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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 2  |  Issue : 3  |  Page : 58-61

Epithelioid hemangioendothelioma of liver mimicking as metastasis in treated case of carcinoma of cervix: A rare clinical issue with literature review


1 Department of Radiotherapy, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Pathology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Web Publication21-Sep-2018

Correspondence Address:
Dr. Dillip Kumar Parida
Department of Radiotherapy, All India Institute of Medical Sciences, Bhubaneswar-751019, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/oji.oji_27_18

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  Abstract 


Epithelioid hemangioendothelioma (EH) is a rare tumor of vascular origin. Hepatic involvement of EH is a rare incidence and radiological finding may confuse with metastasis, particularly in a previously existing primary carcinoma. Biopsy from the lesion followed by immunohistochemistry (IHC) examination should be done for confirmation of the diagnosis. The clinical presentation of EH is variable, and the majority cases present with multifocal disease during the diagnosis. The therapeutic criteria of EH are still unclear since its natural history is unpredictable. We report a case of EH of the liver in a previously treated squamous cell carcinoma of the cervix. The case was found to have a solitary hepatic mass lesion in the right lobe of liver on radiological investigation. Biopsy from liver lesion was found to be EH and confirmed on IHC study.

Keywords: Cervix, epithelioid hemangioendothelioma, metastasis, liver, squamous cell carcinoma


How to cite this article:
Mishra S, Das Majumdar SK, Patra S, Parida DK. Epithelioid hemangioendothelioma of liver mimicking as metastasis in treated case of carcinoma of cervix: A rare clinical issue with literature review. Oncol J India 2018;2:58-61

How to cite this URL:
Mishra S, Das Majumdar SK, Patra S, Parida DK. Epithelioid hemangioendothelioma of liver mimicking as metastasis in treated case of carcinoma of cervix: A rare clinical issue with literature review. Oncol J India [serial online] 2018 [cited 2018 Nov 19];2:58-61. Available from: http://www.ojionline.org/text.asp?2018/2/3/58/241843




  Introduction Top


Epithelioid hemangioendothelioma (EH) is a rare vascular tumor originating from vascular endothelial or pre-endothelial cells and constitutes <1% of all vascular tumors. It commonly occurs in lungs, liver, and bones followed by head and neck area, breast, lymph nodes, mediastinum, brain and meninges, spine, skin, abdomen, and many other sites.[1],[2] Liver involvement may be seen as metastatic or rarely as primary tumors.[3] We report a case of EH of the liver in a treated case of squamous cell carcinoma of the cervix, diagnosed on histopathological study, and confirmed by immunohistochemistry (IHC), which shows positive for CD31, CD34, hepatocyte, and pan-cytokeratin markers.


  Case Report Top


A 56-year-old woman presented to us with the complaint of occasional pain abdomen and vomiting. She had a history of postmenopausal bleeding 60 months back, for which evaluated and diagnosed as squamous cell carcinoma of the uterine cervix with clinical FIGO stage IB1 and tumor size <3 cm. The patient was treated with type 2 radical hysterectomy at that time and the postoperative histopathological report showed features of squamous cell carcinoma of the cervix with lymphovascular space invasion (LVSI) and deep stromal invasions positive. Other parameters including surgical margins and lymph nodes were found to be free of malignancy. She received external beam radiotherapy of 50 Gy in 25 fractions to pelvis at 2 Gy per fraction by CO60 followed by 3 fractions of intracavitary brachytherapy with a dose of 6.5 Gy per fractions by HDR technique. Last session of brachytherapy was performed in June 2011. Subsequently, she was under regular follow-up. After 58 months of follow-up, she developed occasional pain abdomen and vomiting. Magnetic resonance imaging (MRI) of the abdomen showed a hypointense, nodular enhancing lesion measuring 1.8 cm × 1.8 cm with well-defined margin in the right lobe segment VII of liver [Figure 1]a. The patient was nonalcoholic and nonsmoker; there was no history of oral contraceptive use and no chemical exposure. Clinical examination showed only mild abdominal tenderness over the right side. Routine hematological and biochemical investigations were within normal limit. Serological test for hepatitis B and C were negative. The patient did not come for further management, and after a gap of 9 months, the patient again visited to us with complaint of mild abdominal pain. Triphasic Contrast-enhanced computed tomography (CECT) scan of the abdomen and pelvis showed no local recurrence, but a hypodense lesion of size 2 cm × 2 cm found in the segment VII of liver with no enhancement during arterial and portovenous phase with an insignificant necrotic para-aortic lymph node [Figure 1]b and c]. Solitary hepatic lesion was slightly increased in size in comparison to previous MRI in a gap of 9 months. CT-guided biopsy from the hepatic lesion revealed presence of tumor tissue containing proliferated capillaries with dysplastic endothelial cells and several spindle cells with hyperchromatic and pleomorphic nuclei. There was formation of intracellular lumina containing red blood cells (RBCs) within it and partly hyalinised stroma with total ischemic necrosis [Figure 2]. IHC showed positive for CD31, CD34, hepatocyte, and pan-cytokeratin (CK–AE1/AE3) in favor of EH [Figure 3]a and [Figure 1]b. Now, the patient was on close surveillance for the last 10 months in view of slightly increased in size of solitary hepatic lesion on CECT scan in comparison to the size on MRI scan within a gap period of 9 months.
Figure 1: (a) Magentic resonance imaging pelvis showing solitary hypointense nodular enhancing mass in segment VII, right lobe of liver with well-defined margins, (b) sagittal computed tomography reformation showed no evidence of recurrence between bladder and contrast-filled rectum, and (c) coronal section computed tomography reformation showed well-defined hypodense lesion in the right lobe laterally with small enhancing foci in the margin and a small necrotic para-aortic lymph node of size

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Figure 2: Computed tomography-guided biopsy from liver lesion showed cellular pleomorphism and intracytoplasmic neolumen with red blood cell inside it (H and E, ×400)

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Figure 3: Immunohistochemistry showed positive for CD31 (a) and positive for CD34 (b)

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  Discussion Top


The first case of primary hepatic EH was reported by Ishaket al. in 1984.[3] Review of literature for hepatic EH showed less than 500 reported cases.[4]

EH was classified as a malignant vascular tumor according to the 2002 WHO classification. The natural course and prognosis are still unpredictable. Furui et al. described two different types of EH, nodular and diffuse type.[5] According to them, nodular lesions were an earlier form which later changed into diffuse lesions, only 11.1% were nodular type at initial presentation, and 66% had multiple lesions. EH most frequently shows multifocality during diagnosis; therefore, this kind of manifestation (solitary presentation) in the present case is rare. The etiology or risk factors are unknown although it is most frequently seen in middle-aged women. Clinical manifestations are nonspecific.[6] Twenty-five percent of cases were asymptomatic, and right upper quadrant abdominal pain, hepatomegaly, and weight loss are the most frequent symptoms. Serum levels of CEA, CA19-9, and alpha-fetoprotein remain within normal limit. Clinical symptoms, and laboratory data, may become worse when disease advances. The diagnosis of hepatic EH is difficult. Radiologically, EH looks as a hypodense lesion in CT scan, and in MRI, it gives low-signal intensity on T1-weighted images and heterogeneous high-signal intensity on T2 sequences with peripheral enhancement with a thin nonenhancing rim.[7] These features suggest a diagnosis of metastatic carcinoma. In the present case, MRI shows hypointense nodular enhancing lesion in the right lobe of liver apparently representing a secondary.

Lymphatic spread and hematogenous dissemination are the two common modes of distant metastasis for carcinoma of the cervix. The common pattern of recurrence after curative treatment of cervix carcinoma is locoregional recurrence followed by distant metastasis. Distant metastasis in carcinoma of the cervix have a higher incidence of LVSI and aggressive cell types in early stage cervix cancer.[8] Hematogenous dissemination is relatively unusual and involves commonly lungs (36.3%) and bone (16.3%) followed by liver, brain, and other sites.[9]

Hepatic metastasis in carcinoma of the cervix is uncommon with a reported incidence of 2.2% and is usually associated with uncontrolled locoregional disease and/or other extrahepatic metastases such as pelvic or para-aortic lymph nodes, lungs, and bones. Isolated liver metastasis without involvement of other sites is rarer with an incidence of 0.3%. Eighty percent of liver metastasis in carcinoma cervix is usually presented as multiple hepatic nodules of varying sizes.[10] Although liver metastasis is uncommon in carcinoma of the cervix, an existing such primary malignancy in our case with enhancing liver nodule creates an initial thought of liver metastasis in a treated case of carcinoma of cervix. Kim et al., in a series of 1665 cervical carcinomas, found liver metastasis in only 1.2% and isolated liver metastasis in 0.06% (1 case) without extrahepatic metastatic foci.[11]

Pathologic examination remains the mainstay of diagnosis. EH is composed of pleomorphic cells with rare multinucleated giant cells and intracytoplasmic lumina formation containing erythrocyte or leukocyte inside cells revealing its vascular nature. The endothelial nature may be confirmed by the IHC detection of CD31, CD34, factor VIII-related antigen, podoplanin (D2-40 antibody), and Fli-1.[1] In the present case, histopathological examination revealed cells with intracytoplasmic neolumen formation with RBC inside it, and IHC revealed that CD31 and CD34 were positive and MIB-1 expression index was 1%–2%.

There is no standard guideline for the treatment of hepatic EH due to rarity of the disease. Liver transplantation, liver resection, chemotherapy, radiotherapy, and close surveillance are the different possible treatment approaches for hepatic EH. Surgical resection for localized EH seems to be accepted as a standard therapeutic strategy. Orthoptic liver transplantation appears to be the only hope for multifocality.[5] Few literature reported that a malignant EH of the liver successfully treated with pegylated liposomal doxorubicin and metastatic hepatic EH successfully treated with thalidomide.[12],[13] In a recent study by Mehrabi et al., the overall survival rate of patients undergoing liver resection was longer than undergoing orthoptic liver transplantation in case of solitary EH.[4] Furthermore, few literature mentioned close surveillance in case of solitary EH. However, less is known about truly long-term (>5 years) outcome. In our case, the patient is kept under close surveillance and asymptomatic for the last 10 months for EH, and in addition, the patient is disease free for cervix carcinoma for 5 years.

In summary, EH of the liver is a rare vascular tumor and its association with an existing primary malignancy makes a diagnostic dilemma with metastasis. Careful histopathological examination followed by IHC study is necessary to confirm the lesion whether metastatic or any benign or second malignancy to follow proper, necessary treatment. The treatment of hepatic EH is not clear till date due to rarity of disease and close surveillance can be an option in solitary EH. Our case of solitary liver EH in a previously treated carcinoma of the cervix needs to be documentation due to its rarity and as a second malignancy mimicking as liver metastasis.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. Epithelioid hemangioendothelioma: An overview and update on a rare vascular tumor. Oncol Rev 2014;8:259.  Back to cited text no. 1
    
2.
Kim SG, Jung MK, Jeon SW, Cho CM, Tak WY, Kweon YO, et al. A case of primary hepatic epithelioid hemangioendothelioma mimicking metastatic carcinoma. Korean J Gastroenterol 2007;50:61-5.  Back to cited text no. 2
    
3.
Ishak KG, Sesterhenn IA, Goodman ZD, Rabin L, Stromeyer FW. Epithelioid hemangioendothelioma of the liver: A clinicopathologic and follow-up study of 32 cases. Hum Pathol 1984;15:839-52.  Back to cited text no. 3
    
4.
Mehrabi A, Kashfi A, Fonouni H, Schemmer P, Schmied BM, Hallscheidt P, et al. Primary malignant hepatic epithelioid hemangioendothelioma: A comprehensive review of the literature with emphasis on the surgical therapy. Cancer 2006;107:2108-21.  Back to cited text no. 4
    
5.
Furui S, Itai Y, Ohtomo K, Yamauchi T, Takenaka E, Iio M, et al. Hepatic epithelioid hemangioendothelioma: Report of five cases. Radiology 1989;171:63-8.  Back to cited text no. 5
    
6.
Choi KH, Moon WS. Epithelioid hemangioendothelioma of the liver. Clin Mol Hepatol 2013;19:315-9.  Back to cited text no. 6
    
7.
Chen Y, Yu RS, Qiu LL, Jiang DY, Tan YB, Fu YB. Contrast-enhanced multiple-phase imaging features in hepatic epithelioid hemangioendothelioma. World J Gastroenterol 2011;17:3544-53.  Back to cited text no. 7
    
8.
Hanprasertpong J, Jiamset I, Geater A, Rattanaburi A, Thannil S. Clinical aspects and prognostic factors for survival in patients with recurrent cervical cancer after radical hysterectomy. Oncol Res Treat 2016;39:704-11.  Back to cited text no. 8
    
9.
Li H, Wu X, Cheng X. Advances in diagnosis and treatment of metastatic cervical cancer. J Gynecol Oncol 2016;27:e43.  Back to cited text no. 9
    
10.
Singla V, Virmani V, Dey P, Khandelwal N. Solitary giant cystic liver metastasis mimicking an abscess – a word of caution. Indian J Cancer 2011;48:127-9.  Back to cited text no. 10
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11.
Kim GE, Lee SW, Suh CO, Park TK, Kim JW, Park JT, et al. Hepatic metastases from carcinoma of the uterine cervix. Gynecol Oncol 1998;70:56-60.  Back to cited text no. 11
    
12.
Grenader T, Vernea F, Reinus C, Gabizon A. Malignant epithelioid hemangioendothelioma of the liver successfully treated with pegylated liposomal doxorubicin. J Clin Oncol 2011;29:e722-4.  Back to cited text no. 12
    
13.
Salech F, Valderrama S, Nervi B, Rodriguez JC, Oksenberg D, Koch A, et al. Thalidomide for the treatment of metastatic hepatic epithelioid hemangioendothelioma: A case report with a long term follow-up. Ann Hepatol 2011;10:99-102.  Back to cited text no. 13
    


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