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  • Case Report
  • Open Access

Management of intrahepatic splenosis:a case report and review of the literature

  • 1, 2,
  • 1, 2,
  • 1, 2,
  • 1, 2,
  • 3,
  • 1 and
  • 1, 2Email author
World Journal of Surgical Oncology201816:119

https://doi.org/10.1186/s12957-018-1419-1

  • Received: 2 May 2018
  • Accepted: 22 June 2018
  • Published:

Abstract

Background

Splenosis is the heterotopic autotransplantation and implantation of splenic tissue after splenic trauma or splenectomy. Considering that splenosis often occurs in the mesentery, omentum, and peritoneum, intrahepatic splenosis has seldom been reported. We report a rare case of isolated intrahepatic splenosis in a 54-year-old man who presented with a liver mass thought to be hepatocellular carcinoma.

Case presentation

A 54-year-old man was referred to our hospital for further evaluation of a liver lesion. The patient was asymptomatic and had a history of emergent splenectomy after a high-altitude falling accident. Abdominal contrast-enhanced computed tomography revealed a 4.5 × 3.3 cm lesion that was located in segment IV of the left liver lobe. The lesion had an inhomogeneous enhancement during the arterial phase and diminished enhancement during the portal and equilibrium phases. Similar radiological features were also observed on a contrast magnetic resonance imaging scan. Partial hepatectomy was performed with the suspicion of hepatocellular carcinoma. Pathological examination of the liver specimen revealed intrahepatic splenosis.

Conclusion

Splenosis should be considered in differential diagnosis of a liver mass discovered years after splenic trauma or surgery. A proposed scoring system may be helpful in evaluating the suspicious degree of intrahepatic mass to be splenosis. Invasive treatments are not recommended for asymptomatic patients, since the splenosis can provide beneficial immunologic function.

Keywords

  • Liver neoplasm
  • Intrahepatic splenosis
  • Splenectomy
  • Trauma

Background

Splenosis is the heterotopic autotransplantation of splenic tissue throughout the peritoneal and pelvic cavities, even the thoracic cavity, following splenic trauma or elective splenectomy [1]. The splenic fragments usually seed onto exposed vascularized peritoneal surface, receiving blood supply from the surrounding tissue. Intrahepatic splenosis is quite rare, as the majority of splenosis reported in the English literature was found to be located in the mesentery, omentum, and peritoneum [2]. The lack of typical radiological features makes it difficult to distinguish splenosis from liver tumors and reach a correct diagnosis. Herein, we present a case of isolated intrahepatic splenosis and summarize the relevant radiological and pathological characteristics. On the basis of literature review, imaging techniques that may contribute to the diagnosis and appropriate treatment measures are also discussed.

Case presentation

A 54-year-old Chinese male was referred to our hospital for further evaluation of a liver mass, which was discovered incidentally during routine physical examination in a local hospital. The patient had a 10-year history of hypertension and was diagnosed with diabetes mellitus approximately 5 years before. He denied history of liver cirrhosis and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The patient underwent splenectomy 5 years earlier owing to a high-altitude falling accident. No mass was identifiable on abdominal palpation exam. Serum tumor markers (alpha-fetoprotein, CA199, and CA125) were within the normal range. Abdominal ultrasonography (US) revealed a 5 cm iso-echoic lesion that located in the left hepatic lobe near the capsule. A 1.2 cm gallstone was also observed. An abdominal plane-computed tomography (CT) scan revealed an oval, slightly hypodense mass located in segment IV of the left liver lobe measuring 4.5 × 3.3 cm. The lesion had an inhomogeneous enhancement during the arterial phase and diminished enhancement during the portal and equilibrium phases on a contrast-enhanced CT scan (Fig. 1). Abdominal magnetic resonance imaging (MRI) showed a slightly hypointense mass on both T1- and T2-weighted images, which appeared slightly hyperintense on diffusion-weighted images. After the injection of gadoxetic acid, the lesion appeared strongly heterogeneous and hyperintense during the arterial phase and relatively hypointense during the portal and equilibrium phases (Fig. 2). An indication of a pseudo-capsule was also observed. Partial hepatectomy and cholecystectomy were performed with the suspicion of hepatocellular carcinoma (HCC).
Fig. 1
Fig. 1

Contrast-enhanced computed tomography scan of intrahepatic splenosis. The lesion had an inhomogeneous enhancement during the arterial phase (a) and diminished enhancement during the portal phase (b) and equilibrium phase(c)

Fig. 2
Fig. 2

Magnetic resonance imaging scan of intrahepatic splenosis. Note a slightly hypointense mass on both T1-weighted (a) and T2-weighted (b) images. After the injection of gadoxetic acid, the mass became strongly heterogeneous and hyperintense during the arterial phase (c) and relatively hypointense during the portal phase (d)

During the operation, the intrahepatic mass was found to be located in segment IV of the liver, measuring 4.0 cm in diameter. It was completely embedded in the liver tissue, and no other mass was found. Postoperative hematoxylin and eosin staining revealed sinusoidal structures and lymphoid tissue hyperplasia. A capsule separating the spleen tissue from liver tissue could be clearly detected (Fig. 3), which confirmed intrahepatic splenosis. Detailed immunohistochemical staining showed positivity for CD3 and CD20, specific markers for lymphocyte T cells and B cells, respectively. Meanwhile, the expression of the Ki-67 antigen was quite limited. The polyclonal nature of the lymphocytes and the low proliferation activity further confirmed the benign characteristic of the mass, as malignant tumors are always monoclonal with active proliferation. The patient discharged uneventfully after the operation, and no symptoms of recurrence have been observed during 2 years of follow-up.
Fig. 3
Fig. 3

Histopathological features of intrahepatic splenosis. Hematoxylin and eosin staining. a A capsule clearly separated the liver (white arrow) and spleen (black arrow) parenchyma, × 100. b Intrahepatic splenosis with lymphoid tissue hyperplasia and sinusoidal structures, × 400

Literature review

We searched the PubMed and Scopus databases for relevant English literature from the year 2000 through March 2018 using the Medical Subject Headings (MeSH) “Hepatocellular Carcinoma,” “Liver Neoplasm,” and “Splenosis.” In total, 37 cases of intrahepatic splenosis were identified and reviewed [337]. Characteristics of the cases such as age and sex of patients, clinical symptoms, diagnostic modality, and location of the masses were reviewed and analyzed (Table 1). There were 31 (83.8%) male and 6 (16.2%) female patients, and the mean age of the patients was 49.2 years (ranging from 21 to 73 years).
Table 1

Clinical data of 37 cases of intrahepatic splenosis

Author, year

Age (years), gender

Trauma, splenectomy

Liver diseases

Time interval (years)

Symptoms

Diagnostic modality

Number

Subcapsular location

Capsule

Diagnostic hypothesis

Segment, size (mm)

Invasive measure

Follow-up

Teles 2018 [3]

73, M

Splenectomy

No

N/D

Lower back pain

US, CT, MRI

scintigraph

2

Yes

Yes

hepatic neoplasia

II, III

36

Surgery

No symptoms for 2 years

Wang 2017 [4]

54, M

Both

HBV

23

Abdominal pain

US, CT, MRI

1

Yes

Yes

HCC

Right posterior lobe 31 × 27

Surgery

No symptoms for 18 months

Wang 2017 [5]

42, M

Both

HBV/BCV

16

Lower back pain

CT, MRI

1

Yes

Yes

HCC

IV

3 × 3

Surgery

N/D

Keck 2017 [6]

66, M

Both

HCV

N/D

No

MRI

2

Yes

N/D

HCC

VII, VIII

53

Biopsy

N/D

Jereb 2016 [7]

22, M

Both

No

18

No

US, CT, MRI

5

Yes

N/D

Liver metastases

II, VI, VII

26 × 26

Surgery

N/D

He 2016 [8]

51, M

Both

No

20

No

US, CT, MRI

2

N/D

N/D

HCC

Left lobe, right lobe 33 × 26

Biopsy

N/D

Liu 2015 [9]

33, M

Both

No

30

No

US, CT, MRI

3

Yes

N/D

HCC/Liver metastases

III, Right lobe

42 × 30

Biopsy

No symptoms for 2 years

Li 2015 [10]

67, F

Both

HCV, cirrhosis

5

No

CT, MRI

angiography

1

N/D

Yes

HCC

Left lobe

Surgery

No symptoms for 3 years

Sato 2014 [11]

58, M

Neither

HCV, cirrhosis

No

No

US, CT, MRI

1

Yes

Yes

HCC

Right lateral lobe 39 × 30

Surgery

No symptoms for 1 year

Levi Sandri 2014 [12]

54, M

Both

HBV, cirrhosis

25

N/D

CT

1

N/D

Yes

HCC

III

45 × 35 × 15

Surgery

N/D

Leong 2013 [13]

56, M

Both

No

25

Abdominal pain

US, CT, MRI

PET

1

N/D

N/D

Neuroendocrine tumor

III

46 × 37 × 31

Surgery

No symptoms for 6 months

Krawczyk 2013 [14]

39, F

Both

No

N/D

Abdominal pain

CT, MRI, scintigraphy

1

Yes

N/D

Hepatocellular adenoma

II

32 × 20

No

No symptoms for 3 months

Inchingolo 2013 [15]

53, M

Both

Non alcoholic steatohepatitis

33

No

US, CT, MRI

1

Yes

N/D

HCC/hepatic adenoma

III, IV

35

Surgery

N/D

Liu 2012 [16]

49, F

Both

No

20

Subxiphoid pain

US, CT

3

Yes

N/D

Liver tumor

Left lateral lobe

50 × 50

Surgery

No symptoms for 4 months

Liu 2012 [17]

38, M

Both

HBV

14

No

US, CT

1

Yes

Yes

Liver tumor

Left lateral lobe

33 × 27

Surgery

N/D

Kang 2011 [18]

54, M

Both

No

15

No

US, CT, MRI

PET-CT

2

Yes

Yes

Liver metastatic

nodules

II

23 × 19

Surgery

N/D

Mescoli 2010 [19]

68, F

Neither

Hepatitis, cirrhosis

No

Abdominal pain

US, CT, MRI

3

N/D

N/D

Liver tumor

III, V, VII

150

Biopsy

N/D

Mescoli 2010 [19]

54, M

Splenectomy

No

12

No

CT, PET-CT

1

N/D

No

Liver metastatic

nodule

Left lobe

30

Surgery

No symptoms for 8 months

Yu 2009 [20]

54, M

Both

No

20

No

US, CT, MRI

1

Yes

Yes

N/D

Left lobe

40

Surgery

No symptoms for 6 months

Menth 2009 [21]

43, M

Both

HCV, cirrhosis

30

Fatigue

US, CT, MRI

angiography, scintigraphy

Multiple

Yes

N/D

HCC

II

36

Biopsy

No symptoms for 9 months

Kashgari

2009 [22]

52, M

Both

HCV, cirrhosis

30

No

US, MRI

1

Yes

N/D

HCC

VII

21 × 15

Biopsy

No symptoms for 4 months

Abu Hilal

2009 [23]

60, M

Both

HCV, cirrhosis

46

Flu-like symptoms

US, CT, MRI

1

Yes

N/D

HCC

VII

30

Surgery

No symptoms for 2 years

Yeh 2008 [24]

64, M

Both

HCV

8

No

US, CT, MRI

angiography

1

Yes

Yes

HCC

VI

25

Surgery

N/D

Nakajima 2008 [25]

41, M

Both

N/D

21

Abdominal pain and diarrhea

US, CT, MRI

1

Yes

N/D

N/D

VI

N/D

Biopsy

N/D

Imbriaco

2008 [26]

39, M

Both

No

24

Abdominal pain

US, CT, MRI

Multiple

Yes

N/D

Liver metastatic

nodules

Left lobe, right lobe 30

Surgery

N/D

Grande

2008 [27]

41, M

Both

No

35

No

US, CT,

scintigraphy

Multiple

Yes

N/D

N/D

VII

45

No

N/D

Choi

2008 [28]

32, M

Both

HBV

26

No

CT, MRI

angiography

3

Yes

Yes

HCC

IVa, IVb, VI

30

Surgery

N/D

Brancatelli

2005 [29]

38, F

Both

No

32

No

CT, MRI

scintigraphy

1

Yes

N/D

Liver adenoma

Left lobe

50

Biopsy

N/D

Zhao

2004 [30]

49, M

Both

No

17

No

US, CT

1

Yes

Yes

Liver adenoma/HCC

VII

50 × 30 × 30

Surgery

No symptoms for 1 year

Kondo

2004 [31]

55, M

Both

HCV

31

No

US, CT, MRI(SPIO)

angiography

2

N/D

N/D

HCC

VII

35 × 35

Biopsy

N/D

Izzo

2004 [32]

60, M

Both

HCV

43

Jaundice

US, CT, MRI

1

N/D

N/D

HCC

Near the hilum 60

Biopsy

N/D

Di Costanzo

2004 [33]

58, M

Both

HBV, cirrhosis

46

No

US, CT,

scintigraphy

1

Yes

N/D

HCC

III

48

Biopsy

N/D

Di Costanzo

2004 [33]

48, F

Both

HCV, cirrhosis

41

No

US, CT

1

Yes

Yes

HCC

III

31

Biopsy

N/D

Kim

2003 [34]

43, M

Both

HBV, cirrhosis

21

No

US, CT,

angiography

1

Yes

Yes

HCC

Right lobe

30

Surgery

N/D

Pekkafali

2002 [35]

21, M

Both

No

15

Epigastric pain

US, CT, MRI

scintigraphy

1

Yes

Yes

No

Left lobe

34 × 23

No

N/D

Lee

2002 [36]

43, M

Both

HBV, cirrhosis

20

Fatigue

US, CT, angiography

1

Yes

Yes

HCC

VI

33 × 20

Surgery

N/D

De Vuysere

2000 [37]

50, M

Both

No

34

No

US, CT, MRI(SPIO)

3

N/D

Yes

No

Left lobe, right lobe 60

Biopsy

N/D

HBV hepatitis B virus, HCV hepatitis C virus, HCC hepatocellular carcinoma, US ultrasonography, CT computed tomography, MRI magnetic resonance imaging, PET positron emission tomography, M male, F female, N/D not disclosed

aTime interval: time elapsing between trauma/splenectomy and diagnosis of intrahepatic splenosis

bWhen multiple lesions, only the size of the largest one was presented

cSurgery: included laparoscopic resection and laparotomy

In the 37 documented cases, 35 (94.6%) patients had histories of trauma or/and splenectomy, and the mean time elapsing between trauma/splenectomy and diagnosis of intrahepatic splenosis was 24.9 years (ranging from 5 to 46 years). A total of 20 (54.1%) patients had related liver diseases, among which 8 (40%) had HBV infection, 11 (55%) had HCV infection, and 11 (55%) had cirrhosis. Most of the patients were asymptomatic upon admission, except for 6 (16.2%) who had abdominal pain. US, CT, and MRI were common imaging techniques, but they did not clearly differentiate intrahepatic splenosis from other liver lesions, such as HCC, liver metastases, or liver adenoma. Scintigraphy was used in 7 (18.9%) patients, and in 3 (42.9%) of them, the imaging led to the correct diagnosis without further invasive measures. The majority of intrahepatic splenosis were located in the subcapsular region of the liver, surrounded by capsules. A total of 34 (91.9%) patients had undergone invasive procedures. Surgery in 21 (61.8%) patients, including laparoscopic resection and laparotomy, was the most common invasive procedure followed by biopsy in 13 (38.2%).

Discussion

Splenosis represents the heterotopic autotransplantation and implantation of splenic tissue after elective splenectomy or traumatic spleen rupture. Once considered to be a rare condition, a recent estimated incidence is up to 67% of patients who have a history of splenic rupture or surgery [38]. Intrahepatic splenosis is still rare, as most of the splenoses were located in the mesentery, omentum, or peritoneum. Except for some extraordinary cases, almost all of the cases with intrahepatic splenosis have a history of splenic trauma or splenectomy [11, 19]. Hence, intrahepatic splenosis should be taken into consideration in patients with a relevant history, especially if the mass is found to be located close to the liver capsule.

The absence of typical radiological features makes it difficult to reach a correct diagnose with common imaging techniques, such as US, CT, and MRI. As a result, intrahepatic splenosis can be confused with HCC, adenoma, or other liver diseases, leading to unnecessary surgery or other invasive treatments. Therefore, more sensitive novel methods to diagnose intrahepatic splenosis are needed. Scintigraphy with sensitive technetium-99 m-labeled heat-denatured red blood cells (Tc-99 m-DRBC) is reported to be the most specific and efficient diagnostic method [20]. As approximately 90% of damaged erythrocytes will be trapped by splenic tissue, remarkable differences in uptake of the radioactive isotope can be observed between intrahepatic splenic tissue and normal liver tissue. Krawczyk et al. [14], Grande et al. [27], and Pekkafali et al. [35] reported three cases that successfully avoided invasive treatments by using Tc-99 m-DRBC scintigraphy. Scintigraphy with sulfur colloid is considered to be another useful diagnostic method, but has a lower sensitivity in identification of splenosis [39]. Superparamagnetic iron oxide (SPIO) contrast magnetic resonance imaging may be helpful for the diagnosis of splenosis. As reported, intrahepatic splenosis will remain hyperintense relative to the liver parenchyma, while HCC will become hypointense after the SPIO administration [37].

In fact, most of the cases with intrahepatic splenosis that had been reported were treated with invasive procedures, including biopsy and surgical resection. However, intrahepatic splenosis may be beneficial in the patients who have undergone splenectomy, since it can replace part of the immunologic function of the removed spleen [40]. Hence, conservative treatment is strongly recommended for asymptomatic intrahepatic splenosis, except for some special situations, such as idiopathic thrombocytopenic purpura and Felty syndrome.

In order to avoid unnecessary invasive treatment, accurate diagnosis is essential. Although some novel imaging methods, such as scintigraphy, have shown promising application prospects in diagnosis of intrahepatic splenosis, they will not likely be used worldwide for quite some time. Instead, we think it may be helpful to use a scoring system to evaluate the suspicious degree of intrahepatic mass to be splenosis (Table 2). Compared with the CT/MRI Li-Rads v2017 [41], our scoring system seems to be more effective in diagnosing intrahepatic splenosis. The major imaging features (washout, enhancing “capsule” and threshold growth) of Li-Rads were not enough to distinguish intrahepatic splenosis from liver neoplasm. According to the table, the higher the total score is, the stronger is the possibility that the mass will be splenosis. When the total score is greater than 3, it is better to use biopsy to clarify the diagnosis, instead of taking more aggressive measures directly.
Table 2

Suspicious degree of intrahepatic mass to be splenosis

Parameters

Score

Methods

0

1

Alpha-fetoprotein

> 400 μg/L for 4 weeks

> 200 μg/L for 8 weeks

No

ELISA

Cirrhosis

Yes

No

US, CT, MRI

Hepatitis

Yes

No

ELISA, PCR

Splenic trauma

No

Yes

History taking/

US, CT, MRI

Splenectomy

No

Yes

History taking/

US, CT, MRI

Mass location

Non-subcapsular

subcapsular

US, CT, MRI

Mass capsule

No

Yes

US, CT, MRI

Howell-Jolly and Heinz bodies after splenectomy

Yes

No

Hematological examination

ELISA enzyme-linked immunosorbent assay, US ultrasonography, CT computed tomography, MRI magnetic resonance imaging, PCR polymerase chain reaction

aFor alpha-fetoprotein, exclude pregnancy, acute severe hepatitis, embryonic gonad tumors, and other digestive system tumor

Conclusion

Although isolated intrahepatic splenosis is rarely encountered, it should be taken into account in the differential diagnosis of a liver lesion, especially if the patient has a history of splenic trauma or splenectomy. The proposed scoring system may be useful in diagnosing intrahepatic splenosis when effective diagnostic methods, like scintigraphy and SPIO MRI, are lacking. If intrahepatic splenosis has been confirmed, conservative treatment is strongly recommended for the patient without any symptoms.

Abbreviations

CT: 

Computed tomography

ELISA: 

Enzyme-linked immunosorbent assay

PCR: 

Polymerase chain reaction

F: 

Female

HBV: 

Hepatitis B virus

HCC: 

Hepatocellular carcinoma

HCV: 

Hepatitis C virus

M: 

Male

MeSH: 

Medical Subject Headings

MRI: 

Magnetic resonance imaging

N/D: 

Not disclosed

PET: 

Positron emission tomography

SPIO: 

Superparamagnetic iron oxide

Tc-99 m-DRBC: 

Technetium-99 m-labeled heat-denatured red blood cells

US: 

Ultrasonography

Declarations

Funding

This work was supported by the Major program of National Natural Science Foundation of China (91542205) to SSZ, the National Natural Science Foundation of China (81570575) to PHS.

Authors’ contributions

SSZ performed the partial hepatectomy and cholecystectomy, and designed the analysis. ZFX and JC drafted the manuscript. DLW reviewed the literature; PHS and YHD supervised the draft and managed the patient’s follow-up. LJW participated in the interpretation of pathological data. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The ethics committee of First Affiliated Hospital, School of Medicine, Zhejiang University approved the study.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Competing interests

The authors declare that they have no competing interests.

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Authors’ Affiliations

(1)
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China
(2)
Collaborative innovation center for Diagnosis treatment of infectious diseases, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China
(3)
Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China

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