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An unusual recurrence site for HCC!
Clinics and Research in Hepatology and Gastroenterology (2013) 37, e29—e31
Available online at
www.sciencedirect.com
CASE REPORT
An unusual recurrence site for HCC! Edouard Auclin ∗, Cécile Camiliéri , Olivier Dubreuil , Céline Lepère , Aziz Zannan , Philippe Rougier , Julien Taieb Digestive oncology department, European hospital Georges-Pompidou, AH—PH, Paris, France Available online 4 July 2012
Summary Background: Hepatocellular carcinoma (HCC) is the first malignant hepatic tumor in frequency, with an incidence of 10 new cases per 100,000 people a year, in France. HCC metastasis disseminate hematogenously. The most frequent metastatic sites are lungs, bones, and liver. Patients and methods: We detail the approach to diagnosis and the treatment of a patient with an unusual late recurrence of HCC, which was discovered fortuitously. The metastasis was located in the subcutaneous tissue of the right gluteal fold. Conclusion: This case poses a problem of detection in the clinical practice. Indeed, the recurrence occurred 9 years after the HCC. Molecular analysis of our case could make us progress in our knowledge of this disease, and to associate it to a patient’s group with similar HCC evolutive profile. © 2012 Elsevier Masson SAS. All rights reserved.
Introduction
Case report
Hepatocellular carcinoma (HCC) is the first malignant hepatic tumor in frequency; with an incidence of 10 new cases per 100,000 people a year, in France [1]. HCC metastasis disseminate hematogenously. The most frequent metastatic sites are lungs, bones, liver, and pancreas. Some cases from the literature describe the occurrence of distant metastasis in soft tissue such as subcutaneous tissue, muscles or skin. This article relates the case of a metachronous metastasis from a HCC in distant soft tissues more than 8 years after the diagnosis and treatment of the primary disease.
A 68-year-old patient with medical history of HCC secondary to alcoholic cirrhosis surgically removed in 2003 and hypopharynx squamous cell carcinoma treated by radiotherapy and chemotherapy in 2011 came to our institution for a recently diagnosed soft tissue tumor. During the follow-up of his hypopharynx carcinoma, the patient had a PET-scan in January 2012 showing a suspect hypermetabolic lesion corresponding to a soft tissue formation (SUV max = 4.1) from the right gluteal region. Physical examination showed a 4 cm tissue mass renitent, well limited, painless, and not adherent to deep tissues. A MRI was performed to better characterize this lesion, its origin and local extension. It found an oblong tissue mass of 25 × 38 mm, located in the fat of the right gluteal fold, on the deep internal face of the greatest gluteal mus-
∗ Corresponding author. 10, rue Tiphaine, 75015 Paris, France. Tel.: +33 6 73 00 19 59. E-mail address: [email protected] (E. Auclin).
2210-7401/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.clinre.2012.05.008
e30
E. Auclin et al. The patient’s case was discussed in a pluridisciplinary staff that decided a surgical treatment completed with external beam radiotherapy. Surgery was performed on the 26th of February 2012. There was no postoperative complication. Pathological examination of the tumor found a metastasis of a welldifferentiated HCC, with necrotic and fibrotic changes. The resection margins were tumor-free. Radiotherapy started 1 month after surgery, four fractions of 23 Gy in 17 days are planned.
Discussion
Figure 1
A. MRI T1 FatSat axial view. B. MRI STIR frontal view.
cle. The mass was well limited, in hyposignal T1 and in heterogeneous hypersignal T2, with high contrast enhancement delimiting central necrotic zones (Fig. 1). No other secondary lesion was found, and alphafoetoprotein level was normal. A biopsy was performed and pathological exam found a well-differentiated adenocarcinoma. Immunohistochemistry showed a tumor negative for CK20 and ACE but positive for anti-hepatocyte staining (Fig. 2A and B), suggesting a soft tissue metastasis of the primary liver cancer removed in 2003.
HCC metastatic process is almost exclusively hematogenous. The presence of secondary lesions at the time of primary diagnosis is reported in 40 to 85% of the cases. The most common extra-hepatic metastatic sites are: lungs, lymph nodes, and bones. Soft tissue dissemination is an exceptional phenomenon. Only three cases have been reported in the literature during the past 30 years [2,3]. Two of them described subcutaneous metastases located in the peri hepatic region. They were reported as due to local procedure made for diagnosis (biopsy), or treatment of the tumor (thermoablation). Only one case was really similar to ours in recurrence delay, type of soft tissue metastase, which was located in the subcutaneous tissue of one arm [2,3]. In all cases, the discovery of the metastatic lesion was made fortuitously, or when the mass was big enough to be palpated during the physical examination. This late discovery is probably due to a slow evolution of the tumor. The rate of alphafoetoprotein being normal in most cases, its regular measurement is probably useless for early detection of this type of recurrence. Median time to relapse after curative treatment for HCC generally ranges from 9 to 26 months [4], with a 5 years recurrence rate from 50 to 100% [5]. Late recurrences occurring more than 3 years after treatment of a primary HCC are mostly located in the liver and considered as a de novo tumors due to the underlying chronic hepatopathy rather than the intra-hepatic metastases from the initial HCC. In the present case no hepatic lesions were detected in the staging of the tumor, we assumed that this soft tissue
Figure 2 Pathological exam of the operative specimen with standard coloration (A) and after immunohistochemistry with antihepatocytes antibodies (B).
An unusual recurrence site for HCC! distant metastasis was a late recurrence of the HCC removed 9 years earlier. Little is known about late extra-hepatic recurrences of HCC. It is a rare phenomenon described in only 1.41% of cases from a large cohort of 1489 patients [6]. Another retrospective study with 139 patients treated by liver transplantation for a HCC showed a similar percentage of late distant recurrences [7]. The rarity of the situation does not allow us to have a consensual therapeutic strategy to treat these patients. However, in the absence of other secondary lesion, a surgical ‘‘curative’’ resection of the metastasis seems to be a reasonable therapeutic attitude. Many studies have looked for factors that predict HCC metastatic potential on one hand, and the risk of intrahepatic recurrence on the other hand. But none of them focused on late HCC’s recurrences (> 5 years), nor in soft tissue metastatic risk. Recent molecular analyses made on large series of HCC showed that this disease, more than other cancers, is represented by heterogeneous tumor types with different molecular events, etiologies, and evolutive profiles [8—10]. Molecular analysis of our case could make us progress in our knowledge of this disease, and to associate it to a patients’ group with similar HCC evolutive profile. If we could find such predictive factors, a specific follow-up could be proposed to patients having a HCC with high risk of late distant recurrence, knowing that in most cases the alphafoetoprotein rate is normal.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
e31
References [1] Blanc JF, Bioulac-Sage P, Trillaud H, Zucman-Rossi J, Balabaud C. Les lésions précancéreuses sur foie cirrhotique et non cirrhotique. Gastroenterol Clin Biol 2004;28:D158—70. [2] Yano S, Nakamura K, Yamane K, Kakinuma T, Asahina A, Tamaki K. Subcutaneous metastasis following percutaneous ethanol injection therapy for hepatocellular carcinoma. Acta Derm Venereol 2001;81(3):213—4. [3] Chen YY, Yen HH. Subcutaneous metastases after laparoscopicassisted partial hepatectomy for hepatocellular carcinoma. Surg Laparosc Endosc Percutan Tech 2011;21(1):e41—3. [4] Zhou Y, Sui C, Li B, Yin Z, Tan Y, Yang J, et al. Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review. World J Surg Oncol 2010;8:55. [5] Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000;232(1):10—24. [6] Huang YJ, Tung WC, Hsu HC, Wang CY, Huang EY, Fang FM. Radiation therapy to non-iatrogenic subcutaneous metastasis in hepatocellular carcinoma: results of a case series. Br J Radiol 2008;81(962):143—50. [7] Chok KSH, Chan SC, Cheung TT, Chan ACY, Fan ST, Lo CM. Late recurrence of hepatocellular carcinoma after liver transplantation. World J Surg 2011;35(9):2058—62. [8] Hagiwara S, Kudo M, Chung H, Ueshima K, Inoue T, Haji S, et al. Activation of c-Jun N-terminal kinase in non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma. Hepatol Res 2012;42(4):394—400. [9] Zucman-Rossi J, Clément B, Buendia MA, Lerat H, Van Beers B, Bedossa P, et al. Recherche fondamentale et translationnelle sur le carcinome hépatocellulaire en 2008 : avancées récentes et perspectives. Bull Cancer 2010;96(1):45. [10] Utsunomiya T, Shimada M, Imura S, Morine Y, Ikemoto T, Mori M. Molecular signatures of non-cancerous liver tissue can predict the risk for late recurrence of hepatocellular carcinoma. J Gastroenterol 2010;45(2):146—52.
Available online at
www.sciencedirect.com
CASE REPORT
An unusual recurrence site for HCC! Edouard Auclin ∗, Cécile Camiliéri , Olivier Dubreuil , Céline Lepère , Aziz Zannan , Philippe Rougier , Julien Taieb Digestive oncology department, European hospital Georges-Pompidou, AH—PH, Paris, France Available online 4 July 2012
Summary Background: Hepatocellular carcinoma (HCC) is the first malignant hepatic tumor in frequency, with an incidence of 10 new cases per 100,000 people a year, in France. HCC metastasis disseminate hematogenously. The most frequent metastatic sites are lungs, bones, and liver. Patients and methods: We detail the approach to diagnosis and the treatment of a patient with an unusual late recurrence of HCC, which was discovered fortuitously. The metastasis was located in the subcutaneous tissue of the right gluteal fold. Conclusion: This case poses a problem of detection in the clinical practice. Indeed, the recurrence occurred 9 years after the HCC. Molecular analysis of our case could make us progress in our knowledge of this disease, and to associate it to a patient’s group with similar HCC evolutive profile. © 2012 Elsevier Masson SAS. All rights reserved.
Introduction
Case report
Hepatocellular carcinoma (HCC) is the first malignant hepatic tumor in frequency; with an incidence of 10 new cases per 100,000 people a year, in France [1]. HCC metastasis disseminate hematogenously. The most frequent metastatic sites are lungs, bones, liver, and pancreas. Some cases from the literature describe the occurrence of distant metastasis in soft tissue such as subcutaneous tissue, muscles or skin. This article relates the case of a metachronous metastasis from a HCC in distant soft tissues more than 8 years after the diagnosis and treatment of the primary disease.
A 68-year-old patient with medical history of HCC secondary to alcoholic cirrhosis surgically removed in 2003 and hypopharynx squamous cell carcinoma treated by radiotherapy and chemotherapy in 2011 came to our institution for a recently diagnosed soft tissue tumor. During the follow-up of his hypopharynx carcinoma, the patient had a PET-scan in January 2012 showing a suspect hypermetabolic lesion corresponding to a soft tissue formation (SUV max = 4.1) from the right gluteal region. Physical examination showed a 4 cm tissue mass renitent, well limited, painless, and not adherent to deep tissues. A MRI was performed to better characterize this lesion, its origin and local extension. It found an oblong tissue mass of 25 × 38 mm, located in the fat of the right gluteal fold, on the deep internal face of the greatest gluteal mus-
∗ Corresponding author. 10, rue Tiphaine, 75015 Paris, France. Tel.: +33 6 73 00 19 59. E-mail address: [email protected] (E. Auclin).
2210-7401/$ – see front matter © 2012 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.clinre.2012.05.008
e30
E. Auclin et al. The patient’s case was discussed in a pluridisciplinary staff that decided a surgical treatment completed with external beam radiotherapy. Surgery was performed on the 26th of February 2012. There was no postoperative complication. Pathological examination of the tumor found a metastasis of a welldifferentiated HCC, with necrotic and fibrotic changes. The resection margins were tumor-free. Radiotherapy started 1 month after surgery, four fractions of 23 Gy in 17 days are planned.
Discussion
Figure 1
A. MRI T1 FatSat axial view. B. MRI STIR frontal view.
cle. The mass was well limited, in hyposignal T1 and in heterogeneous hypersignal T2, with high contrast enhancement delimiting central necrotic zones (Fig. 1). No other secondary lesion was found, and alphafoetoprotein level was normal. A biopsy was performed and pathological exam found a well-differentiated adenocarcinoma. Immunohistochemistry showed a tumor negative for CK20 and ACE but positive for anti-hepatocyte staining (Fig. 2A and B), suggesting a soft tissue metastasis of the primary liver cancer removed in 2003.
HCC metastatic process is almost exclusively hematogenous. The presence of secondary lesions at the time of primary diagnosis is reported in 40 to 85% of the cases. The most common extra-hepatic metastatic sites are: lungs, lymph nodes, and bones. Soft tissue dissemination is an exceptional phenomenon. Only three cases have been reported in the literature during the past 30 years [2,3]. Two of them described subcutaneous metastases located in the peri hepatic region. They were reported as due to local procedure made for diagnosis (biopsy), or treatment of the tumor (thermoablation). Only one case was really similar to ours in recurrence delay, type of soft tissue metastase, which was located in the subcutaneous tissue of one arm [2,3]. In all cases, the discovery of the metastatic lesion was made fortuitously, or when the mass was big enough to be palpated during the physical examination. This late discovery is probably due to a slow evolution of the tumor. The rate of alphafoetoprotein being normal in most cases, its regular measurement is probably useless for early detection of this type of recurrence. Median time to relapse after curative treatment for HCC generally ranges from 9 to 26 months [4], with a 5 years recurrence rate from 50 to 100% [5]. Late recurrences occurring more than 3 years after treatment of a primary HCC are mostly located in the liver and considered as a de novo tumors due to the underlying chronic hepatopathy rather than the intra-hepatic metastases from the initial HCC. In the present case no hepatic lesions were detected in the staging of the tumor, we assumed that this soft tissue
Figure 2 Pathological exam of the operative specimen with standard coloration (A) and after immunohistochemistry with antihepatocytes antibodies (B).
An unusual recurrence site for HCC! distant metastasis was a late recurrence of the HCC removed 9 years earlier. Little is known about late extra-hepatic recurrences of HCC. It is a rare phenomenon described in only 1.41% of cases from a large cohort of 1489 patients [6]. Another retrospective study with 139 patients treated by liver transplantation for a HCC showed a similar percentage of late distant recurrences [7]. The rarity of the situation does not allow us to have a consensual therapeutic strategy to treat these patients. However, in the absence of other secondary lesion, a surgical ‘‘curative’’ resection of the metastasis seems to be a reasonable therapeutic attitude. Many studies have looked for factors that predict HCC metastatic potential on one hand, and the risk of intrahepatic recurrence on the other hand. But none of them focused on late HCC’s recurrences (> 5 years), nor in soft tissue metastatic risk. Recent molecular analyses made on large series of HCC showed that this disease, more than other cancers, is represented by heterogeneous tumor types with different molecular events, etiologies, and evolutive profiles [8—10]. Molecular analysis of our case could make us progress in our knowledge of this disease, and to associate it to a patients’ group with similar HCC evolutive profile. If we could find such predictive factors, a specific follow-up could be proposed to patients having a HCC with high risk of late distant recurrence, knowing that in most cases the alphafoetoprotein rate is normal.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
e31
References [1] Blanc JF, Bioulac-Sage P, Trillaud H, Zucman-Rossi J, Balabaud C. Les lésions précancéreuses sur foie cirrhotique et non cirrhotique. Gastroenterol Clin Biol 2004;28:D158—70. [2] Yano S, Nakamura K, Yamane K, Kakinuma T, Asahina A, Tamaki K. Subcutaneous metastasis following percutaneous ethanol injection therapy for hepatocellular carcinoma. Acta Derm Venereol 2001;81(3):213—4. [3] Chen YY, Yen HH. Subcutaneous metastases after laparoscopicassisted partial hepatectomy for hepatocellular carcinoma. Surg Laparosc Endosc Percutan Tech 2011;21(1):e41—3. [4] Zhou Y, Sui C, Li B, Yin Z, Tan Y, Yang J, et al. Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review. World J Surg Oncol 2010;8:55. [5] Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000;232(1):10—24. [6] Huang YJ, Tung WC, Hsu HC, Wang CY, Huang EY, Fang FM. Radiation therapy to non-iatrogenic subcutaneous metastasis in hepatocellular carcinoma: results of a case series. Br J Radiol 2008;81(962):143—50. [7] Chok KSH, Chan SC, Cheung TT, Chan ACY, Fan ST, Lo CM. Late recurrence of hepatocellular carcinoma after liver transplantation. World J Surg 2011;35(9):2058—62. [8] Hagiwara S, Kudo M, Chung H, Ueshima K, Inoue T, Haji S, et al. Activation of c-Jun N-terminal kinase in non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma. Hepatol Res 2012;42(4):394—400. [9] Zucman-Rossi J, Clément B, Buendia MA, Lerat H, Van Beers B, Bedossa P, et al. Recherche fondamentale et translationnelle sur le carcinome hépatocellulaire en 2008 : avancées récentes et perspectives. Bull Cancer 2010;96(1):45. [10] Utsunomiya T, Shimada M, Imura S, Morine Y, Ikemoto T, Mori M. Molecular signatures of non-cancerous liver tissue can predict the risk for late recurrence of hepatocellular carcinoma. J Gastroenterol 2010;45(2):146—52.