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Clear Cell and Non-Clear Cell Hepatocellular Carcinoma: A Case Report and Literature Review
J.H. Liu, H.L. Tsai, S.M. Hsu, et al
CLEAR CELL AND NON-CLEAR CELL HEPATOCELLULAR CARCINOMA: A CASE REPORT AND LITERATURE REVIEW Jenn-Hwa Liu, Huey-Ling Tsai, Soa-Ming Hsu,1 Dong-Her Hu,2 and Shy-Shen Chen3 Divisions of Gastroenterology, 1Radiology, 2General Surgery, and 3Pathology, Shalu Kuang-Tien Hospital, Taichung, Taiwan.
Clear cell hepatocellular carcinoma (HCC) is an uncommon variant of HCC. It is considered to have a better prognosis than non-clear cell HCC, but recent large studies show that there is some controversy. DNA image cytometry reveals diploid and non-diploid DNA content tumors that have different pleomorphisms and mitosis corresponding to different prognoses. Clear cell HCC is classified as focal or diffuse. Herein, we report a rare case of a 61-year-old male with two adjacent hyper- and hypoechoic hepatic nodules and an α-fetoprotein concentration of 6,370 ng/mL. Pathologic examination of a specimen obtained during wedge hepatectomy showed both clear cell and non-clear cell HCC. Bone metastasis was later found. We suggest that a patient with clear cell HCC should be followed up closely after complete resection.
Key Words: clear cell hepatocellular carcinoma, hyperechoic, hypoechoic (Kaohsiung J Med Sci 2004;20:78–82)
Of 10 major malignancies in Taiwan, hepatocellular carcinoma (HCC) is the leading cause of death [1]. Better prognosis is related to histologic features such as encapsulation of the tumor [2], eosinophilic HCC with lamellar fibrosis, and the presence of clear cells [3]. However, there is controversy about the prognosis of clear cell HCC in recent large studies comparing it to non-clear cell HCC [4]. Clear cell HCC was previously regarded as an uncommon variant of HCC, but the incidence is high, up to 37.5% and 45% of cases in reports from Hong Kong and Japan, respectively [4,5]. It has been classified as focal pattern (clear cells less than one-third of the lesion) or diffuse pattern (more than one-half of the lesion), with a
Received: December 11, 2002 Accepted: September 2, 2003 Address correspondence and reprint requests to: Dr. Jenn-Hwa Liu, Division of Gastroenterology, Shalu Kuang-Tien Hospital, Shalu, Taichung, Taiwan. E-mail: [email protected]
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significantly better survival rate in the report from Hong Kong [4]. Clear cell HCC was reported in 9.5% (42/440) of HCC cases in Taiwan, with no significant difference in survival rate compared with non-clear cell HCC [6]. Here, we report a rare case of HCC with two adjacent clear cell and non-clear cell nodules.
CASE PRESENTATION A 61-year-old male was referred to our hospital in December 2000 for evaluation of a hepatic tumor. Despite symptoms of fatigue and loss of appetite, the patient was robust. He was a chronic hepatitis B carrier. Two nodules were found over the right lobe of the liver during a routine check-up. On physical examination, the liver was palpable 1 cm below the right costal margin with a hard consistency. Significant laboratory findings included serum glutamic oxaloacetic transaminase (52 IU/L; normal, < 28 IU/L), lactic dehydrogenase (337 IU/L; normal, < 255 IU/L), and α-fetoprotein (6,370 ng/mL; normal, < 10 ng/mL). Abdominal ultrasonography revealed a hyperechoic nodule, 2.5 cm in diameter, over the superior aspect of the right lobe of the liver Kaohsiung J Med Sci February 2004 • Vol 20 • No 2 © 2004 Elsevier. All rights reserved.
Clear cell and non-clear cell hepatocellular carcinoma
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Figure 1. Ultrasonography of clear cell hepatocellular carcinoma (HCC) and non-clear cell HCC. The large hyperechoic nodule mass (large arrowheads) corresponds to clear cell HCC and the small hypoechoic mass (small arrow) corresponds to non-clear cell HCC.
(segment 8) and adjacent to its left side, and a hypoechoic ovoid nodule, 2.0 cm in diameter, with separate capsules (Figure 1). The same nodules were detected by computerized tomography (CT) of the abdomen. Celiac angiography suggested two hypervascular malignant tumors. The more hypervascular tumor corresponded to the left side hypoechoic nodule found on sonography (Figure 2). Exploratory laparotomy revealed a yellowish nodule, 2.5 cm in diameter, over segment 8 of the right lobe, corresponding to the hyperechoic ovoid nodule on ultrasonography. Adjacent to this, there was a red solid nodule, 2.0 cm in diameter, corresponding to the hypoechoic tumor on sonography. At hepatic segmentectomy in segment 8, both nodules were resected completely with intact capsules. Pathologic examination showed that the hyperechoic nodule was clear cell HCC (Figure 3) and that the hypoechoic nodule was non-clear cell HCC (Figure 4). The postoperative course was smooth and α-fetoprotein dropped to 128 ng/mL after 1 week. However, 4 months post surgery, a metastatic tumor was detected over the left shoulder on bone scan. The patient died of acute fulminant hepatic failure after local irradiation. Kaohsiung J Med Sci February 2004 • Vol 20 • No 2
Figure 2. Right hepatic angiography of clear cell hepatocellular carcinoma (HCC) and non-clear cell HCC. The large, mildly hypervascular tumor (large V) corresponds to clear cell HCC and the small strongly hypervascular mass (small V) corresponds to non-clear cell HCC.
DISCUSSION The histologic subtypes of HCC can be classified as microtrabecular or macrotrabecular, giant cell carcinoma, pseudoglandular acinar, solid-anaplastic, fibrolamellaroncocytic, clear cell, combined cholangiocellar, or carcinoid. Each subtype has a different prognosis [7]. The case presented here had hepatoma with two different cell type nodules, clear cell (with clear, foamy or vacuolated cytoplasm) and non-clear cells, which is very rare. It is generally accepted that clear cell HCC is mostly due to prominent accumulation of lipid droplets [8] and sometimes glycogen [7]. Electron microscopy study of 10 clear cell HCC disclosed both lipid and glycogen accumulation in the cytoplasm, and cytoplasmic organelles were significantly fewer than in non-clear cell HCC [9]. However, the complete pathogenesis of clear cell HCC is not known. Clear cell HCC has been regarded as an uncommon variant of HCC, and accounts for 5% to 8.7% of cases in western countries [8]. In Taiwan, where HCC is highly prevalent, an incidence of 13.2% (105/795 cases) has been reported by Professor Hsu Hey-Chi of the National Taiwan University Hospital (unpublished). Almost the same incidence, 13.3%, has been reported from China [10]. Yang et al reported from Japan that 9.3% (20/215) of HCC cases were diffuse clear cell HCC and 35.8% (77/215) contained focal clear cells that were moderately differentiated in 80% of cases. The male to female ratio was 2.3:1 [5]. Lai et al reported from Hong Kong that 12.5% (10/80) 79
J.H. Liu, H.L. Tsai, S.M. Hsu, et al
Figure 3. Pathology of clear cell hepatocellular carcinoma (HCC) shows moderately differentiated neoplastic cells forming thickened trabeculae. The tumor cells have apparently empty, clear cytoplasm and hyperchromatic central or peripheral nuclei with pleomorphism (hematoxylin & eosin, × 350).
Figure 4. Pathology of non-clear cell hepatocellular carcinoma (HCC) (common pattern) shows moderately differentiated neoplastic cells arranged in a trabecular or tubular pattern. The tumor cells have prominent nuclei, nucleoli, and basophilic cytoplasm (hematoxylin & eosin, × 350).
of HCC cases were diffuse clear cell and 25% (20/80) contained focal clear cells, with a male to female ratio of 1.6:1 [4]. The paraneoplastic manifestations of HCC have been reported as hypercholesterolemia and hypoglycemia (in around 30% of cases); erythrocytosis is rare. In clear cell HCC, hypoglycemia and hypercholesterolemia have rarely been reported [7]. The diagnosis of both clear cell and non-clear cell HCC depends on imaging study and fine-needle aspiration cytomorphology. On ultrasonography, a low echoic pattern is common among smaller HCCs, and a low echoic periphery pattern tends to prevail with increasing size. The pathologic factors of fatty change and clear cell formation are responsible for elevating the echogenicity [11]. Our case supports this theory. Clear cell HCC is moderately differentiated in 80% of cases, with abundant glycogen storage and a variable degree of fat [5]. About 90% of clear cell HCC cases are associated with liver cirrhosis, more than the 59.3% of non-clear cell HCC cases. Ultrastructurally, clear cells showed a marked reduction in the number and size of organelles in the eight cases examined by Wu et al [9]. Clear cell HCC can be confused with metastatic hepatic lesions of renal, ovarian, or adrenal origin. Singh et al reported that fine-needle aspiration cytomorphology offered a good preoperative diagnosis of clear cell HCC in four cases with anisonucleosis, nuclear hyperchromasia, macronucleoli, and abundant fine vacuolate in clear cytoplasm [12]. Hepatocyte immunostain is the best method to distinguish clear cell HCC
from metastatic lesions, with a sensitivity of 90% and specificity of 100% [13]. In this case, clear cell HCC had greater echoic change on sonography than non-clear cell HCC. This supports the idea that a tumor with fatty changes or clear cell formation has increased echogenicity and sometimes appears like a hemangioma [14]. Fatty changes in HCC may be found using precontrast CT with a low-attenuation area (< –10 H), but it is sometimes difficult to differentiate based on density difference. High signal intensity on T1-weighted magnetic resonance images have been reported in well-differentiated HCC with fatty changes and/or clear cell formation, but controversy exists in decreasing signal intensity on T1weighted magnetic resonance images. The hypervascularity and increasing tumor stain on angiography usually corresponds to tumor vascularity in HCC. However, small tumors that are diffusely infiltrated by fat should be distinguished from benign conditions such as focal fatty change, lipoma, or angiomyolipoma [15]. It has been claimed that clear cell HCC has a better prognosis than non-clear cell HCC [2,4], but there is controversy in recent large serial reports [5,9]. A significantly better prognosis was reported by Lai et al in Hong Kong [4]: patients with diffuse clear cell, focal clear cell, and non-clear cell tumors had 50% survival rates of 14, 6, and 3 weeks, respectively. The differences between each pair were significant (p < 0.001). Clear cell HCC is more sensitive to transcatheter arterial embolization treatment than other subtypes of HCC [10]. However, in one study with 215 patients, the survival rates for clear cell HCC at 3 and 5 years
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Kaohsiung J Med Sci February 2004 • Vol 20 • No 2
Clear cell and non-clear cell hepatocellular carcinoma
were 54.5% and 33.3%, not significantly different from those for non-clear cell HCC (74.3% and 46.1%, respectively) [5]. A similar result was reported from 118 cirrhotic cases in France [16]. What is important in interpreting prognosis? DNA imaging cytometry shows that clear cell HCC is comprised of two groups, one with bland morphologic features and diploid DNA content and the other with aggressive morphologic features and aneuploid DNA content. This may explain the discrepant literature reports regarding the prognosis of this tumor [17]. In this case, clear cell and non-clear cell HCC were found in two adjacent nodules with moderately differentiated neoplasm cells and intact capsules. They were resected completely. However, tumor metastasis was found very soon, leading to a poor prognosis. We suggest that clear cell HCC should be followed up as regularly as non-clear cell HCC.
REFERENCES 1. Whang-Peng J, Chao Y. Clinical trials of HCC in Taiwan. Hepatogastroenterology 1998;45:1937–43. 2. Okuda K, Peters RL. Clinical aspects of hepatocellular carcinoma. In: Okuda K, Peters RL, eds. Hepatocellular Carcinoma. New York: Wiley, 1976;387–436. 3. McDermott WV, Cady B, Georgi B, et al. Primary cancer of the liver. Evaluation, treatment, and prognosis. Arch Surg 1989; 124:552–4. 4. Lai CL, Wu PC, Lam KC, et al. Histologic prognostic indicators in hepatocellular carcinoma. Cancer 1979;44:1677–83. 5. Yang SH, Watanabe J, Nakashima O, et al. Clinicopathologic
Kaohsiung J Med Sci February 2004 • Vol 20 • No 2
study on clear cell hepatocellular carcinoma. Pathol Int 1996; 46:503–9. 6. Lai CR, Liu HC. Hepatocellular carcinoma in Taiwan: clinicopathological study of 440 cases from a consecutive 6000 autopsies. Chin Med J (Taipei) 1993:51:249–56. 7. Ross JS, Kurian S. Clear cell hepatocellular carcinoma: sudden death from severe hypoglycemia. Am J Gastroenterol 1985;80:188–94. 8. Buchanan TF, Huvos AG. Clear cell carcinoma of the liver. A clinicopathologic study of 113 patients. Am J Clin Pathol 1974; 61:529–39. 9. Wu PC, Lai CL, Lam KC, et al. Clear cell carcinoma of the liver. An ultrastructural study. Cancer 1983;52:504–7. 10. Wang Y, Zhang J, Gao Y, et al. Therapeutic efficacy of transcatheter arterial embolization of primary hepatocellular carcinoma: discrepancy in different histopathologic subtypes. Chin Med J (Engl) 1999;112:264–8. 11. Nihei T, Ebara M, Ohto M, Kondo F. Study of sonographic findings of small hepatocellular carcinoma based on its pathologic findings. Nippon Shokakibyo Gakkai Zasshi 1992;89:1360–8. 12. Singh HK, Silverman JF, Geisinger KR, et al. Fine-needle aspiration cytomorphology of clear-cell hepatocellular carcinoma. Diagn Cytopathol 1997;17:306–10. 13. Murakata LA, Ishak KG, Nzeako UC. Clear cell carcinoma of the liver: a comparative immunohistochemical study with renal clear cell carcinoma. Mod Pathol 2000;13:874–81. 14. Monzawa S, Omata K, Shimazu N, et al. Well-differentiated hepatocellular carcinoma: findings of US, CT, and MR imaging. Abdom Imaging 1999;24:392–7. 15. Yoshikawa J, Matsui O, Takashima T, et al. Fatty metamorphosis in hepatocellular carcinoma: radiologic features in 10 cases. AJR Am J Roentgenol 1988;151:717–20. 16. Emile JF, Lemoine A, Azoulay D, et al. Histological, genomic and clinical heterogeneity of clear cell hepatocellular carcinoma. Histopathology 2001;38:225–31. 17. Orsatti G, Arnold MM, Paronetto F. DNA image cytometric analysis of primary clear cell carcinoma of the liver. Arch Pathol Lab Med 1994;118:1226–9.
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CLEAR CELL AND NON-CLEAR CELL HEPATOCELLULAR CARCINOMA: A CASE REPORT AND LITERATURE REVIEW Jenn-Hwa Liu, Huey-Ling Tsai, Soa-Ming Hsu,1 Dong-Her Hu,2 and Shy-Shen Chen3 Divisions of Gastroenterology, 1Radiology, 2General Surgery, and 3Pathology, Shalu Kuang-Tien Hospital, Taichung, Taiwan.
Clear cell hepatocellular carcinoma (HCC) is an uncommon variant of HCC. It is considered to have a better prognosis than non-clear cell HCC, but recent large studies show that there is some controversy. DNA image cytometry reveals diploid and non-diploid DNA content tumors that have different pleomorphisms and mitosis corresponding to different prognoses. Clear cell HCC is classified as focal or diffuse. Herein, we report a rare case of a 61-year-old male with two adjacent hyper- and hypoechoic hepatic nodules and an α-fetoprotein concentration of 6,370 ng/mL. Pathologic examination of a specimen obtained during wedge hepatectomy showed both clear cell and non-clear cell HCC. Bone metastasis was later found. We suggest that a patient with clear cell HCC should be followed up closely after complete resection.
Key Words: clear cell hepatocellular carcinoma, hyperechoic, hypoechoic (Kaohsiung J Med Sci 2004;20:78–82)
Of 10 major malignancies in Taiwan, hepatocellular carcinoma (HCC) is the leading cause of death [1]. Better prognosis is related to histologic features such as encapsulation of the tumor [2], eosinophilic HCC with lamellar fibrosis, and the presence of clear cells [3]. However, there is controversy about the prognosis of clear cell HCC in recent large studies comparing it to non-clear cell HCC [4]. Clear cell HCC was previously regarded as an uncommon variant of HCC, but the incidence is high, up to 37.5% and 45% of cases in reports from Hong Kong and Japan, respectively [4,5]. It has been classified as focal pattern (clear cells less than one-third of the lesion) or diffuse pattern (more than one-half of the lesion), with a
Received: December 11, 2002 Accepted: September 2, 2003 Address correspondence and reprint requests to: Dr. Jenn-Hwa Liu, Division of Gastroenterology, Shalu Kuang-Tien Hospital, Shalu, Taichung, Taiwan. E-mail: [email protected]
78
significantly better survival rate in the report from Hong Kong [4]. Clear cell HCC was reported in 9.5% (42/440) of HCC cases in Taiwan, with no significant difference in survival rate compared with non-clear cell HCC [6]. Here, we report a rare case of HCC with two adjacent clear cell and non-clear cell nodules.
CASE PRESENTATION A 61-year-old male was referred to our hospital in December 2000 for evaluation of a hepatic tumor. Despite symptoms of fatigue and loss of appetite, the patient was robust. He was a chronic hepatitis B carrier. Two nodules were found over the right lobe of the liver during a routine check-up. On physical examination, the liver was palpable 1 cm below the right costal margin with a hard consistency. Significant laboratory findings included serum glutamic oxaloacetic transaminase (52 IU/L; normal, < 28 IU/L), lactic dehydrogenase (337 IU/L; normal, < 255 IU/L), and α-fetoprotein (6,370 ng/mL; normal, < 10 ng/mL). Abdominal ultrasonography revealed a hyperechoic nodule, 2.5 cm in diameter, over the superior aspect of the right lobe of the liver Kaohsiung J Med Sci February 2004 • Vol 20 • No 2 © 2004 Elsevier. All rights reserved.
Clear cell and non-clear cell hepatocellular carcinoma
➤
➞
➤
➤
➤
Figure 1. Ultrasonography of clear cell hepatocellular carcinoma (HCC) and non-clear cell HCC. The large hyperechoic nodule mass (large arrowheads) corresponds to clear cell HCC and the small hypoechoic mass (small arrow) corresponds to non-clear cell HCC.
(segment 8) and adjacent to its left side, and a hypoechoic ovoid nodule, 2.0 cm in diameter, with separate capsules (Figure 1). The same nodules were detected by computerized tomography (CT) of the abdomen. Celiac angiography suggested two hypervascular malignant tumors. The more hypervascular tumor corresponded to the left side hypoechoic nodule found on sonography (Figure 2). Exploratory laparotomy revealed a yellowish nodule, 2.5 cm in diameter, over segment 8 of the right lobe, corresponding to the hyperechoic ovoid nodule on ultrasonography. Adjacent to this, there was a red solid nodule, 2.0 cm in diameter, corresponding to the hypoechoic tumor on sonography. At hepatic segmentectomy in segment 8, both nodules were resected completely with intact capsules. Pathologic examination showed that the hyperechoic nodule was clear cell HCC (Figure 3) and that the hypoechoic nodule was non-clear cell HCC (Figure 4). The postoperative course was smooth and α-fetoprotein dropped to 128 ng/mL after 1 week. However, 4 months post surgery, a metastatic tumor was detected over the left shoulder on bone scan. The patient died of acute fulminant hepatic failure after local irradiation. Kaohsiung J Med Sci February 2004 • Vol 20 • No 2
Figure 2. Right hepatic angiography of clear cell hepatocellular carcinoma (HCC) and non-clear cell HCC. The large, mildly hypervascular tumor (large V) corresponds to clear cell HCC and the small strongly hypervascular mass (small V) corresponds to non-clear cell HCC.
DISCUSSION The histologic subtypes of HCC can be classified as microtrabecular or macrotrabecular, giant cell carcinoma, pseudoglandular acinar, solid-anaplastic, fibrolamellaroncocytic, clear cell, combined cholangiocellar, or carcinoid. Each subtype has a different prognosis [7]. The case presented here had hepatoma with two different cell type nodules, clear cell (with clear, foamy or vacuolated cytoplasm) and non-clear cells, which is very rare. It is generally accepted that clear cell HCC is mostly due to prominent accumulation of lipid droplets [8] and sometimes glycogen [7]. Electron microscopy study of 10 clear cell HCC disclosed both lipid and glycogen accumulation in the cytoplasm, and cytoplasmic organelles were significantly fewer than in non-clear cell HCC [9]. However, the complete pathogenesis of clear cell HCC is not known. Clear cell HCC has been regarded as an uncommon variant of HCC, and accounts for 5% to 8.7% of cases in western countries [8]. In Taiwan, where HCC is highly prevalent, an incidence of 13.2% (105/795 cases) has been reported by Professor Hsu Hey-Chi of the National Taiwan University Hospital (unpublished). Almost the same incidence, 13.3%, has been reported from China [10]. Yang et al reported from Japan that 9.3% (20/215) of HCC cases were diffuse clear cell HCC and 35.8% (77/215) contained focal clear cells that were moderately differentiated in 80% of cases. The male to female ratio was 2.3:1 [5]. Lai et al reported from Hong Kong that 12.5% (10/80) 79
J.H. Liu, H.L. Tsai, S.M. Hsu, et al
Figure 3. Pathology of clear cell hepatocellular carcinoma (HCC) shows moderately differentiated neoplastic cells forming thickened trabeculae. The tumor cells have apparently empty, clear cytoplasm and hyperchromatic central or peripheral nuclei with pleomorphism (hematoxylin & eosin, × 350).
Figure 4. Pathology of non-clear cell hepatocellular carcinoma (HCC) (common pattern) shows moderately differentiated neoplastic cells arranged in a trabecular or tubular pattern. The tumor cells have prominent nuclei, nucleoli, and basophilic cytoplasm (hematoxylin & eosin, × 350).
of HCC cases were diffuse clear cell and 25% (20/80) contained focal clear cells, with a male to female ratio of 1.6:1 [4]. The paraneoplastic manifestations of HCC have been reported as hypercholesterolemia and hypoglycemia (in around 30% of cases); erythrocytosis is rare. In clear cell HCC, hypoglycemia and hypercholesterolemia have rarely been reported [7]. The diagnosis of both clear cell and non-clear cell HCC depends on imaging study and fine-needle aspiration cytomorphology. On ultrasonography, a low echoic pattern is common among smaller HCCs, and a low echoic periphery pattern tends to prevail with increasing size. The pathologic factors of fatty change and clear cell formation are responsible for elevating the echogenicity [11]. Our case supports this theory. Clear cell HCC is moderately differentiated in 80% of cases, with abundant glycogen storage and a variable degree of fat [5]. About 90% of clear cell HCC cases are associated with liver cirrhosis, more than the 59.3% of non-clear cell HCC cases. Ultrastructurally, clear cells showed a marked reduction in the number and size of organelles in the eight cases examined by Wu et al [9]. Clear cell HCC can be confused with metastatic hepatic lesions of renal, ovarian, or adrenal origin. Singh et al reported that fine-needle aspiration cytomorphology offered a good preoperative diagnosis of clear cell HCC in four cases with anisonucleosis, nuclear hyperchromasia, macronucleoli, and abundant fine vacuolate in clear cytoplasm [12]. Hepatocyte immunostain is the best method to distinguish clear cell HCC
from metastatic lesions, with a sensitivity of 90% and specificity of 100% [13]. In this case, clear cell HCC had greater echoic change on sonography than non-clear cell HCC. This supports the idea that a tumor with fatty changes or clear cell formation has increased echogenicity and sometimes appears like a hemangioma [14]. Fatty changes in HCC may be found using precontrast CT with a low-attenuation area (< –10 H), but it is sometimes difficult to differentiate based on density difference. High signal intensity on T1-weighted magnetic resonance images have been reported in well-differentiated HCC with fatty changes and/or clear cell formation, but controversy exists in decreasing signal intensity on T1weighted magnetic resonance images. The hypervascularity and increasing tumor stain on angiography usually corresponds to tumor vascularity in HCC. However, small tumors that are diffusely infiltrated by fat should be distinguished from benign conditions such as focal fatty change, lipoma, or angiomyolipoma [15]. It has been claimed that clear cell HCC has a better prognosis than non-clear cell HCC [2,4], but there is controversy in recent large serial reports [5,9]. A significantly better prognosis was reported by Lai et al in Hong Kong [4]: patients with diffuse clear cell, focal clear cell, and non-clear cell tumors had 50% survival rates of 14, 6, and 3 weeks, respectively. The differences between each pair were significant (p < 0.001). Clear cell HCC is more sensitive to transcatheter arterial embolization treatment than other subtypes of HCC [10]. However, in one study with 215 patients, the survival rates for clear cell HCC at 3 and 5 years
80
Kaohsiung J Med Sci February 2004 • Vol 20 • No 2
Clear cell and non-clear cell hepatocellular carcinoma
were 54.5% and 33.3%, not significantly different from those for non-clear cell HCC (74.3% and 46.1%, respectively) [5]. A similar result was reported from 118 cirrhotic cases in France [16]. What is important in interpreting prognosis? DNA imaging cytometry shows that clear cell HCC is comprised of two groups, one with bland morphologic features and diploid DNA content and the other with aggressive morphologic features and aneuploid DNA content. This may explain the discrepant literature reports regarding the prognosis of this tumor [17]. In this case, clear cell and non-clear cell HCC were found in two adjacent nodules with moderately differentiated neoplasm cells and intact capsules. They were resected completely. However, tumor metastasis was found very soon, leading to a poor prognosis. We suggest that clear cell HCC should be followed up as regularly as non-clear cell HCC.
REFERENCES 1. Whang-Peng J, Chao Y. Clinical trials of HCC in Taiwan. Hepatogastroenterology 1998;45:1937–43. 2. Okuda K, Peters RL. Clinical aspects of hepatocellular carcinoma. In: Okuda K, Peters RL, eds. Hepatocellular Carcinoma. New York: Wiley, 1976;387–436. 3. McDermott WV, Cady B, Georgi B, et al. Primary cancer of the liver. Evaluation, treatment, and prognosis. Arch Surg 1989; 124:552–4. 4. Lai CL, Wu PC, Lam KC, et al. Histologic prognostic indicators in hepatocellular carcinoma. Cancer 1979;44:1677–83. 5. Yang SH, Watanabe J, Nakashima O, et al. Clinicopathologic
Kaohsiung J Med Sci February 2004 • Vol 20 • No 2
study on clear cell hepatocellular carcinoma. Pathol Int 1996; 46:503–9. 6. Lai CR, Liu HC. Hepatocellular carcinoma in Taiwan: clinicopathological study of 440 cases from a consecutive 6000 autopsies. Chin Med J (Taipei) 1993:51:249–56. 7. Ross JS, Kurian S. Clear cell hepatocellular carcinoma: sudden death from severe hypoglycemia. Am J Gastroenterol 1985;80:188–94. 8. Buchanan TF, Huvos AG. Clear cell carcinoma of the liver. A clinicopathologic study of 113 patients. Am J Clin Pathol 1974; 61:529–39. 9. Wu PC, Lai CL, Lam KC, et al. Clear cell carcinoma of the liver. An ultrastructural study. Cancer 1983;52:504–7. 10. Wang Y, Zhang J, Gao Y, et al. Therapeutic efficacy of transcatheter arterial embolization of primary hepatocellular carcinoma: discrepancy in different histopathologic subtypes. Chin Med J (Engl) 1999;112:264–8. 11. Nihei T, Ebara M, Ohto M, Kondo F. Study of sonographic findings of small hepatocellular carcinoma based on its pathologic findings. Nippon Shokakibyo Gakkai Zasshi 1992;89:1360–8. 12. Singh HK, Silverman JF, Geisinger KR, et al. Fine-needle aspiration cytomorphology of clear-cell hepatocellular carcinoma. Diagn Cytopathol 1997;17:306–10. 13. Murakata LA, Ishak KG, Nzeako UC. Clear cell carcinoma of the liver: a comparative immunohistochemical study with renal clear cell carcinoma. Mod Pathol 2000;13:874–81. 14. Monzawa S, Omata K, Shimazu N, et al. Well-differentiated hepatocellular carcinoma: findings of US, CT, and MR imaging. Abdom Imaging 1999;24:392–7. 15. Yoshikawa J, Matsui O, Takashima T, et al. Fatty metamorphosis in hepatocellular carcinoma: radiologic features in 10 cases. AJR Am J Roentgenol 1988;151:717–20. 16. Emile JF, Lemoine A, Azoulay D, et al. Histological, genomic and clinical heterogeneity of clear cell hepatocellular carcinoma. Histopathology 2001;38:225–31. 17. Orsatti G, Arnold MM, Paronetto F. DNA image cytometric analysis of primary clear cell carcinoma of the liver. Arch Pathol Lab Med 1994;118:1226–9.
81