Hypervascular nodule in a fibrotic liver overloaded with iron: identification of a premalignant area with preserved liver architecture
© Sá Cunha et al; licensee BioMed Central Ltd. 2005
Received: 21 December 2004
Accepted: 04 May 2005
Published: 04 May 2005
The presence of a hypervascular nodule in a patient with cirrhosis is highly suggestive of a hepatocellular carcinoma.
A 55 year old man with idiopathic refractory anaemia was addressed for the cure of a recently appeared 3.3 cm hypervascular liver nodule. The nodule was not visible on the resected fresh specimen, but a paler zone was seen after formalin fixation. The surrounding liver was fibrotic (METAVIR score F3) and overloaded with iron. However, the paler zone, thought to be the nodule, had in fact a normal architecture, was less fibrotic, and contained some "portal tract-like structures" (but with arteries only); moreover, this paler area was devoid of iron, contained less glycogen and was characterized by foci of clear hepatocytes.
In spite of the absence of architectural distortion, and a normal proliferative index, the possibility of premalignancy or malignancy should be considered in this type of hypervascular and hyposiderotic nodule, occurring in the context of an iron overloaded liver.
The presence of a hypervascular nodule in a patient with liver disease is highly suggestive of a hepatocellar carcinoma (HCC) . Increased iron stores in patients with HCC developed on a non-cirrhotic liver is well documented [2–5]; iron stores are seldom depleted at the time of the discovery of the HCC . Few cases of premalignant nodules associated with HCC have also been reported under these circumstances [7, 8]. In a fibrotic liver overloaded with iron, we report a case of a hypervascular and hyposiderotic nodule with premalignant features, but with a normal architecture.
A 55 year old man with idiopathic refractory anaemia was addressed to our Unit for the cure of a recently appeared 3.3 cm hypervascular liver nodule in segment II (November, 2003). Physical examination was normal, including BMI. Liver function tests were as follows: ASAT = 53 IU/L (Normal = 40); ALAT = 58 IU/L (N = 50); Billirubin = 44 μmol/L (N = 17); PT = 70% (N = 70–100); V = 65% (N = 70–100); RBC = 2.9 × 106 cells/μl; Ht = 22.5% and Hb = 7.3 gm/dl; WBC = 4.6 × 103 cells/μl; and platelets = 210 × 109 /l. Ferritinemia was 1891 ng/l (N < 300), transferrin saturation was 100% (N < 40), iron concentration was 290 μmol/g (assessed by MRI, N < 36). AFP in blood was within the normal range. The patient, of Italian origin, was C282 Y -/-, H63D +/-, and S65C -/-, with no family history of iron overload. Markers for viral and autoimmune diseases were negative. Blood glucose was normal. He used to smoke 30 cigarettes per day; but had stopped for the last 8 years. He drank alcohol only occasionally. The treatment of his refractory anaemia consisted in blood transfusion (total of 10 packs), Desferoxamine, and Deferiprone.
The mechanism accounting for the major hepatic iron overload is possibly multifactorial, including refractory sideroblastic anemia and blood transfusion, although the patient received only a limited number (<10) of blood transfusions. An associated hereditary iron overload such as transferrin receptor 2 haemochromatosis in this Italian patient cannot be ruled out.
Premalignant lesions have previously been described in iron overloaded patients in the absence of cirrhosis, although these lesions were discovered in the clinical context of a HCC [7, 8]. To our knowledge, this is the first reported case of a premalignant area mimicking by imaging a HCC, but exhibiting microscopically a still well-preserved architecture, in an otherwise fibrotic liver.
The hyperarterialized nodule did not correspond to a macroscopically visible nodule, but rather to an ill-defined area with preserved architectural organization. However, this area was considered as premalignant based on the following arguments: arterial hypervascularization with isolated arteries in the parenchyma ; loss of iron , and of glycogen; and presence of clear hepatocytes foci . The diagnosis of a focal nodular hyperplasia (FNH)-like nodule as described in cirrhosis [12–14], particularly related to alcohol, seems unlikely due to the loss of iron and to the presence of clear hepatocytes foci. Nonetheless, that diagnosis cannot be ruled out, and should always be kept in mind, especially if a liver transplantation is foreseen. Recently, it has been reported that coexisting iron overload could significantly worsen the course of FNH . Unfortunately, and because no frozen material of the lesion (which was not visible) was available, in this case no specific molecular studies could be carried out to settle that important issue.
The possibility of premalignancy or malignancy should be considered even in the absence of cirrhosis, when a nodule is observed in a patient with past or present liver iron overload.
List of abbreviations used
cellular retinol-binding protein 1
focal nodular hyperplasia
magnetic resonance imaging
periodic acid Schiff
red blood cells
α-smooth muscle actin
white blood cells.
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