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Chromophobe renal cell carcinoma with microcystic and adenomatous arrangement and pigmentation—a diagnostic pitfall. Morphological, immunohistochemical, ultrastructural and molecular genetic report of 20 cases

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Abstract

We present clinical, morphological, immunohistochemical, ultrastructural and molecular genetic features of 20 cases of a peculiar form of chromophobe renal cell carcinoma (CRCC) with morphology differing from that of conventional CRCC. Microscopically, the typical features of the tumors were microcystic arrangement and formation of adenomatous structures. Microcystic areas were composed of smaller eosinophilic and bigger pale cells having cytological appearance typical of conventional CRCC. Cytological features of the adenomatous structures were mostly different from those of conventional CRCC. They had a typical columnar arrangement with nuclei positioned at the base of the glandular structures and a small amount of a deeply eosinophilic cytoplasm often endowed with brush border facing the lumen of the glands. In addition, all the tumors showed a brown pigmentation. The pigmentation was located mostly extracellularly, where it formed pools of heavy deposits. Microscopic calcifications present in all cases formed psammoma bodies or else the calcifications were more extensive and amorphous in shape. Ultrastructurally, the cells showed features characteristic of CRCC: typical cytoplasmic vesicles were 100–700 nm in size and mitochondria had tubulovesicular, lamellar or circular cristae. Some tumor cells contained dark, variously sized electron-dense pigment granules. Neither melanosomes nor membrane-bound neurosecretory granules were seen. Using fluorescence in-situ hybridization probes for chromosomes 1, 2, 6, 10, 13, 17 and 21, the tumors revealed massive loss of tested chromosomes typical for conventional CRCC. Monosomy of chromosomes 1, 2, 6, 10, 13 and 21 was found in 100, 36, 91, 82, 82, 82 and 64% of cases, respectively. None of the cases showed mutation of exons 9, 11, 13 and 17 of the c-kit gene. The important feature of pigmented microcystic chromophobe renal cell carcinoma is a relatively benign biological behavior and the absence of distant metastases and sarcomatoid transformation.

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References

  1. Akhtar M, Kardar H, Linjawi T, McClintock J, Ali MA (1995) Chromophobe cell carcinoma of the kidney. A clinicopathologic study of 21 cases. Am J Surg Pathol 19:1245–1256

    Google Scholar 

  2. Akhtar M, Tulbach A, Kardar H, Ali MA (1997) Sarcomatoid renal cell carcinoma: the chromophobe connection. Am J Surg Pathol 21:1188–1195

    Google Scholar 

  3. Alexander CB, Herrera GA, Jaffe K, Yu H (1985) Black thyroid. Clinical manifestations, ultrastructural findings, and possible mechanisms. Hum Pathol 16:72–78

    Google Scholar 

  4. Amin MB, Crotty TB, Tickoo SK, Farrow G (1997) Renal oncocytoma, a reappraisal of morphologic features with clinicopathologic findings in 80 cases. Am J Surg Pathol 21:1–12

    Article  Google Scholar 

  5. Baker MR (1938) A pigmented adenoma of the adrenal. Arch Pathol 26:845–852

    Google Scholar 

  6. Bonsib SM (1996) Renal chromophobe cell carcinoma. The relationship between cytoplasmic vesicles and colloidal iron stain. J Urol Pathol 4:9–14

    Google Scholar 

  7. Bonsib SM, Lager DJ (1990) Chromophobe cell carcinoma. Am J Surg Pathol 14:260–267

    Google Scholar 

  8. Bugert P, Kovacs G (1996) Molecular differential diagnosis of renal cell carcinomas by microsatellite analysis. Am J Pathol 149:2081–2088

    Google Scholar 

  9. Caplan RH, Virata RL (1974) Functional black adenoma of the adrenal cortex. A rare cause of primary aldosteronism. Am J Clin Pathol 62:97–103

    Google Scholar 

  10. Cochand-Priollet B, Molinié V, Bougaran J, Bouvier R, Dauge-Geffroy, Desligniéres S, Fournet JC, Gross P, Lesourd A, Saint-André JP, Toublanc M, Vieillefond A, Wassef M, Fontaine A, Groleau L (1997) Renal chromophobe cell carcinoma and oncocytoma. A comparative morphologic, histochemical, and immunohistochemical study of 124 cases. Arch Pathol Lab Med 121:1081–1086

    Google Scholar 

  11. Crotty TB, Farrow GM, Lieber MM (1995) Chromophobe cell renal carcinoma: clinicopathological features of 50 cases. J Urol 154:964–967

    Article  Google Scholar 

  12. Damron TA, Schelper RL, Sorensen L (1987) Cytochemical demonstration of neuromelanin in black pigmented adrenal nodules. Am J Clin Pathol 87:334–341

    Google Scholar 

  13. DeLong WH, Sakr W, Grignon DJ (1996) Chromophobe renal cell carcinoma. A comparative histochemical and immunohistochemical study. J Urol Pathol 4:1–8

    Google Scholar 

  14. Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds) (2004) Tumours of the urinary system and male genital organs. IARC Press, Lyon

  15. Fukuda T, Kamishima T, Emura I, Takastuka H, Suzuki T (1997) Pigmented renal cell carcinoma: accumulation of abnormal lysozomal granules. Histopathology 31:38–46

    Google Scholar 

  16. Ghadially FN, Walley VM (1994) Melanoses of the gastrointestinal tract. Histopathology 25:197–207

    Google Scholar 

  17. Hale CW (1946) Histochemical demonstration of acid mucopolysaccharides in animal tissues. Nature 204:745–747

    Google Scholar 

  18. Hes O, Michal M (2001) Small cell variant of renal oncocytoma—a rare and misleading type of benign renal tumor. Int J Surg Pathol 9:215–222

    Google Scholar 

  19. Iqbal MA, Akhtar M, Ulmer C, Al-Dayel F, Paterson MC (2000) FISH analysis in chromophobe renal-cell carcinoma. Diagn Cytopathol 22:3–6

    Google Scholar 

  20. Jennings TA, Sheehan ChE, Chodos RB, Figge J (1996) Follicular carcinoma associated with minocycline-induced black thyroid. Endocrin Pathol 7:345–348

    Google Scholar 

  21. Junker K, Weirich G, Amin MB, Moravek P, Hindermann W, Schubert J (2003) Genetic subtyping of renal cell carcinoma by comparative genomic hybridization. Recent Results Cancer Res 162:169–175

    Google Scholar 

  22. Kamishima T, Fukuda T, Emura I, Tanigawa T, Naito M (1995) Pigmented renal cell carcinoma. Am J Surg Pathol 19:350–356

    Google Scholar 

  23. Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, Ritz E, Roos G, Schmidt D, Srigley JR, Storkel S, van den Berg E, Zbar B (1997) The Heidelberg classification of renal cell tumours. J Pathol 183:131–133

    Article  CAS  PubMed  Google Scholar 

  24. Lam KY, Wat MS (1996) Adrenal cortical black adenoma. Report of two cases and review of the literature. J Urol Pathol 4:183–190

    Google Scholar 

  25. Latham B, Dickersin R, Oliva E (1999) Subtypes of chromophobe renal cell carcinoma. An ultrastructural and histochemical study of 13 cases. Am J Surg Pathol 23:530–535

    Google Scholar 

  26. Lei JY, Middleton LP, Guo XD, Duray PH, McWilliams G, Linehan WM, Merino MJ (2001) Pigmented renal clear cell carcinoma with melanotic differentiation. Hum Pathol 32:233–236

    Google Scholar 

  27. Lindgren V, Paner GP, Omeroglu A, Campbell SC, Waters WB, Flanigan RC, Picken MM (2004) Cytogenetic analysis of a series of 13 renal oncocytomas. J Urol 171:602–604

    Google Scholar 

  28. Longley BJ, Reguera MJ, Ma Y (2001) Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy. Leuk Res 25:571–576

    Google Scholar 

  29. Macadam RF (1971) Black adenoma of the human adrenal cortex. Cancer 27:116–119

    Google Scholar 

  30. Martignoni G, Eble JN, Brunelli M, Cheng L, Pea M, Delahunt B (2003) Chromophobe renal cell carcinoma: a clicopathologic study of 100 cases. Mod Pathol 16:161A

    Google Scholar 

  31. Michal M, Hes O, Švec A, Ludvíková M (1998) Pigmented microcystic chromophobe cell carcinoma: a unique variant of renal cell carcinoma. Ann Diagn Pathol 2:149–153

    Google Scholar 

  32. Morell-Quadreny L, Gregori-Romero M, Llombart-Bosch A (1996) Chromophobe renal cell carcinoma. Pathologic, ultrastructural, immunohistochemical, cytofluorometric and cytogenetic findings. Pathol Res Pract 192:1275–1281

    Google Scholar 

  33. Muller G (1955) Uber eine Vereinfachung der Reaktion nach Hale (1946). Acta Histochem 2:68–70

    Google Scholar 

  34. Murad T, Komaiko W, Oyasu R, Bauer K (1991) Multilocular cystic renal cell carcinoma. Am J Clin Pathol 95:633–637

    Google Scholar 

  35. Nagy A, Buzogany I, Kovacz G (2004) Microsatellite allelotyping differentiates chromophobe renal cell carcinomas from oncocytomas and identifies new genetic changes. Histopathology 44:542–546

    Google Scholar 

  36. Paternoster SF, Brockman SR, McClure RF, Remstein ED, Kurtin PJ, Dewald GW (2002) A new method to extract nuclei from paraffin-embedded tissue to study lymphomas using interphase fluorescence in situ hybridization. Am J Pathol 160:1967–1972

    Google Scholar 

  37. Perez-Ordonez B, Hamed G, Campbell S, Erlandson RA, Russo P, Gaudin PB, Reuter VE (1997) Renal oncocytoma: A clinicopathologic study of 70 cases. Am J Surg Pathol 21:871–883

    Google Scholar 

  38. Petit A, Castillo M, Santos M, Mellado B, Alcover JB, Mallofré C (2004) KIT expression in chromophobe renal cell carcinoma. Comparative immunohistochemical analysis of KIT expression in different renal cell neoplasms. Am J Surg Pathol 28:676–678

    Google Scholar 

  39. Shenoy BV, Carpenter PC, Carney JA (1984) Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing syndrome. Am J Surg Pathol 8:335–344

    Google Scholar 

  40. Speicher MR, Schoell B, du Manoir S, Schrock E, Ried T, Cremer T, Storkel S, Kovacs A, Kovacs G (1994) Specific loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 in chromophobe renal cell carcinomas revealed by comparative genomic hybridization. Am J Pathol 145:356–364

    Google Scholar 

  41. Steger G (1994) Thermal denaturation of double-stranded nucleic acids: prediction of temperatures critical for gradient gel electrophoresis and polymerase chain reaction. Nucleic Acids Res 25:2760–2768

    Google Scholar 

  42. Taki A, Nakatani Y, Misugi K, Yao M, Nagashima Y (1999) Chromophobe renal cell carcinoma: an immunohistochemical study of 21 Japanese cases. Mod Pathol 12:310–317

    Google Scholar 

  43. Thoenes W, Storkel S, Rumpelt HJ (1985) Human chromophobe cell renal carcinoma. Virch Arch B 48:207–217

    Google Scholar 

  44. Thoenes W, Storkel S, Rumpelt HJ, Moll R, Baum HP, Werner S (1988) Chromophobe cell renal carcinoma and its variants-A report on 32 cases. J Pathol 155:277–287

    Google Scholar 

  45. Tickoo SK, Amin MB (1998) Discriminant nuclear features of renal oncocytoma and chromophobe renal cell carcinoma. Analysis of their potential utility in the differential diagnosis. Am J Surg Pathol 110:782–787

    Google Scholar 

  46. Travis WD, Tsokos M, Doppman JL, Nieman L, Chrousos GP, Cutler Jr GB, Lynn Loriaux D, Norton JA (1989) Primary pigmented nodular adrenocortical disease. Am J Surg Pathol 13:921–930

    Google Scholar 

  47. Wardelmann E, Neidt I, Bierhoff E, Speidel N, Manegold C, Fischer HP, Pfeifer U, Pietsch T (2002) C-kit mutations in gastrointestinal stromal tumors occur preferentially in the spindle rather than in the epithelioid cell variant. Mod Pathol 15:125–136

    Article  PubMed  Google Scholar 

  48. Widehn S, Kindblom LG (1988) A rapid and simple method for electron microscopy of paraffin embedded tissue. Ultrastr Pathol 12:131–136

    Google Scholar 

  49. Wilhelm M, Veltman JA, Olshen AB, Jain AN, Moore DH, Presti JC Jr, Kovacs G, Waldman FM (2002) Array-based comparative genomic hybridization for the differential diagnosis of renal cell cancer. Cancer Res 62:957–960

    CAS  PubMed  Google Scholar 

  50. Wu SL, Fishman IJ, Shannon RL (2002) Chromophobe renal cell carcinoma with extensive calcification and ossification. Ann Diagn Pathol 6:244–247

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University Hospital, Charles University, Plzen, Czech Republic

    O. Hes, T. Vanecek & M. Michal

  2. Department of Pathology, INCAN, Mexico City, United States of Mexico

    D. M. Perez-Montiel

  3. Department of Pathology, Centro Medico, Mexico City, United States of Mexico

    I. Alvarado Cabrero

  4. Department of Urology, University Hospital, Charles University, Plzen, Czech Republic

    M. Hora

  5. Department of Pathology, OSU, Columbus, OH, USA

    S. Suster

  6. Department of Pathology, Institute of Oncology, Ljubljana, Slovenia

    J. Lamovec

  7. Department of Pathology, University Hospital Ostrava, Czech Republic

    R. Curik

  8. Department of Pathology, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic

    V. Mandys

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  1. O. Hes
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Correspondence to M. Michal.

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Hes, O., Vanecek, T., Perez-Montiel, D.M. et al. Chromophobe renal cell carcinoma with microcystic and adenomatous arrangement and pigmentation—a diagnostic pitfall. Morphological, immunohistochemical, ultrastructural and molecular genetic report of 20 cases. Virchows Arch 446, 383–393 (2005). https://doi.org/10.1007/s00428-004-1187-x

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