Hepatic haemangioma causing isolated right-sided pleural effusion and bilateral pedal oedema

Abstract

Hepatic haemangioma (HH) is a common benign tumour of the liver and is usually asymptomatic. HH causing isolated right-sided pleural effusion and bilateral pedal oedema due to inferior vena cava (IVC) compression have never been reported in the literature. We report a 35-year-old male patient who presented with breathlessness and mass per abdomen. On examination, the patient was found to have right-sided pleural effusion, bilateral pedal oedema, hepatomegaly. Contrast-enhanced CT showed compression of the IVC by the HH. The patient was managed with right-sided intercostal drain insertion for pleural effusion and hepatic artery embolisation. The patient improved gradually with reduced pleural effusion and resolving pedal oedema.

Background

Hepatic haemangioma (HH) is the most common benign liver tumour.¹ It is more common in females than in males.²HH measuring 5 cm or more is called giant haemangiomas and may worsen with thrombosis, fibrosis, and calcifications. The exact pathogenesis is unknown; however, the hormonal effect may have a role in the pathogenesis. It is more common in women, and accelerated growth occurs in pregnant patients, patients receiving oral contraceptive pills or androgen treatment.³ Most HHs are asymptomatic, and very few may present with compressive symptoms or coagulopathy when they become large.⁴ Patients with HH with inferior vena cava (IVC) compression may present with Budd Chiari syndrome, bilateral pedal oedema or pulmonary embolism. There is a lack of literature about the patient of HH presenting with IVC compression. Diagnosis of HH is mainly made by imaging. Blood parameters and liver function tests (LFT) are usually normal. Treatment is indicated for symptomatic patients.^{5 6} This includes hepatic resection (definitive treatment),⁵ embolisation,⁷ hepatic artery ligation,⁸ radiation therapy,⁹ radiofrequency ablation (RFA)¹⁰ and liver transplantation.¹¹To the best of our knowledge, it is the first case of HH causing IVC compression, isolated right-sided pleural effusion and bilateral pedal oedema.

Case presentation

A 35-year-old man presented with reports of mass per abdomen for the last 4 years. He also had breathlessness for 1 month. The abdominal examination revealed hepatomegaly about 5 cm below the right costal margin, non-tender, smooth surface and well-defined sharp edge. Ultrasonography (USG) of the abdomen was suggestive of HH of the right lobe of the liver, measuring 15×20 cm. X-ray chest showed the presence of moderate right-sided pleural effusion with lung atelectasis (figure 1A). Contrast-enhanced CT (CECT) thorax and abdomen were taken, which showed moderate right pleural effusion with subsegmental atelectasis of the right lower lobe, causing a mild mediastinal shift to the left side (figure 1B). There was well-defined heterogeneous, hypodense lesion measuring 16.6×24.1×24 cm, showing peripheral nodular puddling of contrast on arterial phase with radial centripetal filling in delayed phases with few cystic areas replacing the right lobe of the liver (figure 2). The lesion was displacing the remaining of the right lobe and left lobe towards the left hypochondriac region. The lesion compressed the infrahepatic and intrahepatic portions of the IVC.

Figure 1.

Image showing; (A): X-ray chest with right-sided pleural effusion (arrow) and right lung atelectasis and (B): CT thorax showing right-sided pleural effusion with right lung lower zone atelectasis (arrow).

Figure 2.

Contrast-enhanced CT images showing; (A–C)—hepatic haemangioma of liver depicted by arrow (arterial phase), (D)—hepatic haemangioma depicted by arrow (venous phase), (E)—prominent azygous vein depicted by arrow, and (F)—hepatic haemangioma depicted by arrow (portal phase).

Diagnostic pleural fluid tapping was done for biochemical, microbiological and cytological analysis. Pleural fluid cytology smears were highly cellular with clusters of benign reactive mesothelial cells. Cytology and immunohistochemical markers were negative for malignancy (figure 3). Pleural fluid was negative for routine bacterial culture, mycobacterial culture and cartridge-based nucleic acid amplification test for tuberculosis. Biochemical analysis was suggestive of fluid being transudative. Whole-body positron emission tomography-CT (PET-CT) was done, and there was no pathological focus of fluorodeoxyglucose uptake in the chest region. The right lobe of the liver showed a hypermetabolic, hypodense lesion measuring 25×18×20 cm in size with intense peripheral areas of focal contrast enhancement, which was suggestive of HH (figure 4A).

Figure 3.

Cytological images of pleural fluid analysis; (A)—cell block showing rich lymphocytes (red arrow) and mesothelial cell (black arrow), (B)—desmin staining of the mesothelial cell (arrow), (C)—MGG staining (arrow) and (D)—PAP staining (arrow). MGG, May-Grunwald Giemsa; PAP, Papanicolaou stain.

Figure 4.

Image showing; (A): positron emission tomography-CT with FDG uptake in hepatic haemangioma (yellow arrow) and (B): chest X-ray showing persistent pleural effusion. FDG, fluorodeoxyglucose.

Therapeutic tapping of the pleural effusion was done twice—repeat chest X-ray showed recurrence of effusion (figure 4B). Despite multiple investigations, the cause for right-sided pleural effusion was not clear. After a few days patient started developing bilateral pedal and scrotal oedema (figure 5). Intercostal drain (ICD) was placed for pleural effusion due to its refractory nature (figure 6). Tube drainage was charted and was found to have persistent 500 mL to 700 mL effluent everyday.

Figure 5.

Clinical picture; (A): bilateral pedal oedema (arrows) and (B): penile and scrotal oedema (arrows).

Figure 6.

Chest X-ray showing intercostal drain (arrow).

Cardiac causes for the bilateral pedal oedema were ruled out. Renal and LFT were within normal limits. Colour Doppler of the IVC was done, which showed compression of IVC without any thrombus in the lumen. The patient was started on a diuretic and salt-restricted diet. With conservative treatment, oedema was persistent, although the severity was reduced. A venogram was performed to evaluate the status of IVC. Venogram revealed a shift of IVC towards the left side with compression without any thrombus with prominent azygous and hemiazygous veins.

Due to the persistence of the symptoms, we did embolisation of the right hepatic artery (video 1). The postprocedure patient improved well without any complications. Over 1 week, bilateral pedal oedema, penile oedema and scrotal oedema were resolved (figure 7), and ICD output was reduced to less than 100 mL/day. High-resolution CT thorax was done, which showed minimal right-sided pleural effusion (figure 8). ICD was removed once the drainage became less than 30 mL. The patient was discharged after 1-week asymptomatic period following ICD drain removal. The patient was followed up after discharge from the hospital. The patient had improved symptomatically.

Video 1.

bcr-2021-245374supp000.mp4 ^{(668.9KB, mp4)}

DOI: 10.1136/bcr-2021-245374.video01

Figure 7.

Image showing; (A): resolved pedal oedema (arrows) and (B): resolved penile and scrotal oedema (arrow).

Figure 8.

High-resolution CT showing right-sided intercostal drain (arrow) with minimal pleural effusion.

Outcome and follow-up

The patient was followed up every 3 months for 2 years after discharge from the hospital. The patient had improved symptomatically. There was no evidence of the recurrence of the pleural effusion and pedal oedema. CECT scan of the chest and abdomen was done during the follow-up after 1 year. There was a moderate reduction in the size of the haemangioma. The width had reduced from 21.63 cm to 17.10 cm, and length had reduced from 25.01 cm to 23.4 cm (figure 9). The infrahepatic IVC, which was 2.27 cm in diameter before right hepatic artery embolisation, had reduced to a size of 1.79 cm in diameter (figure 10). The patient also had improved symptomatically, without any recurrence of the symptoms.

Figure 9.

Contrast-enhanced CT abdomen (at the same level) comparing the size of the hepatic haemangioma; (A) (before the right hepatic artery embolisation) the length is 25.01 cm and the width is 21.63 cm, and (B) (after 1 year of right hepatic artery embolisation): the length is 23.40 cm and the width is 17.10 cm.

Figure 10.

Contrast-enhanced CT abdomen (at the same level) comparing the size of the infrahepatic inferior vena cava (IVC) (yellow arrow); (A) (before the right hepatic artery embolisation): Diameter of the IVC was 2.27 cm, and (B) (after 1 year of right hepatic artery embolisation): Diameter of the IVC was 1.79 cm.

Discussion

HH is the most common solid liver tumours, accounting for 70% of all benign liver lesions. HH is seen most commonly in women with a man–woman ratio of 1:5. The majority of haemangiomas are less than 5 cm. HH larger than 5 cm is considered as giant HH.

HH arises from the small blood vessels and capillaries of the liver and consists of vascular spaces lined by the endothelial cells. The pathogenesis of HH is unclear, but it is found to have some hormonal influence. It has been found that there is an accelerated growth of haemangioma during high oestrogen states like puberty, pregnancy, oral contraceptive use and androgen treatment. In our patient, there were no such predisposing factors that could increase haemangioma size.

Haemangiomas are heterogeneous tumours consisting of endothelial cells, supporting pericytes, myeloid cells and fibroblast cells. Haemangiomas are thought to be arising from uncontrolled proliferation of the endothelial cells, which can be due to somatic mutations or abnormal cellular signals. There are two theories proposed to explain the origin of the HH from the endothelial cells.¹² According to the one theory, it was found that the early haemangioma expresses CD34 and lymphatic endothelial hyaluronan receptor (LYVE)-1. As these markers are found on the angioblast, which is arrested in an early stage of vascular development, it was thought that the endothelial cells of the haemangioma are derived from these angioblasts. Another theory states that the endothelial cells in the liver might have been derived from non-clonal sources such as bone marrow and placenta. It is hypothesised that the placental endothelial cells might have embolised to receptive fetal tissues during gestation.¹² The aetiology and the molecular origin of HH have been summarised (table 1).

Table 1.

HH origin and aetiology

HH features	Explanation
Origin of the HH	HH arises from the small blood vessels and capillaries of the liver and consists of vascular spaces lined by the endothelial cells.
Cause of HH	The pathogenesis of HH is unclear, but it is found to have some hormonal influence.
Molecular origin	These arise due to uncontrolled proliferation of the endothelial cells derived from clonal expansion or nonclonal expansion.

HH, hepatic haemangioma.

Haemangiomas are usually found incidentally. Although haemangiomas remain stable, there are few reports in the literature about their rapid growth. Age is one of the factors that are known to accelerate haemangioma. Liu et al. had conducted a study and found that age is an essential factor affecting the prevalence and growth rate of liver haemangioma. Maximum growth was observed between 30 and 39 years of age.¹³ Although our patient was 35-year old, we could not predict how much it has contributed to the growth of the haemangioma.

Large HH are usually asymptomatic. However, giant HH cases present with abdominal mass or compressive symptoms to the adjacent organ. There are case reports published in the literature where patients presented with Budd Chiari syndrome,¹⁴ IVC compression leading to pedal oedema,¹⁵ fever due to inflammatory changes in haemangioma,¹⁶ obstructive jaundice due to bile duct compression and Kasabach Merritt syndrome¹⁷ as a result of giant HH. Our patient had isolated right-sided pleural effusion and pedal oedema, probably due to compression of the IVC by HH.

As right-sided effusion was proven to be non-malignant and transudative, we presumed that the effusion is secondary to HH. We hypothesise that compression and obstruction to IVC lead to the reversal of flow. Blood flows through the common iliac vein and then into the ascending lumbar veins, draining into the azygous vein and then to the superior vena cava. The transudative pleural effusion resulted from increased hydrostatic pressure in the azygous vein, draining the intercostal veins.

Blood parameters like LFT and other blood investigations are usually normal. Diagnosis is mainly by imaging. USG abdomen shows a homogenous hyperechoic mass with well-defined margins with acoustic enhancement. The echogenicity may vary as cystic and fibrotic areas may be present. The CECT abdomen shows peripheral and globular lesion enhancement, followed by a central enhancement on delayed phases.¹⁸ MRI shows a hypointense lesion on T1-weighted sequences and a strongly hyperintense lesion on heavily T2-weighted sequences with a ‘light bulb’ pattern.¹⁹ In our patient, USG and CECT abdomen were diagnostics of HH; hence, we did not do MRI.

There are various differential diagnoses of the HH. These space-occupying liver lesions can be diagnosed and categorised by the liver imaging studies like USG, CT and MRI. The selection of the imaging modality always depends on the diagnostic accuracy of the test and the safety of the patients. USG is the preferred initial investigation of choice, as it is widely available, low cost and lacks radiation exposure. CT scan is the usual investigation of the choice for the space-occupying lesion of the liver. It provides the exact anatomical details and multiphase image acquisition with intravenous contrast agents. MRI has the advantage of excellent soft tissue contrast enhancement and no exposure to ionising radiation but is associated with higher cost and lack of widespread availability. The various differential of the HH and their CT features have been summarised (table 2).

Table 2.

Various differential diagnoses of space-occupying lesion of the liver and their imaging features

Lesion of the liver	Ultrasonography and Doppler features	CT features	MRI features
Haemangioma	A homogenous hyperechoic lesion with low flow	Peripheral nodular enhancement on arterial phase with centripetal filling in the delayed phase.	Hypointense on T1-weighted images and hyperintense on T2 weighted images.
Focal nodular hyperplasia	Homogenous hypoechoic or isoechoic with central arterial signal	Homogenous enhancement on arterial phase, isodense on portal venous phase and a hyperdense scar on delayed phase.	Isointense on T1-weighted images and isointense to slightly hyperintense on T2-weighted images.
Hepatic epithelioid haemangioendothelioma	A variable pattern of echogenicity	Minimal enhancement in the arterial phase, rim-like enhancement in the portal venous phase, and gradual centripetal fill-in enhancement in the delayed phase.	Low signal intensity on T1-weighted images and homogenous target shaped high signal intensity on T2-weighted images.
Hepatic adenoma	Heterogenous echogenicity	Homogenous enhancement on arterial phase and isodense on the venous phase.	Hyperintense on T1-weighted images and isointense or hyperintense on T2-weighted images with loss of signal on out of phase T1-weighted images
Nodular regenerative hyperplasia	Normal liver with multiple isoechoic or hyperechoic nodule	Non-enhancing sub-centimetric nodules	Hyperintense on T1-weighted images and variable intensity on T2-weighted images.
Hepatic cyst	Sharply defined anechoic with posterior acoustic shadowing	Water attenuated on non-contrast phase and does not enhance on contrast CT	Hypointense on T1-weighted images and markedly hyperintense on T2 weighted images
Hepatocellular carcinoma	Hyperechoic, hypoechoic or mixed pattern	Enhancement in the arterial phase and rapid washout in the portal venous phase and hypodense in the delayed phase.	Variable intensity on T1-weighted images and hyperintense on T2-images.
Fibrolamellar variant of hepatocellular carcinoma	Well-defined mass with mixed echogenicity with a central area of hyperechogenicity	Heterogeneously enhancing on arterial phase with variable enhancement pattern on portal venous and delayed phases.	Hypointense to isointense on T1-weighted images and slightly hyperintense on T2-weighted images. A central scar is hypointense on both phases
Intrahepatic cholangiocarcinoma	Hypoechoic mass lesion	A peripheral rim of enhancement on the arterial phase with progressive central enhancement in the portal venous phase and delayed phase.	Isointense to hypointense on T1-weighted images and hyperintense on T2-weighted images

Treatment of HH is indicated only in symptomatic patients. Surgical resection remains the definitive treatment. Hepatic artery ligation,⁸ radiation therapy,⁹ hepatic artery embolisation,⁷ RFA¹⁰ and liver transplantation¹¹ are various other modalities of treatment. Although embolisation of the HH is not the definitive treatment, we successfully managed our patient of symptomatic HH with selective embolisation of the branch of the right hepatic artery, as it was not feasible to do hepatectomy owing to its large size. To the best of our knowledge, it is the first case of giant HH causing IVC compression manifesting with right-sided pleural effusion and bilateral pedal oedema.

Patient’s perspective.

I came to the hospital with mild breathlessness and mass in my abdomen. I was seen by my treating doctors and was admitted to the hospital. My doctors had noticed a swelling in my neck. I underwent several imaging investigations and was informed that there is benign tumour in the liver and fluid in my thorax.

I started developing bilateral limb swelling, which was gradually increasing along with scrotal and penile swelling. My treating surgeons and radiologist had discussed with me the need for embolisation for large liver tumours.

After the procedure, they shifted me to ICU. Thanks to my doctors who had counselled my family and me as we were much apprehended. Almost after 3 months of staying in the hospital, I was discharged and was asked for a frequent follow-up. I improved symptomatically well with reduction with both limb swelling and breathlessness. I was pleased to go back home. I will always be thankful to my treating surgeons that they never let the confidence down in me and were always ready to help me.

Learning points.

• Hepatic haemangioma (HH) is usually asymptomatic and does not need intervention unless they grow enormously and become symptomatic. Patients with giant HH may present with unusual clinical features of retrohepatic IVC compression-like bilateral pedal oedema, scrotal oedema or penile oedema and pleural effusion. Hence, patients with isolated right-sided pleural effusion should be thoroughly investigated for the underlying cause.

• Surgical treatment ranging from resection to transplantation and other minimally invasive treatment modalities like radiotherapy, radiofrequency ablation and embolisation are available.

• Hepatic artery embolisation should be considered the first treatment modality in the surgical candidate or in patients where surgery is not feasible. However, further studies are needed to prove the effectiveness of embolisation in HH.

• In cases of giant hepatic haemangioma, surgeons should never forget that HH may grow in size in the future, causing more symptoms. Hence regular follow-up visits are required.

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