Testicular germ cell tumors are the most common solid organ malignancy in young adult men. The presence of non-pulmonary visceral
metastasis is an independent factor that places such patients into the higher risk group. Hepatic hemangiomas are the most common
tumors of the liver and are entirely benign. Overlap between these entities may occur, particularly when metastases are hypervascular.
We describe a case of a 27-year-old man with a testicular germ cell tumor and a nodule in the right hepatic lobe suggestive of hemangioma.
After three cycles of chemotherapy, a size reduction in the hepatic nodule was confirmed, and this lesion was removed. Pathology revealed a
fibrosing hemangioma.
In this case report, the authors discuss the possible mechanisms for the hemangioma chemotherapy response

Esteves, D.

Ferreira, J.

Magalhães, M.

Marques, F.

Repositório Científico do Centro Hospitalar do Porto

San Lucas Medical, LLCMetastatic Testicular Germ Cell Tumor or aChemoresponsive Liver Hemangioma?Joa˜o Pedro Ferreira1, Manuel Magalha˜es2, Diane Esteves3, and Franklin Marques2Affiliations: 1Internal Medicine Department, Centro Hospitalar do Porto, Porto, Portugal; 2Oncology Department, Centro Hospitalar do Porto, Porto, Portugal and3Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal(Submission Date: 12 September 2012; Acceptance Date: 12 September 2012; Publication Date: xxxxxxxxxxx)A B S T R A C TTesticular germ cell tumors are the most common solid organ malignancy in young adult men. The presence of non-pulmonary visceralmetastasis is an independent factor that places such patients into the higher risk group. Hepatic hemangiomas are the most commontumors of the liver and are entirely benign. Overlap between these entities may occur, particularly when metastases are hypervascular.We describe a case of a 27-year-old man with a testicular germ cell tumor and a nodule in the right hepatic lobe suggestive of hemangioma.After three cycles of chemotherapy, a size reduction in the hepatic nodule was confirmed, and this lesion was removed. Pathology revealed afibrosing hemangioma.In this case report, the authors discuss the possible mechanisms for the hemangioma chemotherapy response.Keywords: germ cell tumor, chemoresponsive, liver hemangiomaINTRODUCTIONTesticular germ cell tumors are the most common solidorgan malignancy in young adult men. Of testicular tumors,40% are seminomas and 60% non-seminomas.1 Non-seminoma is the more clinically aggressive tumor. Thepresence of non-pulmonary visceral metastasis is an inde-pendent factor that places such patients into the higher riskgroup.2 Management of patients with non-pulmonary visceralmetastasis from non-seminoma includes full schedule che-motherapy with bleomycin, etoposide, and cisplatin (BEP) forfour cycles (standard), given as 5-day schedule, and resectionof any residual radiographic abnormality if technicallyfeasible.1Hepatic hemangiomas are the most common tumors of theliver and are entirely benign.3 Treatment is unnecessaryunless their expansion causes symptoms. Liver metastasesand hemangiomas may be distinguished with imagingmodalities, including magnetic resonance imaging (MRI),on the basis of lesion morphology and T2 measurements.4However, overlap between these entities may occur, particu-larly when metastases are hypervascular.5CASE REPORTA 27-year-old man detected a mass in testicular auto-examination. Ultrasound confirmed testicular mass wassuspicious for malignancy. Alpha-fetoprotein (AFP) andhuman chorionic gonadotropin (HCG) levels were 33 ng/mLand 16 mIU/mL, respectively. Thoracic, abdominal, and pelviccomputed tomography (CT) showed two micronodules(5 mm) in the anterior segment of the left lung lobe and a27-mm nodule in the right hepatic lobe suggestive ofhemangioma, hypothesis that was corroborated by MRI(Figure 1).The patient was submitted to radical orchiectomy. Pathologyrevealed a 3-cm germ cell tumor with teratocarcinoma andembrionary carcinoma components (Figure 2). After orch-iectomy, an elevation of tumor markers was registered (AFP:428.2 mg/dL, HCG: 46.7 U/L), and the patient received primarychemotherapy. Because hepatic lesion was assumed a heman-gioma, the tumor was classified as IS, and three cycles of BEPwere given. With chemotherapy, the tumor markers normal-ized, as expected. The reevaluation CT scan showed a sizereduction of the hepatic nodule (from 27 to 18 mm)(Figure 3). With these unexpected findings, the multidisci-plinary group decision was to perform hepatic lesion excision.Pathology revealed a fibrosing hemangioma (Figure 4).DISCUSSIONThis clinical case presented a diagnosis and decision-making challenge. Even though the hepatic lesion had alow pretest probability of being malignant, if this lesion didrepresent metastatic disease, the treatment plan and prog-nosis would be different. The shrinking of the hepatic lesionraised the possibility for the lesion to be metastatic.Hepatic hemangioma is the most common liver tumor.Hemangiomas are often solitary, but multiple lesions may bepresent in both the right and left lobes of the liver in up to40% of the patients.6 The point prevalence of hepatichemangiomas may reach 20%.7 This observation is confirmedby the increasing recognition of hemangiomas in asympto-matic patients undergoing radiologic imaging tests of theabdomen for other reasons. However, hepatic hemangiomacan be confirmed in more than 90% of patients by a CT scanEUROPEAN JOURNAL OF CLINICAL & MEDICAL ONCOLOGY CASE REPORTwww.slm-oncology.com 1 EJCMO 2012; 000:(000). Month 2012San Lucas Medical, LLCor an MRI.8 Other studies showed that the diagnosis ofhepatic hemangioma remained dubious in nearly 10% of thepatients using three different imaging modalities (includingultrasound, CT, MRI, scintigraphy, and angiography).9 Mi-croscopically, the tumor is composed of cavernous vascularspaces of varying sizes lined by a single layer of flatendothelium and filled with blood. The vascular compart-ments are separated by thin fibrous septae and may containthrombi.10 The etiology of hepatic hemangiomas isincompletely understood. They are considered to be vascularmalformations of congenital origin that enlarge by ectasiarather than by hyperplasia or hypertrophy. Hormonal influ-ence over tumor growth is suggested by enlargement duringpregnancy and estrogen and progesterone therapy andregression after withdrawal of therapy.8,1113 Vascular en-dothelial growth factor (VEGF) is recognized as an essentialregulator of normal and abnormal blood vessel growth.14 It ispostulated that higher expression of VEGF and angiopoietinsleads to increased angiogenic activity in cavernous heman-gioma endothelial cells.15 Stromal cells cultured from surgi-cally removed life-threatening hemangiomas released anendothelial cell mitogen in vitro that was indistinguishablefrom VEGF, and systemic injections of neutralizing anti-VEGF antibodies inhibited the angiogenic response in nudemice grafted with neonatal hemangioma cells.16 Bevacizumabis a recombinant monoclonal antibody against VEGF and hasbeen shown to be effective in the hemangioma size reduc-tion.15 Another case report, very similar to ours, reported apatient with testis cancer with a hepatic hemangioma thatresponded partially to systemic chemotherapy.17 Our hypoth-esis is that the decreased size of the hemangioma in ourpatient could have been a result of chemotherapy, perhapsthrough antiangiogenic mechanisms.18CONCLUSIONOur case report shows that, in the absence of definitiveimaging criteria, a chemotherapy-induced response of he-mangioma can mimic a chemotherapy response of metastaticFigure 1. Hepatic MRI: hepatic lesion with hypersinal in T2 ponderation,corresponding to a provable fibrosing hemangioma.Figure 2. Germ cell tumor: teratoma (*) and embrionary carcinomacomponents (#).Figure 4. Fibrosing hepatic hemangioma.Figure 3. Downsizing of hepatic lesion during chemotherapy, from 27 mm (left image) to 18 mm (right image).2European Journal of Clinical & Medical OncologyEJCMO 2012; 000:(000). Month 2012 2 www.slm-oncology.comSan Lucas Medical, LLCdisease. Differentiating these two entities solely on clinicalgrounds can become a huge challenge, if not impossible.Disclosure: The authors declare no conflict of interest.REFERENCES1. Schmoll HJ, Jordan K, Huddart R. et al. Testicular non-seminoma: ESMOClinical Practice Guidelines for diagnosis, treatment and follow-up. AnnOncol. 2010; 21(Suppl. 5):v147v154.2. Copson E, McKendrick J, Hennesey N. Liver metastases in germ cellcancer: defining a role for surgery after chemotherapy. BJU Int.2004;94:552558.3. John TG, Greig JD, Crosbie JL, Miles WF, Garden OJ. Superior staging ofliver tumors with laparoscopy and laparoscopic ultrasound. Ann Surg.1994;220:711719.4. McFarland EG, Mayo-Smith WW, Saini S, Hahn PF, Goldberg MA, LeeMJ. Hepatic hemangiomas and malignant tumors: improved differentia-tion with heavily T2-weighted conventional spin-echo MR imaging.Radiology. 1994;193:4347.5. Kim T, Federle MP, Baron RL, Peterson MS, Kawamori Y. Discriminationof small hepatic hemangiomas from hypervascular malignant tumorssmaller than 3 cm with three-phase helical CT. Radiology. 2001;219:699706.6. Tait N, Richardson AJ, Muguti G, Little JM. Hepatic cavernoushaemangioma: a 10 year review. Aust N Z J Surg. 1992;62:521524.7. Karhunen PJ. Benign hepatic tumours and tumour like conditions inmen. J Clin Pathol. 1986;39:183188.8. Toshikuni N, Kawaguchi K, Miki H, et al. Focal nodular hyperplasiacoexistent with hemangioma and multiple cysts of the liver. J Gastroenterol.2001;36:206211.9. Conter RL, Longmire WP Jr. Recurrent hepatic hemangiomas. Possibleassociation with estrogen therapy. Ann Surg. 1988;207:115119.10. Giuliante F, Ardito F, Vellone M. Reappraisal of surgical indications andapproach for liver hemangioma: single center experience on 74 patients.Am J Surg. 2010;201:741748.11. Saegusa T, Ito K, Oba N, et al. Enlargement of multiple cavernoushemangioma of the liver in association with pregnancy. Intern Med.1995;34:207211.12. Graham E, Cohen AW, Soulen M, Faye R. Symptomatic liver hemangiomawith intra-tumor hemorrhage treated by angiography and embolizationduring pregnancy. Obstet Gynecol. 1993;81:813816.13. Winkfield B, Vuillemin E, Rousselet MC, Bellec V, Aube C, Cale`s P.[Progression of a hepatic hemangioma under progestins]. GastroenterolClin Biol. 2001;25:108110.14. Homsi J, Daud AI. Spectrum of activity and mechanism of action ofVEGF/PDGF inhibitors. Cancer Control. 2007;14:285294.15. Mahajan D, Miller C, Hirose K. Incidental reduction in the size of liverhemangioma following use of VEGF inhibitor bevacizumab. J Hepatol.2008;49:867870.16. Berard M, Sordello S, Ortega N, Carrier JL, Peyri N, Wassef M. Vascularendothelial growth factor confers a growth advantage in vitro and in vivoto stromal cells cultured from neonatal hemangiomas. Am J Pathol.1997;150:13151326.17. Djaladat H, Nichols CR, Daneshmand S. Chemoresponsive liver heman-gioma in a patient with a metastatic germ cell tumor. J Clin Oncol.2011;29:e842e844.18. Zang Q, Li Y, Chen Y. Gigantic cavernous hemangioma of the liver treatby intra-arterial embolization with pingyangmycin-lipoidol emulsion: amulti-center study. Cardiovasc Intervent Radiol. 2004;27:481485.31Metastatic Testicular Germ Cell Tumorwww.slm-oncology.com 3 EJCMO 2012; 000:(000). Month 2012San Lucas Medical, LLCAuthors QueriesJournal: European Journal of Clinical & Medical OncologyPaper: EJCMO55961Title: Metastatic Testicular Germ Cell Tumor or a Chemoresponsive Liver Hemangioma?Dear AuthorDuring the preparation of your manuscript for publication, the questions listed below have arisen. Please attend to thesematters and return this form with your proof. Many thanks for your assistance.QueryReferenceQuery Remarks1 Please check and confirm whether the given short title is ok for yourmanuscript.2 Please note references have been renumbered to be in order.3 Please verify the disclosure statement.European Journal of Clinical & Medical OncologyEJCMO 2012; 000:(000). Month 2012 4 www.slm-oncology.com

Metastatic Testicular Germ Cell Tumor or a Chemoresponsive Liver Hemangioma?

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Metastatic Testicular Germ Cell Tumor or a Chemoresponsive Liver Hemangioma?

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