Papillary Renal-Cell Carcinoma: Fine-Needle Aspiration of 15 Cases R. Dekmezian, M.D., N. Sneige, M.D., and N. Shabb, M.D.
Although papillary carcinoma of the kidney is a distinct clinical and pathological entity, there are few descriptions of its cytologic features in the literature. We describe the cytologic features of aspiratesfrom 1.5 papillary carcinomas of the kidney. The smears showed abundant papillary clusters with vascular cores and relatively few single cells. Tumor cells contained moderate to scant cytoplasm, nuclei were usually small and uniform, mild to moderate hyperchromasia was routine, nucleoli were single and small, and nuclear grooves were often prominent. Histiocytes and psammoma bodies were present in only four cases. Hemosiderin pigment within tumor cells was also present in four cases. Differential diagnosis should consider low-grade transitional-cell carcinoma, metastatic adenocarcinoma, normal renal tubular epithelium, mesothelial cells, and, occasionally, Wilms ’ tumor. Cytologically recognizing the distinct entity ofpapillary carcinoma is important in the workup of primary renal neoplasms and metastatic papillary neoplasms of unknown origin. Diagn Cytopathol 1991;7:
Specimens were processed by the radiologist under computerized tomography (CT) scan or ultrasound guidance using a 22-gauge needle. The following features were examined: nuclear/cytoplasmic ( N K ) ratio, nuclear shape, chromatin, nucleoli, cellularity, papillary fragments, bare nuclei, cytoplasmic vacuoles, pigment, histiocytes, and psammoma bodies.
Results The results are shown in Table I. Both renal-cell carcinomas (RCCs) and papillary renal carcinomas (PRCs) had cellular smears, but the papillary tumors also contained many tridimentional papillary fragments with fibrovascular cores (Fig. l), tight or cohesive clusters, and Table I. Comparison of Cytologic Features of Renal-Cell Carcinoma and Papillary Renal Carcinoma
198-203.
Key Words: Psammoma bodies; Nuclear grooves; Hemosiderin;
Renal-cell carcinoma
Metastatic carcinoma; Transitional-cell carcinoma; Mesothelial cells Although papillary renal carcinoma has been recognized as a distinct radiological 1-3 and pathological 3-5 entity, its cytologic features have rarely been described. Since this neoplasm may present first as metastases in distant sites, familiarity with its cytologic features is essential in making a differential diagnosis between metastatic papillary carcinomas and primary renal neoplasms.
Cellularity Papillary fragments Single tumor cells Stripped nuclei Psammoma bodies Nuclear features Chromatin
Nucleoli
++
++
Usually absent
Abundant with vascular cores
++ ++
Received December 7, 1989. Accepted May 8, 1990. From the University of Texas M.D. Anderson Cancer Center, Houston, TX. Address reprint requests to Roupen Dekmezian, M.D., University of Texas M.D. Anderson Cancer Center, Division of Pathology, 1515 Holcombe, Box 085, Houston, TX 77030.
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Diagnostic Cytopathology, Val 7, No 2
Contour
Pleomorphism Cytoplasmic features Nucleas/cytoplasmic ratio Pigment Vacuoles Glycogen . Key:
+
+
.
Absent
Present (4 cases)
Open (except sarcomatoid variant) Very prominent
Slight to moderate hyperchromasia
Materials and Methods Fine-needle aspiration material from 15 cases of histologically proven papillary renal carcinoma was reviewed and compared with material from 45 renal-cell carcinomas. In 13 cases, the primary renal tumor was aspirated, and in 2 the aspiration material was obtained from metastases.
Papillary renal carcinoma
Smooth (except sarcomatoid variant) Va riab 1e
Always low None Variable Present
Small, inconspicuous, single Smooth to irregular with grooves Absent in 12 of 15 cases Moderate to high Present in 3 of 15 cases Variable Present
+, few; + +, abundant. ,q1991 WILEY-LISS, INC.
PAPILLARY RENAL-CELL CARCINOMA
Fig. 1. (A) Direct smear from a PRC showing tight clusters of complex papillary formations. Even at low magnification the absence of nuclear pleomorphism can be appreciated (Papanicolaou, x 25). (B) An air-dried smear of the same aspirate shows papillary fronds supported by vascular cores (Diff-Quik, X 100). (C)Histologic section of surgically removed specimen showing many papillary structures lined by a single layer of epithelial cells and supported by large clusters of foamy histiocytes (H&E, x 25).
a paucity of single tumor cells (Fig. 2). In contrast, RCCs showed loosely cohesive monolayer groups of many single tumor cells (Fig. 3). Stripped nuclei, frequently seen in RCC, were rarely encountered in the papillary form. Psammoma bodies were seen in PRCs, whereas none were visible in the RCCs (Fig. 4). Twelve of the 15 PRCs had small, uniform, ovoid nuclei with slight to moderate hyperchromasia. The other three showed moderate nuclear pleomorphism and hyperchromasia (Fig. 5), whereas RCCs almost always had open chromatin. Nucleoli were usually prominent in RCCs, whereas the PRCs had small though distinct nucleoli (Fig. 5A). Nuclear grooves were frequently present in PRCs but only rarely in RCCs (Fig. 5B).Cytoplasm was abundant in RCC (Fig. 3B) but either scant or moderate in PRC (Fig. 5 A ) . Hemosiderin pigment was present in the tumor cells of four papillary tumors; in one case, it was finely granular initially raising a suspicion of melanoma (Fig. 6).
Discussion Although reports describing the cytologic features of clear-cell renal carcinoma abound in the literature (see review by Orell et al. ’), only a single report has discussed the cytologic characteristics of PRC. Yet PRCs constitute approximately 15% of all renal neoplasms.3 They have characteristic radiologic features (usually hypovascular 2,3,8); their histology, although variable, typically features papillary adenocarcinomas with foamy histiocytes within the stroma of the papillae. Even cytogenetic studies indicate that PRCs may have a pathogenesis different from that of RCC; a study of six cases of RCC showed the same chromosome 3 abnormality in the 3p12-14 region to be present in all, while two PRCs contained different (random) abnormalities. Our study shows that fine-needle aspirates of PRCs contain many distinct cytologic features that make their Diagnostic Cytopathology, Vol 7, No 2
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DEKMEZIAN ET AL.
Fig. 2. Direct smear of PRC showing cohesive (A) and tight (B) clustering of tumor cells with few single cells scattered in the smear (Papanicolaou: A, X 100; B, X25).
Fig. 3. (A) Direct smear of RCC showing many single cells and naked nuclei (Papanicolaou, x 160). (B) Direct smear of RCC showing loosely cohesive tumor cells with ill-defined cytoplasmic borders, round nuclei, and prominent nucleoli (Papanicolaou, X 400).
Fig. 4. (A) Direct FNA smear of PRC showing tight epithelial clusters with interspersed psammoma bodies; note the paucity of single tumor cells (Papanicolaou, X 2 5 ) . (B) Histologic section of the resected tumor showing an area of tubular predominance and a psammoma body within a papillary frond (inset) (H&E, x 250).
200
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PAPILLARY RENAL-CELL CARCINOMA
Fig. 5. (A) Direct smear of PRC showing scant cytoplasm, hyperchromasia, and small but distinct nucleoli (Papanicolaou, x 25). (B) Direct smear of PRC demonstrating prominent nuclear grooves (Papanicolaou, x 250).
Fig. 6. (A) A direct smear of PRC showing hemosiderin pigment within the cytoplasm of tumor cells (Papanicolaou, X 400). (B) Corresponding histologic section showing the same pigment in epithelial (tumor) cells. The epithelial nature of these cells was proven by positive staining for keratin (H&E, X400).
recognition possible. Differences between PRC and the clear-cell type are seen in the smear pattern, nuclear features, and cytoplasmic features. The most distinguishing features, however, are nuclear; nuclear grooves are frequently evident (Fig. 5 ) , nuclear pleomorphism is unusual (Fig. 5B),and nucleoli are inconspicuous. A peculiar feature seen in four of our cases was cytoplasmic hemosiderin in tumor cells (Fig. 6). The presence of this pigment in neoplasms is not widely acknowledged; Lohr and Leder lo illustrated it in a case of RCC without any further comment. We have occasionally seen hemosiderin pigment in tumor cells, particularly RCCs, usually associated with hemorrhage in adjacent areas. The epithelial nature of the pigment-bearing cells in our smears was proven by positive staining for cytokeratin, after applying antikeratin antibodies (AEVAE3) on direct smears by the Avidin-Biotin Complex method. The likely origin of the hemosiderin pigment is hemorrhage within the necrotic areas that are so frequently seen in these
neoplasms. Since renal tubular cells have the indigenous capacity to absorb large amounts of the glomerular filtrates, it is logical to assume that neoplasms arising from the renal tubular epithelium can absorb substances surrounding them. The presence of the pigment was problematic in one case in which melanoma was considered at initial assessment. An iron stain promptly resolved the problem. Hemosiderin-containing cells of PRCs may be mistaken for hepatocytes, particularly if the pigment is finely granular, or histiocytes. In a hypocellular specimen, this might pose a serious diagnostic problem. The differential diagnosis of PRC should include papillary transitional-cell carcinoma, metastatic carcinoma (from breast, lung, ovaries, etc.), Wilms’ tumor, mesothelial cells, hepatocytes, and even normal renal tubular cells (Table 11). The clinical history and radiographic (including angiographic) appearances of renal tumors are of paramount importance in making a differential diagnosis and may occasionally provide the only clues. Ancillary studies Diagnostic Cytopathology, Vol 7, No 2
201
DEKMEZIAN ET AL. Table 11. Differential Diagnosis of Papillary Renal Neoplasms ~~
Type of cells
Papillary TCC Metastatic carcinoma Wilms’ tumor Mesothelial cells Hepatocytes Normal renal structures
Comment
Epithelial lining of papillae is stratified Rely on mucin stain, and glycogen content, and clinical history Look for heterogeous elements, tubules, and blastema; age Usually there is a paucity of cells Pigments (iron not helpful) Usuallv hvDocehiar sDecimen
such as mucicarmine staining and periodic acid-Schiff staining for glycogen may be helpful, because papillary carcinoma is mucicarmine-negative and contains varying amounts of glycogen. Collecting duct carcinomas are mucin-positive; however, these tumors are rare and show considerable pleomorphism. A rare case of papillary carcinoma has been reported to be mucin-positive. l 2 Mucinous metaplasia of the stroma may occasionally be mistaken for a mucin-producing carcinoma. Psammoma bodies, when present, are of extreme importance in making a diagnosis of PRC. We saw them in four of our cases, and they are reported to be present in approximately 40% of these neoplasms.3 In addition to psammoma bodies, calcification lacking lamellation in the rim of the tumor occurs in 30% of cases3 and is another helpful clue in diagnosing PRCs. An occasional aspirate of PRC may mimic the well differentiated tubular areas of Wilms’ tumor (Fig. 4 B ) and vice versa. Wilms’ tumor usually shows heterologous, stromal, and blastemal elements in addition to the epithelial component. PRC may be difficult to distinguish from low-grade papillary transitional-cell carcinoma (TCC), particularly on smears alone. One helpful clue, which may be easier to find in cell block sections, is that in PRCs, the papillary fronds are lined by a single layer of cells (Fig. lC), whereas TCCs show stratification of the lining epithelium. Mesothelial cells, particularly when they are in large sheets, can be mistaken for PRC and vice versa. One case had many flat sheets of tumor cells with bland nuclei interpreted as mesothelial cells (Fig. 2A); the cell block section, however, was diagnostic of PRC. The overabundance of these sheets can be the only clue to the diagnosis. Finally, PRC may be mistaken for normal renal tubular cells, particularly in a hypocellular specimen. One clue against a PRC would be the presence of glomeruli, although in two cases glomeruli were found in admixture with malignant cells (Fig. 7) and glomeruli might look like a papillary tumor to the inexperienced observer. PRCs have distinct cytologic features, recognition of which is important in the differential diagnosis of primary renal cell and metastatic carcinomas with papillary features. 202
Diagnostic Cytopathology, Yo1 7, No 2
Fig. 7. Papillary fragments of renal carcinoma adjacent to a glomerulus. The latter can be mistaken for a papillary fragment of a carcinoma by an unwary observer (Papanicolaou, x 100).
References 1. Ekelund L. Hypovascular renal tumors: an aggressive diagnostic
approach required. J Urol 1977;119:566-8. 2. Press GA, McClennan BL, Melson GL, et al. Papillary renal cell carcinoma: CT and sonographic evaluation. Am J Radio1 1984; 143:1005-9. 3. Mancilla-Jimenez R, Stanley RJ, Blath RA. Papillary renal cell carcinoma: a clinical, radiologic, and pathologic study of 34 cases. Cancer 1976;38:2469-80. 4. Reis M, Faria V. Renal carcinoma: reevaluation of prognostic factors. Cancer 1988;61:1192-9.
5. Ulrich W, Buxbaum P, Holzner JH. Pathology of renal cancer and its metastases. Semin Surg Oncol 1988;4:143-8. 6. Flint A, Cookingham C. Cytologic diagnosis of the papillary variant of renal-cell carcinoma. Acta Cytol 1987;31:325-9. 7. Orell SR, Langlois SLP, Marshall VR. Fine needle aspiration cytology in the diagnosis of solid renal and adrenal masses. Scand J Urol Nephrol 1985;19:211-6. 8. Mydlo JH, Bard RH. Analysis of papillary renal adenocarcinoma. Urology 1987;30:529-34.
PAPILLARY RENAL-CELL CARCINOMA 9. Carroll PR, Murty VVS, Reuter V, et al. Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma. Cancer Genet Cytogenet 1987;26:253-9. 10. Lohr E, Leder L-D. Renal and adrenal tumors. Berlin: SpringerVerlag, 1987:13-20.
11. Grignon DJ, Ro JR, Ayala AG. Primary mucin-secreting adenocarcinomd of the kidney. Arch Pathol Lab Med 1988;112: 847-9. 12. Fleming S, Lewi HJE. Collecting duct carcinoma of the kidney. Histopathology 1986;10:113 1 4 1 .
Diagnostic Cytopathology, Vol 7, No 2
203
Although papillary carcinoma of the kidney is a distinct clinical and pathological entity, there are few descriptions of its cytologic features in the literature. We describe the cytologic features of aspiratesfrom 1.5 papillary carcinomas of the kidney. The smears showed abundant papillary clusters with vascular cores and relatively few single cells. Tumor cells contained moderate to scant cytoplasm, nuclei were usually small and uniform, mild to moderate hyperchromasia was routine, nucleoli were single and small, and nuclear grooves were often prominent. Histiocytes and psammoma bodies were present in only four cases. Hemosiderin pigment within tumor cells was also present in four cases. Differential diagnosis should consider low-grade transitional-cell carcinoma, metastatic adenocarcinoma, normal renal tubular epithelium, mesothelial cells, and, occasionally, Wilms ’ tumor. Cytologically recognizing the distinct entity ofpapillary carcinoma is important in the workup of primary renal neoplasms and metastatic papillary neoplasms of unknown origin. Diagn Cytopathol 1991;7:
Specimens were processed by the radiologist under computerized tomography (CT) scan or ultrasound guidance using a 22-gauge needle. The following features were examined: nuclear/cytoplasmic ( N K ) ratio, nuclear shape, chromatin, nucleoli, cellularity, papillary fragments, bare nuclei, cytoplasmic vacuoles, pigment, histiocytes, and psammoma bodies.
Results The results are shown in Table I. Both renal-cell carcinomas (RCCs) and papillary renal carcinomas (PRCs) had cellular smears, but the papillary tumors also contained many tridimentional papillary fragments with fibrovascular cores (Fig. l), tight or cohesive clusters, and Table I. Comparison of Cytologic Features of Renal-Cell Carcinoma and Papillary Renal Carcinoma
198-203.
Key Words: Psammoma bodies; Nuclear grooves; Hemosiderin;
Renal-cell carcinoma
Metastatic carcinoma; Transitional-cell carcinoma; Mesothelial cells Although papillary renal carcinoma has been recognized as a distinct radiological 1-3 and pathological 3-5 entity, its cytologic features have rarely been described. Since this neoplasm may present first as metastases in distant sites, familiarity with its cytologic features is essential in making a differential diagnosis between metastatic papillary carcinomas and primary renal neoplasms.
Cellularity Papillary fragments Single tumor cells Stripped nuclei Psammoma bodies Nuclear features Chromatin
Nucleoli
++
++
Usually absent
Abundant with vascular cores
++ ++
Received December 7, 1989. Accepted May 8, 1990. From the University of Texas M.D. Anderson Cancer Center, Houston, TX. Address reprint requests to Roupen Dekmezian, M.D., University of Texas M.D. Anderson Cancer Center, Division of Pathology, 1515 Holcombe, Box 085, Houston, TX 77030.
198
Diagnostic Cytopathology, Val 7, No 2
Contour
Pleomorphism Cytoplasmic features Nucleas/cytoplasmic ratio Pigment Vacuoles Glycogen . Key:
+
+
.
Absent
Present (4 cases)
Open (except sarcomatoid variant) Very prominent
Slight to moderate hyperchromasia
Materials and Methods Fine-needle aspiration material from 15 cases of histologically proven papillary renal carcinoma was reviewed and compared with material from 45 renal-cell carcinomas. In 13 cases, the primary renal tumor was aspirated, and in 2 the aspiration material was obtained from metastases.
Papillary renal carcinoma
Smooth (except sarcomatoid variant) Va riab 1e
Always low None Variable Present
Small, inconspicuous, single Smooth to irregular with grooves Absent in 12 of 15 cases Moderate to high Present in 3 of 15 cases Variable Present
+, few; + +, abundant. ,q1991 WILEY-LISS, INC.
PAPILLARY RENAL-CELL CARCINOMA
Fig. 1. (A) Direct smear from a PRC showing tight clusters of complex papillary formations. Even at low magnification the absence of nuclear pleomorphism can be appreciated (Papanicolaou, x 25). (B) An air-dried smear of the same aspirate shows papillary fronds supported by vascular cores (Diff-Quik, X 100). (C)Histologic section of surgically removed specimen showing many papillary structures lined by a single layer of epithelial cells and supported by large clusters of foamy histiocytes (H&E, x 25).
a paucity of single tumor cells (Fig. 2). In contrast, RCCs showed loosely cohesive monolayer groups of many single tumor cells (Fig. 3). Stripped nuclei, frequently seen in RCC, were rarely encountered in the papillary form. Psammoma bodies were seen in PRCs, whereas none were visible in the RCCs (Fig. 4). Twelve of the 15 PRCs had small, uniform, ovoid nuclei with slight to moderate hyperchromasia. The other three showed moderate nuclear pleomorphism and hyperchromasia (Fig. 5), whereas RCCs almost always had open chromatin. Nucleoli were usually prominent in RCCs, whereas the PRCs had small though distinct nucleoli (Fig. 5A). Nuclear grooves were frequently present in PRCs but only rarely in RCCs (Fig. 5B).Cytoplasm was abundant in RCC (Fig. 3B) but either scant or moderate in PRC (Fig. 5 A ) . Hemosiderin pigment was present in the tumor cells of four papillary tumors; in one case, it was finely granular initially raising a suspicion of melanoma (Fig. 6).
Discussion Although reports describing the cytologic features of clear-cell renal carcinoma abound in the literature (see review by Orell et al. ’), only a single report has discussed the cytologic characteristics of PRC. Yet PRCs constitute approximately 15% of all renal neoplasms.3 They have characteristic radiologic features (usually hypovascular 2,3,8); their histology, although variable, typically features papillary adenocarcinomas with foamy histiocytes within the stroma of the papillae. Even cytogenetic studies indicate that PRCs may have a pathogenesis different from that of RCC; a study of six cases of RCC showed the same chromosome 3 abnormality in the 3p12-14 region to be present in all, while two PRCs contained different (random) abnormalities. Our study shows that fine-needle aspirates of PRCs contain many distinct cytologic features that make their Diagnostic Cytopathology, Vol 7, No 2
199
DEKMEZIAN ET AL.
Fig. 2. Direct smear of PRC showing cohesive (A) and tight (B) clustering of tumor cells with few single cells scattered in the smear (Papanicolaou: A, X 100; B, X25).
Fig. 3. (A) Direct smear of RCC showing many single cells and naked nuclei (Papanicolaou, x 160). (B) Direct smear of RCC showing loosely cohesive tumor cells with ill-defined cytoplasmic borders, round nuclei, and prominent nucleoli (Papanicolaou, X 400).
Fig. 4. (A) Direct FNA smear of PRC showing tight epithelial clusters with interspersed psammoma bodies; note the paucity of single tumor cells (Papanicolaou, X 2 5 ) . (B) Histologic section of the resected tumor showing an area of tubular predominance and a psammoma body within a papillary frond (inset) (H&E, x 250).
200
Diagnostic Cytopathoiogy, Voi 7, No 2
PAPILLARY RENAL-CELL CARCINOMA
Fig. 5. (A) Direct smear of PRC showing scant cytoplasm, hyperchromasia, and small but distinct nucleoli (Papanicolaou, x 25). (B) Direct smear of PRC demonstrating prominent nuclear grooves (Papanicolaou, x 250).
Fig. 6. (A) A direct smear of PRC showing hemosiderin pigment within the cytoplasm of tumor cells (Papanicolaou, X 400). (B) Corresponding histologic section showing the same pigment in epithelial (tumor) cells. The epithelial nature of these cells was proven by positive staining for keratin (H&E, X400).
recognition possible. Differences between PRC and the clear-cell type are seen in the smear pattern, nuclear features, and cytoplasmic features. The most distinguishing features, however, are nuclear; nuclear grooves are frequently evident (Fig. 5 ) , nuclear pleomorphism is unusual (Fig. 5B),and nucleoli are inconspicuous. A peculiar feature seen in four of our cases was cytoplasmic hemosiderin in tumor cells (Fig. 6). The presence of this pigment in neoplasms is not widely acknowledged; Lohr and Leder lo illustrated it in a case of RCC without any further comment. We have occasionally seen hemosiderin pigment in tumor cells, particularly RCCs, usually associated with hemorrhage in adjacent areas. The epithelial nature of the pigment-bearing cells in our smears was proven by positive staining for cytokeratin, after applying antikeratin antibodies (AEVAE3) on direct smears by the Avidin-Biotin Complex method. The likely origin of the hemosiderin pigment is hemorrhage within the necrotic areas that are so frequently seen in these
neoplasms. Since renal tubular cells have the indigenous capacity to absorb large amounts of the glomerular filtrates, it is logical to assume that neoplasms arising from the renal tubular epithelium can absorb substances surrounding them. The presence of the pigment was problematic in one case in which melanoma was considered at initial assessment. An iron stain promptly resolved the problem. Hemosiderin-containing cells of PRCs may be mistaken for hepatocytes, particularly if the pigment is finely granular, or histiocytes. In a hypocellular specimen, this might pose a serious diagnostic problem. The differential diagnosis of PRC should include papillary transitional-cell carcinoma, metastatic carcinoma (from breast, lung, ovaries, etc.), Wilms’ tumor, mesothelial cells, hepatocytes, and even normal renal tubular cells (Table 11). The clinical history and radiographic (including angiographic) appearances of renal tumors are of paramount importance in making a differential diagnosis and may occasionally provide the only clues. Ancillary studies Diagnostic Cytopathology, Vol 7, No 2
201
DEKMEZIAN ET AL. Table 11. Differential Diagnosis of Papillary Renal Neoplasms ~~
Type of cells
Papillary TCC Metastatic carcinoma Wilms’ tumor Mesothelial cells Hepatocytes Normal renal structures
Comment
Epithelial lining of papillae is stratified Rely on mucin stain, and glycogen content, and clinical history Look for heterogeous elements, tubules, and blastema; age Usually there is a paucity of cells Pigments (iron not helpful) Usuallv hvDocehiar sDecimen
such as mucicarmine staining and periodic acid-Schiff staining for glycogen may be helpful, because papillary carcinoma is mucicarmine-negative and contains varying amounts of glycogen. Collecting duct carcinomas are mucin-positive; however, these tumors are rare and show considerable pleomorphism. A rare case of papillary carcinoma has been reported to be mucin-positive. l 2 Mucinous metaplasia of the stroma may occasionally be mistaken for a mucin-producing carcinoma. Psammoma bodies, when present, are of extreme importance in making a diagnosis of PRC. We saw them in four of our cases, and they are reported to be present in approximately 40% of these neoplasms.3 In addition to psammoma bodies, calcification lacking lamellation in the rim of the tumor occurs in 30% of cases3 and is another helpful clue in diagnosing PRCs. An occasional aspirate of PRC may mimic the well differentiated tubular areas of Wilms’ tumor (Fig. 4 B ) and vice versa. Wilms’ tumor usually shows heterologous, stromal, and blastemal elements in addition to the epithelial component. PRC may be difficult to distinguish from low-grade papillary transitional-cell carcinoma (TCC), particularly on smears alone. One helpful clue, which may be easier to find in cell block sections, is that in PRCs, the papillary fronds are lined by a single layer of cells (Fig. lC), whereas TCCs show stratification of the lining epithelium. Mesothelial cells, particularly when they are in large sheets, can be mistaken for PRC and vice versa. One case had many flat sheets of tumor cells with bland nuclei interpreted as mesothelial cells (Fig. 2A); the cell block section, however, was diagnostic of PRC. The overabundance of these sheets can be the only clue to the diagnosis. Finally, PRC may be mistaken for normal renal tubular cells, particularly in a hypocellular specimen. One clue against a PRC would be the presence of glomeruli, although in two cases glomeruli were found in admixture with malignant cells (Fig. 7) and glomeruli might look like a papillary tumor to the inexperienced observer. PRCs have distinct cytologic features, recognition of which is important in the differential diagnosis of primary renal cell and metastatic carcinomas with papillary features. 202
Diagnostic Cytopathology, Yo1 7, No 2
Fig. 7. Papillary fragments of renal carcinoma adjacent to a glomerulus. The latter can be mistaken for a papillary fragment of a carcinoma by an unwary observer (Papanicolaou, x 100).
References 1. Ekelund L. Hypovascular renal tumors: an aggressive diagnostic
approach required. J Urol 1977;119:566-8. 2. Press GA, McClennan BL, Melson GL, et al. Papillary renal cell carcinoma: CT and sonographic evaluation. Am J Radio1 1984; 143:1005-9. 3. Mancilla-Jimenez R, Stanley RJ, Blath RA. Papillary renal cell carcinoma: a clinical, radiologic, and pathologic study of 34 cases. Cancer 1976;38:2469-80. 4. Reis M, Faria V. Renal carcinoma: reevaluation of prognostic factors. Cancer 1988;61:1192-9.
5. Ulrich W, Buxbaum P, Holzner JH. Pathology of renal cancer and its metastases. Semin Surg Oncol 1988;4:143-8. 6. Flint A, Cookingham C. Cytologic diagnosis of the papillary variant of renal-cell carcinoma. Acta Cytol 1987;31:325-9. 7. Orell SR, Langlois SLP, Marshall VR. Fine needle aspiration cytology in the diagnosis of solid renal and adrenal masses. Scand J Urol Nephrol 1985;19:211-6. 8. Mydlo JH, Bard RH. Analysis of papillary renal adenocarcinoma. Urology 1987;30:529-34.
PAPILLARY RENAL-CELL CARCINOMA 9. Carroll PR, Murty VVS, Reuter V, et al. Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma. Cancer Genet Cytogenet 1987;26:253-9. 10. Lohr E, Leder L-D. Renal and adrenal tumors. Berlin: SpringerVerlag, 1987:13-20.
11. Grignon DJ, Ro JR, Ayala AG. Primary mucin-secreting adenocarcinomd of the kidney. Arch Pathol Lab Med 1988;112: 847-9. 12. Fleming S, Lewi HJE. Collecting duct carcinoma of the kidney. Histopathology 1986;10:113 1 4 1 .
Diagnostic Cytopathology, Vol 7, No 2
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