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Clinical, histopathological, and immunohistochemical spectrum of hepatolithiasis: a tertiary care center-based study from north India

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Abstract

Hepatolithiasis (HL), an uncommon disease among Indians, occurs due to a complex interplay of various structural and functional factors. We retrospectively evaluated the clinical and histopathological spectrum of HL (N = 19) with immunohistochemical evaluation for biliary apomucins and canalicular transporter proteins, both crucial for lithogenesis. Nineteen surgically resected cases were included. Histopathology was systematically evaluated. Immunohistochemistry for apomucins (MUC1, MUC2, MUC4, MUC5AC, and MUC6) and canalicular transporter proteins (BSEP and MDR3) was applied to all cases. The median age was 51 years with female preponderance (F:M = 1.4:1). The stone was cholesterol-rich in 71.4% and pigmented in 28.6% (n = 14). Histopathology showed variable large bile-duct thickening due to fibrosis and inflammation with peribiliary gland hyperplasia. Structural causes (Caroli disease, choledochal cyst, and post-surgical complication) were noted in 15.8% of cases (secondary HL). Expression of gel-forming apomucin MUC1, MUC2, and MUC5AC was seen in either bile duct epithelia or peribiliary glands in 84.2%, 10.5%, and 84.2% cases respectively. Loss of canalicular expression of MDR3 was noted in 42.1% of cases while BSEP was retained in all. Primary HL in the north Indian population can be associated with the loss of MDR3 expression (with retained BSEP) and/ or a shift in the phenotype of biliary apomucins to gel-forming apomucins. The former factor alters the bile acid/ phospholipid ratio while the latter parameter promulgates crystallization. In conjunction, these factors are responsible for the dominantly cholesterol-rich stones in the index population.

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The data can be accessed from the corresponding author on considerable request.

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Acknowledgements

The authors thank Dr. Abhiman Baloji, Dept. of Radiodiagnosis, for his assistance.

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  1. Sangamitra Rajasekaran and Suvradeep Mitra have contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Histopathology, PGIMER, 160012, Chandigarh, India

    Sangamitra Rajasekaran, Suvradeep Mitra, Mayur Parkhi & Ashim Das

  2. Department of Biophysics, PGIMER, 160012, Chandigarh, India

    Shalmoli Bhattacharyya

  3. Department of Surgical Gastroenterology, PGIMER, 160012, Chandigarh, India

    Rajesh Gupta, Vikas Gupta & Kailash Kurdia

  4. Department of Radiodiagnosis, PGIMER, 160012, Chandigarh, India

    Naveen Kalra

  5. Department of Hepatology, PGIMER, 160012, Chandigarh, India

    Ajay Duseja

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  1. Sangamitra Rajasekaran
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Contributions

SR collected the data, performed the statistical analysis, and prepared the first draft. MP collected the data and reviewed the manuscript. AD was involved in the diagnosis of the cases and histological analysis. SB was involved in the analysis of the stones and provided the data regarding the same. RG, VG, and KK were involved in the surgical procedures and provided the surgical data. NK was involved in the radiological diagnosis and provided data regarding the same. AD was involved in the clinical management of the cases. SM was involved in the histological diagnosis and analysis of the cases, conceptualized the idea, interpreted the data, and prepared the final draft.

Corresponding author

Correspondence to Suvradeep Mitra.

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Ethical approval

This is a retrospective study and is performed as per the Declaration of Helsinki. There is no additional cost incurred to the patient. No deferral/deviation of treatment occurred due to the inclusion in the study.

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The authors declare no competing interests.

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Rajasekaran, S., Mitra, S., Parkhi, M. et al. Clinical, histopathological, and immunohistochemical spectrum of hepatolithiasis: a tertiary care center-based study from north India. Virchows Arch 484, 491–505 (2024). https://doi.org/10.1007/s00428-023-03613-7

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