaki V, Gennatas C. Chromophobe renal cell carcinoma with prolonged response to targeted therapy: A case report. J Med Case Rep 2012;6:115. |
|4.||Shuch B, Vourqanti S, Friend JC, Zehnqebot LM, Linehan M, Srinivasan R. Targeting the mTOR pathway in Chromophobe Kidney Cancer.J Cancer 2012;3:152-7. |
|5.||Lopez-Beltran A, Carrasco JC, Cheng L, Scarpelli M, Kirkali Z, Montironi R. 2009 update on the classification of renal epithelial tumors in adults. Int J Urol 2009;16:432-43. |
|6.||Geramizadeh B, Ravanshad M, Rahsaz M. Useful markers for differential diagnosis of oncocytoma, chromophobe renal cell carcinoma and conventional renal cell carcinoma. Indian J Pathol Microbiol 2008;51:167-71. |
|7.||Sakai Y, Watanabe S, Matsukuma S. Chromophobe renal cell carcinoma showing oncocytoma-like hyalinized and edematous stroma: A case report and review of the literature. Urol Oncol 2004;22:461-4. |
|8.||Tickoo SK, Reuter VE, Amin MB, Srigley JR, Epstein JI, Min KW, et al. Renal oncocytosis: A morphologic study of fourteen cases. Am J Surg Pathol 1999;23:1094-101. |
|9.||Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG. Immunohistochemical Analysis of Chromophobe Renal Cell Carcinoma, Renal Oncocytoma, and Clear Cell Carcinoma: An Optimal and Practical Panel for Differential Diagnosis. Arch Pathol Lab Med 2007;131:1290-7. |
|10.||Skinnider BF, Amin MB. An immunohistochemical approach to the differential diagnosis of renal tumors. Semin Diagn Pathol 2005;22:51-68 . |
|11.|| Adley BP, Papavero V, Sugimura J, Teh BT, Yang XJ. Diagnostic value of cytokeratin 7 and parvalbumin in differentiating chromophobe renal cell carcinoma from renal oncocytoma. Anal Quant Cytol Histol 2006;28:228-36. |
|12.||Avery AK, Beckstead J, Renshaw AA, Corless CL. Use of Antibodies to RCC and CD10 in the Differential Diagnosis of Renal Neoplasms. Am J Surg Pathol 2000;24:203-10. |
|13.||Tickoo SK, Amin MB, Zarbo RJ. Colloidal iron staining in renal epithelial neoplasms, including chromophobe renal cell carcinoma: Emphasis on technique and patterns of staining. Am J Surg Pathol 1998;22:419-24. |
|14.||Tickoo SK, Lee MW, Eble JN, Amin M, Christopherson T, Zarbo RJ, et al. Ultrastructural observations on mitochondria and microvesicles in renal oncocytoma, chromophobe renal cell carcinoma and eosinophilic variant of conventional (clear cell) renal cell carcinoma. Am J Surg Pathol 2000 24:1247-56. |
|15.||Pradhan D, Kakkar N, Bal A, Singh SK, Joshi K. Sub-typing of renal cell tumors; Contribution of ancillary techniques. Diagn Pathol 2009;4:21. |
[Figure 1], [Figure 2]