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Abstract

Hepatic splenosis is an uncommon condition that occurs following traumatic splenic rupture or splenectomy. The case of a 41-year-old male patient with multiple isolated liver masses indistinguishable from primary and metastatic liver tumours is reported. Following laparotomy, the liver lesions were resected and histopathology confirmed a diagnosis of hepatic splenosis. At an 18-month follow-up examination, no abnormalities in routine blood test, liver function, and liver computed tomography (CT) scanning were observed. After review of the literature, the following diagnostic criteria for hepatic splenosis are proposed: (1) a history of splenic trauma or splenectomy; (2) lesion(s) with a surrounding rim, particularly near the liver capsule identified by CT scanning; (3) findings on superparamagnetic iron oxide-enhanced magnetic resonance imaging or technetium-99m heat-damaged red cell scanning; and (4) histopathological findings (needle biopsy or surgical pathology). The following diagnostic process is also proposed: suspect diagnosis when criteria 1 and 2 are met; make diagnosis when criterion 3 is met; confirm diagnosis when criterion 4 is met. Laparotomy is recommended for either diagnosis or treatment when invasive procedures are necessary.

Keywords

Hepatic splenosis diagnosis treatment

Introduction

Splenosis is a benign condition commonly resulting from traumatic splenic rupture or splenectomy.^1,2 Hepatic splenosis is rare and is usually diagnosed accidentally.³ Due to its low prevalence, hepatic splenosis is difficult to diagnose by non-invasive methods, particularly when the mass presents as a malignant disease on imaging or the patient has a risk of liver tumour or a history of cancer. Thus, the diagnosis of hepatic splenosis remains elusive and requires further investigation. Here, the case of a patient with hepatic splenosis mimicking liver metastases is reported. In addition, the PubMed database was searched between January 1993 and December 2016 for literature relating to splenosis, and the resultant literature was analysed in order to provide information on the diagnosis and treatment of this disease.

Case report

This work was conducted following approval by the ethics committees at Chongqing University Cancer Hospital. The patient provided written informed consent.

The patient was a 41-year-old male who was referred to Chongqing Cancer Hospital in December 2015 with liver tumours of unknown origin. He had no history of weight loss, abdominal pain or jaundice. His medical history included an urgent splenectomy due to traumatic rupture of the spleen as the result of a traffic accident in July 1994. There was no self-reported history of smoking or alcohol misuse. There was no positive sign on physical examination, except for a previous surgical scar. Routine blood analysis showed a platelet count of 521 × 10⁹/l and haemoglobin of 76 g/l. His liver function was normal and graded as A (score, 5) according to the Child-Turcotte-Pugh classification.⁴ His α-fetoprotein (AFP) level was 1.3 ng/ml (normal range, 0–8.1 ng/ml), carcinoembryonic antigen was 1.27 ng/ml (normal range, 1–5 ng/ml), and carbohydrate antigen 19-9 was 10.76 U/ml (normal range, 0–30.9 U/ml). Chest radiography was normal. Ultrasonography revealed a mass in the right liver region and an abdominal computed tomography (CT) scan showed multiple lesions in the liver, abdominal wall and splenectomy bed (Figure 1). A metastatic process was initially suspected due to anaemia and multiple lesions. No tumours were found by oesophagogastroduodenoscopy and colonoscopy, however, a duodenal ulcer was found. Since the liver lesions had an unknown aetiology, a biopsy was recommended. The patient refused a transcutaneous biopsy, and thus, an exploratory laparoscopy was indicated following a multidisciplinary consultation.

Figure 1.

Abdominal computed tomography scan showing lesions in the liver located near the liver capsule (arrows) with a rim surrounding the lesion (triangle): (A) low density lesions located near the capsule in unenhanced phase; (B) lesions washed-in and enhanced during hepatic arterial phase revealing a rim surrounding the lesion (triangle); and (C) lesions washed-out in portal venous phase

The patient underwent an exploratory laparoscopy. General anaesthesia was induced using sufentanil (15 µg total dose), midazolam (2 mg total dose), propofol (100 mg total dose) and rocuronium bromide (50 mg total dose), and anaesthesia was maintained using remifentanil (2 mg total dose), propofol (1400 mg total dose) and sevoflurane (50 ml total dose). Sufentanil (45 µg) and atracurium (15 mg) were administered according the patient’s condition during surgery. A 1.3-cm incision was made along the superior umbilical fold. A pneumoperitoneum was created with a Veress needle, and a 10-mm trocar was placed as a camera port. Two 12-mm trocars and two 5-mm trocars were then introduced with direct visual observation at the right upper quadrant, subxiphoid, right midclavicular, and anterior axillary lines, respectively. Operative findings showed an intrahepatic lesion of 4 × 2 cm in size located on the surface of liver segment VIII and a nodule of 1.5 × 1.3 cm on the abdominal wall. A lesion in segment VII adhered to the diaphragm and dented the surface of the liver. All lesions had clear boundaries with the liver, and were rapidly removed without hepatic resection. Subsequent histopathological results confirmed that the lesions consisted of spleen tissue (Figure 2).

Figure 2.

Representative photomicrographs of a liver lesion tissue section stained with haematoxylin and eosin showing hepatic splenosis and normal liver tissue: (A) fibrous tissue isolates the liver and spleen parenchyma (arrow) with liver tissue on the left and spleen tissue on the right including lymphoid follicular tissue (triangle), original magnification × 100; and (B) lymphoid follicular tissue (triangle), original magnification × 200.

The diagnosis of hepatic splenosis was thus established. Follow-up examination including routine blood analysis, liver function, and liver CT scanning at 18 months did not show any abnormalities. No adverse or unanticipated events occurred.

Discussion

The first case of splenosis was described by Albrecht in 1896⁵ and the condition was named by Buchbinder and Lipkoff in 1939.⁶ Splenosis is mainly found in patients who have undergone splenectomy¹ and although is considered a rare event, its incidence can be up to 67% in cases of traumatic splenic rupture.² Splenosis can be found in any part of the body, but common sites include the serosal surface of the small bowel, greater omentum, and parietal peritoneum, and the serosal surface of the large intestine and mesentery.³

Hepatic splenosis is frequently found in the left lobe of the liver and is usually located near the liver capsule. The most likely mechanism underlying splenosis is the seeding of splenic fragments onto serosal surfaces during splenic trauma or splenectomy⁷ and cell proliferation, promoted by local hypoxia of the liver.⁸ Hepatic splenosis is rarely identified in the clinic, with no more than 41 cases published between 1993 and 2016 (Table 1),^1,8–44 and due to its low prevalence, knowledge of the clinical features and diagnosis of splenosis remains limited. Hepatic splenosis has no specific symptoms, although abdominal pain may arise due to heterotopic splenic infarction or compression, resulting in missed diagnosis.^10,11 Hepatic splenosis is difficult to distinguish from adenoma and hepatocellular carcinoma, and can occur as single or multiple lesions at the surface or within the liver,^1,12,13 which may be misinterpreted as metastatic lesions in patients with malignant tumours.

Table 1.

Results summary from a literature review of hepatic splenosis showing 38 articles detailing 41 cases of hepatic splenosis published between 1993 and 2016.

Author, year	Age, years/sex	Reason for splenectomy	AFP level	Lesion location/size, cm	Number	Primary diagnosis	Method to confirm diagnosis
Yoshimitsu, 1993⁹	51/F	Banti syndrome	N	S3/2.5	1	HCC	Surgery
Gruen, 1996¹⁰	38/F	Trauma	NM	S3.4/3.9	1	Adenoma,FNH	Surgery
D’Angelica, 1997¹¹	38/F	Trauma	NM	S3/4	1	Adenoma,FNH	Surgery
Davidson, 1997¹²	54/M	Surgicaltrauma	NM	LL/2	1	NA	Necropsy
DeVuysere, 1999¹³	50/M	Trauma	N	S2/6.0	Multiple	Splenosis	Biopsy
Foroudi, 1999¹⁴	59/F	Trauma	NM	S6	Multiple	Metastasis	Tc-99mHDRS
Pekkafali, 2002¹⁵	21/M	Trauma	NM	LL/3.4	1	Splenosis	Tc-99mHDRS
Gamulin, 2002¹⁶	49/M	Trauma	NM	LL/6.6	1	Lymphoma	Surgery
Kim, 2003¹⁷	43/M	Trauma	N	S6	1	HCC	Surgery
Costanzo, 2004¹⁸	58/M	Trauma	412	LL/4.8	1	HCC	Biopsy Tc-99mHDRS
Costanzo, 2004¹⁸	48/F	Trauma	327	S3/3.1	1	HCC	Biopsy
Kondo, 2004¹⁹	55/M	Trauma	NM	S7	1	Tumour	Biopsy
Ferraioli, 2005²⁰	40/M	Trauma	N	S7/6.0	1	Hepatic Splenosis	Biopsy
Yeh, 2008²¹	64/M	Trauma	N	S6/2.5	1	HCC	Surgery
Lu, 2008²²	59/M	Trauma	N	S7	Multiple	Splenosis	Tc-99mHDRS
Choi, 2008⁷	32/M	Trauma	17.3	S4,S6	Multiple	HCC	Surgery
Grande, 2008²³	41/M	Trauma	N	S7	Multiple	Splenosis	Tc-99mHDRS
Nakajima, 2008²⁴	41/M	Trauma	NM	S6	1	Splenosis	Biopsy
Yu, 2009²⁵	54/M	Trauma	N	S2/4	1	Hepatoma	Surgery
Abu Hilal, 2009²⁶	60/M	Trauma	Mild rise	S7/2.5	Multiple	HCC	Surgery
Kashgari, 2009²⁷	52/M	Trauma	N	S7/2.1	1	HCC	Biopsy
Menth, 2009²⁸	43/M	Trauma	6.4	S2	Multiple	HCC	Tc-99mHDRS
Mescoli, 2010²⁹	68/F	NH	NM	S3,5,7	Multiple	FNH	Biopsy
Mescoli, 2010²⁹	54/M	Trauma	NM	LL/3	1	Metastasis	Surgery
Tsitouridis, 2010³⁰	63/M	Trauma	NM	LL/8	1	Splenosis	Surgery
Tsitouridis, 2010³⁰	64/M	Gastric leiomyosarcoma	NM	S4/5	1	Peritoneal implantation	Biopsy
Kang, 2011³¹	54/M	Trauma	NM	S2/3.5	Multiple	Metastasis	Surgery
Liu, 2012³²	49/F	Trauma	NM	LL	Multiple	Metastasis	Surgery
Li, 2012³³	61/M	Trauma	NM	S4,S7	Multiple	Splenosis	Biopsy
Liu, 2012³⁴	38/M	Trauma	N	S2/3.3	1	Hepatic tumour	Laparoscopy
Inchingolo, 2013³⁵	53/M	Trauma	N	S3/3.5	1	HCC, Adenoma	Surgery
Krawczyk, 2013³⁶	39/F	Trauma	NM	S2/3.2	Multiple	Splenosis	Tc-99mHDRS
Röther, 2013³⁷	62/M	Trauma	N	S5/1.8	Multiple	HCC	Laparoscopy
Kandil, 2014³⁸	45/F	Haemolyticanaemia	N	S2/5.0	1	HCC	Surgery
Wu, 2015¹	33/M	Trauma	N	S2/3.5	1	HCC	Surgery
Liu, 2015³⁹	33/M	Trauma	N	S3/4.2	Multiple	Hepatic tumour	Biopsy
Aramoana, 2015⁴⁰	58/M	Trauma	NM	S6/4.6	1	Splenosis	Surgery
Grambow, 2015⁴¹	53/M	Trauma	N	3.5	1	HCC	Surgery
Fung, 2016⁴²	55/M	Trauma	N	S6/4.7	Multiple	Hepatic tumour	Surgery
He, 2016⁴³	51/M	Trauma	NM	S2,S6	Multiple	Metastasis	Biopsy
Jereb, 2016⁴⁴	22/M	Trauma	N	S6,S2	Multiple	Metastasis	Biopsy

AFP, α-fetoprotein; F, female; FNH, focal nodular hyperplasia; HCC, hepatocellular carcinoma; LL, left lobe; M, male; N, normal; NA, not associated with hepatic splenosis; NM, not mentioned; NH, no history of splenectomy; S2, 3, 4, 5, 6, 7, hepatic segments II, III, IV, V, VI, VII; Tc-99m HDRS, technetium-99m heat-damaged red cell scanning.

In the present case, secondary liver cancer was initially suspected due to ultrasonography and CT findings of multiple lesions in the liver, abdominal wall and splenectomy bed. Furthermore, low AFP levels and negative results for hepatitis increased the possibility of metastatic lesions. Due to negative findings on endoscopy, and patient refusal to undergo a transcutaneous liver biopsy, laparoscopic exploration was performed. The intrahepatic lesions were removed and diagnosed as hepatic splenosis by pathology.

False diagnoses not only have the potential to increase medical costs and the risk of adverse effects due to an invasive procedure, but also result in incorrect treatment. In the published case studies found in the present study, only 10 patients were appropriately diagnosed^{13,15,20,22–24,30,33,36,40} and the remaining patients were incorrectly diagnosed with liver tumours. Misdiagnosis of liver cancer due to chronic hepatitis and abnormal AFP usually results in patients receiving unnecessary transcatheter arterial chemoembolization⁷ or surgeries,²⁶ or losing the opportunity of liver transplantation.¹⁸ Such incorrect treatments have resulted in secondary damage in these patients.^17,18 With the increased prevalence of abdominal trauma,^45,46 hepatic splenosis may occur more often. Therefore, standard and effective diagnostic criteria need to be established for this disease.

In addition to a history of splenic trauma and splenectomy, alternative techniques have been used to distinguish hepatic splenosis from other hepatic masses, such as CT scans,¹⁵ technetium-99m heat-damaged red cell scanning (Tc-99m HDRS) and superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI).^13,23,28 Low AFP level has been suggested as an index for diagnosing hepatic splenosis, however, in patients who also have hepatocellular carcinoma (HCC) or chronic hepatitis, the splenosis could be misinterpreted as a liver tumour, resulting in incorrect disease staging and loss of opportunity for optimal surgery/transplant or conservative treatments. Thus, pathological evidence was also required to confirm diagnosis according to the results of surgery or biopsy in 35 of the reported patients.^{1,7,9–11,13,16–21,24–27,29,35,37–44} Based on current knowledge, the present authors propose the following criteria and process for diagnosing hepatic splenosis. Criteria: (1) a history of splenic trauma or splenectomy; (2) lesion(s) with a surrounding rim, particularly near the liver capsule identified by CT scanning; (3) findings on SPIO-MRI or Tc-99m HDRS; and (4) histopathological findings (needle biopsy or surgical pathology). Diagnostic process: suspect diagnosis of hepatic splenosis when criteria 1 and 2 are met; make diagnosis when criterion 3 is met; confirm diagnosis when criterion 4 is met.

Splenosis treatment relies on the reason for splenectomy and complications of the lesion. For patients who have undergone splenectomy for splenic trauma, conservative treatment may be given in most cases without compressive symptoms. For patients who have undergone splenectomy for haematologic disorders, removing the splenosis may prevent disease recurrence.⁴⁷ If invasive procedures are necessary (for either diagnosis or treatment), laparotomy is recommended.

The present results may be limited by the retrospective nature of the case study and literature review. Thus, data on more cases should be continuously collected to further assess and verify the proposed diagnostic criteria, and a future observational study remains necessary to elucidate the specificity and sensitivity of each of the criteria.

In conclusion, due to the rareness and asymptomatic nature of hepatic splenosis, it remains difficult to diagnose, leading to missed and false diagnoses. Following a case study and review of the literature, the present authors have proposed criteria and a process for diagnosing hepatic splenosis. Laparotomy is recommended for either diagnosis or treatment when invasive procedures are necessary.

Declaration of conflicting interest

The authors declare that there is no conflict of interest.

Footnotes

Funding

This work was supported by grants to NQ Gong from the Clinical Research Physician Program of Tongji Medical college, HUST and to XF Sun from the Major State Basic Research Development Program of China (No. 2013CB530803, 973).

References

Zhang

Chen

et al . Solitary perihepatic splenosis mimicking liver lesion: a case report and literature review. Medicine (Baltimore) 2015; 94: e586.

Livingston

Levine

Lecklitner

et al . Incidence and function of residual splenic tissue following splenectomy for trauma in adults. Arch Surg 1983; 118: 617–620.

Ksiadzyna

Peña

AS.

Abdominal splenosis.

Rev Esp Enferm Dig 2011; 103: 421–426.

Hong

Kim

Cho

et al . Comparison of the Child-Turcotte-Pugh classification and the model for end-stage liver disease score as predictors of the severity of the systemic inflammatory response in patients undergoing living-donor liver transplantation. J Korean Med Sci 2011; 26: 1333–1338.

Albrecht

A case of very numerous, over the whole peritoneum, scattered accessory spleens. Beitr z Path Anat 1896; 20: 513–527 [In German].

Buchbinder

Lipkoff

CJ.

Splenosis: multiple peritoneal splenic implants following abdominal injury: A report of a case and review of the literature. Surgery 1939; 6: 927–934.

Choi

Kim

et al . Hepatic splenosis preoperatively diagnosed as hepatocellular carcinoma in a patient with chronic hepatitis B: a case report. J Korean Med Sci 2008; 23: 336–341.

Kwok

Chen

Lin

et al . Portal vein entrance of splenic erythrocytic progenitor cells and local hypoxia of liver, two events cause intrahepatic splenosis. Med Hypotheses 2006; 67: 1330–1332.

Yoshimitsu

Aibe

Nobe

et al . Intrahepatic splenosis mimicking a liver tumor. Abdom Imaging 1993; 18: 156–158.

10.

Gruen

Gollub

MJ.

Intrahepatic splenosis mimicking hepatic adenoma.

AJR Am J Roentgenol 1997; 168: 725–726.

11.

D'Angelica

Fong

Blumgart

LH.

Isolated hepatic splenosis: first reported case.

HPB Surg 1998; 11: 39–42.

12.

Davidson

Reid

IN.

Intrahepatic splenic tissue.

J Clin Pathol 1997; 50: 532–533.

13.

De Vuysere

Van Steenbergen

Aerts

et al . Intrahepatic splenosis: imaging features. Abdom Imaging 2000; 25: 187–189.

14.

Foroudi

Ahern

Peduto

Splenosis mimicking metastases from breast carcinoma.

Clin Oncol (R Coll Radiol) 1999; 11: 190–192.

15.

Pekkafali

Karsli

Silit

et al . Intrahepatic splenosis: a case report. Eur Radiol 2002; 12(Suppl 3): S62–S65.

16.

Gamulin

Oberholzer

Rubbia-Brandt

et al . An unusual, presumably hepatic mass. Lancet 2002; 360: 2066.

17.

Kim

Park

Kim

et al . An interesting hepatic mass: splenosis mimicking a hepatocellular carcinoma (2003:9b). Eur Radiol 2003; 13: 2713–2715.

18.

Di Costanzo

Picciotto

Marsilia

et al . Hepatic splenosis misinterpreted as hepatocellular carcinoma in cirrhotic patients referred for liver transplantation: report of two cases. Liver Transpl 2004; 10: 706–709.

19.

Kondo

Okazaki

Takai

et al . Intrahepatic splenosis in a patient with chronic hepatitis C. J Gastroenterol 2004; 39: 1013–1015.

20.

Ferraioli

Di Sarno

Coppola

et al . Contrast-enhanced low-mechanical-index ultrasonography in hepatic splenosis. J Ultrasound Med 2006; 25: 133–136.

21.

Yeh

Wang

Huang

et al . Abdominal splenosis mimicking hepatic tumor: a case report. Kaohsiung J Med Sci 2008; 24: 602–606.

22.

et al . Hepatic splenosis diagnosed by spleen scintigraphy. Am J Gastroenterol 2008; 103: 1842–1844.

23.

Grande

Lapecorella

Ianora

et al . Intrahepatic and widely distributed intraabdominal splenosis: multidetector CT, US and scintigraphic findings. Intern Emerg Med 2008; 3: 265–267.

24.

Nakajima

Fujiwara

Yamaguchi

et al . Intrahepatic splenosis with severe iron deposition presenting with atypical magnetic resonance images. Intern Med 2008; 47: 743–746.

25.

Xia

et al.

Intrahepatic splenosis mimicking hepatoma. BMJ Case Rep 2009; 2009.

26.

Abu Hilal

Harb

Zeidan

et al . Hepatic splenosis mimicking HCC in a patient with hepatitis C liver cirrhosis and mildly raised alpha feto protein; the important role of explorative laparoscopy. World J Surg Oncol 2009; 7: 1.

27.

Kashgari

Al-Mana

Al-Kadhi

YA.

Intrahepatic splenosis mimicking hepatocellular carcinoma in a cirrhotic liver. Saudi Med J 2009; 30: 429–432.

28.

Menth

Herrmann

Haug

et al . Intra-hepatic splenosis as an unexpected cause of a focal liver lesion in a patient with hepatitis C and liver cirrhosis: a case report. Cases J 2009; 2: 8335.

29.

Mescoli

Castoro

Sergio

et al . Hepatic spleen nodules (HSN). Scand J Gastroenterol 2010; 45: 628–632.

30.

Tsitouridis

Michaelides

Sotiriadis

et al . CT and MRI of intraperitoneal splenosis. Diagn Interv Radiol 2010; 16: 145–149.

31.

Kang

Cho

Chung

et al . Intrahepatic splenosis mimicking liver metastasis in a patient with gastric cancer. J Gastric Cancer 2011; 11: 64–68.

32.

Liu

Wang

et al . Abdominal multiple splenosis mimicking liver and colon tumors: a case report and review of the literature. Int J Med Sci 2012; 9: 174–177.

33.

Snow-Lisy

Klein

EA.

Hepatic splenosis diagnosed after inappropriate metastatic evaluation in patient with low-risk prostate cancer.

Urology 2012; 79: e73–e74.

34.

Liu

Liang

et al . Laparoscopic resection of isolated hepatic splenosis mimicking liver tumors: case report with a literature review. Surg Laparosc Endosc Percutan Tech 2012; 22: e307–e311.

35.

Inchingolo

Peddu

Karani

Hepatic splenosis presenting as arterialised liver lesion in a patient with NASH.

Eur Rev Med Pharmacol Sci 2013; 17: 2853–2856.

36.

Krawczyk

Schneider

Farmakis

et al . Splenosis mimicking hepatic adenoma. J Clin Exp Hepatol 2013; 3: 351–352.

37.

Rother

Dufour

Schnuriger

An uncommon cause of a focal liver lesion. Post-traumatic splenosis.

Gastroenterology 2013; 144: 510, 659.

38.

Kandil

El Sorogy

Naiem

et al . Post-splenectomy splenosis presenting as hepatocellular carcinoma in the left lateral section of the liver: a case report. Int J Surg Case Rep 2014; 5: 877–878.

39.

Liu

Wang

Intrahepatic splenosis mimicking liver cancer: report of a case and review of literature. Int J Clin Exp Pathol 2015; 8: 1031–1035.

40.

Aramoana

Wylie

Koea

JB.

Hepatic splenosis. ANZ J Surg 2018; 88: E359–E360.

41.

Grambow

Weinrich

Zimpfer

et al . Ectopic spleen tissue - an underestimated differential diagnosis of a hypervascularised liver tumour. Viszeralmedizin 2015; 31: 445–447.

42.

Fung

Chok

et al . Hepatobiliary and pancreatic: hepatic splenosis: a rare differential of a liver mass in an HBV endemic area. J Gastroenterol Hepatol 2016; 31: 1238.

43.

et al . Successful diagnosis of intrahepatic splenosis mimicking hepatic tumor. Kaohsiung J Med Sci 2016; 32: 224–225.

44.

Jereb

Trotovsek

Skrbinc

Hepatic splenosis mimicking liver metastases in a patient with history of childhood immature teratoma.

Radiol Oncol 2016; 50: 212–217.

45.

McCraig

Burt

CW.

National hospital ambulatory medical care survey: 2003 emergency department summary. Adv Data 2005; 358: 1–40.

46.

Pitts

Niska

et al . National hospital ambulatory medical care survey: 2006 emergency department summary. National Health Statistics Reports. Report no. 7, 6 August 2008, www.cdc.gov/nchs/data/nhsr/nhsr007.pdf (2008, accessed 24 February 2010).

47.

Wekerle

Eichinger

Maier

et al . Intrahepatic splenic tissue in a patient with recurrent idiopathic thrombocytopenic purpura. Surgery 1998; 123: 596–599.

Hepatic splenosis: Rare yet important – A case report and literature review

Abstract

Keywords

Introduction

Case report

Discussion

Declaration of conflicting interest

Footnotes

Funding

References