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Autoimmune pancreatitis-related diabetes: quantitative analysis of endocrine islet cells and inflammatory infiltrate

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Abstract

In autoimmune pancreatitis (AIP), mechanism(s) of paradoxical glycemic control improvement (GCI) often occurring after pancreatic resection and steroid therapy are not fully elucidated. Using image quantitation, AIP cases (n = 10) with pre- and post-surgical glucose values were compared with chronic pancreatitis (CP) and normal pancreas (NP) regarding percent chromogranin immunohistochemistry (IHC) positivity as a surrogate marker of endocrine endowment; intra-islet T and B lymphocyte and plasma cell enumeration with CD3, CD20, and IgG4 IHC; and CD34 IHC islet vascularity quantitation. Postsurgical GCI, noted in 8/10 (80%) AIP cases, approached statistical significance (P = 0.07) compared to CP. Endocrine endowment reduction, noted by a lower percent of chromogranin + pancreatic parenchyma, was seen in AIP (4.54%) and CP (3.20%) compared to NP (7.95%); only the CP decrease was statistically significant (P = 0.02) since AIP often had ductular endocrine neogenesis. Regression suggested an inverse correlation between endocrine endowment and GCI in AIP (R = 0.62, P = 0.06). AIP islets were smaller and disrupted by inflammatory cell infiltration. Compared to CP, AIP islets had higher CD3 + and CD20 + cell densities. IgG4 + plasma cells were often present at a high density in AIP but typically preserved the islets. Intra-islet CD34 staining showed a lower average vascularity in AIP compared to NP (P = 0.05). This study reaffirms postsurgical GCI in AIP. Prominent intra-islet inflammation and decreased vascularity in AIP may contribute to diabetogenic effects. Endocrine cell neogenesis and relative islet preservation despite islet inflammatory infiltration may explain the paradoxical GCI in AIP.

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Acknowledgements

The authors would like to acknowledge the laboratory assistance of the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital. The authors have no disclosures or conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Emory University Hospital, 1364 Clifton Road NE, Room H-188, Atlanta, GA, 30322, USA

    Alton B. Farris III

  2. Pathology Service, Massachusetts General Hospital, Boston, MA, USA

    Alton B. Farris III, Gregory Y. Lauwers & Vikram Deshpande

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  1. Alton B. Farris III
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  2. Gregory Y. Lauwers
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  3. Vikram Deshpande
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Correspondence to Alton B. Farris III.

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Farris, A.B., Lauwers, G.Y. & Deshpande, V. Autoimmune pancreatitis-related diabetes: quantitative analysis of endocrine islet cells and inflammatory infiltrate. Virchows Arch 457, 329–336 (2010). https://doi.org/10.1007/s00428-010-0948-y

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  • DOI: https://doi.org/10.1007/s00428-010-0948-y

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