Journal of Postgraduate Medicine
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Year : 1984  |  Volume : 30  |  Issue : 2  |  Page : 129-32  

Nodular transformation (multifocal regenerative hyperplasia) of the liver (a case report).

IM Vora, SS Deodhare 

Correspondence Address:
I M Vora

How to cite this article:
Vora I M, Deodhare S S. Nodular transformation (multifocal regenerative hyperplasia) of the liver (a case report). J Postgrad Med 1984;30:129-32

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Vora I M, Deodhare S S. Nodular transformation (multifocal regenerative hyperplasia) of the liver (a case report). J Postgrad Med [serial online] 1984 [cited 2023 Jun 7 ];30:129-32
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In spite of the availability of modern investigative techniques to determine the cause of portal hypertension, about 5% of cases remain undiagnosed. Nodular transformation of the liver is one such important, often unrecognised and a rarely reported disorder[3],[7],[9],[17] in which the nodules of hyperplastic hepatocytes develop in the liver replacing the normal architecture, and clinically mimic cirrhosis with portal hypertension. We report here such an unusual case with a brief review of the literature.


A 10 year old girl was admitted at the King Edward VII Memorial Hospital, Bombay complaining of difficulty in opening the mouth and pain in the neck since one day. There was no history of spasms, injury, otorrhoea or immunisation. A past history of repeated episodes of fever with rigors since 2 to 3 years was elicited but details of the treatment were not available.

The patient was pale, febrile and conscious with no marks of external injury. Her pulse was 120/minute. There was neck-rigidity and trismus. The left lobe of the liver was palpable 2 cm below the costal margin and was firm. The spleen was also palpable 10 cm below the costal margin. and was firm. Other systemic examination was unremarkable. A clinical diagnosis of ?idiopathic tetanus with anaemia and hepato-splenomegaly was made. However, the patient expired within 2 days. As investigations of any type are usually avoided in patients suffering from tetanus till they recover, no laboratory studies could be done on this patient.

Autopsy findings

The patient was found to be poorly nourished and anaemic. There was no icterus. The peritoneal cavity contained about 150 ml of straw coloured, watery fluid with proteins 1.5 gm%-a transudate. The liver weighed 700 gm and was firm. The surface was brownish with multiple, yellowish nodular areas all over. The cut surface showed multiple, well-circumscribed, yellowish nodules, varying from 0.5 to 3.00 cm in diameter, and all over in the liver substance; the largest nodule was 3 x 3 x 2 cm in size, located at the antero-superior surface of the left lobe (See Fig. 1 on page 132 A). In between the nodules, the liver parenchyma looked normal or congested without any fibrosis. The spleen was markedly enlarged, weighed 450 gm and was firm, with congested cut surface. There was no lymphadenopathy. Other organs were unremarkable.

The normal architecture of the liver was found to be distorted due to multiple nodules, which were either smaller or larger than the normal liver lobule (See [Fig. 2] on page 132 A). The hepatic cords in these nodules were more than one cell thick, indicating regenerative hyperplasia (See [Fig. 3] on page 132 A). This was well demarketed in the reticulin-stained preparation (See Fig. 4 on page 132 B). Occasional hepatocyte was binucleate. The hepatic venous radicles appeared to be reduced. Many smaller nodules were seen arising near the portal tract, compressing and obliterating the central vein and stretching the portal triad. This, at places, gave an impression of reverse of lobularity. Sinusoids were markedly dilated. The parenchyma adjacent to the nodules showed varying degree of compression atrophy. Further away, the sinusoids were markedly congested and dilated. The Kupffer cells looked prominent. The portal areas showed mild increase in the periportal fibrous tissue but there was no fibrosis around the nodules. Minimal condensation of reticulin fibres was seen around the nodules (See Fig. 4 on page ... ). Orcein stain for HBsAg and copper binding proteins was negative; the prussian blue reaction was also negative for haemosiderin pigment. No malarial parasites were seen. There was a solitary non-caseating granuloma; however, no organisms including acid fast facilli, parasites or fungi could be detected in it. There was no evidence of tuberculous lesion in any- of the organs. The portal vein was normal. The spleen showed features of chronic passive-congestion and showed occasional - haemopoietic focus.


The morphologic features tally with those of partial nodular transformation of the liver which was first reported by Sherlock et al, in 1966[15] However, the nodules in the present case were distributed all over instead of only perihilar distribution as described by the above authors.[15] A few more similar cases have been sporadically reported using different terminologies.[2],[3],[4],[7],[14] The various synonyms used in the literature include partial nodular transformation of the liver[2],[15] nodular regenerative hyperplasia,[14],[17],[18] non-cirrhotic nodulation,[16]hepatocellular adenomatosis[19] and adenomatous hyperplasia.[5] Stromeyer and Ishak[18] recently described the largest series of 30 cases referred from different centres elaborating the clinical and morphologic spectrum and coined the term "Nodular Trans formation of the Liver".

The aetiology remains obscure. Several associated lesions are noted with this condition. The important ones are rheumatoid arthritis,[6] Felty's syndrome,[1],[12] CRST-(calcinosis, Raynaud's phenomenon, sclero-dactyly, telangiectasia)-syndrome,[9] polycythaemia vera,[21] collagen vascular disorders,[18] lymphoproli-ferative disorders[18] and other malignant neoplasms.[18] In our case, no associated lesion was seen. Prolonged use of certain drugs such as corticosteroids, oral contraceptives, antineoplastic and immunosuppressive drugs may produce similar lesions in the livers.[10],[18],[20] The past history of drugs could not be elicited in this case. The associated features suggest an immunologic basis for pathogenesis[14],[18] The experimental evidence supports that drugs, chemicals or hormones may initiate or stimulate the growth of nodular transformation.[8],[20]

Portal hypertension is the main consequence of this lesion.[2],[4],[14] Our case showed the evidence of portal hypertension such as ascites, fibrocongestive splenomegaly and sinusoidal dilatation outside the nodules. The mechanism of portal hypertension in this condition is uncertain. Sherlock et al[15] have emphasized the compression of portal vein at the hilum by the expanding nodules. The diffuse nature of hyperplastic process makes it capable of causing interference with the hepatic vasculature at all levels, possibly producing portal hypertension. Large nodules due to size alone may give rise to compression of hepatic veins which may disturb the intrahepatic microcirculation and increase the portal pressure.[2]

Histological recognition of this lesion may be difficult or even impossible by needle biopsy material, but it may be possible by wedge-biopsy; very often, it is found as an incidental finding at autopsy as in this case.

Whether nodular transformation is premalignant or not, is still not certain, although some cases show dysplasia and an occasional association with hepatocellular carcinoma is noted.[18] Progression of similar hyperplastic nodules to carcinoma has been noted in experimental animals.[11],[13]


We thank Dr. C. K. Deshpande, Dean, Seth G.S. Medical College and K.E.M. Hospital, Bombay for allowing us to publish this case. We also thank Dr, (Smt.) Suman G. Kinare, Prof. & Head of the Department of Pathology, for making valuable suggestions in the presentation of this article.


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