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Table of Contents
CASE REPORT
Year : 2019  |  Volume : 6  |  Issue : 1  |  Page : 34-36

Metastatic hepatocellular carcinoma manifesting as primary esophageal carcinoma: A rare case report


1 Department of Pathology, K S Hegde Medical Academy, Nitte (deemed to be University), Mangalore, Karnataka, India
2 Department of Oncology, K S Hegde Medical Academy, Nitte(deemed to be University), Mangalore, Karnataka, India

Date of Web Publication24-Apr-2019

Correspondence Address:
Dr. H L Kishan Prasad
Department of Pathology, K S Hegde Medical Academy, Mangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/BMRJ.BMRJ_2_18

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  Abstract 


Hepatocellular carcinoma (HCC) metastasizing to the esophagus and mimicking as a primary tumor of the esophagus is extremely rare, being present in <0.4% in some autopsy series. This report describes a case of 70-year-old male with metastatic HCC to esophagogastric junction causing diagnostic dilemma. An endoscopic examination revealed an ulcerative lesion in the lower end of the esophagus. The biopsy specimen obtained from a tumor revealed the pseudoglandular arrangement of tumor cells. Ultrasound abdomen showed liver nodule with biopsy confirming as HCC. Immunohistochemistry (IHC) of the esophageal mass showed positivity for Hep par 1, Glypican-3, Arginase, CA 19-9, CK 19, CDX2, pCEA, SATB2, and Ki-67 having 70% positivity confirming the HCC. Among these IHC panels, all are specific markers of HCC, but CDX2 and SATB2 were aberrantly expressed in our case. He was started on six cycles of chemotherapy (apristar 125 mg, epirubicin 40 mg, oxaliplatin 100 mg, and capecitabine 500 mg). After 8 months of follow-up, he was symptomatically improved. However, later, the patient was lost to follow-up. The accurate pretreatment staging and then providing stage-appropriate treatment is crucial in optimizing esophageal and hepatocellular cancer outcomes. Cases of premortem-diagnosed esophageal metastasis from HCC are extremely rare. Our case was ideal for IHC, which plays an important role in arriving at proper cases. Furthermore, it confirmed and highlighted the rare manifestations of hepatocellular carcinoma.

Keywords: Esophageal carcinoma, Hep par 1, hepatocellular carcinoma, immunohistochemistry, metastasis


How to cite this article:
Shetty K J, Kishan Prasad H L, Bhat S, Mathias M, Shetty V. Metastatic hepatocellular carcinoma manifesting as primary esophageal carcinoma: A rare case report. Biomed Res J 2019;6:34-6

How to cite this URL:
Shetty K J, Kishan Prasad H L, Bhat S, Mathias M, Shetty V. Metastatic hepatocellular carcinoma manifesting as primary esophageal carcinoma: A rare case report. Biomed Res J [serial online] 2019 [cited 2019 May 23];6:34-6. Available from: http://www.brjnmims.org/text.asp?2019/6/1/34/257034




  Introduction Top


Hepatocellular carcinoma (HCC) metastasizing to the esophagus and mimicking as the primary tumor of the esophagus is extremely rare, being present in <0.4% in some autopsy series. This metastasis is brought about by tumor thrombi infiltrating through the portal system and is disseminated by hepatofugal portal blood flow to the gastrointestinal tract (GIT).[1],[2] The reported case series of esophageal metastasis from HCC presented with major symptoms such as GI bleeding and dysphagia. Endoscopic examination of such cases presents with a polypoid lesion or submucosal mass mimicking as primary esophageal carcinoma.[3],[4],[5],[6],[7],[8] We present here a rare case of metastatic HCC to esophagogastric junction causing diagnostic difficulties. This case is reported due to its rarity with significant diagnostic difficulties.


  Case Report Top


A 70-year-old man presented with pain abdomen for 3 weeks with recent onset dysphagia. Family and personal history was unremarkable. General physical examination showed mild pallor. Ultrasound abdomen showed an enlarged liver with a nodular mass measuring 4 cm × 3 cm in the right lobe. Upper GI endoscopy done for the evaluation of dysphagia showed semi-circumferential ulcerative lesion in the esophagogastric junction [Figure 1]a and [Figure 1]b. Preoperative serum alpha-fetoprotein was 1200 IU/ml. The biopsy from the liver was performed with a clinical diagnosis of esophageal carcinoma with liver secondaries showed tumor cells in sheets, pseudoglandular arrangement, and few single cells with granular cytoplasm [Figure 1]c and [Figure 1]d suggesting poorly differentiated HCC. Biopsy from the esophagus showed similar histological features causing diagnostic difficulty in identifying primary, is it esophageal carcinoma metastasis to liver or HCC metastasizing to esophagus? To resolve this diagnostic difficulty, immunohistochemistry (IHC) was done which showed positivity for Hep par 1 [Figure 2]a, Glypican-3 [Figure 2]b, Arginase [Figure 2]c, CA 19-9 [Figure 2]d, CK 19 [Figure 3]a, CDX2, pCEA [Figure 3]b, SATB2, and Ki-67 having 70% positivity [Figure 3]c confirming the HCC. Among these IHC panels, all are specific markers of HCC, but CDX2 and SATB2 are rarely expressed in such cases. In our case, CDX2 and SATB2 aberrant expression was seen with moderate nuclear immunoreactivity. He was started on six cycles of chemotherapy (apristar 125 mg, epirubicin 40 mg, oxaliplatin 100 mg, and capecitabine 500 mg). After 8 months of follow-up, he was symptomatically improved. However, later, the patient was lost to follow-up.
Figure 1: (a and b) Upper gastrointestinal endoscopic showing circumferential growth in the lower end of the esophagus. (c and d) Histopathology of the esophageal mass showing tumor cells arranged in sheets, the pseudo glandular pattern having pleomorphic nuclei (H and E, 100)

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Figure 2: (a-d) Immunohistochemistry showing diffuse cytoplasmic/membranous immunoreactivity for Hep par 1 (a), Glypican-3 (b), Arginase (c), and CA 19-9 (d)

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Figure 3: (a-c) Immunohistochemistry showing cytoplasmic immunoreactivity for CK 19 (a), nuclear immunoreactivity for pCEA (b), and Ki-67 having 70% positivity (c)

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  Discussion Top


HCC is a most common primary malignancy of liver, and extrahepatic metastasis in these cases frequently occurs in 30%–75% of patients. Distant metastasis commonly was seen with advanced malignancies. The most common sites of metastasis are the lung, bone, intraperitoneal organ, and adrenal gland. It also frequently involves the regional lymph nodes.[2],[3],[4],[5],[6]

GI involvement is rarely found in only 4%–12% of cases in autopsy series, whereas it has been reported that GIT involvement is seen in 0.5%–2% of case series. The most common involved site was the duodenum, followed by the stomach, colon, and the jejunum. The esophagus is the rare site of metastasis. Metastases to the esophagus are very rare, being present in <0.4% of patients with HCC. During the one decade, only a few cases of HCC with esophageal metastases have been reported.[4],[7],[8],[9]

There are two different hypotheses concerning the way HCC metastasizes to the esophagus: either by direct invasion of the GIT through continuation between the serosal side of a liver tumor and the esophagus or through the hematogenous spread of tumor emboli infiltrating through the portal vein system and being disseminated by hepatofugal portal blood flow to the esophagus. The portal blood flow which will be reversed by increased intrahepatic resistance and arteriovenous communications in patients with liver cirrhosis and associated HCC, thus causing retrograde metastasis of HCC through the portal system.[3],[4],[5]

There are many cases with esophageal metastasis from HCC which might be incidentally discovered in the future since many patients with the terminal stage of HCC are not strictly followed by endoscopic examinations.[4],[5],[6],[7],[8],[9],[10] Endoscopists should be aware that esophageal metastasis from HCC may exhibit the endoscopic characteristics similar to the primary esophageal tumor and it may exhibit rapid growth as in the present case, and it may present with dysphagia or upper GI bleeding. In our case, the esophageal tumor had the manifestation of dysphagia. There are few case reports of esophageal and gastric metastases of HCC after liver transplantation as a cause of upper GI bleeding. Some cases show the varices at endoscopy implying that hematogenous spread is a possible route of metastasis from HCC to esophagus and stomach.[2],[4],[5] Furthermore, the presence of immunosuppressant drugs may facilitate tumor cell metastasis.[3] In metastatic cases, it will pose the diagnostic challenge in identifying primary. These cases the extensive use of IHC markers are needed. The immunoreactivity for Hep par 1, Glypican-3, Arginase, CA19-9, CK 19, and pCEA is compatible with an origin in HCC. However, in our case, apart from these markers, it also showed aberrant expression of CDX2 and SATB2 with moderate nuclear immunoreactivity. The expression and mechanism of SATB2 in HCC remain unknown. However, few case reports of CDX2 and SATB2 aberrant expression is noted in HCCs. These results demonstrate that SATB2 is a functional target gene of miR-211 in HCC.[7],[8]

The majority of metastatic esophageal carcinomas are associated with diffuse metastases or with mediastinal carcinomatosis and thus are not candidates for aggressive local treatments.[4],[5] Recently, few cases report with managing with robot-assisted local resection of an isolated partially obstructing metastatic esophageal tumor using the da Vinci surgical system in a patient who had undergone liver transplantation for cirrhotic liver associated with HCC.[6] The accurate pretreatment staging and then providing stage-appropriate treatment is crucial in optimizing esophageal cancer outcomes. Overall 5-year survival for patients with esophageal cancer remains poor although some improvement has been achieved with an increase from 5% to 17%–19% over the past few decades.[4],[8],[9] Despite advancements in diagnostic techniques, only 14 cases of esophageal metastasis in living HCC patients have been reported in the last 20 years on PubMed. Majority of these patients will have terminal disease with distant metastases at multiple sites. Hence, palliative chemotherapy or radiation therapy will be the treatment choice. The interval between diagnosis of esophageal metastasis and death was short in such cases, with a mean of only 5.5 months. Thus, esophageal metastasis from HCC will have an extremely poor prognosis, and therapy for these HCC cases should be individualized and tailored.


  Conclusion Top


The cases of premortem-diagnosed esophageal metastasis from HCC are extremely rare causing diagnostic and therapeutic challenges to pathologists and clinicians. Despite advancements in diagnostic techniques, only 14 cases of esophageal metastasis in living HCC patients have been reported in the last 20 years on PubMed. Majority of these patients will have terminal disease with distant metastases at multiple sites. In such cases, extensive utilization of immunomarkers is essential to arrive at proper diagnosis and management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

We would like to acknowledge the pathology technicians for meticulous IHC staining which helped us in arriving at specific diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chen JX, Jeng LB, Lin YS, Lu TY, Kao PY, Fang HY, et al. Amimicking esophageal cancer after liver transplant for hepatocellular carcinoma: A rare posttransplant metastasis. Exp Clin Transplant 2016;14:571-4.  Back to cited text no. 1
    
2.
Tsubouchi E, Hirasaki S, Kataoka J, Hidaka S, Kajiwara T, Yamauchi Y, et al. Unusual metastasis of hepatocellular carcinoma to the esophagus. Intern Med 2005;44:444-7.  Back to cited text no. 2
    
3.
Skurla B, Mlinaric A, Katicic SN, Mihalic SN. Oesophageal metastases of hepatocellular carcinoma following liver transplantation. Int J Case Rep Images 2010;1:7-11.  Back to cited text no. 3
    
4.
Fukatsu H, Miura S, Kishida H, Takagi S, Morishita H, Uchino K, et al. Gastrointestinal: Esophageal metastasis from hepatocellular carcinoma. J Gastroenterol Hepatol 2012;27:1536.  Back to cited text no. 4
    
5.
Hsu KF, Hsieh TY, Yeh CL, Shih ML, Hsieh CB. Polypoid esophageal and gastric metastases of recurrent hepatocellular carcinoma after liver transplantation. Endoscopy 2009;41 Suppl 2:E82-3.  Back to cited text no. 5
    
6.
Boonnuch W, Akaraviputh T, Nino C, Yiengpruksawan A, Christiano AA. Successful treatment of esophageal metastasis from hepatocellular carcinoma using the da vinci robotic surgical system. World J Gastrointest Surg 2011;3:82-5.  Back to cited text no. 6
    
7.
Jiang G, Cui Y, Yu X, Wu Z, Ding G, Cao L, et al. MiR-211 suppresses hepatocellular carcinoma by downregulating SATB2. Oncotarget 2015;6:9457-66.  Back to cited text no. 7
    
8.
Berry MF. Esophageal cancer: Staging system and guidelines for staging and treatment. J Thorac Dis 2014;6 Suppl 3:S289-97.  Back to cited text no. 8
    
9.
Skurla B, Mlinaric A, Nadalin S, Katicic M, Naumovski MS. Esophageal metastases of hepatocellular carcinoma following liver transplantation. Int J Case Rep Images 2010;1:7-11.  Back to cited text no. 9
    
10.
Harada JI, Matsutani T, Hagiwara N, Kawano Y, Matsuda A, Taniai N, et al. Metastasis of hepatocellular carcinoma to the esophagus: Case report and review. Case Rep Surg 2018;2018:8685371.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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