|
1
|
Du X, Wang HL. Rare Liver Diseases With Near-Normal Histology: A Review Focusing on Metabolic, Storage, and Inclusion Disorders. Adv Anat Pathol 2025:00125480-990000000-00139. [PMID: 39973759 DOI: 10.1097/pap.0000000000000488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Despite the growing availability of noninvasive and faster diagnostic modalities, biopsy remains an important tool in the diagnosis and management of liver diseases. However, it is not uncommon that liver biopsies reveal normal or near normal histologic findings in patients with abnormal liver biochemistries, elevated autoantibodies, clinical findings suggestive of portal hypertension, systemic autoimmune or inflammatory diseases, hepatomegaly, cirrhosis by imaging, or other indications. These scenarios present significant diagnostic challenges and are rarely discussed in detail in the literature or textbooks. This article aims to provide a comprehensive review of a group of selected rare liver diseases, with a focus on metabolic, storage and inclusion disorders, that may exhibit a near-normal histology on biopsy. By recognizing subtle histologic features and correlating with clinical history, laboratory results and imaging findings, it is often possible to narrow down the differential diagnosis. In many cases, this integrative approach can yield a definitive diagnosis, allowing for tailored treatment and better patient outcomes.
Collapse
Affiliation(s)
- Xiaotang Du
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine and Ronald Reagan UCLA Medical Center, University of California Los Angeles, Los Angeles, CA
| | | |
Collapse
|
|
2
|
Fischer AK, Baba H, Lainka E, Kälsch J, Müller M, Zens U, Büttner R, Fischer HP. Rapid development of pseudo-ground-glass bodies in liver transplants. Histopathology 2024; 85:190-192. [PMID: 38622086 DOI: 10.1111/his.15188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 03/01/2024] [Accepted: 03/16/2024] [Indexed: 04/17/2024]
Affiliation(s)
| | - Hideo Baba
- Institute of Pathology, University Duisburg-Essen, Essen, Germany
| | - Elke Lainka
- Department of Paediatric Gastroenterology, Hepatology, and Transplant Medicine, Children's Hospital, University Duisburg-Essen, Essen, Germany
| | - Julia Kälsch
- Department of Gastroenterology, Hepatology and Transplant Medicine, University Duisburg-Essen, Essen, Germany
| | - Marion Müller
- Institute of Pathology, University of Cologne, Cologne, Germany
| | - Uschi Zens
- Institute of Pathology, University of Cologne, Cologne, Germany
| | | | - Hans-Peter Fischer
- MVZ of Pathology and Cytology Rhein-Sieg, Troisdorf, Germany
- Institute of Pathology, University of Bonn, Bonn, Germany
| |
Collapse
|
|
3
|
Shaheen M, Lei GS, Relich RF, Jarasvaraparn C, Tolliver KM, Molleston JP, González IA. Granulomas in Pediatric Liver Biopsies: Single Center Experience. Pediatr Dev Pathol 2024; 27:218-227. [PMID: 38221675 DOI: 10.1177/10935266231221908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2024]
Abstract
BACKGROUND Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago. METHODS Single-center retrospective study of GPLB. RESULTS Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Histoplasma-like yeast; microbiological cultures were negative in all cases (no: 4). A 18S and 16S rRNA gene sequencing performed in 15 cases revealed only 1 with a pathogenic microorganism, Mycobacterium angelicum. CONCLUSION In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.
Collapse
Affiliation(s)
- Muhammad Shaheen
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Guang-Sheng Lei
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Ryan F Relich
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Chaowapong Jarasvaraparn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Kyla M Tolliver
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Jean P Molleston
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Iván A González
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| |
Collapse
|
|
4
|
Bellamy CO, Burt AD. Liver in Systemic Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:1039-1095. [DOI: 10.1016/b978-0-7020-8228-3.00015-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
5
|
Quaglia A, Roberts EA, Torbenson M. Developmental and Inherited Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:122-294. [DOI: 10.1016/b978-0-7020-8228-3.00003-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
6
|
Soon GST, Torbenson M. The Liver and Glycogen: In Sickness and in Health. Int J Mol Sci 2023; 24:ijms24076133. [PMID: 37047105 PMCID: PMC10094386 DOI: 10.3390/ijms24076133] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/20/2023] [Accepted: 03/23/2023] [Indexed: 04/14/2023] Open
Abstract
The liver is a major store of glycogen and is essential in maintaining systemic glucose homeostasis. In healthy individuals, glycogen synthesis and breakdown in the liver are tightly regulated. Abnormal glycogen metabolism results in prominent pathological changes in the liver, often manifesting as hepatic glycogenosis or glycogen inclusions. This can occur in genetic glycogen storage disease or acquired conditions with insulin dysregulation such as diabetes mellitus and non-alcoholic fatty liver disease or medication effects. Some primary hepatic tumors such as clear cell hepatocellular carcinoma also demonstrate excessive glycogen accumulation. This review provides an overview of the pathological manifestations and molecular mechanisms of liver diseases associated with abnormal glycogen accumulation.
Collapse
Affiliation(s)
- Gwyneth S T Soon
- Department of Pathology, National University Hospital, Singapore 119074, Singapore
| | - Michael Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
| |
Collapse
|
|
7
|
Clavien PA, Dutkowski P, Mueller M, Eshmuminov D, Bautista Borrego L, Weber A, Muellhaupt B, Sousa Da Silva RX, Burg BR, Rudolf von Rohr P, Schuler MJ, Becker D, Hefti M, Tibbitt MW. Transplantation of a human liver following 3 days of ex situ normothermic preservation. Nat Biotechnol 2022; 40:1610-1616. [PMID: 35641829 DOI: 10.1038/s41587-022-01354-7] [Citation(s) in RCA: 91] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 05/09/2022] [Indexed: 01/13/2023]
Abstract
Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure.
Collapse
Affiliation(s)
- Pierre-Alain Clavien
- Department of Surgery and Transplantation, Swiss Hepato-Pancreato-Biliary (HPB) and Transplant Center, University Hospital Zurich, Zurich, Switzerland. .,Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland.
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss Hepato-Pancreato-Biliary (HPB) and Transplant Center, University Hospital Zurich, Zurich, Switzerland
| | - Matteo Mueller
- Department of Surgery and Transplantation, Swiss Hepato-Pancreato-Biliary (HPB) and Transplant Center, University Hospital Zurich, Zurich, Switzerland.,Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland
| | - Dilmurodjon Eshmuminov
- Department of Surgery and Transplantation, Swiss Hepato-Pancreato-Biliary (HPB) and Transplant Center, University Hospital Zurich, Zurich, Switzerland.,Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland
| | - Lucia Bautista Borrego
- Department of Surgery and Transplantation, Swiss Hepato-Pancreato-Biliary (HPB) and Transplant Center, University Hospital Zurich, Zurich, Switzerland.,Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland
| | - Achim Weber
- Department of Pathology and Molecular Pathology, and Institute of Molecular Cancer Research, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Beat Muellhaupt
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Richard X Sousa Da Silva
- Department of Surgery and Transplantation, Swiss Hepato-Pancreato-Biliary (HPB) and Transplant Center, University Hospital Zurich, Zurich, Switzerland.,Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland
| | - Brian R Burg
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland.,Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.,Pixium Vision, Paris, France
| | - Philipp Rudolf von Rohr
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland.,Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
| | - Martin J Schuler
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland.,Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
| | - Dustin Becker
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland.,Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
| | - Max Hefti
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland.,Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
| | - Mark W Tibbitt
- Wyss Zurich Translational Center, ETH Zurich and University of Zurich, Zurich, Switzerland.,Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
| |
Collapse
|
|
8
|
Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation. Int J Mol Sci 2022; 23:ijms23179996. [PMID: 36077394 PMCID: PMC9456521 DOI: 10.3390/ijms23179996] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 07/27/2022] [Accepted: 08/03/2022] [Indexed: 11/17/2022] Open
Abstract
Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor’s liver. Under the electron microscope (EM), the stored material within the cytosol appeared as non-membrane-bound aggregates of electron-lucent globoid or fibrillar granules, previously described as abnormally structured glycogen and identified as Polyglucosan bodies (PB). The appearance of GGG in our children was analogous to that of PB-GGG occurring in a number of congenital diseases due to gene mutations such as Lafora’s d., Andersen’s d., Adult Polyglucosan Body Disease and glycogenin deficiency. The same type of GGG was previously reported in the liver of patients undergoing transplants, immunosuppressive or antiblastic treatment. To explore the potential mechanism of GGG formation, we examined whether the drugs after whose treatment this phenomenon was observed could have a role. By carrying out molecular docking, we found that such drugs somehow present a high binding affinity for the active region of glycogenin, implicating that they can inactivate the protein, thus preventing its interaction with glycogen synthase (GS), as well as the maturation of the nascent glycogen towards gamma, beta or alfa glycogen granules. We could also demonstrate that PG inclusions consist of a complex of PAS positive material (glycogen) and glycogen-associated proteins, i.e., glicogenin-1 and -2 and ubiquitin. These features appear to be analogous to congenital GGG, suggesting that, in both cases, they result from the simultaneous dysregulation of glycogen synthesis and degradation. Drug-induced GGG appear to be toxic to the cell, despite their reversibility.
Collapse
|
|
9
|
Ground-glass hepatocellular inclusions are associated with polypharmacy. Ann Diagn Pathol 2021; 52:151740. [PMID: 33836412 DOI: 10.1016/j.anndiagpath.2021.151740] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/18/2021] [Accepted: 03/28/2021] [Indexed: 11/22/2022]
Abstract
Ground-glass (GG) hepatocytes are classically associated with chronic hepatitis B (HBV) infection, storage disorders, or cyanamide therapy. In a subset of cases, an exact etiology cannot be identified. In this study, we sought to characterize the clinical, histological, and ultrastructural findings associated with HBV-negative GG hepatocytes. Our institutional laboratory information system was searched from 2000 to 2019 for all cases of ground-glass hepatocytes. Ten liver biopsies with GG hepatocellular inclusions and negative HBV serology, no known history of storage disorders, or cyanamide therapy were reviewed. Half of the patients had history of organ transplantation and/or malignancy. These patients took on average 8.1 medications (range: 3-14) with the most common medications being immunosuppressive and health supplements. Histologically, GG hepatocytes show either peri-portal or centrizonal distribution. The inclusions are PAS-positive and diastase sensitive. Electron microscopy showed intracytoplasmic granular inclusions with low electron density, consistent with unstructured glycogen. In summary, GG hepatocytes are a rare finding in liver biopsies, but are more common in patients with hepatitis B. They can also be seen in HBV-negative patients who have polypharmacy. In these cases, they are the result of unstructured glycogen accumulation putatively due to altered cell metabolism.
Collapse
|
|
10
|
Deniz K. Ground Glass-Like Inclusions: Associated with Liver Toxicity. Turk Patoloji Derg 2021; 37:51-55. [PMID: 33021734 PMCID: PMC10508930 DOI: 10.5146/tjpath.2020.01510] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 09/11/2020] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE The etiology of ground glass-like inclusions is heterogenous and the pathology has been described in various conditions including HBV infection, Lafora's disease, fibrinogen storage disease, type IV glycogenosis, and alcohol reversion therapy. Similar ground glass-like inclusions are also associated with immunosuppressed conditions and multiple medications, for which the clinical significance is still unclear. Additional cases, some with previously unreported unique etiologies, and their follow-up were described in this study. MATERIALS AND METHODS Eleven cases were examined between 2008 and 2019 for this study. The clinical data and histologic slides were reviewed. All of the cases were negative for Hepatitis B virus. None of the patients declared alcohol intake or a history of epilepsy. RESULTS Liver histology showed mild lobular inflammation in most of the cases (72%). Ground glass-like hepatocytes were distributed in the patchy-panlobular, periportal, and centrizonal pattern at 55%, 27%, and 18%, respectively. Clinical history revealed medication use in nine (82%) patients including NSAIDs, steroids, and chemotherapy. Ground glass-like inclusions were related to herbal toxicity in two of the patients. Liver function tests were elevated in all of the cases. Follow-up data revealed four patients with malignancy who died of their cancer. Seven patients showed resolution of elevated liver enzymes with a median follow-up period of 37 months (range 7-132 months). CONCLUSIONS Medication is the most relevant etiology for the development of these inclusions. Ground glass-like inclusions may also seen in herbal toxicity. Transplantation was not an etiologic factor in our patients. Most of the patients displayed an indolent course with resolution of the elevated transaminases.
Collapse
Affiliation(s)
- Kemal Deniz
- Department of Pathology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| |
Collapse
|
|
11
|
Besnard C, Schmitt C, Galmiche-Rolland L, Debray D, Fabre M, Molina T, Gouya L, Ged C, Castelle M, Cavazzana M, Magrin E, Neven B, Moshous D, Blanche S, Frémond ML. Bone Marrow Transplantation in Congenital Erythropoietic Porphyria: Sustained Efficacy but Unexpected Liver Dysfunction. Biol Blood Marrow Transplant 2019; 26:704-711. [PMID: 31843562 DOI: 10.1016/j.bbmt.2019.12.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 11/29/2019] [Accepted: 12/09/2019] [Indexed: 12/11/2022]
Abstract
Congenital erythropoietic porphyria (CEP) is a rare disease characterized by erosive photosensitivity and chronic hemolysis due to a defect of the enzyme uroporphyrinogen-III-synthase (UROS). To date, hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the devastating early and severe form of the disease. We describe 6 patients with CEP treated with HSCT (3 of them twice after failure of a first graft) between 1994 and 2016 in our center, including 2 of the very first living patients treated more than 20 years ago. Four patients are doing well at 6 to 25 years post-HSCT, with near-normal biochemical parameters of porphyrin metabolism without the cutaneous or hematologic features of CEP. One patient died within the first year after HSCT from severe graft-versus-host disease (GVHD), and 1 child died of unexplained acute hepatic failure at 1 year after HSCT, despite full donor chimerism. Retrospectively, it appears that all but 1 child had increased transaminase activity with onset from the early postnatal period, which was significantly more marked in the child who died of liver failure. In contrast, liver function values progressively normalized after engraftment in all other children. Liver pathology before HSCT for 3 patients revealed varying degrees of portal, centrilobular, and perisinusoidal fibrosis; clarification of hepatocytes; and cytosolic porphyrin deposits. The liver porphyrin content in biopsy specimens was >60 times the normal values. Despite difficult engraftment, the long-term efficacy of HSCT in CEP appears to be favorable and reinforces its benefits for the severe form of CEP. Hepatic involvement requires careful evaluation before and after HSCT and further investigation into its pathophysiology and care.
Collapse
Affiliation(s)
- Caroline Besnard
- Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France
| | - Caroline Schmitt
- French Center of Porphyrias, Louis Mourier Hospital, AP-HP, Colombes and Research Center of Inflammation, UMR1149 INSERM, Université de Paris, Paris, France
| | | | - Dominique Debray
- Pediatric Hepatology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France
| | - Monique Fabre
- Pathology Department, Necker Enfants Malades Hospital, AP-HP, Paris, France
| | - Thierry Molina
- Pathology Department, Necker Enfants Malades Hospital, AP-HP, Paris, France
| | - Laurent Gouya
- French Center of Porphyrias, Louis Mourier Hospital, AP-HP, Colombes and Research Center of Inflammation, UMR1149 INSERM, Université de Paris, Paris, France
| | - Cécile Ged
- Biotherapy of Genetic Diseases, Inflammatory Disorders, and Cancers, U1035 INSERM, Bordeaux University, Bordeaux, France
| | - Martin Castelle
- Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France
| | - Marina Cavazzana
- Biotherapy Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France
| | - Elisa Magrin
- Biotherapy Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France
| | - Bénédicte Neven
- Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France
| | - Despina Moshous
- Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France
| | - Stéphane Blanche
- Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France.
| | - Marie-Louise Frémond
- Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France
| |
Collapse
|
|
12
|
Meyerson C, Naini BV. Something old, something new: liver injury associated with total parenteral nutrition therapy and immune checkpoint inhibitors. Hum Pathol 2019; 96:39-47. [PMID: 31669893 DOI: 10.1016/j.humpath.2019.10.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 10/09/2019] [Indexed: 02/06/2023]
Abstract
Drug-induced liver injury (DILI) is a challenging and constantly changing field. The pathologist plays a key role in interpreting liver biopsies by classifying the pattern of injury, grading the severity of injury, and evaluating for other possible causes. Reports of iatrogenic liver injury are reviewed here with a focus on total parenteral nutrition (ie, intestinal failure-associated liver disease [IFALD]) and immune checkpoint inhibitors (ICIs). The hallmark features of IFALD are cholestasis and steatosis. Cholestasis is more common in infants, whereas steatosis and steatohepatitis are more commonly seen in older children and adults. Infants tend to have a faster progression to fibrosis and cirrhosis. Perivenular fibrosis and ductopenia may also be seen in IFALD. Although fish oil-based lipid emulsions can reverse cholestasis, recent studies have shown persistent or progressive fibrosis. ICI-induced liver injury usually presents as an acute hepatitis with features similar to those seen in idiopathic autoimmune hepatitis and drug-induced autoimmune hepatitis. However, it lacks a prominent plasma cell infiltrate and serological markers of autoimmune hepatitis. Other features such as fibrin ring granulomas and cholangitis have also been reported in association with ICIs. Treatment for ICI-induced liver injury includes corticosteroids and other immunosuppressants.
Collapse
Affiliation(s)
- Cherise Meyerson
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA
| | - Bita V Naini
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA.
| |
Collapse
|
|
13
|
Buglioni A, Wu TT, Mounajjed T. Immunohistochemical and Ultrastructural Features of Hepatocellular Cytoplasmic Globules in Venous Outflow Impairment. Am J Clin Pathol 2019; 152:563-569. [PMID: 31268521 DOI: 10.1093/ajcp/aqz068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES To examine the immunohistochemical and ultrastructural features of hepatocellular cytoplasmic globules in venous outflow impairment (VOI). METHODS Sixty-four liver core biopsies were screened. Patients with α-1 antitrypsin (AAT) deficiency were excluded. All biopsies were stained with H&E, Masson trichrome, periodic acid-Schiff with diastase digestion (PAS-D), phosphotungstic acid hematoxylin (PTAH), complement protein 4d (C4d) immunostain, and AAT immunostain. Electron microscopy was also performed. RESULTS Hepatocellular globules were identified in 8% of in-house cases. Causes of VOI included heart failure and Budd-Chiari syndrome. The hepatocellular cytoplasmic globules showed size variability, random distribution, and positivity for PAS-D, PTAH, and AAT. C4d was inconsistently positive. Electron microscopy showed that the globules were lysosome-bound inclusions containing microfibrillar material and fibrinogen. CONCLUSIONS PAS-D-positive hepatocellular globules occur in VOI. They cross-react with AAT but have different appearance, localization, and ultrastructural composition from globules in AAT deficiency.
Collapse
Affiliation(s)
- Alessia Buglioni
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Tsung-Teh Wu
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Taofic Mounajjed
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| |
Collapse
|
|
14
|
Koch LK, Yeh MM. Nonalcoholic fatty liver disease (NAFLD): Diagnosis, pitfalls, and staging. Ann Diagn Pathol 2018; 37:83-90. [PMID: 30312882 DOI: 10.1016/j.anndiagpath.2018.09.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 09/25/2018] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and strongly associated with obesity, diabetes and the metabolic syndrome, not only in the Western societies, but also in most regions of the world in the 21st century. The spectrum of its histopathology ranges from steatosis to nonalcoholic steatohepatitis (NASH), with risk for progressive fibrosis that may lead to cirrhosis and hepatocellular carcinoma (HCC). Benign and malignant liver tumors have also been more frequently reported with the increasing prevalence of obesity and diabetes. This review addresses the pathology of NAFLD and NASH, and their diagnostic features, diagnostic pitfalls, grading and staging, and clinical correlation.
Collapse
Affiliation(s)
- Lisa K Koch
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States of America
| | - Matthew M Yeh
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States of America; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, United States of America.
| |
Collapse
|
|
15
|
Abstract
Drug-induced liver injury (DILI) is constantly changing as new drugs are approved and as new herbals and dietary supplements (HDS) reach the market. The pathologist plays a key role in the evaluation of DILI by classifying and interpreting the histologic findings considering patients' medical history and drug exposure. The liver biopsy findings may suggest alternative explanations of the injury and additional testing that should be performed to exclude non-DILI causes. Recent reports of iatrogenic liver injury are reviewed with attention to immunomodulatory and antineoplastic agents as well as reports of injury associated with HDS use.
Collapse
Affiliation(s)
- David E Kleiner
- Laboratory of Pathology, National Cancer Institute, 10 Center Drive, Building 10, Room 2S235, MSC1500, Bethesda, MD 20892, USA.
| |
Collapse
|
|
16
|
Hytiroglou P. Hepatitis B. PRACTICAL HEPATIC PATHOLOGY: A DIAGNOSTIC APPROACH 2018:211-221. [DOI: 10.1016/b978-0-323-42873-6.00014-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
17
|
|
|
18
|
Quaglia A, Roberts EA, Torbenson M. Developmental and Inherited Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2018:111-274. [DOI: 10.1016/b978-0-7020-6697-9.00003-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
|
|
19
|
Bannasch P, Ribback S, Su Q, Mayer D. Clear cell hepatocellular carcinoma: origin, metabolic traits and fate of glycogenotic clear and ground glass cells. Hepatobiliary Pancreat Dis Int 2017; 16:570-594. [PMID: 29291777 DOI: 10.1016/s1499-3872(17)60071-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 08/14/2017] [Indexed: 02/05/2023]
Abstract
Clear cell hepatocellular carcinoma (CCHCC) has hitherto been considered an uncommon, highly differentiated variant of hepatocellular carcinoma (HCC) with a relatively favorable prognosis. CCHCC is composed of mixtures of clear and/or acidophilic ground glass hepatocytes with excessive glycogen and/or fat and shares histology, clinical features and etiology with common HCCs. Studies in animal models of chemical, hormonal and viral hepatocarcinogenesis and observations in patients with chronic liver diseases prone to develop HCC have shown that the majority of HCCs are preceded by, or associated with, focal or diffuse excessive storage of glycogen (glycogenosis) which later may be replaced by fat (lipidosis/steatosis). In ground glass cells, the glycogenosis is accompanied by proliferation of the smooth endoplasmic reticulum, which is closely related to glycogen particles and frequently harbors the hepatitis B surface antigen (HBsAg). From the findings in animal models a sequence of changes has been established, commencing with preneoplastic glycogenotic liver lesions, often containing ground glass cells, and progressing to glycogen-poor neoplasms via various intermediate stages, including glycogenotic/lipidotic clear cell foci, clear cell hepatocellular adenomas (CCHCA) rich in glycogen and/or fat, and CCHCC. A similar process seems to take place in humans, with clear cells frequently persisting in CCHCC and steatohepatitic HCC, which presumably represent intermediate stages in the development rather than particular variants of HCC. During the progression of the preneoplastic lesions, the clear and ground glass cells transform into cells characteristic of common HCC. The sequential cellular changes are associated with metabolic aberrations, which start with an activation of the insulin signaling cascade resulting in pre-neoplastic hepatic glycogenosis. The molecular and metabolic changes underlying the glycogenosis/lipidosis are apparently responsible for the dramatic metabolic shift from gluconeogenesis to the pentose phosphate pathway and Warburg-type glycolysis, which provide precursors and energy for an ever increasing cell proliferation during progression.
Collapse
Affiliation(s)
| | - Silvia Ribback
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald, Germany
| | - Qin Su
- Cell Marque, Millipore-Sigma Rocklin, USA
| | - Doris Mayer
- German Cancer Research Center, Heidelberg, Germany
| |
Collapse
|
|
20
|
Abstract
Histochemical and immunostains are routinely used to evaluate medical liver biopsy specimens. The use of these special stains allows the identification of more clinically important information than is available on hematoxylin and eosin stains alone. These special stains are important for evaluating active and chronic injury and for establishing a specific diagnosis. The skillful use of these stains greatly improves patient care. Information on the use of special stains can be scattered in different sources, making the information hard to access. In this article, the use of special stains in medical liver biopsies is concisely reviewed.
Collapse
|
|
21
|
Shulman HM, Cardona DM, Greenson JK, Hingorani S, Horn T, Huber E, Kreft A, Longerich T, Morton T, Myerson D, Prieto VG, Rosenberg A, Treister N, Washington K, Ziemer M, Pavletic SZ, Lee SJ, Flowers MED, Schultz KR, Jagasia M, Martin PJ, Vogelsang GB, Kleiner DE. NIH Consensus development project on criteria for clinical trials in chronic graft-versus-host disease: II. The 2014 Pathology Working Group Report. Biol Blood Marrow Transplant 2015; 21:589-603. [PMID: 25639770 DOI: 10.1016/j.bbmt.2014.12.031] [Citation(s) in RCA: 201] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Accepted: 12/24/2014] [Indexed: 12/17/2022]
Abstract
The 2005 National Institute of Health (NIH) Consensus Conference outlined histopathological diagnostic criteria for the major organ systems affected by both acute and chronic graft-versus-host disease (GVHD). The 2014 Consensus Conference led to this updated document with new information from histopathological studies of GVHD in the gut, liver, skin, and oral mucosa and an expanded discussion of GVHD in the lungs and kidneys. The recommendations for final histological diagnostic categories have been simplified from 4 categories to 3: no GVHD, possible GVHD, and likely GVHD, based on better reproducibility achieved by combining the previous categories of "consistent with GVHD" and "definite GVHD" into the single category of "likely GVHD." Issues remain in the histopathological characterization of GVHD, particularly with respect to the threshold of histological changes required for diagnostic certainty. Guidance is provided for the incorporation of biopsy information into prospective clinical studies of GVHD, particularly with respect to biomarker validation.
Collapse
Affiliation(s)
- Howard M Shulman
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Diana M Cardona
- Department of Pathology, Duke University Medical Center, Durham, North Carolina
| | - Joel K Greenson
- Department of Pathology, University of Michigan, Ann Arbor, Michigan
| | - Sangeeta Hingorani
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Departments of Pediatrics, Gastroenterology and Pathology, University of Washington, Seattle, Washington; Seattle Children's Hospital, Seattle, Washington
| | - Thomas Horn
- Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts
| | - Elisabeth Huber
- Institute of Pathology, University of Regensburg, Regensburg, Germany
| | - Andreas Kreft
- Institute of Pathology, University Medical Center Mainz, Mainz, Germany
| | - Thomas Longerich
- Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany
| | - Thomas Morton
- Departments of Pediatrics, Gastroenterology and Pathology, University of Washington, Seattle, Washington
| | - David Myerson
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington
| | - Victor G Prieto
- Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
| | - Avi Rosenberg
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Nathaniel Treister
- Division of Oral Medicine and Dentistry, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
| | - Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee
| | - Mirjana Ziemer
- Department of Dermatology, University Hospital of Leipzig, Leipzig, Germany
| | - Steven Z Pavletic
- Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland
| | - Stephanie J Lee
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Mary E D Flowers
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Kirk R Schultz
- Department of Pediatrics, BC Children's Hospital/University of British Columbia, Vancouver, British Columbia
| | - Madan Jagasia
- Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Paul J Martin
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Georgia B Vogelsang
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - David E Kleiner
- Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
| |
Collapse
|
|
22
|
Strnad P, Nuraldeen R, Guldiken N, Hartmann D, Mahajan V, Denk H, Haybaeck J. Broad Spectrum of Hepatocyte Inclusions in Humans, Animals, and Experimental Models. Compr Physiol 2013; 3:1393-436. [DOI: 10.1002/cphy.c120032] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
|
|
23
|
Bannasch P. Glycogenotic hepatocellular carcinoma with glycogen-ground-glass hepatocytes: A heuristically highly relevant phenotype. World J Gastroenterol 2012; 18:6701-6708. [PMID: 23239906 PMCID: PMC3520157 DOI: 10.3748/wjg.v18.i46.6701] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Revised: 09/21/2012] [Accepted: 11/15/2012] [Indexed: 02/06/2023] Open
Abstract
Glycogenotic hepatocellular carcinoma (HCC) with glycogen-ground-glass hepatocytes has recently been described as an allegedly “novel variant” of HCC, but neither the historical background nor the heuristic relevance of this observation were put in perspective. In the present contribution, the most important findings in animal models and human beings related to the emergence and further evolution of excessively glycogen storing (glycogenotic) hepatocytes with and without ground glass features during neoplastic development have been summarized. Glycogenotic HCCs with glycogen-ground-glass hepatocytes represent highly differentiated neoplasms which contain subpopulations of cells phenotypically resembling those of certain types of preneoplastic hepatic foci and benign hepatocellular neoplasms. It is questionable whether the occurrence of glycogen-ground-glass hepatocytes in a glycogenotic HCC justifies its classification as a specific entity. The typical appearance of ground-glass hepatocytes is due to a hypertrophy of the smooth endoplasmic reticulum, which is usually associated with an excessive storage of glycogen and frequently also with an expression of the hepatitis B surface antigen. Sequential studies in animal models and observations in humans indicate that glycogen-ground-glass hepatocytes are a facultative, integral part of a characteristic cellular sequence commencing with focal hepatic glycogenosis potentially progressing to benign and malignant neoplasms. During this process highly differentiated glycogenotic cells including ground-glass hepatocytes are gradually transformed via various intermediate stages into poorly differentiated glycogen-poor, basophilic (ribosome-rich) cancer cells. Histochemical, microbiochemical, and molecular biochemical studies on focal hepatic glycogenosis and advanced preneoplastic and neoplastic lesions in tissue sections and laser-dissected specimens in rat and mouse models have provided compelling evidence for an early insulinomimetic effect of oncogenic agents, which is followed by a fundamental metabolic switch from gluconeogenesis towards the pentose-phosphate pathway and the Warburg type of glycolysis during progression from preneoplastic hepatic glycogenosis to the highly proliferative malignant phenotype.
Collapse
|
|
24
|
Sacher VY, Bejarano PA, Pham SM. Tacrolimus induced hepatotoxicity in a patient with bilateral lung transplant. Transpl Int 2012; 25:e111-2. [PMID: 22909288 DOI: 10.1111/j.1432-2277.2012.01546.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
25
|
Drebber U, Torbenson M, Wedemeyer I, Dienes H. Aktuelle Aspekte zur Histopathologie im Rahmen der Lebertransplantation. DER PATHOLOGE 2011; 32:113-23. [DOI: 10.1007/s00292-010-1405-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
26
|
Khamashta MA, Ramos-Casals M. Complex Situations in Patients with Adult-Onset Still’s Disease. Autoimmune Dis 2011. [PMCID: PMC7122824 DOI: 10.1007/978-0-85729-358-9_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology, characterized by quotidian or double quotidian fever, a peri-febrile cutaneous eruption, polyarthritis, and multiorgan involvement. AOSD is a challenging disease with protean disease manifestations and rare, albeit potentially life-threatening, complications. In such cases, prompt diagnosis and treatment may prove life-saving. The purpose of this chapter is to review the diagnosis and management of challenging clinical situations in AOSD patients that are associated with significant morbidity and mortality and to provide the readers with information that could aid their decision-making process.
Collapse
Affiliation(s)
- Munther A. Khamashta
- Rayne Institute, Lupus Research Unit, St. Thomas' Hospital, London, SE1 7EH United Kingdom
| | - Manuel Ramos-Casals
- Barcelona, Surgey, Hospital Clinic, Calle Villarroel, 170, Barcelona, 08036 Spain
| |
Collapse
|
|
27
|
Hytiroglou P. Hepatitis B. PRACTICAL HEPATIC PATHOLOGY: A DIAGNOSTIC APPROACH 2011:215-224. [DOI: 10.1016/b978-0-443-06803-4.00017-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
28
|
|
|
29
|
Sari A, Tunakan M, Ozmen M, Turkkan E. Ground-glass-like hepatocellular inclusions in the course of adult-onset Still's disease. Mod Rheumatol 2009; 20:90-2. [PMID: 19802652 DOI: 10.1007/s10165-009-0233-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 08/31/2009] [Indexed: 11/28/2022]
Abstract
Ground-glass hepatocytes are the cardinal biopsy feature of chronic hepatitis B virus (HBV) infection and may also be present in other specific conditions, including Lafora's disease, cyanamide aversion therapy for alcohol use, patients with transplantation, uremia, and metabolic disorders. In this report, we present the case of a patient with adult-onset Still's disease who underwent percutaneous liver biopsy, which revealed ground-glass-like cytoplasmic inclusions and which is a very unusual finding.
Collapse
Affiliation(s)
- Ayşegul Sari
- Pathology Department, Izmir Ataturk Training and Research Hospital, Izmir, Turkey.
| | | | | | | |
Collapse
|
|
30
|
Brown RM, Gray G, Poulton K, Wassmer E, Gupte G. Ground glass hepatocellular inclusions caused by disturbed glycogen metabolism in three children on parenteral nutrition. Pediatr Dev Pathol 2009; 12:79-80. [PMID: 19006417 DOI: 10.2350/08-09-0523.1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2008] [Accepted: 10/19/2008] [Indexed: 11/20/2022]
Affiliation(s)
- Rachel Mary Brown
- Department of Histopathology, Birmingham Childrens, Hospital, Birmingham, United Kingdom
| | - George Gray
- Department of Clinical Chemistry, Birmingham Childrens, Hospital, Birmingham, United Kingdom
| | - Kelvin Poulton
- Muscle Biopsy Service, University Hospital, Birmingham, United Kingdom
| | - Evangaline Wassmer
- Department of Neurology, Birmingham Childrens Hospital, University Hospital, Birmingham, United Kingdom
| | - Girish Gupte
- Department of Hepatology, Birmingham Childrens Hospital, University Hospital, Birmingham, United Kingdom
| |
Collapse
|
|
31
|
Micchelli STL, Thomas D, Boitnott JK, Torbenson M. Hepatic giant cells in hepatitis C virus (HCV) mono-infection and HCV/HIV co-infection. J Clin Pathol 2008; 61:1058-61. [PMID: 18682418 DOI: 10.1136/jcp.2008.058560] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The clinical and biological significance of syncytial giant cell change of hepatocytes in hepatitis C viral (HCV) infection is poorly understood. AIM To investigate the clinical and histological correlates of giant cell transformation in the setting of HCV mono-infection and co-infection with HCV and HIV. METHODS The prevalence of hepatocyte giant cell transformation was determined and serological, biochemical and histological findings examined. RESULTS Among 856 liver biopsy specimens, 22 cases (2.6%) showed giant cell transformation, representing 18 individuals. The median serum ALT was 37 IU/l, AST 49 IU/l, and alkaline phosphatase 97 IU/l. Eleven cases had HCV RNA loads available, with a median HCV RNA of 5.52 log IU/ml. Twelve of 17 individuals with available test results were also HIV positive (71%), compared to 46% of controls (p = 0.08). Giant cell transformation was found exclusively in zone 3 hepatocytes; the accompanying histological findings were otherwise typical of chronic HCV. The hepatic giant cells typically had a cytoplasmic appearance that resembled smooth endoplasmic reticulum proliferation. Most cases had only mild inflammation and fibrosis, with a median modified hepatic activity index (MHAI) grade of 3/18 and a median MHAI stage of 1/6. Three individuals had follow-up biopsies; all continued to have giant cell change. CONCLUSION Giant cell transformation occurs most commonly in the setting of HCV/HIV co-infection, but can also be seen in chronic HCV infection alone. Histologically, giant cells were located in zone 3 hepatocytes, were persistent over time, and do not appear to be a marker of aggressive hepatitis.
Collapse
Affiliation(s)
- S T L Micchelli
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | | | | |
Collapse
|
|
32
|
O'Shea AM, Wilson GJ, Ling SC, Minassian BA, Turnbull J, Cutz E. Lafora-like ground-glass inclusions in hepatocytes of pediatric patients: a report of two cases. Pediatr Dev Pathol 2007; 10:351-7. [PMID: 17929993 DOI: 10.2350/06-12-01948.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2006] [Accepted: 01/14/2007] [Indexed: 11/20/2022]
Abstract
We report 2 cases of ground-glass hepatocyte inclusions occurring in pediatric patients. Case 1 had alpha-thalassaemia major and was receiving iron chelation therapy, whereas case 2 had trisomy 21 with a history of bone marrow transplantation for acute myeloid leukemia. The liver sections in both cases showed eosinophilic, periodic acid-Schiff diastase-positive intracytoplasmic inclusions that were negative for hepatitis B surface antigen. Immunohistochemically the inclusions showed positive staining with KM279, a monoclonal antibody against polyglucosan derived from Lafora inclusions. On electron microscopy, in case 1, intracytoplasmic inclusions were composed of degenerate organelles, glycogen, and irregular fibrillar structures; in case 2, they were composed of vesicular structures containing granular material. Ultrastructural changes in both cases differed from classical Lafora inclusions and ruled out hepatitis B surface antigen, glycogenosis type IV, and fibrinogen storage disease. Genetic analysis of the Lafora's disease genes performed in case 2 revealed no mutations. The development of hepatocyte cytoplasmic inclusions in both our cases could be related to medication effects, because similar inclusions were reported in patients using cyanamide. Drug-induced inclusions, mimicking Lafora's disease, should be included in the differential diagnosis of hepatocyte ground-glass inclusions.
Collapse
Affiliation(s)
- Anne-Marie O'Shea
- Department of Pathology and Laboratory Medicine, The Mount Sinai Hospital, Toronto, Ontario, Canada
| | | | | | | | | | | |
Collapse
|
|
33
|
Abstract
PURPOSE OF REVIEW Recent papers on disorders of the liver and biliary tract which clarify their pathogenesis and attendant morphologic changes are highlighted. RECENT FINDINGS The concept of 'bystander hepatitis' was cited in studies showing hepatic infiltration of CD8-positive T cells in the setting of extrahepatic infections such as influenza virus and severe acute respiratory syndrome. Diabetic liver lesions include glycogenic hepatopathy (in which poor diabetic control leads to swollen, glycogen-filled hepatocytes without fat, steatohepatitis or fibrosis) and diabetic hepatosclerosis in which there is diffuse perisinusoidal fibrosis (type IV collagen) without zonal predilection. Ground-glass hepatocellular inclusions (positive with periodic acid-Schiff stain for glycogen) were reported in three separate series of patients who were hepatitis B virus-negative, often transplant recipients, immunosuppressed and on multiple medications. A Banff consensus paper expertly compared and contrasted the histologic features which characterize the various causes of late liver allograft dysfunction. SUMMARY Informative papers emerged this past year concerning collateral damage to the liver in extrahepatic infections, diabetic lesions and causes of liver dysfunction after transplantation, among other topics.
Collapse
Affiliation(s)
- Jay H Lefkowitch
- Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
| |
Collapse
|