Extramedullary haematopoiesis presenting as a periportal mass

Abstract

Extramedullary haematopoiesis (EMH) is defined as haematopoiesis occurring in organs outside the bone marrow. The liver is one of the rare sites of EMH, and to the best of our knowledge, a few cases of adult EMH of the liver have been reported in the last 20 years. Here, we reported the case of a 68-year-old man with a known history of myelofibrosis presented with vague abdominal pain. An abdominal CT scan showed a hypoattenuating periportal mass encasing the portal vein. The final diagnosis of EMH was made through the histopathological examination. This is a rare presentation of EMH, which may be easily mistaken for other pathologies such as metastases. Familiarity with this type of presentation aids in correctly diagnosing it in an appropriate clinical setting.

Background

Extramedullary haematopoiesis (EMH) is defined as haematopoiesis occurring outside the bone marrow. It occurs in various organs including liver, spleen, lymph nodes, kidney, paravertebral regions, peritoneum and pleural cavity. EMH in the liver may present as mass-like lesions that can easily mimic the appearance of tumorous infiltration on imaging workup including CT scan. Recognition of radiological presentations of EMH in various organs, such as liver, is helpful for making a correct diagnosis.

Case presentation

A 68-year-old man, a known case of myelofibrosis, presented with vague abdominal pain for 2 months. The diagnosis was established 3 years before, using bone marrow biopsy after the patient’s initial presentation with fatigue, dyspnoea and easy bruising. During the physical examination, no fever, jaundice or abdominal distension was noted, and the only abnormal finding was a palpable spleen. Laboratory findings at the time of admission were haemoglobin of 120 g/L, platelet count of 84×10⁹/L and leucocyte count of 17×10⁹/L.

Investigations

As a further evaluation, a contrast-enhanced abdominal CT scan was performed, which showed an infiltrative hypoattenuating periportal mass with subtle enhancement in the equilibrium phase. No intravenous invasion or venous thrombosis was observed (figure 1). A percutaneous biopsy was obtained under the guide of sonography. The histopathological examination revealed multiple megakaryocytes and erythroid cells with some myeloid precursors within sinusoids and portal tracts, consistent with the diagnosis of EMH (figure 2).

Figure 1.

Axial sections of the dynamic contrast-enhanced CT scan of the abdomen at the liver level demonstrating two periportal hypoattenuating mass-like lesions (black arrows) encasing portal tracts in the arterial (A, B) and equilibrium (C, D) phases. The periportal masses show slight enhancement during the equilibrium phase (C, D). No portal vein thrombosis or invasion was detected.

Figure 2.

H&E staining. (A) Lower power micrograph showing extramedullary haematopoiesis in the background of the liver tissue. (B) A high power view of the same section showing megakaryocytes (white arrows) and erythroid series (yellow arrow), confirming the diagnosis of extramedullary haematopoiesis.

Differential diagnosis

The main differential diagnosis for multiple liver lesions includes metastases, abscesses and a nodular type of fatty deposition. Metastatic lesions and liver abscesses often show a variable degree of enhancement. Focal fatty changes generally do not have a well-defined border or cause any mass effect; however, nodular fatty infiltration can be problematic, and may require other imaging techniques or biopsy for confirmation.

Outcome and follow-up

Based on the result of the biopsy, no specific treatment was pursued for the liver lesions. The patient was discharged with cytoreductive medication (hydroxyurea). At the 3-month follow-up sonography, detectable lesions were similar to those of the previous study, and no new lesion was found.

Discussion

EMH is a physiological compensatory phenomenon occurring secondary to insufficient bone marrow function.¹ This marrow productive dysfunction results from either marrow failure (eg, infiltrative disease) or ineffective circulation of mature blood elements (eg, haemoglobinopathies).² Ineffective erythropoiesis and the body compensatory mechanism lead to mass-like haematopoietic tissue proliferation outside the bone medulla.³

Many organs may be involved by EMH, including the spleen, liver, lymph nodes, thymus, heart, breast, intestine, kidneys, adrenal glands, pleura, retroperitoneal tissue, paraspinal region and even intracranial haematopoiesis.^{4 5} Hepatic involvement by EMH in adults is rare and usually shows a diffuse infiltrative pattern. However, it may also appear as focal mass mimicking a neoplastic process.⁶

The first intrahepatic EMH was reported in 1989 by Kobayashi et al.⁷ To our knowledge, among the reported intrahepatic cases of EMH, less than 12% occurred in the periportal location (table 1).

Table 1.

Clinical and radiological presentation of extramedullary haematopoiesis in liver

Author	Age/sex	Location in liver	Underlying disease	Clinical presentation	Sonography	CT	MRI
Lee et al8	33 F	Single focal intrahepatic	Myelofibrosis and essential thrombocytaemia	Lt flank mass Hepatosplenomegaly	_	Hypodense lesion with enhancement in venous phase	T1: low T2: hyper intense Arterial enhancement No dropout in opp and in SPIO T2*
Kwak and Lee9	59 F	Single focal intrahepatic	Idiopathic myelofibrosis	Fever and malaise, hepatomegaly	Ill-defined inhomogeneous hypoechoic	Ill-defined hypodense focal surface retraction Patchy enhancement	_
Belay et al 12	52 M	Single focal intrahepatic	Myelofibrosis	W/u for bone marrow transplant	Hypoechoic Internal vascularity	_	T1: hypo T2: iso heterogeneous Mild arterial enhancement and iso in venous Not vivible in T2*
Wong et al13	51 F	Single focal intrahepatic	Beta thalassaemia	Referred for splenectomy	Heterogenous hypoechoic	Heterogeneously hypodense Hyperdense post contrast Central stellate hypo in delayed	T1: hyper to liver T2: heterogenous (iso to muscle) Central stellate, moderate enhancement, stellate delayed enhance.
Jelali et al14	32 F	Multiple	Sickle cell homozygote	Twofold increased bili Positive HCV	Normal liver size without mass	Iso-dense in precontrast Homogenous enhance in venous phase	T1\T2: hyper to liver iso to muscle Moderate enhances on later images
La Fianza et al15	59 M	Single near the hepatic hilum	Myelofibrosis	Hepatic failure Hepatosplenomegaly and abdominal LAP No biliary obstruction	Near hepatic hilum hypoechoic tissue Irregular margin	Hypodense mass involving intrahepatic bile ducts and encasing the common duct and GB Minimal delayed enhance.	Solid tissue surrounding biliary tree T2: slight hyper and T1: hypo, contrast-enhanced: in homogenously filled on delayed
Gupta et al16	44 M	Multiple intrahepatic masses	Noonan syndrome	Generalised weakness Hypokalaemia Cushingoid appearance	Multiple hyperechoic masses	Multiple well-defined slightly heterogeneous fat density lesions No enhancement	_
Aytaç et al17	60 M	Single focal intrahepatic	Idiopathic myelofibrosis	Fatigue Weight loss Hepatosplenomegaly	Well-defined, inhomogeneous solid mass	Well-marginated lobulated hypodense No enhancement	_
Panda et al18	35 M	Periportal mass	Idiopathic myelofibrosis	Fatigue, abdominal distention	_	Normal	T2: periportal hypointense lesions
Pulini et al19	23 F	Single focal intrahepatic	Idiopathic myelofibrosis	Abdominal pain and oral bleed	_	_	T2: non-homogeneous liver with hypointense areas T1: hyperintense without nodular lesions
Nvarro et al20	82 M	Periportal mass massive	Newly diagnosed myelofibrosis	Pre-op w\u for inguinal hernia operation	Solid hyperechoic lesion in periportal	Well-defined, lobulated, hypodense No enhancement	_
Tamiolakis et al21	62 M	Single focal intrahepatic	Newly diagnosed idiopathic myelofibrosis	General malaise, fever Hepatomegaly	Ill-defined inhomogenous hypoechoic mass	Ill-defined low attenuation mass with post contrast patchy enhancement	_
Priola et al22	36 F	Multiple intrahepatic masses	Alfa thalassemia intermedia	Asymptomatic Splenomegaly	Two hypoechoic lesions	_	Note: confirmation by Fe52 scintigraphy
Shakeri et al23	15 F	Single focal intrahepatic	Beta thalassaemia major	Asymptomatic	Large hypoechoic mass	Well-defined hypodense solid mass with homogenous enhancement and central necrosis	_
Barrier et al24	7 F	Single focal intrahepatic	Sickle cell disease	Abdominal distension, fever, anaemia, respiratory distress, fatigue	Large solid echogenic mass	_	_
Maffione et al25	38 M	Single focal intrahepatic	Burkitt lymphoma after filgrastim administration	Asymptomatic	_	_	Note: abnormal FDG uptake in PET/CT
Al-Dalahmah et al26	_	Multiple intrahepatic masses	Sickle cell disease	Asymptomatic	_	Well-demarcated non-enhancing	T1 hypointense, T2 hyperintense with diffusion restriction

FDG, fluorodeoxyglucose; GB, Gallbladder; HCV, Hepatitis C virus; LAP, lymphadenopathy; Lt, Left; opp, out of phase; SPIO, superparamagnetic iron oxide; w/u, work up.

Ultrasonographic studies of focal intrahepatic EMH show homogenously hypoechoic or hyperechoic lesions encircling the portal vein and its branches.⁸ All reported EMH lesions located in the periportal area are hypoattenuating on CT scan, and show no or mild enhancement after injection of contrast, which appears to be related to the intralesion fibrosis.⁹ This pattern of enhancement is in contrast to infiltrative periportal neoplastic processes such as lymphoma, leukaemia and peribiliary colorectal cancer metastases.¹⁰ The other non-neoplastic differential diagnosis with similar imaging appearance is periportal oedema in patients with congestive heart failure or acute hepatitis.¹¹ The histopathological examination, in which multiple megakaryocytes as well as erythroid and myeloid precursors in sinusoids and portal tracts are noted, confirms the final diagnosis of EMH.

In recent studies on intrahepatic EMH, the T2* MR sequence is also used to differentiate the mass forming intrahepatic EMH from other neoplastic processes. While tumefactive haematopoiesis appears as isointense to background liver on the T2*-weighted gradient echo sequence, neoplastic lesions such as adenoma or hepatic metastasis appear hyperintense.¹² However, more data are needed on imaging manifestations of periportal EMH for establishing a definite diagnosis solely based on imaging findings. Such radiological characteristics obviate invasive procedures in the proper clinical setting and exclude radiological mimickers of periportal mass lesions, most notably lymphoma and leukaemia.

Learning points.

• Extramedullary haematopoiesis (EMH) can be found in various organs.

• EMH in the liver may present as single or multiple mass lesions.

• The periportal region is an important site of involvement in the liver.

• Non-enhancing or slowly enhancing lesions, especially in the periportal region, in those with predisposing factors for EMH should be regarded as highly suspicious for EMH.