CASE REPORT – OPEN ACCESS International Journal of Surgery Case Reports 5 (2014) 115–117
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International Journal of Surgery Case Reports journal homepage: www.casereports.com
Isolated nasopharyngeal metastasis from hepatocellular carcinoma夽 Abhay K. Kattepur ∗ , Darshan B. Patil 1 , Naveen Krishnamoorthy 2 , K.G. Srinivas 3 , Shivananda Swamy 4 , S. Amarendra 5 , K.S. Gopinath 6 Department of Surgical Oncology and Onco-pathology, HCG-Bangalore Institute of Oncology, 44-45/2, 2nd Cross, RRMR Extension, Bangalore 560027, India
a r t i c l e
i n f o
Article history: Received 2 November 2013 Received in revised form 16 November 2013 Accepted 12 December 2013 Available online 3 January 2014 Keywords: Hepatocellular carcinoma Nasopharynx Metastasis
a b s t r a c t INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, the incidence of which parallels that of areas with high prevalence of chronic hepatitis. HCC commonly metastasizes to the lungs, lymph nodes, adrenals and bones with the overall prognosis of metastatic HCC being dismal. PRESENTATION OF CASE: We herein with present a case of a 70-year-old male who was referred to our institution with history of nasal obstruction and nasal bleeding which on further evaluation was diagnosed to have an isolated metastasis to nasopharynx from liver primary. DISCUSSION: Extrahepatic metastasis in HCC occurs in about 30–50% of patients, the commonest site being the lung. Rare sites of extrahepatic metastasis from HCC to the ovaries, kidneys, skeletal and cardiac musculature and brain have been reported. Unusual sites of metastasis in the head and neck area like the mandible have also been documented. With the changing trends in the treatment modalities, these patients are often treated using target therapy. CONCLUSION: This article presents an unusual isolated metastasis to nasopharynx from HCC in the absence of disseminated disease. This case report illustrates the distinctive pathological features of metastatic HCC. © 2013 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. All rights reserved.
1. Introduction Hepatocellular carcinoma (HCC) ranks amongst one of the most common types of cancers worldwide. This cancer is more common in South East Asian countries where hepatitis B and C infections are the usual predisposing factors. The disease generally manifests in the 6th and 7th decade of life. Most cases come into clinical picture at an advanced stage minimizing the chance of cure. HCC commonly spreads to the lungs, peritoneum, adrenal glands and bones.1 Extra-hepatic metastasis at first presentation, although
夽 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. ∗ Corresponding author. Tel.: +91 80 40206503; fax: +91 80 22485962; mobile: +91 09448055292. E-mail addresses: [email protected] (A.K. Kattepur), [email protected] (D.B. Patil), [email protected] (N. Krishnamoorthy), [email protected] (K.G. Srinivas), [email protected] (S. Swamy), [email protected] (S. Amarendra), [email protected] (K.S. Gopinath). 1 Tel.: +91 09886765866. 2 Tel.: +91 09972085483. 3 Tel.: +91 09916257537. 4 Tel.: +91 09448447362. 5 Tel.: +91 09845403604. 6 Tel.: +91 09844017191.
uncommon, is frequently recognized as advanced disease with a poor prognosis. 2. Case details A 70-year-old male with no comorbidities presented with history of recurrent nasal obstruction and nasal discharge since 6 months and bleeding through the nose since 15 days. There was no ear pain or hoarseness of voice. Patient was a known smoker and alcoholic since 40 years. Patient was evaluated elsewhere with nasopharyngoscopy and biopsy and was then referred to us. Systemic examination was normal. Head and neck examination including nasopharyngoscopy was normal. Biopsy from the nasopharynx that was done outside revealed moderately differentiated adenocarcinoma (Figs. 1 and 2). IHC done at our hospital showed that the cells were positive for Glypican-3, AFP, CK, Hepar-1 and CK 7 (occasional) and were negative for CK 20 that suggested metastatic hepatocellular carcinoma (Figs. 3 and 4). Hence a PET-CT scan was done which showed cirrhosis of liver with signs of portal hypertension in the form of splenomegaly and multiple porto-systemic collaterals, a 1.9 cm × 1.2 cm ill-defined hypodense focal lesion in liver and minimal ascites (Fig. 5). There was no metabolic activity or an obvious mass in the region of nasopharynx (Fig. 6). Serum AFP was >10,000 IU/l. USG guided FNAC of the liver lesion showed only sheets of benign liver cells. The patient however, refused further CT guided biopsy.
2210-2612/$ – see front matter © 2013 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijscr.2013.12.009
CASE REPORT – OPEN ACCESS 116
A.K. Kattepur et al. / International Journal of Surgery Case Reports 5 (2014) 115–117
Fig. 1. Low power view.
Fig. 4. IHC-AFP positivity.
Fig. 5. Metabolically active SOL in liver. Fig. 2. High power view showing hepatocytes.
The patient was advised radiation to the nasopharynx and target therapy for the liver lesion but patient refused treatment. 3. Discussion Extrahepatic metastasis of HCC occurs in about 30–50% of patients,1 and it depends on HCC stages. The commonest site
Fig. 3. IHC-Hepar-1 positivity.
of extra-hepatic metastasis is the lung. In a study by Sawabe et al.,2 extrahepatic metastases of HCC was found in 64% of the 98 autopsies conducted and most of them (97%) were pulmonary metastases. Katyal et al.3 found extrahepatic metastasis in 148 (32%) of the 463 patients with HCC. The most common sites were lung (55%), lymph nodes (41%), bones (28%), adrenals (11%) and peritoneal deposits (11%). In another study by Natsuizaka et al.,4 65 (13%) of the 482 patients with HCC had extrahepatic metastases.
Fig. 6. No obvious mass in nasopharynx.
CASE REPORT – OPEN ACCESS A.K. Kattepur et al. / International Journal of Surgery Case Reports 5 (2014) 115–117
The most common location was lung followed by bone and lymph nodes. The pathological diagnosis of metastatic HCC at extrahepatic sites can be made by demonstrating acidophilic cells in trabecular and pseudo-glandular patterns. Detection of bile and mallory bodies strongly suggests HCC.1 Immunohistochemical studies are of great value. HepPar1 is a relatively specific marker of hepatocytes and HCC.5 AFP is also a specific marker of HCC. Cytokeratins 8 and 18 are hepatocyte cytokeratins which are also expressed in other tumors.1 Rare sites of metastasis from HCC to the ovaries,6,7 kidneys,8 muscles,9 brain10 and heart11 have been documented. An isolated mandibular metastasis has been reported from a locally advanced HCC.12 In this part of the subcontinent, advanced HCC is a common presentation with poor prognosis. The median survival time from diagnosis to end point is 4–7 months.11 HCC is historically a chemo and radioresistant tumour. The treatment of metastatic HCC involves the use of targeted agents like sorafenib. To the best of our knowledge, this is the first case report of an isolated nasopharyngeal metastasis at presentation from a liver primary. 4. Conclusion HCC metastasizing to the nasopharynx is extremely rare. Treatment involves addressing the nasopharynx with radiation and the liver primary with targeted therapy. Conflict of interest The authors do not have any conflict of interest. Funding None. Consent Written informed consent was obtained from the patient for publication of this case report and case series and accompanying
117
images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. Authors’ contributions Dr. Abhay Kattepur and Dr. Darshan Patil were involved in the literature search, manuscript writing and editing. Dr. Shivanand Swamy and Dr. K.G. Srinivas were involved in the literature search, manuscript writing. Dr. Naveen Krishnamoorthy analyzed the pathology slides and reported. Dr. Amarendra and Dr. K.S. Gopinath were involved in the final editing. References 1. Terada T, Maruo H. Unusual extrahepatic metastatic sites from hepatocellular carcinoma. Int J Clin Exp Pathol 2013;6(5):816–20. 2. Sawabe M, Nakamura T, Kanno J, Kasuga T. Analysis of morphological factors of hepatocellular carcinoma in 98 autopsy cases with respect to pulmonary metastasis. Acta Pathol Jpn 1987;37:1389–404. 3. Katyal S, Oliver JH, Peterson MS, Ferris JV, Carr BS, Baron RL. Extrahepatic metastases of hepatocellular carcinoma. Radiology 2000;216:698–703. 4. Natsuizaka M, Omura T, Akaike T, Kuwata Y, Yamazaki K, Sato T, et al. Clinical features of hepatocellular carcinoma with extrahepatic metastasis. J Gastroenterol Hepatol 2005;20:1781–7. 5. Lugli A, Tornillo L, Miriacher M, Bundi M, Sauter G, Terracciano LM. Hepatocyte paraffin 1 expression in human normal and neoplastic tissues: tissue microarray analysis of 3,940 tissue samples. Am J Clin Pathol 2004;122:721–7. 6. Lee JM, Park K-M, Lee SY, Choi J, Hwang DW, Lee YJ. Metastasis of hepatocellular carcinoma to the ovary: a case report and review of the literature. Gut Liver 2011;5(4):543–7. 7. Young RH, Gersell DJ, Clement PB, Scully RE. Hepatocellular carcinoma metastatic to the ovary: a report of three cases discovered during life with discussion of the differential diagnosis of hepatoid tumors of the ovary. Hum Pathol 1992;23(5):574–80. 8. D’Antonio A, Caleo A, Caleo O, Addesso M, Boscaino A. Hepatocellular carcinoma metastatic to the kidney mimicking renal oncocytoma. Hepatobiliary Pancreat Dis Int 2010;9(October (5)):550–2. 9. Michalaki V, Zygogianni A, Kouloulias V, Balafouta M, Vlachodimitropoulos D, Gennatas CG. Muscle metastasis from hepatocellular carcinoma. J Cancer Res Ther 2011;7(1):81–3. 10. Tunc B, Filik L, Tezer-Filik I, Sahin B. Brain metastasis of hepatocellular carcinoma: a case report and review of the literature. World J Gastroenterol 2004;10(11):1688–9. 11. Lin YS, Jung SM, Tsai FC, Yeh CN, Shiu TF, Wu HH, et al. Hepatoma with cardiac metastasis: an advanced cancer requiring advanced treatment. World J Gastroenterol 2007;13(25):3513–6. 12. Doval DC, Kannan V, Kumaraswamy SV, Reddy BKM, Bapsy PP, Rama Rao C. Mandibular metastasis in hepatocellular carcinoma. Int J Oral Maxillofac Surg 1992;21(2):97–8.
Open Access This article is published Open Access at sciencedirect.com. It is distributed under the IJSCR Supplemental terms and conditions, which permits unrestricted non commercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Contents lists available at ScienceDirect
International Journal of Surgery Case Reports journal homepage: www.casereports.com
Isolated nasopharyngeal metastasis from hepatocellular carcinoma夽 Abhay K. Kattepur ∗ , Darshan B. Patil 1 , Naveen Krishnamoorthy 2 , K.G. Srinivas 3 , Shivananda Swamy 4 , S. Amarendra 5 , K.S. Gopinath 6 Department of Surgical Oncology and Onco-pathology, HCG-Bangalore Institute of Oncology, 44-45/2, 2nd Cross, RRMR Extension, Bangalore 560027, India
a r t i c l e
i n f o
Article history: Received 2 November 2013 Received in revised form 16 November 2013 Accepted 12 December 2013 Available online 3 January 2014 Keywords: Hepatocellular carcinoma Nasopharynx Metastasis
a b s t r a c t INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, the incidence of which parallels that of areas with high prevalence of chronic hepatitis. HCC commonly metastasizes to the lungs, lymph nodes, adrenals and bones with the overall prognosis of metastatic HCC being dismal. PRESENTATION OF CASE: We herein with present a case of a 70-year-old male who was referred to our institution with history of nasal obstruction and nasal bleeding which on further evaluation was diagnosed to have an isolated metastasis to nasopharynx from liver primary. DISCUSSION: Extrahepatic metastasis in HCC occurs in about 30–50% of patients, the commonest site being the lung. Rare sites of extrahepatic metastasis from HCC to the ovaries, kidneys, skeletal and cardiac musculature and brain have been reported. Unusual sites of metastasis in the head and neck area like the mandible have also been documented. With the changing trends in the treatment modalities, these patients are often treated using target therapy. CONCLUSION: This article presents an unusual isolated metastasis to nasopharynx from HCC in the absence of disseminated disease. This case report illustrates the distinctive pathological features of metastatic HCC. © 2013 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. All rights reserved.
1. Introduction Hepatocellular carcinoma (HCC) ranks amongst one of the most common types of cancers worldwide. This cancer is more common in South East Asian countries where hepatitis B and C infections are the usual predisposing factors. The disease generally manifests in the 6th and 7th decade of life. Most cases come into clinical picture at an advanced stage minimizing the chance of cure. HCC commonly spreads to the lungs, peritoneum, adrenal glands and bones.1 Extra-hepatic metastasis at first presentation, although
夽 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. ∗ Corresponding author. Tel.: +91 80 40206503; fax: +91 80 22485962; mobile: +91 09448055292. E-mail addresses: [email protected] (A.K. Kattepur), [email protected] (D.B. Patil), [email protected] (N. Krishnamoorthy), [email protected] (K.G. Srinivas), [email protected] (S. Swamy), [email protected] (S. Amarendra), [email protected] (K.S. Gopinath). 1 Tel.: +91 09886765866. 2 Tel.: +91 09972085483. 3 Tel.: +91 09916257537. 4 Tel.: +91 09448447362. 5 Tel.: +91 09845403604. 6 Tel.: +91 09844017191.
uncommon, is frequently recognized as advanced disease with a poor prognosis. 2. Case details A 70-year-old male with no comorbidities presented with history of recurrent nasal obstruction and nasal discharge since 6 months and bleeding through the nose since 15 days. There was no ear pain or hoarseness of voice. Patient was a known smoker and alcoholic since 40 years. Patient was evaluated elsewhere with nasopharyngoscopy and biopsy and was then referred to us. Systemic examination was normal. Head and neck examination including nasopharyngoscopy was normal. Biopsy from the nasopharynx that was done outside revealed moderately differentiated adenocarcinoma (Figs. 1 and 2). IHC done at our hospital showed that the cells were positive for Glypican-3, AFP, CK, Hepar-1 and CK 7 (occasional) and were negative for CK 20 that suggested metastatic hepatocellular carcinoma (Figs. 3 and 4). Hence a PET-CT scan was done which showed cirrhosis of liver with signs of portal hypertension in the form of splenomegaly and multiple porto-systemic collaterals, a 1.9 cm × 1.2 cm ill-defined hypodense focal lesion in liver and minimal ascites (Fig. 5). There was no metabolic activity or an obvious mass in the region of nasopharynx (Fig. 6). Serum AFP was >10,000 IU/l. USG guided FNAC of the liver lesion showed only sheets of benign liver cells. The patient however, refused further CT guided biopsy.
2210-2612/$ – see front matter © 2013 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijscr.2013.12.009
CASE REPORT – OPEN ACCESS 116
A.K. Kattepur et al. / International Journal of Surgery Case Reports 5 (2014) 115–117
Fig. 1. Low power view.
Fig. 4. IHC-AFP positivity.
Fig. 5. Metabolically active SOL in liver. Fig. 2. High power view showing hepatocytes.
The patient was advised radiation to the nasopharynx and target therapy for the liver lesion but patient refused treatment. 3. Discussion Extrahepatic metastasis of HCC occurs in about 30–50% of patients,1 and it depends on HCC stages. The commonest site
Fig. 3. IHC-Hepar-1 positivity.
of extra-hepatic metastasis is the lung. In a study by Sawabe et al.,2 extrahepatic metastases of HCC was found in 64% of the 98 autopsies conducted and most of them (97%) were pulmonary metastases. Katyal et al.3 found extrahepatic metastasis in 148 (32%) of the 463 patients with HCC. The most common sites were lung (55%), lymph nodes (41%), bones (28%), adrenals (11%) and peritoneal deposits (11%). In another study by Natsuizaka et al.,4 65 (13%) of the 482 patients with HCC had extrahepatic metastases.
Fig. 6. No obvious mass in nasopharynx.
CASE REPORT – OPEN ACCESS A.K. Kattepur et al. / International Journal of Surgery Case Reports 5 (2014) 115–117
The most common location was lung followed by bone and lymph nodes. The pathological diagnosis of metastatic HCC at extrahepatic sites can be made by demonstrating acidophilic cells in trabecular and pseudo-glandular patterns. Detection of bile and mallory bodies strongly suggests HCC.1 Immunohistochemical studies are of great value. HepPar1 is a relatively specific marker of hepatocytes and HCC.5 AFP is also a specific marker of HCC. Cytokeratins 8 and 18 are hepatocyte cytokeratins which are also expressed in other tumors.1 Rare sites of metastasis from HCC to the ovaries,6,7 kidneys,8 muscles,9 brain10 and heart11 have been documented. An isolated mandibular metastasis has been reported from a locally advanced HCC.12 In this part of the subcontinent, advanced HCC is a common presentation with poor prognosis. The median survival time from diagnosis to end point is 4–7 months.11 HCC is historically a chemo and radioresistant tumour. The treatment of metastatic HCC involves the use of targeted agents like sorafenib. To the best of our knowledge, this is the first case report of an isolated nasopharyngeal metastasis at presentation from a liver primary. 4. Conclusion HCC metastasizing to the nasopharynx is extremely rare. Treatment involves addressing the nasopharynx with radiation and the liver primary with targeted therapy. Conflict of interest The authors do not have any conflict of interest. Funding None. Consent Written informed consent was obtained from the patient for publication of this case report and case series and accompanying
117
images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. Authors’ contributions Dr. Abhay Kattepur and Dr. Darshan Patil were involved in the literature search, manuscript writing and editing. Dr. Shivanand Swamy and Dr. K.G. Srinivas were involved in the literature search, manuscript writing. Dr. Naveen Krishnamoorthy analyzed the pathology slides and reported. Dr. Amarendra and Dr. K.S. Gopinath were involved in the final editing. References 1. Terada T, Maruo H. Unusual extrahepatic metastatic sites from hepatocellular carcinoma. Int J Clin Exp Pathol 2013;6(5):816–20. 2. Sawabe M, Nakamura T, Kanno J, Kasuga T. Analysis of morphological factors of hepatocellular carcinoma in 98 autopsy cases with respect to pulmonary metastasis. Acta Pathol Jpn 1987;37:1389–404. 3. Katyal S, Oliver JH, Peterson MS, Ferris JV, Carr BS, Baron RL. Extrahepatic metastases of hepatocellular carcinoma. Radiology 2000;216:698–703. 4. Natsuizaka M, Omura T, Akaike T, Kuwata Y, Yamazaki K, Sato T, et al. Clinical features of hepatocellular carcinoma with extrahepatic metastasis. J Gastroenterol Hepatol 2005;20:1781–7. 5. Lugli A, Tornillo L, Miriacher M, Bundi M, Sauter G, Terracciano LM. Hepatocyte paraffin 1 expression in human normal and neoplastic tissues: tissue microarray analysis of 3,940 tissue samples. Am J Clin Pathol 2004;122:721–7. 6. Lee JM, Park K-M, Lee SY, Choi J, Hwang DW, Lee YJ. Metastasis of hepatocellular carcinoma to the ovary: a case report and review of the literature. Gut Liver 2011;5(4):543–7. 7. Young RH, Gersell DJ, Clement PB, Scully RE. Hepatocellular carcinoma metastatic to the ovary: a report of three cases discovered during life with discussion of the differential diagnosis of hepatoid tumors of the ovary. Hum Pathol 1992;23(5):574–80. 8. D’Antonio A, Caleo A, Caleo O, Addesso M, Boscaino A. Hepatocellular carcinoma metastatic to the kidney mimicking renal oncocytoma. Hepatobiliary Pancreat Dis Int 2010;9(October (5)):550–2. 9. Michalaki V, Zygogianni A, Kouloulias V, Balafouta M, Vlachodimitropoulos D, Gennatas CG. Muscle metastasis from hepatocellular carcinoma. J Cancer Res Ther 2011;7(1):81–3. 10. Tunc B, Filik L, Tezer-Filik I, Sahin B. Brain metastasis of hepatocellular carcinoma: a case report and review of the literature. World J Gastroenterol 2004;10(11):1688–9. 11. Lin YS, Jung SM, Tsai FC, Yeh CN, Shiu TF, Wu HH, et al. Hepatoma with cardiac metastasis: an advanced cancer requiring advanced treatment. World J Gastroenterol 2007;13(25):3513–6. 12. Doval DC, Kannan V, Kumaraswamy SV, Reddy BKM, Bapsy PP, Rama Rao C. Mandibular metastasis in hepatocellular carcinoma. Int J Oral Maxillofac Surg 1992;21(2):97–8.
Open Access This article is published Open Access at sciencedirect.com. It is distributed under the IJSCR Supplemental terms and conditions, which permits unrestricted non commercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
