J C O Chemoresponsive Liver Hemangioma in a

VOLUME 29 䡠 NUMBER 35 䡠 DECEMBER 10 2011
JOURNAL OF CLINICAL ONCOLOGY
Chemoresponsive Liver Hemangioma in a
Patient With a Metastatic Germ Cell Tumor
Introduction
Testicular germ cell tumors are the most common solid organ
malignancy in young adult men. Approximately 25% of patients with
disseminated cancer present with symptoms of regional or disseminated spread of disease. The presence of nonpulmonary visceral metastasis is an independent factor that places such patients into the
higher risk groups with a predicted 5-year survival of 41% for nonseminoma and 67% for seminoma.1 Management of patients with
nonpulmonary visceral metastases from nonseminoma includes fullschedule chemotherapy with bleomycin, etoposide, and cisplatin
(BEP) for four courses and resection of any residual radiographic
abnormality if technically feasible.2
Hepatic hemangiomas are the most common benign tumors of
the liver.3 These tumors are generally asymptomatic, although they
may present as a mass that is associated with vague abdominal pain,
abdominal compartment syndrome, heart failure, hepatic failure, and
even death.4 Although observation is recommended for small, asymptomatic hemangiomas, symptomatic and/or large hemangiomas (⬎ 4
cm) may require surgical intervention.3 Liver metastases and hemangiomas may be distinguished with imaging modalities, including magnetic resonance imaging (MRI), on the basis of lesion morphology and
T2 measurements. However, overlap between these entities may occur, particularly when metastases are hypervascular.5
Case Report
A healthy 39-year-old man presented with left testicular pain and
swelling. The physical examination and ultrasound were suspicious
for malignancy. Alpha-fetoprotein and human chorionic gonadotropin levels were 20.4 ng/mL and 2.1 mIU/mL, respectively. An orchiectomy was performed and pathology revealed a 3.5-cm mixed germ
cell tumor (80% embryonal cell carcinoma and 20% seminoma) without lymphovascular invasion. An abdominal scan showed bulky paraaortic adenopathy and a right hepatic lesion with low intensity and
peripheral enhancement (Figs 1A and 1B). After the orchiectomy,
tumor markers remained elevated and the patient received primary
chemotherapy. Although hepatic hemangioma was strongly suspected, the initial plan was to consider the patient as having International Germ Cell Consensus Classification good-risk nonseminoma,
and restaging was planned during the third cycle of therapy to ensure
that the paraortic mass was decreasing in size and that the presumed
hemangioma remained unchanged. With BEP, the mildly elevated
alpha-fetoprotein and human chorionic gonadotropin levels normalized rapidly, as expected. However, follow-up imaging studies that
were performed 1 month after chemotherapy showed a decreased but
still present retroperitoneal mass as well as a substantially shrunken
liver lesion (Fig 2).
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© 2011 by American Society of Clinical Oncology
D I A G N O S I S
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O N C O L O G Y
A
B
Fig 1.
With these unexpected findings, the decision was made to
proceed with postchemotherapy retroperitoneal lymph node dissection along with intraoperative evaluation of the liver abnormality. If the shrinking liver lesion was proven to be related to the
metastatic germ cell tumor, additional postoperative chemotherapy would be considered.
A right nerve–sparing bilateral template retroperitoneal lymph
node dissection was performed with an intraoperative core liver biopsy. Retroperitoneal pathology was necrosis/fibrosis and a liver biopsy showed masses of blood vessels that were atypical and/or
irregular in arrangement and size, findings that favored hepatic hemangioma (Fig 3).
Journal of Clinical Oncology, Vol 29, No 35 (December 10), 2011: pp e842-e844
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Diagnosis in Oncology
Fig 2.
Discussion
This patient case presented unique challenges in terms of
initial diagnostics and ongoing clinical decision making. From a
clinical viewpoint, the chance that the hepatic lesion represented
metastatic dissemination to the liver was low. There was no evidence of other distant dissemination, and the level of tumor
marker elevation was also low. However, if this liver lesion did
represent metastatic disease, there would have been a substantially
different prognosis and treatment plan. Thus, a reassessment was
planned after three cycles of therapy to allow for adjustment of the
treatment plan if necessary. Surprisingly, the liver lesion decreased
substantially; this raised the possibility that this unusual lesion did
indeed represent atypical metastases.
Hepatic hemangioma is the most common benign liver tumor
and the second most common cause of liver mass after metastases,
with an incidence of 0.4% to 7.3% in autopsies and 1.7% on routine
abdominal ultrasound. It is confirmed in more than 90% of patients
by a computed tomography (CT) scan or MRI.3 Histologically, hemangiomas are composed of large endothelium-lined vascular spaces
that are separated by fibrous septa of varying thicknesses. The pathogenesis of cavernous hemangioma remains unclear, but vascular endothelial growth factor (VEGF) is recognized as an essential regulator
of normal and abnormal angiogenesis.6 Liver metastases may mimic
the appearance of hemangiomas on a variety of commonly employed
imaging techniques. On CT, hemangiomas are usually hypoattenuating compared with the adjacent parenchyma. However, they may be
iso- or hyperattenuating, especially in patients with steatosis.7 The
feature of globular enhancement has been found to be 88% sensitive
and 84% to 100% specific for differentiating hemangiomas from
hypervascular metastases.8 On MRI, similar signal intensity on T2weighted images has been described for metastases and hemangiomas.5 Although there are some pathognomonic features for hepatic
hemangiomas on imaging studies, Giuliante et al9 showed that the
diagnosis of hepatic hemangioma remained dubious in nearly 10% of
patients using three different imaging modalities (including ultrasound, CT, MRI, scintigraphy, and angiography).
Different therapeutic approaches have been proposed for liver
hemangiomas, including observation, embolization, hepatic artery
ligation, and surgical resection.10 Bevacizumab is a recombinant
monoclonal antibody against VEGF and has been shown to be effective in the treatment of cavernous hemangioma in case reports.6 Neonatal hemangiomatosis that includes the liver has been treated
successfully with cyclophosphamide.11 Also, parotid hemangiomas
during infancy have been successfully treated with low-dose bleomycin and dexamethasone.12 To the best of our knowledge, there are no
reports of a hepatic hemangioma that responded to systemic chemotherapy in a patient with testis cancer. Hashimoto et al13 described a
histologically confirmed hepatic hemangioma in a patient with an
ovarian yolk sac tumor that decreased in size after BEP chemotherapy.
The authors suggested that development of the hemangioma might be
a result of estrogen.13 Surgery and chemotherapy led to suppressed
ovarian function, which resulted in a diminished estrogen level and
secondary decrease in hemangioma size. Although there are some
conflicting data in the literature with respect to the role of estrogen in
the pathogenesis of hepatic hemangioma,3,14 estrogen might promote
angiogenesis activity and VEGF expression in vascular smooth muscle
cells.15 Hormonal levels were not recorded for our patient. Another
hypothesis is that the decreased size of the hemangioma in our patient
could have been a result of the chemotherapy, perhaps through antiangiogenic mechanisms.16
In conclusion, there is no definitive consensus with respect to an
approach to differentiate hepatic hemangioma from metastasis in a
patient with malignancy. Our patient case demonstrates that in addition to a lack of definitive imaging criteria, a chemotherapy-induced
response of hemangioma can mimic a chemotherapy response of
metastatic disease, making these two entities difficult to distinguish on
clinical grounds.
Hooman Djaladat
Norris Comprehensive Cancer Center, Institute of Urology, University of
Southern California, Los Angeles, CA
Craig R. Nichols
Fig 3.
www.jco.org
British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
Multi-Disciplinary Testicular Cancer Clinic, Virginia Mason Medical Center,
Seattle, WA
© 2011 by American Society of Clinical Oncology
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e843
Djaladat, Nichols, and Daneshmand
Siamak Daneshmand
Norris Comprehensive Cancer Center, Institute of Urology, University of
Southern California, Los Angeles, CA
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
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DOI: 10.1200/JCO.2011.38.1434; published online ahead of print at
www.jco.org on November 7, 2011
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