Clinical Imaging xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT☆ Xin-Yan Wang a, b, Wei-Qi Bao a, Feng-Chun Hua a,⁎, Chuan-Tao Zuo a, Yi-Hui Guan a, Jun Zhao a a b
Division of PET Center, Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai 200235, People's Republic of China Department of Radiology, First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, People's Republic of China
a r t i c l e
i n f o
Article history: Received 22 September 2013 Received in revised form 2 January 2014 Accepted 27 February 2014 Available online xxxx Keywords: Positron emission tomography/computed tomography FDG Hepatoid adenocarcinoma Appendix Alpha-Fetoprotein
a b s t r a c t Hepatoid adenocarcinoma (HAC) is a rare tumor. We described here a rare case of appendix HAC. A 59-yearold man underwent F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for gradually elevated alpha-Fetoprotein level. Multiple masses in the abdominal cavity with moderate FDG uptake were revealed, suggesting malignant tumor with peritoneal metastasis. The patient underwent radical resection, and the postoperative pathological result was HAC originated from the appendix. To our knowledge, it is the first report of HAC of the appendix. Our study suggests that FDG PET/CT may help in detecting the primary tumor and the metastases of HAC.
1. Introduction Hepatoid adenocarcinoma (HAC) is a unique type of extrahepatic adenocarcinoma which resembles hepatocellular carcinoma (HCC) in morphological as well as in biological ways [1,2]. HAC occurs most frequently in the stomach, although it can also occur in the oesophagus and large intestine, lung, ovary, and urinary bladder [2]. HAC is a rare disease, and there have been few studies of HAC with F18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging. To the best of our knowledge, there has been no case report of appendix HAC. We, herein, describe a rare case of appendix HAC together with its FDG PET/CT performance. 2. Case report A 59-year-old man came to our center for a PET/CT scan with a major reason of a progressively elevated level of alpha-Fetoprotein (AFP). His current AFP level was 3000 ng/ml, while it was 630 ng/ml 3 years ago in a routine physical examination. Carcinoma embryonic antigen, β-human chorionic gonadotropin, and other carbohydrate antigen biomarkers were all in their normal ranges. Serum hepatitis B virus (HBV) and ☆ Conflict of interest: The authors declare that they have no potential conflict of interest. ⁎ Corresponding author. Division of PET Center, Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai 200235, People's Republic of China. Tel.: +86-2164280718; fax: +86-21-64283265. E-mail address: [email protected] (F.-C. Hua).
© 2014 Elsevier Inc. All rights reserved.
hepatitis C virus (HCV) tests were all negative. No abnormalities were found from gastrointestinal endoscopy, liver contrast computed tomography (CT) and magnetic resonance imaging (MRI), and ultrasonography, and so was an FDG PET/CT scan performed 3 years ago (Supplementary Fig. 1). The patient did not present any abdominal pain, jaundice, or other symptoms throughout the course of disease. The current PET/CT scan demonstrated several soft tissue masses in the abdominopelvic cavity on CT imaging (Fig. 1A, D, and G). The masses displayed moderate FDG uptake on positron emission tomography (PET) imaging (Fig. 1B, E, and H) and PET/CT infusion imaging (Fig. 1C, F, and I). The biggest one (about 4.0×7.0 cm) located in the right iliac fossa (Fig. 1A–C), which might originate from appendix or cecum with a maximum standardized uptake value (SUVmax) of FDG being 2.8. The SUVmax of the biggest mass elevated to 3.4 on 1-h delayed PET/CT imaging. Exploratory laparotomy was performed after an impression of malignant tumor with peritoneal metastasis on the second PET/CT scan. We found a conglomerate tumor (about 4.0×10.0 cm, Fig. 2A) involving the appendix as well as the greater omentum, mesentery, and ileocecal junction. Ileocecal resection, pelvic lymphadenectomy, and omentectomy were also performed for the purpose of treatment plan development. Almost all the masses were microscopically composed of two closely related areas: hepatoid-like foci and adenocarcinoma (Fig. 2B). Immunohistochemically, cytokeratin 8, CK18, and hepatocytespecific marker hepatocyte paraffin-1 (Hep Par1, Fig. 2C) of the masses were diffusely positive; while CK19 and Periodic acid-Schiff diastase were negative. No positive lymphatic nodes were observed. Serum AFP decreased gradually to a normal level in a month.
http://dx.doi.org/10.1016/j.clinimag.2014.02.019 0899-7071/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Wang X-Y, et al, AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT, Clin Imaging (2014), http://dx.doi.org/10.1016/j.clinimag.2014.02.019
2
X-Y. Wang et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 1. Multiple masses with moderate FDG uptake on the second (current) PET/CT scan (arrows). Axial noncontrast CT scan showed a solid mass in right iliac fossa (A) and several round masses of the greater omentum and mesentery (D and G). On the axial PET image (B, E, and H) and fused PET/CT image (C, F, and I), moderate FDG uptake was seen in the corresponding area (arrows).
3. Discussion The term HAC was first used in 1985 by Ishikura et al. for a tumor located at the stomach [1], which was later found to be the most common site of HAC, followed by ovary, lung, gallbladder, pancreas, uterus, urinary bladder, oesophagus, and colon [2–4]. To the best of our knowledge, this is the first case report of HAC of the appendix. HAC is a rare kind of extrahepatic tumor which is characterized by mimicking the morphological phenotype of HCC. As a possible origin of the tumor, it has been hypothesized that cancer arising from ectopic liver cells embedded in the organs where HAC develops and neoplastic transformation of persistent germ cells or of nonhepatic epithelium is capable of multipotential differentiation [5]. After having radical surgery and subsequent chemotherapy, its 1-year survival rate is approximately 55% [4]. HAC is defined primarily according to its histological manifestation. HAC usually shows morphologic features of hepatic differentiation, and polygonal tumor cells are displayed in hematoxylin and eosin stains [2]. Previous studies showed that the outstanding
diagnostic features of HAC included positive AFP (91.6%), Hep Par1 (38.1%), and EpCAM antibodies HEA125 or MOC31 which showed no reactivity with hepatocytes [2,3]. However, there were HAC cases, which were classified histologically, but no elevation of AFP was observed [6]. Similarly, Hep Par1 was a marker for hepatic carcinoma and had been reported positive in many cases of HAC [7,8]. In our case, histological observation and immunohistochemical results were in agreement with literature. The CT appearance of HAC is not specific. They are usually large masses with the density similar to normal liver tissue in plain CT scan (the presence of necrotic areas, however, can make the masses inhomogeneous) and are moderately enhanced by using an intravenous iodinated contrast agent. As one of the malignant tumors, invasion to the adjacent anatomical structures and metastases of regional lymph nodes and distant areas was frequently observed in HAC [9,10]. Typically, an elevated level of serum AFP is often associated with an occurrence of liver disease, especially of HCC. For this case, taking into account for all the information from liver ultrasonography,
Fig. 2. Macroscopy: A: The specimen and its cross-section. The tumor occupied around the appendix. Microscopy: B: polygonal tumor cells with abundant eosinophilic cytoplasm and round nuclei occasionally with obvious nucleoli and high mitotic activity. (hematoxylin and eosin stain (HE) 10×40) C: Coloration of the immunohistochemistry Hep Par1 (+) (Original magnification 10×40).
Please cite this article as: Wang X-Y, et al, AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT, Clin Imaging (2014), http://dx.doi.org/10.1016/j.clinimag.2014.02.019
X-Y. Wang et al. / Clinical Imaging xxx (2014) xxx–xxx
contrast CT and MRI as well as the decreased AFP level after surgery, it can be assured that it was HAC, not HCC, that increased the level of serum AFP. Previously, there was only one case report of HAC revealed by FDG PET/CT [11]. However, different from the previous report, the primary tumor and the metastases of our case showed a moderate FDG uptake (Fig. 1). Notably, regional lymph nodes of the appendix were not involved in this case although celiac metastases were present. Since there have been so far only two reported cases of HAC, more information is required to conclude the FDG PET/CT manifestation of HAC.
4. Conclusions This is the first case report of HAC of appendix. 18 F-FDG PET/CT may be helpful to detect its primary tumor and metastases. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.clinimag.2014.02.019.
Acknowledgments The authors would like to thank Dr. Yue Chen (PhD, Professor, Department of Epidemiology and Community Medicine, University of Ottawa, Canada) for his improving written English.
3
References [1] Ishikura H, Fukasawa Y, Ogasawara K, Natori T, Tsukada Y, Aizawa M. An AFPproducing gastric carcinoma with features of hepatic differentiation. A case report. Cancer 1985;56:840–8. [2] Su JS, Chen YT, Wang RC, Wu CY, Lee SW, Lee TY. Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: a literature review. World J Gastroenterol 2013;19:321–7. [3] Metzgeroth G, Strobel P, Baumbusch T, Reiter A, Hastka J. Hepatoid adenocarcinoma - review of the literature illustrated by a rare case originating in the peritoneal cavity. Onkologie 2010;33:263–9. [4] Slotta JE, Jungling B, Kim YJ, Wagner M, Igna D, Schilling MK. Hepatoid adenocarcinoma of the transverse colon. Int J Colorectal Dis 2012;27:989–91. [5] Ishikura H, Kanda M, Ito M, Nosaka K, Mizuno K. Hepatoid adenocarcinoma: a distinctive histological subtype of alpha-fetoprotein-producing lung carcinoma. Virchows Arch A Pathol Anat Histopathol 1990;417:73–80. [6] Nakashima H, Nagafuchi K, Satoh H, Takeda K, Yamasaki T, Yonemasu H, Kishikawa H. Hepatoid adenocarcinoma of the gallbladder. J Hepatobiliary Pancreat Surg 2000;7:226–30. [7] Terracciano LM, Glatz K, Mhawech P, Vasei M, Lehmann FS, Vecchione R, Tornillo L. Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: an immunohistochemical and molecular study of eight cases. Am J Surg Pathol 2003;27:1302–12. [8] Akiyama S, Tamura G, Endoh Y, Fukushima N, Ichihara Y, Aizawa K, Kawata S, Motoyama T. Histogenesis of hepatoid adenocarcinoma of the stomach: molecular evidence of identical origin with coexistent tubular adenocarcinoma. Int J Cancer 2003;106:510–5. [9] Wu Z, Upadhyaya M, Zhu H, Qiao Z, Chen K, Miao F. Hepatoid adenocarcinoma: computed tomographic imaging findings with histopathologic correlation in 6 cases. J Comput Assist Tomogr 2007;31:846–52. [10] Lee MW, Lee JY, Kim YJ, Park EA, Choi JY, Kim SH, Lee JM, Han JK, Choi BI. Gastric hepatoid adenocarcinoma: CT findings. Abdom Imaging 2007;32:293–8. [11] Pan JH, Dong MJ, Ouyang XB. A hepatoid adenocarcinoma of the stomach with liver metastasis mimicking hepatocellular carcinoma detected by F-18 FDG PET/CT imaging. Clin Nucl Med 2011;36:1137–9.
Please cite this article as: Wang X-Y, et al, AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT, Clin Imaging (2014), http://dx.doi.org/10.1016/j.clinimag.2014.02.019
Contents lists available at ScienceDirect
Clinical Imaging journal homepage: http://www.clinicalimaging.org
AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT☆ Xin-Yan Wang a, b, Wei-Qi Bao a, Feng-Chun Hua a,⁎, Chuan-Tao Zuo a, Yi-Hui Guan a, Jun Zhao a a b
Division of PET Center, Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai 200235, People's Republic of China Department of Radiology, First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, People's Republic of China
a r t i c l e
i n f o
Article history: Received 22 September 2013 Received in revised form 2 January 2014 Accepted 27 February 2014 Available online xxxx Keywords: Positron emission tomography/computed tomography FDG Hepatoid adenocarcinoma Appendix Alpha-Fetoprotein
a b s t r a c t Hepatoid adenocarcinoma (HAC) is a rare tumor. We described here a rare case of appendix HAC. A 59-yearold man underwent F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for gradually elevated alpha-Fetoprotein level. Multiple masses in the abdominal cavity with moderate FDG uptake were revealed, suggesting malignant tumor with peritoneal metastasis. The patient underwent radical resection, and the postoperative pathological result was HAC originated from the appendix. To our knowledge, it is the first report of HAC of the appendix. Our study suggests that FDG PET/CT may help in detecting the primary tumor and the metastases of HAC.
1. Introduction Hepatoid adenocarcinoma (HAC) is a unique type of extrahepatic adenocarcinoma which resembles hepatocellular carcinoma (HCC) in morphological as well as in biological ways [1,2]. HAC occurs most frequently in the stomach, although it can also occur in the oesophagus and large intestine, lung, ovary, and urinary bladder [2]. HAC is a rare disease, and there have been few studies of HAC with F18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging. To the best of our knowledge, there has been no case report of appendix HAC. We, herein, describe a rare case of appendix HAC together with its FDG PET/CT performance. 2. Case report A 59-year-old man came to our center for a PET/CT scan with a major reason of a progressively elevated level of alpha-Fetoprotein (AFP). His current AFP level was 3000 ng/ml, while it was 630 ng/ml 3 years ago in a routine physical examination. Carcinoma embryonic antigen, β-human chorionic gonadotropin, and other carbohydrate antigen biomarkers were all in their normal ranges. Serum hepatitis B virus (HBV) and ☆ Conflict of interest: The authors declare that they have no potential conflict of interest. ⁎ Corresponding author. Division of PET Center, Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai 200235, People's Republic of China. Tel.: +86-2164280718; fax: +86-21-64283265. E-mail address: [email protected] (F.-C. Hua).
© 2014 Elsevier Inc. All rights reserved.
hepatitis C virus (HCV) tests were all negative. No abnormalities were found from gastrointestinal endoscopy, liver contrast computed tomography (CT) and magnetic resonance imaging (MRI), and ultrasonography, and so was an FDG PET/CT scan performed 3 years ago (Supplementary Fig. 1). The patient did not present any abdominal pain, jaundice, or other symptoms throughout the course of disease. The current PET/CT scan demonstrated several soft tissue masses in the abdominopelvic cavity on CT imaging (Fig. 1A, D, and G). The masses displayed moderate FDG uptake on positron emission tomography (PET) imaging (Fig. 1B, E, and H) and PET/CT infusion imaging (Fig. 1C, F, and I). The biggest one (about 4.0×7.0 cm) located in the right iliac fossa (Fig. 1A–C), which might originate from appendix or cecum with a maximum standardized uptake value (SUVmax) of FDG being 2.8. The SUVmax of the biggest mass elevated to 3.4 on 1-h delayed PET/CT imaging. Exploratory laparotomy was performed after an impression of malignant tumor with peritoneal metastasis on the second PET/CT scan. We found a conglomerate tumor (about 4.0×10.0 cm, Fig. 2A) involving the appendix as well as the greater omentum, mesentery, and ileocecal junction. Ileocecal resection, pelvic lymphadenectomy, and omentectomy were also performed for the purpose of treatment plan development. Almost all the masses were microscopically composed of two closely related areas: hepatoid-like foci and adenocarcinoma (Fig. 2B). Immunohistochemically, cytokeratin 8, CK18, and hepatocytespecific marker hepatocyte paraffin-1 (Hep Par1, Fig. 2C) of the masses were diffusely positive; while CK19 and Periodic acid-Schiff diastase were negative. No positive lymphatic nodes were observed. Serum AFP decreased gradually to a normal level in a month.
http://dx.doi.org/10.1016/j.clinimag.2014.02.019 0899-7071/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Wang X-Y, et al, AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT, Clin Imaging (2014), http://dx.doi.org/10.1016/j.clinimag.2014.02.019
2
X-Y. Wang et al. / Clinical Imaging xxx (2014) xxx–xxx
Fig. 1. Multiple masses with moderate FDG uptake on the second (current) PET/CT scan (arrows). Axial noncontrast CT scan showed a solid mass in right iliac fossa (A) and several round masses of the greater omentum and mesentery (D and G). On the axial PET image (B, E, and H) and fused PET/CT image (C, F, and I), moderate FDG uptake was seen in the corresponding area (arrows).
3. Discussion The term HAC was first used in 1985 by Ishikura et al. for a tumor located at the stomach [1], which was later found to be the most common site of HAC, followed by ovary, lung, gallbladder, pancreas, uterus, urinary bladder, oesophagus, and colon [2–4]. To the best of our knowledge, this is the first case report of HAC of the appendix. HAC is a rare kind of extrahepatic tumor which is characterized by mimicking the morphological phenotype of HCC. As a possible origin of the tumor, it has been hypothesized that cancer arising from ectopic liver cells embedded in the organs where HAC develops and neoplastic transformation of persistent germ cells or of nonhepatic epithelium is capable of multipotential differentiation [5]. After having radical surgery and subsequent chemotherapy, its 1-year survival rate is approximately 55% [4]. HAC is defined primarily according to its histological manifestation. HAC usually shows morphologic features of hepatic differentiation, and polygonal tumor cells are displayed in hematoxylin and eosin stains [2]. Previous studies showed that the outstanding
diagnostic features of HAC included positive AFP (91.6%), Hep Par1 (38.1%), and EpCAM antibodies HEA125 or MOC31 which showed no reactivity with hepatocytes [2,3]. However, there were HAC cases, which were classified histologically, but no elevation of AFP was observed [6]. Similarly, Hep Par1 was a marker for hepatic carcinoma and had been reported positive in many cases of HAC [7,8]. In our case, histological observation and immunohistochemical results were in agreement with literature. The CT appearance of HAC is not specific. They are usually large masses with the density similar to normal liver tissue in plain CT scan (the presence of necrotic areas, however, can make the masses inhomogeneous) and are moderately enhanced by using an intravenous iodinated contrast agent. As one of the malignant tumors, invasion to the adjacent anatomical structures and metastases of regional lymph nodes and distant areas was frequently observed in HAC [9,10]. Typically, an elevated level of serum AFP is often associated with an occurrence of liver disease, especially of HCC. For this case, taking into account for all the information from liver ultrasonography,
Fig. 2. Macroscopy: A: The specimen and its cross-section. The tumor occupied around the appendix. Microscopy: B: polygonal tumor cells with abundant eosinophilic cytoplasm and round nuclei occasionally with obvious nucleoli and high mitotic activity. (hematoxylin and eosin stain (HE) 10×40) C: Coloration of the immunohistochemistry Hep Par1 (+) (Original magnification 10×40).
Please cite this article as: Wang X-Y, et al, AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT, Clin Imaging (2014), http://dx.doi.org/10.1016/j.clinimag.2014.02.019
X-Y. Wang et al. / Clinical Imaging xxx (2014) xxx–xxx
contrast CT and MRI as well as the decreased AFP level after surgery, it can be assured that it was HAC, not HCC, that increased the level of serum AFP. Previously, there was only one case report of HAC revealed by FDG PET/CT [11]. However, different from the previous report, the primary tumor and the metastases of our case showed a moderate FDG uptake (Fig. 1). Notably, regional lymph nodes of the appendix were not involved in this case although celiac metastases were present. Since there have been so far only two reported cases of HAC, more information is required to conclude the FDG PET/CT manifestation of HAC.
4. Conclusions This is the first case report of HAC of appendix. 18 F-FDG PET/CT may be helpful to detect its primary tumor and metastases. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.clinimag.2014.02.019.
Acknowledgments The authors would like to thank Dr. Yue Chen (PhD, Professor, Department of Epidemiology and Community Medicine, University of Ottawa, Canada) for his improving written English.
3
References [1] Ishikura H, Fukasawa Y, Ogasawara K, Natori T, Tsukada Y, Aizawa M. An AFPproducing gastric carcinoma with features of hepatic differentiation. A case report. Cancer 1985;56:840–8. [2] Su JS, Chen YT, Wang RC, Wu CY, Lee SW, Lee TY. Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma: a literature review. World J Gastroenterol 2013;19:321–7. [3] Metzgeroth G, Strobel P, Baumbusch T, Reiter A, Hastka J. Hepatoid adenocarcinoma - review of the literature illustrated by a rare case originating in the peritoneal cavity. Onkologie 2010;33:263–9. [4] Slotta JE, Jungling B, Kim YJ, Wagner M, Igna D, Schilling MK. Hepatoid adenocarcinoma of the transverse colon. Int J Colorectal Dis 2012;27:989–91. [5] Ishikura H, Kanda M, Ito M, Nosaka K, Mizuno K. Hepatoid adenocarcinoma: a distinctive histological subtype of alpha-fetoprotein-producing lung carcinoma. Virchows Arch A Pathol Anat Histopathol 1990;417:73–80. [6] Nakashima H, Nagafuchi K, Satoh H, Takeda K, Yamasaki T, Yonemasu H, Kishikawa H. Hepatoid adenocarcinoma of the gallbladder. J Hepatobiliary Pancreat Surg 2000;7:226–30. [7] Terracciano LM, Glatz K, Mhawech P, Vasei M, Lehmann FS, Vecchione R, Tornillo L. Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: an immunohistochemical and molecular study of eight cases. Am J Surg Pathol 2003;27:1302–12. [8] Akiyama S, Tamura G, Endoh Y, Fukushima N, Ichihara Y, Aizawa K, Kawata S, Motoyama T. Histogenesis of hepatoid adenocarcinoma of the stomach: molecular evidence of identical origin with coexistent tubular adenocarcinoma. Int J Cancer 2003;106:510–5. [9] Wu Z, Upadhyaya M, Zhu H, Qiao Z, Chen K, Miao F. Hepatoid adenocarcinoma: computed tomographic imaging findings with histopathologic correlation in 6 cases. J Comput Assist Tomogr 2007;31:846–52. [10] Lee MW, Lee JY, Kim YJ, Park EA, Choi JY, Kim SH, Lee JM, Han JK, Choi BI. Gastric hepatoid adenocarcinoma: CT findings. Abdom Imaging 2007;32:293–8. [11] Pan JH, Dong MJ, Ouyang XB. A hepatoid adenocarcinoma of the stomach with liver metastasis mimicking hepatocellular carcinoma detected by F-18 FDG PET/CT imaging. Clin Nucl Med 2011;36:1137–9.
Please cite this article as: Wang X-Y, et al, AFP-producing hepatoid adenocarcinoma of appendix: a case report of 18F-FDG PET/CT, Clin Imaging (2014), http://dx.doi.org/10.1016/j.clinimag.2014.02.019
