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Year : 2018  |  Volume : 61  |  Issue : 2  |  Page : 302-304
Liver histology in cholesteryl ester storage disease

1 Department of Pathology, Gleneagles Global Health City, Chennai, Tamil Nadu, India
2 Department of Pediatric hepatology, Rainbow Hospitals, Hyderabad, Telangana, India

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Date of Web Publication20-Apr-2018

How to cite this article:
Vij M, Bachina P. Liver histology in cholesteryl ester storage disease. Indian J Pathol Microbiol 2018;61:302-4

How to cite this URL:
Vij M, Bachina P. Liver histology in cholesteryl ester storage disease. Indian J Pathol Microbiol [serial online] 2018 [cited 2021 Jun 15];61:302-4. Available from: https://www.ijpmonline.org/text.asp?2018/61/2/302/230543


We report a 7-year, 8-month-old girl who is a known case of a cyanotic congenital heart disease (subaortic ventricular septal defect) diagnosed at 2 years of age and now presented to us with a history of fever for 4 days and abdominal distension. She was hemodynamically stable. There was no icterus and lymphadenopathy. Liver was palpable 6 cm below the right costal margin and spleen 2 cm below the left costal margin. Her weight was 19.5 kg. There was a history of twin sibling (sister) death who had liver disease. In view of suspected liver disease, she was admitted. Liver function tests revealed serum glutamic oxaloacetic transaminase 95 U/L, serum glutamic pyruvic transaminase 119 U/L, total bilirubin 0.5 mg/dl, and alkaline phosphatase 351 U/L. Protein was 7.9 g/dl and albumin was 4 g/dl. The patient had significant dyslipidemia. Ultrasound revealed hepatosplenomegaly. A liver biopsy was performed. Light microscopy showed liver tissue with largely maintained lobular architecture. The portal tracts were expanded with fibrosis and extension of thin fibrous septa into adjacent lobular parenchyma with focal porto-portal bridging fibrosis [Figure 1]. Prominent collection of foamy histiocytes with ceroid pigment was noted in the portal tracts [Figure 2]. There was patchy sinusoidal collection of foamy histiocytes containing ceroid [Figure 3]. There was diffuse microvesicular steatosis [Figure 4]. Periodic acid–Schiff after diastase (PASD) highlighted the macrophages. We diagnosed the liver biopsy as suggestive of cholesteryl ester storage disease (CESD). We also advised estimation of Lysosomal Acid Lipase (LAL). The LAL was deficient with approximately 1.1% of mean normal activity being obtained in leukocytes. Her diet modification was done and she is currently doing well.
Figure 1: Liver biopsy with portal expansion and bridging fibrosis (H and E, ×40)

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Figure 2: Cluster of foamy histiocytes is noted in portal tract (H and E, ×200)

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Figure 3: Cluster of foamy histiocytes is noted in perivenular region (H and E, ×200)

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Figure 4: Microvesicular steatosis (periodic acid–Schiff, ×200)

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CESD is a rare autosomal recessive, lysosomal storage disorder caused by LAL deficiency. The lysosomal acid lipase (LIPA) gene is located on chromosome 10.[1] LAL hydrolyses CE and triglycerides, and deficiency states result in lysosomal accumulation of lipids.[2] LAL deficiency can be expressed in two major phenotypic variants: Wolman's disease (WD), which has an early onset in neonatal period/infancy, and the more benign later-onset disease CESD.[3] Complete absence or <1% of LAL activity results in WD, whereas CESD is due to partial loss of enzyme activity (1%–12%).[2] Liver pathology in CESD is characterized by plenty of foamy histiocytes seen in portal and periportal areas and sinusoidal clusters around central veins.[1] These macrophages also contain ceroid pigment. Patchy to diffuse microvesicular steatosis is also identified. Macrovesicular steatosis is rare. Portal and periportal fibrosis may be marked, and there may even be micronodular cirrhotic transformation. Differential diagnosis includes other lysosomal storage diseases.[3],[4] In Gaucher's disease, macrophages and Kupffer cells show characteristic corrugated (wrinkled paper) appearance. In Niemann–Pick disease, sinusoidal macrophages show foamy appearance and some hepatocytes demonstrate vacuolations. Mucopolysaccharidoses show marked vacuolization and swelling of some Kupffer cells and hepatocytes.[5] In infantile GM1, gangliosidosis vacuolation of Kupffer cells and hepatocytes is present. Farber's disease is characterized by collections of histiocytes and systemic lipogranulomas with multinucleated cells progressing to fibrosis. In metachromatic leukodystrophy, liver may show metachromatic granules in some portal macrophages and less often in Kupffer cells and hepatocytes.[3],[4] Severe mitochondrial dysfunction associated with certain drug/toxin injury can show microvesicular steatosis.[2] One important differential diagnosis is nonalcoholic steatohepatitis (NASH), which is characterized by macrovesicular steatosis, hepatocellular ballooning, lobular inflammation, and Mallory–Denk bodies.[4] The presence of macrovesicular steatosis in NASH is important, as its presence is less supportive for a diagnosis of CESD. To conclude, pathological diagnosis of CESD requires a high index of suspicion, and distinctive features can be appreciated in light microscopy, even in routine fixed paraffin-embedded liver samples.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Bernstein DL, Hülkova H, Bialer MG, Desnick RJ. Cholesteryl ester storage disease: Review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol 2013;58:1230-43.  Back to cited text no. 1
Pant M, Oshima K. Cholesteryl ester storage disease: An underdiagnosed cause of cirrhosis in adults. Ann Diagn Pathol 2017;31:66-70.  Back to cited text no. 2
Hůlková H, Elleder M. Distinctive histopathological features that support a diagnosis of cholesterol ester storage disease in liver biopsy specimens. Histopathology 2012;60:1107-13.  Back to cited text no. 3
Jevon GP, Dimmick JE. Histopathologic approach to metabolic liver disease: Part 1. Pediatr Dev Pathol 1998;1:179-99.  Back to cited text no. 4
Resnick JM, Whitley CB, Leonard AS, Krivit W, Snover DC. Light and electron microscopic features of the liver in mucopolysaccharidosis. Hum Pathol 1994;25:276-86.  Back to cited text no. 5

Correspondence Address:
Mukul Vij
Department of Pathology, Gleneagles Global Health City, Chennai - 600 100, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_260_17

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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