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CASE REPORT
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Spontaneous vanishing of hepatocellular carcinoma: A case report of an extremely rare incident


1 Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
2 Department of Tropical Medicine, Faculty of Medicine, Minia University, Minia, Egypt
3 Department of Gastroenterology, Damietta Gastroenterology and Cardiology Center, Damietta, Egypt
4 Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Cairo University, Giza, Egypt

Date of Submission29-Jan-2021
Date of Decision06-Sep-2021
Date of Web Publication11-Nov-2022

Correspondence Address:
Mohamed El-Kassas,
Department of Endemic Medicine, Faculty of Medicine, Helwan University, Ain Helwan 11795, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_177_21

 > Abstract 


One of the very uncommon clinical conditions is the spontaneous remission of tumors, with scarce reports around the world in various types of tumors. Spontaneous remission of hepatocellular carcinoma (HCC) is extremely rare, but it is well documented with a still unclear underlying mechanism. In this case report, we present one of those exceptional incidents of HCC regression with a trial to tackle possible explanations. Our case, which has a history of successfully treated hepatitis C virus, presented with a large infiltrative right lobar mass invading the main portal vein, with markedly elevated alpha fetoprotein (AFP). According to the applied diagnostic and treatment guidelines, the patient was scheduled for conservative management. Although he did not receive any specific treatments for his condition, the mass regressed in size with recanalization of the portal vein and normalization of AFP after 6 months of follow-up and keep the same for the following 3 years. The mechanisms by which spontaneous regression of HCC can occur are still unknown and should be furtherly investigated better to understand the behavior of such aggressive neoplastic disease.

Keywords: Hepatocellular carcinoma, spontaneous regression, spontaneous remissions



How to cite this URL:
El-Kassas M, El Sheemy RY, Sweedy AT, Abdelmaksoud AH. Spontaneous vanishing of hepatocellular carcinoma: A case report of an extremely rare incident. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=361020




 > Introduction Top


Hepatocellular carcinoma (HCC) is the third most common cancer and the fifth most common cause of cancer-related mortality worldwide and carries a poor prognosis if not treated.[1],[2] Unfortunately, and even with proper treatment, the mortality is still very high, with a median overall survival of 17.7 months.[3] Many staging systems are available for the purposes of diagnoses, deciding treatment options, and expecting survival in HCC patients.[2] Spontaneous regression of HCC is a rare phenomenon, and its actual mechanisms remain unclear. Some theories have been postulated to explain the etiology of HCC spontaneous regression, including possible tumor ischemia or systemic inflammatory response.[4]


 > Case Report Top


Our case is a 58 years-old male patient, known hypertensive on 80 mg propranolol daily, with a history of successfully treated chronic hepatitis C with 12-week course of sofosbuvir/daclatasvir combination 7 months before presentation. In June 2017, the patient presented to the hepatology clinic with recent-onset abdominal pain, constipation, fatigue, and somnolence. The patient was vitally stable, and general examination was free, while local examination revealed diffuse abdominal tenderness, with no clinically detected ascites or palpable organomegaly. Abdominal ultrasound was done and revealed a large hepatic focal lesion with malignant criteria and portal vein thrombosis. Triphasic multidetector computerized tomography (TCT) scan confirmed the presence of a large ill-defined infiltrative right lobe mass (segment VII) measuring 12 cm in maximum axial diameters with the characteristic HCC enhancement in the arterial phase. The mass was seen invading and extensively occluding the main portal vein as well as its main branches. The picture was impressive of an aggressive HCC with macro portal venous invasion [Figure 1]. Laboratory data were as follows: alpha fetoprotein (AFP) 32029, alanine aminotransferase (ALT): 46/40, aspartate aminotransferase (AST): 198/40, total bilirubin: 1.5 mg/dl, INR 1.2, albumin: 4.1 g/L, CA19.9: 6.5 U/ml, Carcinoembryonic antigen (CEA): 0.98 ng/ml. Blood sugar, kidney functions, and complete blood picture were all normal apart from mild thrombocytopenia (120,000/mm3). According to Barcelona Clinic Liver Cancer (BCLC) diagnostic criteria, the patient was diagnosed as HCC without the need for histopathological confirmation given the positive characteristics in a dynamic imaging modality in addition to markedly elevated AFP on a background of cirrhosis. Moreover, he was staged as BCLC stage C according to the diagnostic criteria.[2] Therefore, the decision was taken in our HCC multidisciplinary clinic to assign the patient for conservative management as none of the systemic therapies for HCC were available in our center at this time. No medications were prescribed for the patient apart from some analgesics.
Figure 1: Triphasic computerized tomography (arterial and venous phases) (August 9, 2017) at the time of the first presentation showing aggressive right lobar hepatocellular carcinoma with portal invasion reaching the main PV

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A follow-up TCT was done after 6 months and surprisingly revealed marked regression in the large liver mass size with only small oblong-shaped posteriorly located hypodensity [Figure 2]. In addition, there was evident recanalization of the main and right portal vein with multiple small varicosities around the main trunk (portal cavernoma). Laboratory follow-up data showed normalization of AFP: 10.6 ng/ml, and other liver profile tests; Alb: 4.1, T. BIL: 0.6, ALT: 21/40, AST: 22/40, INR: 1.1. After that time, serial follow-up investigations and over 3-year duration were the same with no evidence of any tumoral activity.
Figure 2: Follow-up triphasic computerized tomography (February 28, 2018) showing marked regression in size of the mass with evidence of portal cavernoma 6 months after the initial presentation

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 > Discussion Top


Our case is an uncommon or even rare presentation of HCC that underwent spontaneous regression, which was evidenced and confirmed radiologically by a series of TCT scans and normalization of AFP levels without introducing any medical, surgical, or interventional treatments. Spontaneous regression of tumors is an extremely uncommon and rare condition, previously described by Cole and Everson as complete or incomplete remission of malignancy without the use of any treatment or with the introduction of inadequate therapy that is not believed to exert a significant effect on the neoplastic process.[4] The most commonly described malignant tumors with spontaneous regression are renal cell carcinoma, neuroblastoma, melanoma, and choriocarcinoma, and these tumors account for more than 50% of all reported cases of spontaneous remission.[5] Unfortunately, spontaneous regression of HCC is a very rare clinical event with a documented incidence rate of 1 in 140,000 cases of HCC.[5] The first reported case of spontaneous remission of HCC was described by Johnson and his colleagues in 1972,[6] while the first biopsy confirmed case had been documented in 1992 in Taiwan.[7]

Two possible hypotheses were suggested to explain spontaneous HCC remission mechanisms: tumor hypoxia and activation of the systemic inflammatory response.[5] The presence of some events such as portal vein thrombosis, angiography-induced angiospasm or arterial thrombosis, accelerated growth of the tumor are all accepted explanations just similar in action to transarterial chemoembolization or the anti-angiogenesis medications such as sorafenib.[8] The other postulated theory suggests a possible activation of the systemic inflammatory response due to increased release of different cytokine and other inflammatory biomarkers from tumor tissue (ex: interleukin-2 [IL-2], IL-6, IL-12, IL-18, interferon-gamma, tumor necrosis factor alpha).[9] Moreover, tumor hypoxia theory alone cannot explain the spontaneous regression of HCC associated with distance metastasis.[10] The pathological evidence of activated inflammatory response was confirmed by the presence of overactivated macrophages (CD163) or lymphocytic infiltration.[10]

Here, we discuss a case of HCC, which underwent spontaneous vanishing with no remarkable evidence of hypoxic changes or systemic inflammatory response activation. In our case, the diagnosis of HCC lacked the histopathological confirmation as per the recommendation of BCLC diagnostic criteria based on the characteristic pattern of enhancement in a single contrast mediated imaging study showing arterial hyperperfusion and venous washout together with more than 400 ng/ml of AFP level.[2] The remote possibility of having an inflammatory condition mimicking HCC, which ended abruptly, opens the door again for the discussions about the necessity to get tissue samples to diagnose HCC. Mechanisms that affect the rarely occurring tumor regression in some HCC cases are not well understood. The exciting finding of spontaneous tumor regression always provides new hope for future treatment options for HCC. The accumulation of those exceptional cases is the first step toward advancing the understanding of this extraordinary phenomenon.

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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6.  Back to cited text no. 1
    
2.
Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: The BCLC staging classification. Semin Liver Dis 1999;19:329-38.  Back to cited text no. 2
    
3.
Daniele B, Annunziata M, Barletta E, Tinessa V, Di Maio M. Cancer of the Liver Italian Program (CLIP) score for staging hepatocellular carcinoma. Hepatol Res 2007;37 Suppl 2:S206-9.  Back to cited text no. 3
    
4.
Takeda N, Wakui Y, Asai N, Dan Y, Yamauchi N, Ueki T. et al. Spontaneous complete necrosis of hepatocellular carcinoma: A case report and review of the literature. Oncol Lett 2015;9:1520-6.  Back to cited text no. 4
    
5.
Chang WY. Complete spontaneous regression of cancer: Four case reports, review of literature, and discussion of possible mechanisms involved. Hawaii Med J 2000;59:379-87.  Back to cited text no. 5
    
6.
Arakawa Y, Mori H, Ikegami T, Hanaoka J, Kanamoto M, Kanemura H, et al. Hepatocellular carcinoma with spontaneous regression: Report of the rare case. Hepatogastroenterology 2008;55:1770-2.  Back to cited text no. 6
    
7.
Nam SW, Han JY, Kim JI, Park SH, Cho SH, Han NI, et al. Spontaneous regression of a large hepatocellular carcinoma with skull metastasis. J Gastroenterol Hepatol 2005;20:488-92.  Back to cited text no. 7
    
8.
Zhong JH, Li LQ. Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: A meta-analysis. Hepatol Res 2010;40:943-53.  Back to cited text no. 8
    
9.
Blondon H, Fritsch L, Cherqui D. Two cases of spontaneous regression of multicentric hepatocellular carcinoma after intraperitoneal rupture: Possible role of immune mechanisms. Eur J Gastroenterol Hepatol 2004;16:1355-9.  Back to cited text no. 9
    
10.
Wang Z, Ke ZF, Lu XF, Luo CJ, Liu YD, Lin ZW, et al. The clue of a possible etiology about spontaneous regression of hepatocellular carcinoma: A perspective on pathology. Onco Targets Ther 2015;8:395-400.  Back to cited text no. 10
    


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