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Hepatic Epithelioid Hemangioendothelioma and the Danger of Misdiagnosis: Report of a Case

Hepatic Epithelioid Hemangioendothelioma and the Danger of Misdiagnosis: Report of a Case Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2013, Article ID 243939, 5 pages http://dx.doi.org/10.1155/2013/243939 Case Report Hepatic Epithelioid Hemangioendothelioma and the Danger of Misdiagnosis: Report of a Case 1 1 2 1 Kyriakos Neofytou, Andreas Chrysochos, Nikolas Charalambous, Menelaos Dietis, 1 1 1 Christos Petridis, Charalampos Andreou, and Athanasios Petrou Department of Surgery, NicosiaGovernmentHospital, PalaiosDromosLeofk sias-Lemesou, No.215,2029Strovolos,Nicosia,Cyprus Department of Radiology, Nicosia Government Hospital, Palaios Dromos Leosia fk s-Lemesou, No. 215, 2029 Strovolos, Nicosia, Cyprus Correspondence should be addressed to Kyriakos Neofytou; kneophy2@gmail.com Received 15 January 2013; Accepted 1 February 2013 Academic Editors: J. M. Buchanich, R. Palmirotta, and M. Romkes Copyright © 2013 Kyriakos Neofytou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Malignant hepatic epithelioid hemangioendothelioma (HEHE) is a rare malignant tumor of vascular origin. Nonspecific symptoms and the absence of experience of surgeons, radiologists, and histopathologists due to the rarity of HEHE make the diagnosis of this entity very challenging. Misdiagnosis is not a rare event, and the consequences of such an event are catastrophic. We report a case of a patient suffering from HEHE in which the initial diagnosis was hepatocellular carcinoma (HCC). eTh presence of normal laboratory values, liver function tests, tumor markers along with the absence of a chronic liver disease, or any other predisposing factors for HCC, was in contrast with the diagnosis of HCC. Clinical suspicion drove us to the repetition of a liver biopsy and the reevaluation of the sample by a more experience histopathology department in liver tumors. eTh last biopsy confirmed the diagnosis of HEHE, and the patient escaped any unnecessary treatment for a nonexisting HCC. 1. Case Presentation hypodense lesions were seen with the largest of which in the right liver lobe, with a maximum diameter of 3.7 cm A forty-nine-year old female patient presented with a right (Figure 1). Basedonthe above, thehypothesisofsecondary upper quadrant pain. Based on her medical history, the liver metastasis was proposed. patient underwent thyroidectomy 6 months before because In the following days, both colonoscopy as well as of a papillary thyroid cancer that was not invading the gastroscopy took place with no pathological findings. Tumor thyroid capsule (TNM staging PT1, PNX, PMX Anatomic markers including cancer embryonic antigen (CEA), alpha stage/Prognostic groups 45 years, and older Stage 1). fetoprotein (AFP), and carbohydrate antigen (CA) 19–9 were All of the patient laboratory tests were within nor- all within normal limits. yTh roglobulin was measured at mal limits including alkaline phosphatase (41 U/L), g- 0.2 ng/mL. A follow-up neck ultrasound did not reveal any glutamyl transpeptidase (14 U/L), aspartate aminotransferase mass or enlarge lymph nodes, and I whole body scan did (16 U/L), alanine aminotransferase (12 U/L), and bilirubin not demonstrate any thyroid remnant nor any metastasis. levels (0.44 mg/dL). As part of thepatient diagnostic evaluation,inanattempt An abdominal ultrasound was scheduled which showed to nfi dthe possible primarytumor,awholebodymagnetic several hypoechoic solid nodules, regarding both liver lobes, resonance imaging (MRI) was performed. eTh results showed with an irregular echogenic outline and a few of which with no evidence of an extrahepatic disease. multiple calcifications. Immediately aeft rwards, an abdomi- Percutaneous liver biopsy from the largest liver lesion, nal computed tomography was performed which conrfi med guided under computed tomography, showed massive hepatic necrosis. The patient hepatitis serology was negative these lesions and the related calcifications. Specifically, 2 Case Reports in Oncological Medicine 1982, EHE has been described in many organs, including spleen, bone, brain, meninges, breast, heart, head and neck, soft tissue, stomach, and lymph nodes [ 1–7]. Hepatic epithelioid hemangioendothelioma (HEHE) was reported first in 1984 by Ishak et al. in a series of 32 patients [ 8]. The HEHE is a vascular tumor which originates from endothelial cells and is a rare malignancy with an incidence of<0.1 per 100,000 population [9]. Thistumor hashistologicappearance and behavior between hemangioma and hemangiosarcoma and is classified as a malignant neoplasm by the World Health Organization [10]. HEHE is known to occur in individuals of all ages but is rare in children less than 15 years old. It appears more oen ft in women with a male-to-female ratio, 2 : 3 during the 4th decade of their liver [11]. Until today no definitive etiological factor has been Figure 1: Abdominal CT scan, with intravenous contrast showing clearly identified for HEHE although several risk factors several hypodense lesions on both liver lobes. Arrow shows lesion have been proposed (eg, oral contraceptives, vinyl chloride, with calcifications. asbestos, alcohol, thorotrast, liver trauma, hepatitis virus, alcohol, and chronic liver disease ) [8, 11–17]. Recent studies gave an insight of the genetic basis of EHE. except from the presence of high anti-HAV IgG antibodies. In 2001, Mendlick et al. [18] rfi st revealed an identical chro- Furthermore, all blood tests for primary liver disease were mosomal translocation t(1;3)(p36.3;q25) in two EHE cases. also negative. Since then, many studies have confirmed that this specific MRI of the abdomen took place three months aeft r translocation is unique for EHE among the other epithe- the initial evaluation, which revealed an increase in the lioid vascular tumors (epithelioid hemangiomas, epithelioid maximum diameter of the largest liver lesion, from 3.7 cm to angiosarcomas) [19–21]. The resulting rearrangement pro- 4.1 cm. eTh rest of the lesions were without any alterations, duces a fusion transcript, in which exon 4 of WWTR1 is in respect to their size. Notably, all lesions in T1-weighted fused in frame with either exons 8 or 9 of CAMTA1. Both of images showed hypointense appearance (Figure 2(a))incon- these genes are known to play important roles in oncogenesis trast to the T2 hyperintense (Figure 2(b)). After the intra- [22–26]. The mechanism by which the fused transcript drives venous administration of gadolinium contrast, all lesions the oncogenesis is unknown, but, probing for translocation presented a peripheral ring enhancement in T1-weighted t(1;3)(p36.3;q25) through u fl orescence in situ hybridization, images (Figure 2(c)). can serve as a specific diagnostic test of EHE. Due to the size augmentation of the largest liver lesion, The clinical manifestation of HEHE is heterogeneous and a second liver biopsy was performed, which revealed a well- varies from asymptomatic to the presence of portal hyperten- differentiated hepatocellular carcinoma (HCC). sion or hepatic failure [11]. About 25% of the patients have The presence of normal liver function and normal tumor no clinical symptoms when the tumor is first discovered inci- markersaswellasthe absenceofchronic liverdisease or any dentally by imaging studies. Among symptomatic patients, other HCC predisposing factors drove us to the repetition of the most common clinical manifestations are nonspecific, the CT-guided liver biopsy for a third time. Once again the including right upper quadrant pain, hepatomegaly, and biopsy was performed from the largest liver lesion, presented weight loss [11]. Nonspecific symptoms and the lack of expe- on the right lobe. In contrast to the previous two biopsies, rience of surgeons, radiologists, and histopathologists, due to the specimen was analyzed at a more experienced, in liver the rarity of HEHE, make the diagnosis of this entity very tumors, histopathology department. challenging. For these reasons approximately 60% to 80% of The histopathology report revealed medium- and large- patients with HEH initially are misdiagnosed [13, 27, 28]. sized pleiomorphic cells that were epithelioid in appearance Laboratory parameters are nondiagnostic. 15% of patients and that spread within sinusoids and small veins. eTh se cells do not show any abnormality on blood tests. For the rest 85% stained positive for factor VIII-related antigen as well as the of patients, the most common abnormalities are increased endothelial markers CD31 and CD34 (markers for vascular alkaline phosphatase (68.6%), g-glutamyl transpeptidase endothelial differentiation). eTh overall immunohistochem- (45.1%), aspartate aminotransferase (28.6%), alanine amino- ical n fi dings supported the diagnosis of hepatic epitheliod transferase (23%), and bilirubin (19.9%) [11]. Normal serum hemangioendothelioma. alpha-fetoprotein, carcinoembryonic antigen, and cancer Basedonthe aboveand thediagnosis achieved,the antigen 19–9 are typical lab values of patients with HEHE. eTh patient was enlisted and waiting for a liver transplantation. only potential role of tumor markers is the excluding of other primary and secondary liver tumors with the limitations of 2. Discussion their sensitivity and specificity. Regarding the imaging studies, the disease can be sepa- Epithelioid hemangioendothelioma (EHE) was rst fi described in 1982 by Weiss and Enzinger [1] and since ratedintwo subtypes.Thenodular subtypeispresent in early Case Reports in Oncological Medicine 3 (a) (b) (c) Figure 2: (a) T1-weighted MRI abdomen images showing hypointense lesions. (b) T2-weighted images showing a hyperintense lesion in the right liver lobe. (c) Arrow shows peripheral ring enhancement aeft r intravenous administration of gadolinium. stages and is characterized by the imaging of multifocal nod- is immunoreactive to D2-40 antibody, is a promising new ules. With time, these nodules grow and eventually coalesce, marker in identifying epithelioid hemangioendothelioma. forming large confluent masses preferentially involving the Although this transmembrane protein is detected in some peripheral liver, that is, the diffuse subtype [ 29]. extrahepatic cancers, it is not expressed in the vascular There exists a great heterogeneity regarding imaging tumors of the liver except the HEHE [36]. features of HEHE. eTh liver lesions are typically hypoechoic In our case, because of the lack of experience of our on US [30, 31], with low density on CT, and are usually histopathology department regarding HEHE, we had missed hypointense on T1-weighted images and hyperintense on diagnosisinthe rfi st twocorebiopsiesbecause thepossibility T2-weighted images [11, 32, 33]. Exceptions from the above of endothelial differentiation was not checked with the appro- findings are very frequent. “Capsular retraction sign” (the priate immunohistochemical stains (detection of expression retraction of the adjacent liver capsule, likely caused by of CD31, CD34, and factor VIII-related antigen). Regarding lesion-related fibrosis [ 29]) in correlation with the “halo” sign the rfi st core biopsy, the diagnosis was massive hepatic aer ft intravenous administration of contrast medium (i.e., necrosis,which canbeattributedtothe centralnecrosisofthe the hypointense center and periphery with an intermingled lesion. In the second core biopsy, the results showed evidence hyperintense layer in between) have been proposed as helpful of HCC. in an attempt to improve the diagnostic accuracy of this rare eTh clinical course of epithelioid hemangioendothelioma hepatic tumor [34]. is highly variable with reports for patients succumb within In our case, imaging features included multiple bilobar months aer ft diagnosis in contrast with reports for very hypodense lesions, some of them with calcifications that milder course such as a report for a patient who was alive 27 demonstrated enhancement after the injection of a contrast years after diagnosis without treatment, and another who had medium. es Th e ndin fi gs were in favor with the diagnosis of completed spontaneous regression [13, 37]. liver metastases. For this reason we subjected our patient to The need for aggressive treatment of HEHE was docu- an extended evaluation including colonoscopy, gastroscopy, mented in a review, which analyzed the survival rates of 434 evaluation for thyroid cancer liver metastases, because of patients in relation to the given treatment. In this paper, the previous medical history of papillary thyroid cancer, blood 5-year survival rates of liver transplantation, local or systemic test for tumor markers, and magnetic resonance imaging chemo- and radiotherapy, and no treatment were 55, 30, and (MRI) of the chest, abdomen, and pelvis, in an eo ff rt to find 0%, respectively [11]. the possible primary tumor. Although local resection is not excluded from the ther- Den fi itive diagnosis of epithelioid hemangioendothe- apeutic algorithm, it is only feasible in a small portion of lioma requires histopathologic examination. Histologically, patients because the vast majority (81%) of patients have HEHE appears as nests or cords of epithelioid endothelial multifocal lesions at the time of diagnosis [11]. The efficiency cells spreading within sinusoids. Another classical histologi- of liver transplantation as the treatment of choice for HEHE cal feature of these tumors is the presence of intracellular vas- has been documented in two big studies, one from The United cularluminathatsometimes containred blood cells[35]. The States [38]and onefromEurope[39, 40]. These studies have diagnosis mostly is confirmed by immunohistochemical evi- showed patient survival rates 5 years aer ft liver transplanta- dence of endothelial differentiation. Several well-established tion, 64% and 83%, respectively. An unexpected ndin fi g was endothelial cell markers, such as CD31 (platelet endothelial that disease-free survival was not significantly influenced by cell adhesion molecular 1), CD34 (human hematopoietic lymph node status, extrahepatic disease localization, or even progenitor cell antigen), and factor VIII-related antigen, vascular invasion. are used to confirm epithelioid hemangioendothelioma [ 13]. Other treatment options include chemotherapy, radio- Podoplanin, a small mucin-like transmembrane protein that therapy, hormone therapy, thermoablation, and TACE. 4 Case Reports in Oncological Medicine The experience with these treatments is limited; therefore, the [10] C. D. Fletcher, K. K. Unni, and F. Mertens, “Other intermediate vascular neoplasm,” in WHO Classification of Tumours. Pathol- signicfi anceofthemisdicffi ult to assess. ogy & Genetics. Tumours of Soft Tissue and Bone ,p.173,IARC Press, Lyon, France, 2002. 3. Conclusions [11] A. Mehrabi, A. Kashfi, H. Fonouni et al., “Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive Positive imaging ndin fi gs in addition to certain features, such review of the literature with emphasis on the surgical therapy,” as occurrence in younger adults, the presence of numer- Cancer,vol.107,no. 9, pp.2108–2121,2006. ous intrahepatic tumors in patients with a good clinical [12] J. M. Lauffer, A. Zimmermann, L. Kr ahen ¨ bu¨hl et al., “Epithe- condition, slow course of the disease, absence of chronic lioid haemangioendothelioma of the liver. A rare hepatic liver disease, normal tumor markers, and normal or mild tumor,” Cancer, vol. 78, pp. 2318–2327, 1996. disturbed laboratory parameters, are suggestive for HEHE. [13] H. R. Makhlouf, K. G. Ishak, and Z. D. Goodman, “Epithelioid It is mandatory, for these patients, the histopathologist to be hemangioendothelioma of the liver: a clinicopathologic study of 137 cases,” Cancer,vol.85, pp.562–582,1999. experienced in this entity because misdiagnosis, which is not arareevent [11], will drive to a non appropriate treatment [14] K. G. Ishak, Z. D. Goodman, and J. T. Stocker, “Epithelioid hae- mangioendothelioma,” in Tumors of the Liver and Intrahepatic with impact to thesurvivalofthe patient. In ourcaseifwe Bile Ducts, pp. 282–293, Armed Forces Institute of Pathology, had adopted the report of the second core biopsy, HCC, the Washington, DC, USA, 1999. tumor would be classified as unrespectable, the patient would [15] W. Rhomberg, F. Boehler, H. Eiter, H. Fritzsche, and G. 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Hepatic Epithelioid Hemangioendothelioma and the Danger of Misdiagnosis: Report of a Case

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Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2013, Article ID 243939, 5 pages http://dx.doi.org/10.1155/2013/243939 Case Report Hepatic Epithelioid Hemangioendothelioma and the Danger of Misdiagnosis: Report of a Case 1 1 2 1 Kyriakos Neofytou, Andreas Chrysochos, Nikolas Charalambous, Menelaos Dietis, 1 1 1 Christos Petridis, Charalampos Andreou, and Athanasios Petrou Department of Surgery, NicosiaGovernmentHospital, PalaiosDromosLeofk sias-Lemesou, No.215,2029Strovolos,Nicosia,Cyprus Department of Radiology, Nicosia Government Hospital, Palaios Dromos Leosia fk s-Lemesou, No. 215, 2029 Strovolos, Nicosia, Cyprus Correspondence should be addressed to Kyriakos Neofytou; kneophy2@gmail.com Received 15 January 2013; Accepted 1 February 2013 Academic Editors: J. M. Buchanich, R. Palmirotta, and M. Romkes Copyright © 2013 Kyriakos Neofytou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Malignant hepatic epithelioid hemangioendothelioma (HEHE) is a rare malignant tumor of vascular origin. Nonspecific symptoms and the absence of experience of surgeons, radiologists, and histopathologists due to the rarity of HEHE make the diagnosis of this entity very challenging. Misdiagnosis is not a rare event, and the consequences of such an event are catastrophic. We report a case of a patient suffering from HEHE in which the initial diagnosis was hepatocellular carcinoma (HCC). eTh presence of normal laboratory values, liver function tests, tumor markers along with the absence of a chronic liver disease, or any other predisposing factors for HCC, was in contrast with the diagnosis of HCC. Clinical suspicion drove us to the repetition of a liver biopsy and the reevaluation of the sample by a more experience histopathology department in liver tumors. eTh last biopsy confirmed the diagnosis of HEHE, and the patient escaped any unnecessary treatment for a nonexisting HCC. 1. Case Presentation hypodense lesions were seen with the largest of which in the right liver lobe, with a maximum diameter of 3.7 cm A forty-nine-year old female patient presented with a right (Figure 1). Basedonthe above, thehypothesisofsecondary upper quadrant pain. Based on her medical history, the liver metastasis was proposed. patient underwent thyroidectomy 6 months before because In the following days, both colonoscopy as well as of a papillary thyroid cancer that was not invading the gastroscopy took place with no pathological findings. Tumor thyroid capsule (TNM staging PT1, PNX, PMX Anatomic markers including cancer embryonic antigen (CEA), alpha stage/Prognostic groups 45 years, and older Stage 1). fetoprotein (AFP), and carbohydrate antigen (CA) 19–9 were All of the patient laboratory tests were within nor- all within normal limits. yTh roglobulin was measured at mal limits including alkaline phosphatase (41 U/L), g- 0.2 ng/mL. A follow-up neck ultrasound did not reveal any glutamyl transpeptidase (14 U/L), aspartate aminotransferase mass or enlarge lymph nodes, and I whole body scan did (16 U/L), alanine aminotransferase (12 U/L), and bilirubin not demonstrate any thyroid remnant nor any metastasis. levels (0.44 mg/dL). As part of thepatient diagnostic evaluation,inanattempt An abdominal ultrasound was scheduled which showed to nfi dthe possible primarytumor,awholebodymagnetic several hypoechoic solid nodules, regarding both liver lobes, resonance imaging (MRI) was performed. eTh results showed with an irregular echogenic outline and a few of which with no evidence of an extrahepatic disease. multiple calcifications. Immediately aeft rwards, an abdomi- Percutaneous liver biopsy from the largest liver lesion, nal computed tomography was performed which conrfi med guided under computed tomography, showed massive hepatic necrosis. The patient hepatitis serology was negative these lesions and the related calcifications. Specifically, 2 Case Reports in Oncological Medicine 1982, EHE has been described in many organs, including spleen, bone, brain, meninges, breast, heart, head and neck, soft tissue, stomach, and lymph nodes [ 1–7]. Hepatic epithelioid hemangioendothelioma (HEHE) was reported first in 1984 by Ishak et al. in a series of 32 patients [ 8]. The HEHE is a vascular tumor which originates from endothelial cells and is a rare malignancy with an incidence of<0.1 per 100,000 population [9]. Thistumor hashistologicappearance and behavior between hemangioma and hemangiosarcoma and is classified as a malignant neoplasm by the World Health Organization [10]. HEHE is known to occur in individuals of all ages but is rare in children less than 15 years old. It appears more oen ft in women with a male-to-female ratio, 2 : 3 during the 4th decade of their liver [11]. Until today no definitive etiological factor has been Figure 1: Abdominal CT scan, with intravenous contrast showing clearly identified for HEHE although several risk factors several hypodense lesions on both liver lobes. Arrow shows lesion have been proposed (eg, oral contraceptives, vinyl chloride, with calcifications. asbestos, alcohol, thorotrast, liver trauma, hepatitis virus, alcohol, and chronic liver disease ) [8, 11–17]. Recent studies gave an insight of the genetic basis of EHE. except from the presence of high anti-HAV IgG antibodies. In 2001, Mendlick et al. [18] rfi st revealed an identical chro- Furthermore, all blood tests for primary liver disease were mosomal translocation t(1;3)(p36.3;q25) in two EHE cases. also negative. Since then, many studies have confirmed that this specific MRI of the abdomen took place three months aeft r translocation is unique for EHE among the other epithe- the initial evaluation, which revealed an increase in the lioid vascular tumors (epithelioid hemangiomas, epithelioid maximum diameter of the largest liver lesion, from 3.7 cm to angiosarcomas) [19–21]. The resulting rearrangement pro- 4.1 cm. eTh rest of the lesions were without any alterations, duces a fusion transcript, in which exon 4 of WWTR1 is in respect to their size. Notably, all lesions in T1-weighted fused in frame with either exons 8 or 9 of CAMTA1. Both of images showed hypointense appearance (Figure 2(a))incon- these genes are known to play important roles in oncogenesis trast to the T2 hyperintense (Figure 2(b)). After the intra- [22–26]. The mechanism by which the fused transcript drives venous administration of gadolinium contrast, all lesions the oncogenesis is unknown, but, probing for translocation presented a peripheral ring enhancement in T1-weighted t(1;3)(p36.3;q25) through u fl orescence in situ hybridization, images (Figure 2(c)). can serve as a specific diagnostic test of EHE. Due to the size augmentation of the largest liver lesion, The clinical manifestation of HEHE is heterogeneous and a second liver biopsy was performed, which revealed a well- varies from asymptomatic to the presence of portal hyperten- differentiated hepatocellular carcinoma (HCC). sion or hepatic failure [11]. About 25% of the patients have The presence of normal liver function and normal tumor no clinical symptoms when the tumor is first discovered inci- markersaswellasthe absenceofchronic liverdisease or any dentally by imaging studies. Among symptomatic patients, other HCC predisposing factors drove us to the repetition of the most common clinical manifestations are nonspecific, the CT-guided liver biopsy for a third time. Once again the including right upper quadrant pain, hepatomegaly, and biopsy was performed from the largest liver lesion, presented weight loss [11]. Nonspecific symptoms and the lack of expe- on the right lobe. In contrast to the previous two biopsies, rience of surgeons, radiologists, and histopathologists, due to the specimen was analyzed at a more experienced, in liver the rarity of HEHE, make the diagnosis of this entity very tumors, histopathology department. challenging. For these reasons approximately 60% to 80% of The histopathology report revealed medium- and large- patients with HEH initially are misdiagnosed [13, 27, 28]. sized pleiomorphic cells that were epithelioid in appearance Laboratory parameters are nondiagnostic. 15% of patients and that spread within sinusoids and small veins. eTh se cells do not show any abnormality on blood tests. For the rest 85% stained positive for factor VIII-related antigen as well as the of patients, the most common abnormalities are increased endothelial markers CD31 and CD34 (markers for vascular alkaline phosphatase (68.6%), g-glutamyl transpeptidase endothelial differentiation). eTh overall immunohistochem- (45.1%), aspartate aminotransferase (28.6%), alanine amino- ical n fi dings supported the diagnosis of hepatic epitheliod transferase (23%), and bilirubin (19.9%) [11]. Normal serum hemangioendothelioma. alpha-fetoprotein, carcinoembryonic antigen, and cancer Basedonthe aboveand thediagnosis achieved,the antigen 19–9 are typical lab values of patients with HEHE. eTh patient was enlisted and waiting for a liver transplantation. only potential role of tumor markers is the excluding of other primary and secondary liver tumors with the limitations of 2. Discussion their sensitivity and specificity. Regarding the imaging studies, the disease can be sepa- Epithelioid hemangioendothelioma (EHE) was rst fi described in 1982 by Weiss and Enzinger [1] and since ratedintwo subtypes.Thenodular subtypeispresent in early Case Reports in Oncological Medicine 3 (a) (b) (c) Figure 2: (a) T1-weighted MRI abdomen images showing hypointense lesions. (b) T2-weighted images showing a hyperintense lesion in the right liver lobe. (c) Arrow shows peripheral ring enhancement aeft r intravenous administration of gadolinium. stages and is characterized by the imaging of multifocal nod- is immunoreactive to D2-40 antibody, is a promising new ules. With time, these nodules grow and eventually coalesce, marker in identifying epithelioid hemangioendothelioma. forming large confluent masses preferentially involving the Although this transmembrane protein is detected in some peripheral liver, that is, the diffuse subtype [ 29]. extrahepatic cancers, it is not expressed in the vascular There exists a great heterogeneity regarding imaging tumors of the liver except the HEHE [36]. features of HEHE. eTh liver lesions are typically hypoechoic In our case, because of the lack of experience of our on US [30, 31], with low density on CT, and are usually histopathology department regarding HEHE, we had missed hypointense on T1-weighted images and hyperintense on diagnosisinthe rfi st twocorebiopsiesbecause thepossibility T2-weighted images [11, 32, 33]. Exceptions from the above of endothelial differentiation was not checked with the appro- findings are very frequent. “Capsular retraction sign” (the priate immunohistochemical stains (detection of expression retraction of the adjacent liver capsule, likely caused by of CD31, CD34, and factor VIII-related antigen). Regarding lesion-related fibrosis [ 29]) in correlation with the “halo” sign the rfi st core biopsy, the diagnosis was massive hepatic aer ft intravenous administration of contrast medium (i.e., necrosis,which canbeattributedtothe centralnecrosisofthe the hypointense center and periphery with an intermingled lesion. In the second core biopsy, the results showed evidence hyperintense layer in between) have been proposed as helpful of HCC. in an attempt to improve the diagnostic accuracy of this rare eTh clinical course of epithelioid hemangioendothelioma hepatic tumor [34]. is highly variable with reports for patients succumb within In our case, imaging features included multiple bilobar months aer ft diagnosis in contrast with reports for very hypodense lesions, some of them with calcifications that milder course such as a report for a patient who was alive 27 demonstrated enhancement after the injection of a contrast years after diagnosis without treatment, and another who had medium. es Th e ndin fi gs were in favor with the diagnosis of completed spontaneous regression [13, 37]. liver metastases. For this reason we subjected our patient to The need for aggressive treatment of HEHE was docu- an extended evaluation including colonoscopy, gastroscopy, mented in a review, which analyzed the survival rates of 434 evaluation for thyroid cancer liver metastases, because of patients in relation to the given treatment. In this paper, the previous medical history of papillary thyroid cancer, blood 5-year survival rates of liver transplantation, local or systemic test for tumor markers, and magnetic resonance imaging chemo- and radiotherapy, and no treatment were 55, 30, and (MRI) of the chest, abdomen, and pelvis, in an eo ff rt to find 0%, respectively [11]. the possible primary tumor. Although local resection is not excluded from the ther- Den fi itive diagnosis of epithelioid hemangioendothe- apeutic algorithm, it is only feasible in a small portion of lioma requires histopathologic examination. Histologically, patients because the vast majority (81%) of patients have HEHE appears as nests or cords of epithelioid endothelial multifocal lesions at the time of diagnosis [11]. The efficiency cells spreading within sinusoids. Another classical histologi- of liver transplantation as the treatment of choice for HEHE cal feature of these tumors is the presence of intracellular vas- has been documented in two big studies, one from The United cularluminathatsometimes containred blood cells[35]. The States [38]and onefromEurope[39, 40]. These studies have diagnosis mostly is confirmed by immunohistochemical evi- showed patient survival rates 5 years aer ft liver transplanta- dence of endothelial differentiation. Several well-established tion, 64% and 83%, respectively. An unexpected ndin fi g was endothelial cell markers, such as CD31 (platelet endothelial that disease-free survival was not significantly influenced by cell adhesion molecular 1), CD34 (human hematopoietic lymph node status, extrahepatic disease localization, or even progenitor cell antigen), and factor VIII-related antigen, vascular invasion. are used to confirm epithelioid hemangioendothelioma [ 13]. Other treatment options include chemotherapy, radio- Podoplanin, a small mucin-like transmembrane protein that therapy, hormone therapy, thermoablation, and TACE. 4 Case Reports in Oncological Medicine The experience with these treatments is limited; therefore, the [10] C. D. Fletcher, K. K. Unni, and F. Mertens, “Other intermediate vascular neoplasm,” in WHO Classification of Tumours. Pathol- signicfi anceofthemisdicffi ult to assess. ogy & Genetics. Tumours of Soft Tissue and Bone ,p.173,IARC Press, Lyon, France, 2002. 3. Conclusions [11] A. Mehrabi, A. Kashfi, H. 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