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Pigmented microcystic chromophobe cell carcinoma: A unique variant of renal cell carcinoma
Annals of
DIAGNOSTIC PATHOLOGY JUNE1998
VOL 2, NO 3
ORIGINAL ARTICLES
Pigmented Microcystic Chromophobe Cell Carcinoma: A Unique Variant of Renal Cell Carcinoma Michal Michal, MD, On~ejHes, MD, Alexander Svec, MD, and Marie Ludvfkovd, MD Five cases of pigmented chromophobe renal cell carcinoma are presented. The patients included four men and one woman between the ages of 60 and 73 years (median age, 66.5 years), who presented with symptoms due to their renal mass. Surgical resection of the renal mass was performed in all patients. Grossly, the tumors were well encapsulated, yellow to dark gray, with a vague nodular pattern on cut surface. The tumors varied between 2.5 and 9 cm in greatest diameter. Histologically, all tumors shared similar features, namely, a malignant cellular proliferation composed of deeply eosinophilic to clear cytoplasm with r o u n d nuclei and inconspicuous nucleoli. The cellular proliferation was arranged in a microcystic a n d / o r microalveolar pattern. In one tumor, conventional areas of clear cell carcinoma in association with the chromophobe component were present. In addition, all tumors contained pigmented areas, which were shown by light microscopy to have features of lipochrome pigment. Ultrastructural studies of these areas demonstrated the presence of intracytoplasmic polygonal to round, electron-dense pigment granules, which in some areas seemed to coalesce to form larger granules. In addition, numerous mitochondria and cytoplasmic vesicles were present. The cases described herein highlight an additional morphologic variant of chromophobe renal cell carcinoma. Ann Diagn Pathol 2: 149-153, 1998. Copyright © 1998 by W.B. Saunders Company
Index Words: Kidney, pigmented chromophobe renal cell carcinoma, microcystic, p s a m m o m a bodies, calcifications H R O M O P H O B E RENAL CELL CARCINOMA (CRC) is a rare type of renal cell carcinoma. Until 1995, only 40 cases of CRC had been described.1 Distinguishing morphologic features include the presence of voluminous cells with finely reticulated cytoplasm that stains lightly (chromophobic) with routine hematoxylineosin stains. Histochemically, a distinct positive cytoplasmic reaction with Hale's colloidal iron stain is a charac-
C
teristic finding. A unique ultrastructural feature of chromophobe tumors is the presence of numerous intracytoplasmic membrane-bound microvesicles, the nature of which is unknown. 1-9 The cases described herein represent a distinct variant of chromophobe renal cell carcinoma that expands the morphologic spectrum of changes of this unusual renal tumor.
Materials a n d M e t h o d s From theDepartmentofPathology,FacultyHospital,Pilsen, CzechRepublic," and the DepartmentofPathology,MedicalFaculty, CharlesUniversity,Prague, CzechRepublic. Addressreprintrequeststo MichalMichalMD, FacultyHospital,Department ofPathology,dr.E. Bende 13, 305 99 Pilsen, CzechRepublic. Copyright0 1998by W.B. SaundersCompany 1092-9134/98/0203-0001508.00/0
Two specimens of kidney tumors were retrieved from 1,400 routine renal neoplasms, and three of the cases were retrieved from the consultation files of one of the authors. The tumors were graded according to the grading system of Fuhrman et al. 1° Tissues for light microscopy were fixed in 4% formaldehyde and embedded in paraffin using routine procedures. Five
Annals of Diagnostic Pathology, Vol 2, No 3 (June), 1998: pp 149-153
149
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Michal et al
Table 1. Clinical Features of Pigmented Microcystic Chromophobe Cell Carcinoma Treatment Case No.
Sex/Age (yr)
Gross (cm)
M/62 M/69 M/61 F/60 M/73
7 5< 6 x 5 mass 9 x 9 × 9 mass 3.5 mass 2.5 mass 9 × 7 x 7 mass
Follow-Up A&W A&W A&W A&W A&W
2 yr 2 yr 1 yr 1 yr 6 yr
Kidney Left Left Unknown Unknown Left
Resection Yes Yes Yes Yes Yes
Abbreviation: A&W, alive and well.
micrometer-thick sections were cut from the tissue blocks and stained with hematoxylin-eosin, periodic acid--Schiff with and without diastase digestion, Schmorl method, Ziehl-NeeIsen method, Masson-Fontana method with and without bleaching (4 and 24 hours), iron stain, and Hale's colloidal iron stain. 11,12 For immunohistochemistry, the following primary antibodies were used: synaptophysin (polyclonal, 1:1,000; DAKO, Glostrup), chromogranin (monoclonal, 1:100; DAKO), and HMB45 (monoclonal, 1:200; DAKO). Four micrometer-thick sections were cut from the specimens and placed on slides coated with 3-aminopropyltriethoxysilane (Sigma, St Louis, MO). The sections were then deparaffinized by routine procedures and incubated in a microwave oven 2 × 5 minutes at 700 W in citrate buffer (pH 6.0) or they were predigested with pepsin. The primary antibodies were visualized using the supersensitive streptavidin-biotin-peroxidase complex (Biogenex, San Ramon). Appropriate positive control tissues were used with the primary antibodies. Small pieces of the formaldehyde-fixed wet tissue of three cases were postfixed in glutaraldehyde and routinely processed for electron microscopy.
scopic appearance. The tumors were well encapsulated, soft, yellow to dark in color, and had a vague nodular arrangement (Fig 1). Some nodules were entirely yellow, whereas others looked as though they were sprayed with soot particles. Some tumors showed small cystic areas, focal hemorrhages, and necroses. Microscopically, all tumors shared similar morphologic features. The tumors were composed of eosinophilic to clear cells arranged in microcystic or microalveolar patterns (Fig 2). One of the cases (case 5) showed
Results The clinical features of the five patients are presented in the Table 1. All tumors had a similar gross macro-
Figure 1. The tumors were well encapsulated and had vaguely nodular arrangement with yellow to dark gray color, which was unevenly distributed throughout the tumor.
Figure 2. The tumors were composed of eosinophilic to clear cells arranged in microcystic pattern. Some areas of the tumors have a microalveolar pattern.
Pigmented Chromophobe Cell Carcinoma
151
Figure 3. Case 5 was composed of two components. One component looked like conventional CRC, and the other was microcystically arranged identically to the other four cases.
Figure 4. The typical microscopic feature of all five cases was light to dark brown pigmentation, which was either intracellular or extracellular.
conventional areas of clear cell, renal cell carcinoma (Fig 3). In all five cases, the presence of a light to dark brown pigment was noted in tumoral areas. This brown pigment was seen in intracytoplasmic and extracellular areas of the tumor (Fig 4). In other areas, the microalveolar spaces were filled with red blood cells forming small lakes. In addition, in three of the cases, small microcalcifications were noted (Fig 5). These microcalcifications resembled microspherules, pseudofungi, or psammoma bodies. The tumor cells were PAS negative and stained strongly with Hale's colloidal iron stain (Fig 6). The pigment stained positively with Masson-Fontana stain, PAS with and without diastase pretreatment, and ZiehlNeelsen stain. The pigment stained blue-green with
Figure 5. Other typical feature of the tumors were tiny foci of microscopic calcification (seen in three of five cases).
Figure 6. The tumor ceils stained strongly with Hale's colloidal iron stain. Alveolar spaces are filled with dark brown pigment.
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Schmorl reaction. The iron stain was focally positive in extracellular pigment deposits and positively stained the extracellular calcified deposits. Von Kossa and Alizarin red stains reacted positively with extracellular calcifications. Immunohistochemically, the tumor cells were negative for the antibodies to HMB45, synaptophysin, and chromogranin. Ultrastructural examination revealed cells with poorly formed junctions and external lamina. There were two major intracellular components: typical cytoplasmic vesicles commonly seen in CRC (Fig 7) and mitochondria. Degenerating mitochondria with alternating inner cristae in orientation were present (Fig 8). Some tumor cells contained dark, electron-dense pigment granules (corresponding to the brown pigment at light microscopic level). The pigment granules were round to polygonal (Fig 9). In addition, some tumors contained vesicles that seemed to contain tiny grains of the same dark, electron-dense material as in the granules. This material seemed to coalesce to form larger pigment granules. Neither melanosomes nor neurosecretory granules could be detected in any of the cases. Discussion
Chromophobe renal cell carcinoma is an uncommon variant of renal cell carcinoma that was first described by Thoenes et al in 1985.2 Classic CRC is composed of cells with abundant pale cytoplasm embedded in a delicate reticular background. Some tumors have varying numbers of intermixed eosinophilic cells, whereas others are composed exclusively of these eosinophilic cells. According to the proportion of these two cell types, CRC has been divided into the classic light cell type and the chromophil eosinophilic cell type.2 The cases described herein represent a histologic variant of CRC,
Figure 7. All tumors examined at the ultrastructural level contained cytoplasmic vesicles, typically seen in CRC.
Figure 8. In addition to normal-looking mitochondrias, degenerating mitochondrias with alternating inner cristae are seen.
namely, one composed of pigmented cells. Pigmented renal tumors have been discussed previously. Bonsib,6 using electron microscopy, identified the presence of lipochrome in a CRC, which macroscopicallywas yellowtan. Interestingly, no pigment was identified by light microscopy. In addition, Kamishima et a113 reported a case of renal cell carcinoma in which they identified the presence of pigment at both the ultrastructural and light microscopic levels. The same investigators 14 also reported a series of five cases of pigmented renal cell carcinoma. They found that histochemically and ultrastructurally, the pigment resembled neuromelanin. However, none of the cases included predominantly CRC. Nevertheless, it is possible that case 2 in that series may have CRC-like areas. The occurrence of lipochrome pigment has been described in other lesions, such as primary pigmented nodular adrenocortical disease 15,16and adenomas of the adrenal glands, 17-21and in the thyroid of patients with a history of minocycline ingestion 22,23 as well as in other conditions of the gastrointestinal tract. 24 Histologically, the tumors in our cases exhibited interesting microcystic and microalveolar arrangement, focal calcifications, and pigmentation. These histopathologic features may be secondary to and probably consequences of microhemorrhages and necroses. On the other hand, the resorption and restitution of the necrotic areas of the tumor may have resulted in the microcystic and microalveolar appearance of the tumor (Fig 2). The shape of calcifications should not be confused with various fungal infections. The positive reactions to the iron, Alizarin red, and von Kossa stains of these calcified foci are probably of the same nature as seen in Gamna-Gandy bodies in certain conditions in the spleen? 5 Similar structures have been described in the lymph node. 26,27
Pigmented Chromophobe Cell Carcinoma
Figure 9. The pigment granules were round to polygonal. Because of the p r e s e n c e of p i g m e n t and the m o r p h o logic features of the tumor, which can show p r e d o m i nantly oncocytic features, it is i m p o r t a n t to recognize the lesion as a p r i m a r y renal t u m o r and not a metastasis f r o m a p i g m e n t e d tumor. M e t a s t a t i c m e l a n o m a and a n e u r o e n d o c r i n e n e o p l a s m (namely, oncocytic carcinoid or p a r a g a n g l i o m a ) are the most i m p o r t a n t considerations in the differential diagnosis. T h e use of i m m u n o histochemical studies such as c h r o m o g r a n i n , S-100 protein, and H M B - 4 5 plays an i m p o r t a n t role in arriving at a specific diagnosis. In s u m m a r y , we have described five cases of pigm e n t e d C R C that e x p a n d the morphologic s p e c t r u m of this tumor. In addition, we have highlighted the most i m p o r t a n t differential diagnosis of these tumors. W e believe that the presence of p i g m e n t is not u n i q u e to the conventional clear cell, renal cell c a r c i n o m a but that it also m a y be seen in different p r i m a r y t u m o r s of the kidney, such as the C R C .
Acknowledgments The authors are grateful to Dr P. Mukensnabl for preparing the figures to the paper and to Mr Alan Havlice for providing us with follow-up data of the patients.
References 1. Crotty TB, Farrow GM, Lieber MM, et al: Chromophobe cell renal carcinoma: Clinicopathoiogical features of 50 cases. J UroI 1995; 154:964-967 2. Thoenes W, Storkel S, Rumpelt HJ: Human chromophobe cell renal carcinoma. Virchows Arch B Ceil Pathoi 1985;48:207-217 3. Thoenes W, Storkel S, RumpehJH: Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas). The basic cytological and histopathological elements and their use for diagnosis. Pathol Res Pract 1986;181:125-143 4. Thoenes W, Storkel S, Rumpeh HJ, et al: Chromophobe cell
153
renal carcinoma and its variants~A report on 32 cases. J Pathol 1988;155:277-287 5. Bonsib SM, Lager DJ: Chromophobe cell carcinoma. AmJ Surg Pathol 1990;14:260-267 6. Bonsib SM: Renal chromophobe cell carcinoma. The relationship between cytoplasmic vesicles and colloidal iron stain. J Urol Pathol 1996;4:9-14 7. DeLong WH, Sakr W, Grignon DJ: Chromophobe renal ceil carcinoma. A comparative histochemical and immunohistochemical study.J Urol Pathol 1996;4:1-8 8. Morell-Quadreny L, Gregori-Romero IV[, Llombart-Bosch A: Chromophobe renal cell carcinoma. Pathologic, ultrastructural, immunohistochemical, cytofluorometric and cytogenetic findings. Pathol Res Pract 1996;192:1275-1281 9. Fukushima T, Nagashima Y, Nakatani Y, et al: Chromophobe renal cell carcinoma: A report of two cases. Pathoi Int 1994;44:401-406 10. Fuhrman SA, Lasky LC, Limas C: Prognostic significance of morphologic parameters in renal ceil carcinoma. Am J Surg PathoI 1982;6:655-663 11. Hale CW: Histochemical demonstration of acid mucopolysaccharides in animal tissues. Nature 1946;204:745-747 12. Muller G: Uber eine Vereinfachung der Reaktion nach Hale (1946). Acta Histochem 1955;2:68-70 13. Kamishima T, Fukuda T, Emura I, et ah Pigmented renal cell carcinoma. AmJ Surg Pathol 1995;19:350-356 14. Fukuda T, Kamishima T, Emura I, et al: Pigmented renal cell carcinoma: Accumulation of abnormal lysozomalgranules. Histopathology 1997;31:38-46 15. Shenoy BV, Carpenter PC, Carney JA: Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing syndrome. AmJ Surg Pathol 1984;8:335-344 16. Travis WD, Tsokos M, DoppmanJL, et al: Primary"pigmented nodular adrenocortical disease. AmJ Surg Pathol 1989;13:921-930 17. Baker MR: A pigmented adenoma of the adrenal. Arch Pathol 1938;26:845-852 18. Macadam RF: Black adenoma of the hmnan adrenal cortex. Cancer 1971;27:116-119 19. Caplan RH, Virata RL: Functional black adenoma of the adrenal cortex. A rare cause of primary aldosteronism. Am J Clin PathoI 1974;62:97-103 20. Lam KY, Wat MS: Adrenal cortical black adenoma. Report of two cases and review of the literature.J Urol Pathol 1996;4:183-190 21. Damr°n TA' Schelper RL' S°rensen L: Cyt°chemical dem°nstration of neuromelanin in black pigmented adrenal nodules. AmJ Clin Pathol 1987;87:334-341 22. Alexander CB, Herrera GA, Jaffe K, et al: Black thyToid. Clinical manifestations, uhrastructural findings, and possible mechanisms. Hum Pathol 1985;16:72-78 23. Jennings TA, Sheehan ChE, Chodos RB, et al: Follicular carcinoma associated with minocycline-induced black thyroid. Endocrin Pathol 1996;7:345-348 24. Ghadially FIN, Walley VM: Melanoses of the gastrointestinal tract. Histopathology 1994;25:197-207 25. Michal M, Chlumska A, PovysilovaV: Intranodal "amianthoid" myofibroblastoma. Pathol Res Pract 1992;188:199-204 26. Suster S, Rosai J: Intranodal hemorrhagic spindle cell tumor with "amianthoid" fibers. AmJ Surg Pathol 1989;13:347-357 27. ConnellyJ, RoJY, Cam~'ightJ: Pseudofungi in a lymph node. A case report with energy dispersive x-ray elemental analysis. Arch Pathol Lab Med 1991;115:1166-1168
DIAGNOSTIC PATHOLOGY JUNE1998
VOL 2, NO 3
ORIGINAL ARTICLES
Pigmented Microcystic Chromophobe Cell Carcinoma: A Unique Variant of Renal Cell Carcinoma Michal Michal, MD, On~ejHes, MD, Alexander Svec, MD, and Marie Ludvfkovd, MD Five cases of pigmented chromophobe renal cell carcinoma are presented. The patients included four men and one woman between the ages of 60 and 73 years (median age, 66.5 years), who presented with symptoms due to their renal mass. Surgical resection of the renal mass was performed in all patients. Grossly, the tumors were well encapsulated, yellow to dark gray, with a vague nodular pattern on cut surface. The tumors varied between 2.5 and 9 cm in greatest diameter. Histologically, all tumors shared similar features, namely, a malignant cellular proliferation composed of deeply eosinophilic to clear cytoplasm with r o u n d nuclei and inconspicuous nucleoli. The cellular proliferation was arranged in a microcystic a n d / o r microalveolar pattern. In one tumor, conventional areas of clear cell carcinoma in association with the chromophobe component were present. In addition, all tumors contained pigmented areas, which were shown by light microscopy to have features of lipochrome pigment. Ultrastructural studies of these areas demonstrated the presence of intracytoplasmic polygonal to round, electron-dense pigment granules, which in some areas seemed to coalesce to form larger granules. In addition, numerous mitochondria and cytoplasmic vesicles were present. The cases described herein highlight an additional morphologic variant of chromophobe renal cell carcinoma. Ann Diagn Pathol 2: 149-153, 1998. Copyright © 1998 by W.B. Saunders Company
Index Words: Kidney, pigmented chromophobe renal cell carcinoma, microcystic, p s a m m o m a bodies, calcifications H R O M O P H O B E RENAL CELL CARCINOMA (CRC) is a rare type of renal cell carcinoma. Until 1995, only 40 cases of CRC had been described.1 Distinguishing morphologic features include the presence of voluminous cells with finely reticulated cytoplasm that stains lightly (chromophobic) with routine hematoxylineosin stains. Histochemically, a distinct positive cytoplasmic reaction with Hale's colloidal iron stain is a charac-
C
teristic finding. A unique ultrastructural feature of chromophobe tumors is the presence of numerous intracytoplasmic membrane-bound microvesicles, the nature of which is unknown. 1-9 The cases described herein represent a distinct variant of chromophobe renal cell carcinoma that expands the morphologic spectrum of changes of this unusual renal tumor.
Materials a n d M e t h o d s From theDepartmentofPathology,FacultyHospital,Pilsen, CzechRepublic," and the DepartmentofPathology,MedicalFaculty, CharlesUniversity,Prague, CzechRepublic. Addressreprintrequeststo MichalMichalMD, FacultyHospital,Department ofPathology,dr.E. Bende 13, 305 99 Pilsen, CzechRepublic. Copyright0 1998by W.B. SaundersCompany 1092-9134/98/0203-0001508.00/0
Two specimens of kidney tumors were retrieved from 1,400 routine renal neoplasms, and three of the cases were retrieved from the consultation files of one of the authors. The tumors were graded according to the grading system of Fuhrman et al. 1° Tissues for light microscopy were fixed in 4% formaldehyde and embedded in paraffin using routine procedures. Five
Annals of Diagnostic Pathology, Vol 2, No 3 (June), 1998: pp 149-153
149
150
Michal et al
Table 1. Clinical Features of Pigmented Microcystic Chromophobe Cell Carcinoma Treatment Case No.
Sex/Age (yr)
Gross (cm)
M/62 M/69 M/61 F/60 M/73
7 5< 6 x 5 mass 9 x 9 × 9 mass 3.5 mass 2.5 mass 9 × 7 x 7 mass
Follow-Up A&W A&W A&W A&W A&W
2 yr 2 yr 1 yr 1 yr 6 yr
Kidney Left Left Unknown Unknown Left
Resection Yes Yes Yes Yes Yes
Abbreviation: A&W, alive and well.
micrometer-thick sections were cut from the tissue blocks and stained with hematoxylin-eosin, periodic acid--Schiff with and without diastase digestion, Schmorl method, Ziehl-NeeIsen method, Masson-Fontana method with and without bleaching (4 and 24 hours), iron stain, and Hale's colloidal iron stain. 11,12 For immunohistochemistry, the following primary antibodies were used: synaptophysin (polyclonal, 1:1,000; DAKO, Glostrup), chromogranin (monoclonal, 1:100; DAKO), and HMB45 (monoclonal, 1:200; DAKO). Four micrometer-thick sections were cut from the specimens and placed on slides coated with 3-aminopropyltriethoxysilane (Sigma, St Louis, MO). The sections were then deparaffinized by routine procedures and incubated in a microwave oven 2 × 5 minutes at 700 W in citrate buffer (pH 6.0) or they were predigested with pepsin. The primary antibodies were visualized using the supersensitive streptavidin-biotin-peroxidase complex (Biogenex, San Ramon). Appropriate positive control tissues were used with the primary antibodies. Small pieces of the formaldehyde-fixed wet tissue of three cases were postfixed in glutaraldehyde and routinely processed for electron microscopy.
scopic appearance. The tumors were well encapsulated, soft, yellow to dark in color, and had a vague nodular arrangement (Fig 1). Some nodules were entirely yellow, whereas others looked as though they were sprayed with soot particles. Some tumors showed small cystic areas, focal hemorrhages, and necroses. Microscopically, all tumors shared similar morphologic features. The tumors were composed of eosinophilic to clear cells arranged in microcystic or microalveolar patterns (Fig 2). One of the cases (case 5) showed
Results The clinical features of the five patients are presented in the Table 1. All tumors had a similar gross macro-
Figure 1. The tumors were well encapsulated and had vaguely nodular arrangement with yellow to dark gray color, which was unevenly distributed throughout the tumor.
Figure 2. The tumors were composed of eosinophilic to clear cells arranged in microcystic pattern. Some areas of the tumors have a microalveolar pattern.
Pigmented Chromophobe Cell Carcinoma
151
Figure 3. Case 5 was composed of two components. One component looked like conventional CRC, and the other was microcystically arranged identically to the other four cases.
Figure 4. The typical microscopic feature of all five cases was light to dark brown pigmentation, which was either intracellular or extracellular.
conventional areas of clear cell, renal cell carcinoma (Fig 3). In all five cases, the presence of a light to dark brown pigment was noted in tumoral areas. This brown pigment was seen in intracytoplasmic and extracellular areas of the tumor (Fig 4). In other areas, the microalveolar spaces were filled with red blood cells forming small lakes. In addition, in three of the cases, small microcalcifications were noted (Fig 5). These microcalcifications resembled microspherules, pseudofungi, or psammoma bodies. The tumor cells were PAS negative and stained strongly with Hale's colloidal iron stain (Fig 6). The pigment stained positively with Masson-Fontana stain, PAS with and without diastase pretreatment, and ZiehlNeelsen stain. The pigment stained blue-green with
Figure 5. Other typical feature of the tumors were tiny foci of microscopic calcification (seen in three of five cases).
Figure 6. The tumor ceils stained strongly with Hale's colloidal iron stain. Alveolar spaces are filled with dark brown pigment.
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Michal et al
Schmorl reaction. The iron stain was focally positive in extracellular pigment deposits and positively stained the extracellular calcified deposits. Von Kossa and Alizarin red stains reacted positively with extracellular calcifications. Immunohistochemically, the tumor cells were negative for the antibodies to HMB45, synaptophysin, and chromogranin. Ultrastructural examination revealed cells with poorly formed junctions and external lamina. There were two major intracellular components: typical cytoplasmic vesicles commonly seen in CRC (Fig 7) and mitochondria. Degenerating mitochondria with alternating inner cristae in orientation were present (Fig 8). Some tumor cells contained dark, electron-dense pigment granules (corresponding to the brown pigment at light microscopic level). The pigment granules were round to polygonal (Fig 9). In addition, some tumors contained vesicles that seemed to contain tiny grains of the same dark, electron-dense material as in the granules. This material seemed to coalesce to form larger pigment granules. Neither melanosomes nor neurosecretory granules could be detected in any of the cases. Discussion
Chromophobe renal cell carcinoma is an uncommon variant of renal cell carcinoma that was first described by Thoenes et al in 1985.2 Classic CRC is composed of cells with abundant pale cytoplasm embedded in a delicate reticular background. Some tumors have varying numbers of intermixed eosinophilic cells, whereas others are composed exclusively of these eosinophilic cells. According to the proportion of these two cell types, CRC has been divided into the classic light cell type and the chromophil eosinophilic cell type.2 The cases described herein represent a histologic variant of CRC,
Figure 7. All tumors examined at the ultrastructural level contained cytoplasmic vesicles, typically seen in CRC.
Figure 8. In addition to normal-looking mitochondrias, degenerating mitochondrias with alternating inner cristae are seen.
namely, one composed of pigmented cells. Pigmented renal tumors have been discussed previously. Bonsib,6 using electron microscopy, identified the presence of lipochrome in a CRC, which macroscopicallywas yellowtan. Interestingly, no pigment was identified by light microscopy. In addition, Kamishima et a113 reported a case of renal cell carcinoma in which they identified the presence of pigment at both the ultrastructural and light microscopic levels. The same investigators 14 also reported a series of five cases of pigmented renal cell carcinoma. They found that histochemically and ultrastructurally, the pigment resembled neuromelanin. However, none of the cases included predominantly CRC. Nevertheless, it is possible that case 2 in that series may have CRC-like areas. The occurrence of lipochrome pigment has been described in other lesions, such as primary pigmented nodular adrenocortical disease 15,16and adenomas of the adrenal glands, 17-21and in the thyroid of patients with a history of minocycline ingestion 22,23 as well as in other conditions of the gastrointestinal tract. 24 Histologically, the tumors in our cases exhibited interesting microcystic and microalveolar arrangement, focal calcifications, and pigmentation. These histopathologic features may be secondary to and probably consequences of microhemorrhages and necroses. On the other hand, the resorption and restitution of the necrotic areas of the tumor may have resulted in the microcystic and microalveolar appearance of the tumor (Fig 2). The shape of calcifications should not be confused with various fungal infections. The positive reactions to the iron, Alizarin red, and von Kossa stains of these calcified foci are probably of the same nature as seen in Gamna-Gandy bodies in certain conditions in the spleen? 5 Similar structures have been described in the lymph node. 26,27
Pigmented Chromophobe Cell Carcinoma
Figure 9. The pigment granules were round to polygonal. Because of the p r e s e n c e of p i g m e n t and the m o r p h o logic features of the tumor, which can show p r e d o m i nantly oncocytic features, it is i m p o r t a n t to recognize the lesion as a p r i m a r y renal t u m o r and not a metastasis f r o m a p i g m e n t e d tumor. M e t a s t a t i c m e l a n o m a and a n e u r o e n d o c r i n e n e o p l a s m (namely, oncocytic carcinoid or p a r a g a n g l i o m a ) are the most i m p o r t a n t considerations in the differential diagnosis. T h e use of i m m u n o histochemical studies such as c h r o m o g r a n i n , S-100 protein, and H M B - 4 5 plays an i m p o r t a n t role in arriving at a specific diagnosis. In s u m m a r y , we have described five cases of pigm e n t e d C R C that e x p a n d the morphologic s p e c t r u m of this tumor. In addition, we have highlighted the most i m p o r t a n t differential diagnosis of these tumors. W e believe that the presence of p i g m e n t is not u n i q u e to the conventional clear cell, renal cell c a r c i n o m a but that it also m a y be seen in different p r i m a r y t u m o r s of the kidney, such as the C R C .
Acknowledgments The authors are grateful to Dr P. Mukensnabl for preparing the figures to the paper and to Mr Alan Havlice for providing us with follow-up data of the patients.
References 1. Crotty TB, Farrow GM, Lieber MM, et al: Chromophobe cell renal carcinoma: Clinicopathoiogical features of 50 cases. J UroI 1995; 154:964-967 2. Thoenes W, Storkel S, Rumpelt HJ: Human chromophobe cell renal carcinoma. Virchows Arch B Ceil Pathoi 1985;48:207-217 3. Thoenes W, Storkel S, RumpehJH: Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas). The basic cytological and histopathological elements and their use for diagnosis. Pathol Res Pract 1986;181:125-143 4. Thoenes W, Storkel S, Rumpeh HJ, et al: Chromophobe cell
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