Intra-hepatic splenosis as an unexpected cause of a focal liver lesion in a patient with hepatitis C and liver cirrhosis: a case report.

Abstract

Splenosis is the heterotopic autotransplantation of splenic tissue, mostly found after splenic trauma or surgery in the abdominal, pelvic or thoracic cavity. Here we report a patient with a history of splenectomy after polytrauma with chronic hepatitis C and liver cirrhosis presenting with an hepatic mass of unknown origin.
The lesion could not be exactly classified by ultrasound, computed tomography, angiography and biopsy, classical features of malignancy were not fulfilled, and on the other hand a neoplastic process could neither be excluded. After revision of a MRI performed in our centre it appeared that the liver mass contrasted in the same way as the remaining accessory spleens in the left upper quadrant. A selective Tc-99m-labelled heat-denatured autologous red blood cells scintigraphy of the spleen was performed and showed both the accessory spleens in the left upper quadrant and spleen-typical tissue in projection to the left liver lobe and confirmed the diagnosis of splenosis.
Although intrahepatic splenosis represents an extremely rare condition, this diagnosis should always be taken into consideration in patients with history of abdominal trauma with splenic involvement presenting with an indeterminate focal liver lesion. The diagnosis of splenosis may then be reliably confirmed by Tc-99m-DRBC scintigraphy.

Full text

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Case report
Intra-hepatic splenosis as an unexpected cause of a focal liver lesion
in a patient with hepatitis C and liver cirrhosis: a case report
Marianne Menth1†, Karin Herrmann2†, Alexander Haug3, Bijan Raziorrouh1,
Reinhart Zachoval1, Christina-Maria Jung1and Carsten Otto1*
Open Access
Addresses:1Medical Department 2, University of Munich - Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany
2Institute of Clinical Radiology, University of Munich - Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany
3Department of Nuclear Medicine, University of Munich - Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany
Email: MM - Marianne.menth@web.de; KH - Karin.herrmann@med.uni-muenchen.de; AH - Alexander.haug@med.uni-muenchen.de;
BR - Bijan.raziorrouh@med.uni-muenchen.de; RZ - Reinhart.zachoval@med.uni-muenchen.de;
CMJ - Maria-Christina.jung@med.uni-muenchen.de; CO* - Carsten.otto@med.uni-muenchen.de
†Contributed equally to the work
*Corresponding author
Received: 24 February 2009Accepted: 17 June 2009Published: 19 August 2009
Cases Journal 2009, 2:8335doi: 10.4076/1757-1626-2-8335
This article is available from: http://casesjournal.com/casesjournal/article/view/8335
© 2009 Menth et al.; licensee Cases Network Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introduction: Splenosis is the heterotopic autotransplantation of splenic tissue, mostly found after
splenic trauma or surgery in the abdominal, pelvic or thoracic cavity. Here we report a patient with
a history of splenectomy after polytrauma with chronic hepatitis C and liver cirrhosis presenting with
an hepatic mass of unknown origin.
Case presentation: The lesion could not be exactly classified by ultrasound, computed
tomography, angiography and biopsy, classical features of malignancy were not fulfilled, and on the
other hand a neoplastic process could neither be excluded. After revision of a MRI performed in our
centre it appeared that the liver mass contrasted in the same way as the remaining accessory spleens
in the left upper quadrant. A selective Tc-99m-labelled heat-denatured autologous red blood cells
scintigraphy of the spleen was performed and showed both the accessory spleens in the left upper
quadrant and spleen-typical tissue in projection to the left liver lobe and confirmed the diagnosis of
splenosis.
Conclusion: Although intrahepatic splenosis represents an extremely rare condition, this diagnosis
should always be taken into consideration in patients with history of abdominal trauma with splenic
involvement presenting with an indeterminate focal liver lesion. The diagnosis of splenosis may then
be reliably confirmed by Tc-99m-DRBC scintigraphy.
Introduction
Intrahepatic masses occurring in patients with liver
cirrhosisandhepaticviralinfectionshaveahighlikelihood
to be regenerative nodules or HCC. The differential
diagnosis of benign pseudo-lesions may not be obvious
in this context and comparably rare. Diagnostic imaging
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such as ultrasound, liver MRI and transfemoral arterial
angiography play a pivotal role but may not always be
conclusive at first glance. Diagnostic interpretation in the
clinical context is always warranted.
We report a case of intra-hepatic splenosis in a patient
with hepatitis C, liver cirrhosis and a history of severe
abdominal trauma with multi-organ contusion and
splenic rupture followed by splenectomy. The value of
various diagnostic modalities in this rare distinct pathol-
ogy is discussed.
Case presentation
A 43-year-old Caucasian man from Germany with liver
cirrhosis and chronic hepatitis C virus infection was
referred to our tertiary centre presenting with a tumour
in the left liver lobe of indeterminate origin. Infection with
HCV occurred in 1979, following multiple transfusions in
the context of a severe polytrauma with liver rupture,
diaphragmatic rupture, left kidney rupture and splenic
rupture, the latter requiring subsequent splenectomy.
In 2001, a liver biopsy was performed confirming the
presence of liver cirrhosis. The hepatitis C genotype was 1a
according to Simmonds. Antiviral therapy was started
immediately with pegylated interferon and ribavirin but
was not successful due to virus relapse at the end of the
therapy.
In October 2004, a second try of antiviral therapy was
planned. Routine ultrasound of the liver at that time
revealed a polylobulated mass with regular margins in
segment II of the left liver lobe. Subsequent abdominal
MRI confirmed the presence of multiple confluent nodular
lesions in the left liver lobe measuring 2.5 × 7.0 cm. These
lesions showed hypervascularity on contrast-enhanced
liver MRI and malignancy was suspected. The patient
was admitted to our hospital to confirm the diagnosis and
to establish appropriate treatment of suspected HCC.
At admission, the patient did not complain about any
symptoms except for increased fatigue. He did not suffer
from weight loss, fever or nocturnal sweats. The physical
examination was normal. Clinically, the cirrhosis was
graded Child A. Serum aminotransferases were slightly
elevated (GPT 95 U/l, GOT 80 U/l). AFP was normal with
6.4 ng/ml.
MRI was repeated in double contrast technique including
dynamic imaging after intravenous application of standard
Gadolinium-DTPA (0.1 mmol/kg, Magnevist®, Bayer-
ScheringHealthcare,Berlin,Germany)andSPIO-enhanced
imaginginthesameexamination(Resovist®;Bayer-Schering
Healthcare, Berlin, Germany). Besides the signs of subtle
micro-nodular regenerative liver cirrhosis of the entire liver
parenchyma, multiple nodular lesions between 4 and
36 mm in diameter were identified in the subcapsular
regionofsegmentII.Thepartiallyconfluentnodulesshowed
pronouncedslightlyinhomogeneoushypervascularityinthe
earlyarterialphaseofdynamicGd-enhancedliverMRIanda
lack of contrast uptake of the liver specific superparamag-
neticiron-oxide(SPIO)containingcontrastagent(Figure1).
Enlarged paracaval and hilar lymph nodes and accessory
splenic tissue in the left subdiaphragmatic area were
identified at the same examination. The suspicion of
a potentially malignant process concerning the hepatic
nodules was sustained and further investigation was
considered necessary to confirm or rule out hepatocellular
carcinoma (HCC). Transfemoral intraarterial angiography
of the liver was performed as a primarily diagnostic and
potentially therapeutic procedure. It showed regular
branches of the hepatic artery but no pathologic vessels
or parenchymal foci of hypervascularity.
Figure 1. MRI of the liver. T2-weighted single-shot turbo
spinecho imaging (HASTE) MRI of the liver shows slightly
hyperintense polylobular lesion in the left lobe of the liver,
segment II (A, arrows). Multiple nodular structures are
identified in the splenic recess indicating recurrent
splenic tissue after splenectomy (large arrow).
After intravenous application of Gadolinium-DTPA
(Magnevist, Schering, Berlin, Germany), these lesions exhibit
marked contrast enhancement in the early arterial phase, as
it may also be seen in the case of hepato-cellular carcinoma
(B). With hepato-specific contrast agents (iron-oxide
particles, Resovist“, Schering, Berlin, Germany), the hepatic
lesion lacks iron uptake, which is shown on axial and coronal
T2*-weighted images (C, D) and is indicative of the presence
of non-hepatic tissue. Especially the coronal images delineate
the indenting nature of the space-occupying lesion into the
hepatic tissue and the close relationship to the diaphragm,
suggesting an extrahepatic location of the lesion (D).
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CT-guided biopsy was then considered and attempted
although the peripheral location of the nodules offered
limited approach. The histologic findings showed cirrhotic
liver tissue with chronic periportal inflammation and
steatosis of up to 30 % of the hepatocytes. There was no
confirmation of malignancy.
Despite the negative results of all diagnostic and imaging
modalities, the potential malignancy of the lesions could
stillnotberuledoutatthispoint.Therefore,theMRIwhich
was performed in our center, and all other investigations
were revised for a second time.
Facing a similar arterial contrast enhancement behaviour
of the intrahepatic nodules on MRI when compared to the
residual and accessory splenic tissue observed in the left
subdiaphragmatic region, a selective scintigraphy with
Tc-99m-labelled heat-denatured autologous red blood
cells (Tc-99m-DRBC) was performed in the attempt to
investigate also for the rare differential diagnosis of intra-
hepatic splenosis in this context. Tc-99m-DRBC finally
confirmed this differential diagnosis showing uptake in
both of the accessory spleens in the left upper quadrant
and in the area projecting to the left liver lobe (Figure 2).
A follow-up MRI after nine months revealed no change
and identical findings with respect to all nodular lesions
and the diagnosis of intrahepatic splenosis was estab-
lished. As there was no need for further treatment with
regards to the splenosis, the patient has restarted therapy
with pegylated interferon and ribavirine.
Discussion
Splenosis is the heterotopic autotransplantation of splenic
tissueandoccursin16to67%ofthepatientsaftertraumatic
spleen rupture or spleen surgery [1]. It is important to
distinguish splenosis from accessory spleens. Accessory
spleens are located on the left side of the dorsal mesogas-
trium in the region of the splenopancreatic or gastrosplenic
ligaments. They are supplied by a branch of the splenic
artery. In contrast, splenic implants are supplied by small
arteries of the surrounding tissue penetrating the surround-
ing capsule [1,2].
Splenosis is a rare entity. To date, around 100 cases were
reported in the literature until 2004 [3]. However, only
very few cases with isolated hepatic localisation were
described [3,4]. The most frequent sites of implanted
splenic tissue spread after trauma are the abdominal or
pelvic cavity. Intrathoracic sequestration has been
observed in patients with abdominal trauma penetrating
the diaphragm. Although the diaphragm was ruptured
also in our patient during the trauma, no other site of
implantation was identified.
Hematogenous spread of splenic pulp is supposed to be
a possible mechanism of seeding into the liver. The
subcapsular location of the splenic tissue in our case may
suggest the implantation on the inferior surface of the
diaphragm which was ruptured in the same trauma
mechanism rather than by hematogenous spread into
the liver. However, the marked indentation of the nodules
into the liver parenchyma made exact localization
difficult.
In the vast majority of cases with splenosis, patients are
asymptomatic and an undetermined mass is found
incidentally. Sometimes, non-specific symptoms such as
abdominal pain or diarrhea may lead to the diagnosis.
Gastrointestinal bleeding after rupture of asplenic implant
nodule and intestinal obstruction are rather rare compli-
cations associated with splenosis.
Chronic hepatitis C has a prevalence of about 1% in the
Middle-European population. Transmission of the hepa-
titis used to occur frequently after transfusion in poly-
traumatized patients. 20% of the patients develop liver
cirrhosis. The incidence of HCC in patients with liver
cirrhosis and hepatitis C is about 7 % in 5 years [5]. Thus,
any hepatic mass in a patient with hepatitis C and liver
cirrhosis should always raise suspicion of HCC.
The spectrum of differential diagnosis for focal liver
lesions in diagnostic radiologic imaging is wide but may
be narrowed down in patients with hepatitis C and liver
cirrhosis to hemangioma, adenoma, focal nodular hyper-
plasia, regenerative nodules, dysplastic nodules and
hepatocellular carcinoma.
The EASL (European Association of the Study of the Liver)
criteriaforthediagnosisofHCCrecommendacoincidental
Figure 2. Tc-99m-DRBC scintigram. Heat-damaged and
Tc-99 m-labeled autologous red blood cell scintigram shows
uptake of the labeled cells in the left lobe of the liver (thick
arrow) and in the vicinity of the removed spleen (thin arrow)
in the planar scan (a) and the SPECT-images (b)
corresponding to the masses seen in MRI and CT.
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presence of arterial hypervascularity of a suspect nodule in
twoimagingtechniquesoranAFPlevelover400ng/mland
concomitant arterial hypervascularity in one imaging
technique. According to Bolondi, in a study of small
nodules in patients with liver cirrhosis, 38 % of the HCC
nodules measuring 1-2 cm and 16 % of the HCC nodules
measuring 2-3 cm were not satisfying the EASL criteria
concerning hypervascularity. All nodules larger than 2 cm
resulted to be HCC [6]. Hence, the absence of hypervascu-
larity is not necessarily contradictory to the suspicion of
malignancy.
The respective nodules in our patient showed slightly
inhomogeneous but marked contrast enhancement in the
early arterial phase of dynamic imaging after Gadolinium-
DTPA, evocative of HCC. The additional lack of uptake of
the SPIO contrast agent further supported the suspicion of
malignancy.
Double contrast MRI of the liver using Gadolinium-DTPA
and SPIO as liver specific contrast agent has proven to
enhance the diagnostic accuracy in the detection and
characterization of focal liver lesions and HCC [7] and is
widely accepted as state-of-the art imaging. Due to the
presence of reticuloendothelial system, splenic tissue is
supposed to present some uptake of the iron particles.
Hence, signal void should be observed in splenic tissue to
a certain degree. In our case, iron uptake was completely
absent both in the accessory spleen and in the intrahepatic
nodules of splenosis, leading to confounding results and
misleading image interpretation.
The liver biopsy performed in our centre showed cirrhotic
tissue and did not reveal any components of splenic tissue.
As a consequence, it has to be assumed that the lesion of
interest was missed at biopsy. The limited access to the
lesion in its subcapsular and subdiaphragmatic location in
the left upper abdominal quadrant may be the most
plausible explanation to this negative result. According to
the literature, in CT-guided liver biopsies the diagnostic
yield is 67 to 96 % [8,9].
Itremainsaninterestingobservationthatalargenumberof
the reported cases of hepatic splenosis are patients with
hepatitis B or C with or without liver cirrhosis [3]. It could
be speculated that these patients have a specific vulner-
abilityconcerningsplenosis.However,itseemsmorelikely
that these patients are better investigated with imaging
methods than otherwise healthy people.
The specific diagnosis of splenosis is most reliably
established with help of Tc-99m-DRBC scintigraphy.
Tc-99m-DRBCscintigraphyhasshowntobemoresensitive
than Tc-99m-sulfur colloid scintigraphy [10]. About 90%
of the administered Tc-99m-labeled heat-damaged
autologous red blood cells are sequestered by reticulo-
endothelial cells and can be used to identify splenic tissue.
As splenosis is a quite rare disease there exist no studies
with a larger cohort of patients to evaluate sensitivity and
specificity of Tc-99m-DRBC scintigraphy. Yet, Tc-99m-
DRBC scintigraphy is still considered as the gold standard
in the non-invasive diagnosis of splenosis.
Conclusion
Although intrahepatic splenosis represents an extremely
rare condition, this diagnosis should always be taken into
considerationinpatientswithhistoryofabdominaltrauma
withsplenicinvolvementpresentingwithanindeterminate
focal liver lesion.
At contrast enhanced MRI with Gadolinium-chelates,
splenosis shows a signal behaviour and enhancement
pattern similar to that of potentially present accessory
spleen but does not necessarily exhibit iron uptake on
SPIO enhanced imaging. The diagnosis of splenosis may
then be reliably confirmed by Tc-99m-DRBC scintigraphy
and will help to avoid unnecessary major surgery or other
invasive therapeutic procedures.
Splenosis per se does not require particular follow up with
diagnostic imaging or other investigations. Interferon
therapyofhepatitisCinthecirrhoticpatientwithsplenosis
is safe, however, careful follow-up is crucial.
Abbreviations
AFP, alpha-fetoprotein; CT, computed tomography; DRBC,
heat-denatured autologous red blood cells; DTPA, diethy-
lenetriamine penta-acetic acid; EASL, European Association
of the Study of the Liver; GOT, glutamate-oxalacetate-
transaminase; GPT, glutamate-pyruvate-transaminase;
HCC, hepatocellular carcinoma; HCV, hepatitis C virus;
MRI, magnetic resonance imaging; SPIO, super-paramag-
netic iron oxide; Tc, Technetium.
Consent
Written informed consent was obtained from the patient
for publication of this case report and any accompanying
images. A copy of the written consent is available for the
review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
MM drafted the manuscript, KH confirmed the diagnosis
“splenosis” by MRI and provided the MRI illustrations,
she also helped to draft the manuscript, AH confirmed the
diagnosis “splenosis” by scintigraphy and provided the
scintigraphic illustrations, BR performed the clinical
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coordination of the patient’s diagnostic and therapeutic
procedures, RZ provided medical and scientific advice
concerningthediagnosisof“splenosis”,CMJwastheclinical
supervisor responsible for the patient, and she provided
scientificadvice,COconceivedthestudy,wasresponsiblefor
the coordination, and helped to draft the manuscript. All
authors read and improved the final manuscript.
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