Intriguing Case Globular Cytoplasmic Inclusion Bodies in a Metastatic Hepatocellular Carcinoma of the Iliac Bone

Haratake, Joji; Horie, Akio; Setojima, Masakatsu

doi:10.3109/01913129009076132

Cited by 7 publications

(3 citation statements)

References 13 publications

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“…HCC cells may contain a variety of intracytoplasmic inclusions differing in morphology and chemical composition. [1][2][3][4][5][6][7][8][9][10][11] However, IHBs (globular hyalin 1,2,4,5,11 ) have so far evaded further characterization. The HCC case presented in this communication was exceptional as IHBs were particularly numerous in the tumor cells allowing further analysis of this material.…”

Section: Discussionmentioning

confidence: 99%

“…Different types of intracytoplasmic inclusions, such as hyaline bodies, pale bodies, ␣ 1 -antitrypsin (AAT)-con-taining globules, and Mallory bodies (MBs), have been found in hepatocellular carcinoma (HCC) cells. [1][2][3][4][5][6][7][8][9][10][11] MBs are complex filamentous protein aggregates that are associated with a variety of chronic liver disorders, particularly alcoholic and non-alcoholic steatohepatitis, but also benign and malignant hepatocellular neoplasms in man and experimental animals (for review see Ref. 12).…”

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Analysis of Intracytoplasmic Hyaline Bodies in a Hepatocellular Carcinoma

Stumptner

Heid

Fuchsbichler

et al. 1999

The American Journal of Pathology

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Intracytoplasmic hyaline bodies (IHBs) resemble inclusions in hepatocellular carcinoma cells, which so far have escaped further characterization. A relationship to Mallory bodies was suggested on the basis of light microscopy and filamentous ultrastructure. A hepatocellular carcinoma containing numerous IHBs was studied. Our studies revealed immunoreactivity of IHBs with the monoclonal antibodies SMI 31 and MPM-2, which recognize hyperphosphorylated epitopes present on paired helical filaments in Alzheimer's disease brains (SMI 31) or on diverse proteins hyperphosphorylated by mitotic kinases in the M-phase of the cell cycle (MPM-2). One- and two-dimensional gel electrophoresis of tumor extracts followed by immunoblotting with SMI 31 and MPM-2 antibodies revealed a major immunoreactive protein with an apparent molecular weight between 62 and 65 kd, which was resolved into several highly acidic (pH 4.5) protein components in two-dimensional gels. This protein was undetectable in non-neoplastic liver tissue. Sequence analysis identified the SMI 31 and MPM-2 immunoreactive material as p62, indicating that p62 is a major constituent of IHBs. p62 is an only recently discovered protein that is a phosphotyrosine-independent ligand of the SH2 domain of p56(lck), a member of the c-src family of cytoplasmic kinases. Moreover, p62 binds ubiquitin and may act as an adapter linking ubiquitinated species to other proteins. These features suggest a role of p62 in signal transduction and possibly also carcinogenesis. IHBs observed in the hepatocellular carcinoma cells presented are the first indications of a role of p62 in disease.

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Section: Discussionmentioning

confidence: 99%

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Analysis of Intracytoplasmic Hyaline Bodies in a Hepatocellular Carcinoma

Stumptner

Heid

Fuchsbichler

et al. 1999

The American Journal of Pathology

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“…MBs have been morphologically and tinctorially identified in metastatic lung carcinoma to the brain (183). They have been seen in bone metastases of occult HCCs (184) and in renal cell carcinoma (185,186) and have been suggested in muscle fibers of three children with hereditary congenital neuromuscular disease, but, sadly, no other organ specimens were analyzed (187). Finally, the identical ultrastructural characteristics of MB-like inclusions in the caudate nucleus and possibly in other neurological tissue (188) support the concept of the MB as a generalized marker of impaired cell function.…”

Section: Clinical Studies Of Rare Mb-associated Conditionsmentioning

confidence: 99%

The mallory body: Morphological, clinical and experimental studies (part 1 of a literature survey)

Jensen¹,

Gluud²

1994

Hepatology

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To aid understanding of markers of disease and predictors of outcome in alcohol-exposed systems, we undertook a literature survey of more than 700 articles to view the morphological characteristics and the clinical and experimental epidemiology of the Mallory body. Mallory bodies are filaments of intermediate diameter that contain intermediate filament components (e.g., cytokeratins) observable by conventional light microscopy or immunohistochemical methods, identical in structure regardless of initiating factors or putative pathogenesis. Although three morphological types can be identified under electron microscopy (with fibrillar structure parallel, random or absent), they remain stereotypical manifestations of hepatocyte injury. A summary of the conditions associated with Mallory bodies in the literature and their validity and potential etiological relationships is presented and discussed, including estimates on the combined light microscopic and immunohistochemical prevalences and kinetics. Emphasis is placed on proper confounder control (in particular, alcohol history), which is highly essential but often inadequate. These conditions include (mean prevalence of Mallory bodies in parentheses): Indian childhood cirrhosis (73%), alcoholic hepatitis (65%), alcoholic cirrhosis (51%), Wilson's disease (25%), primary biliary cirrhosis (24%), nonalcoholic cirrhosis (24%), hepatocellular carcinoma (23%), morbid obesity (8%) and intestinal bypass surgery (6%). Studies in alcoholic hepatitis strongly suggest a hit-and-run effect of alcohol, whereas other chronic liver diseases show evidence of gradual increase in prevalence of Mallory bodies with severity of hepatic pathology. Mallory bodies in cirrhosis do not imply alcoholic pathogenesis. Obesity, however, is associated with alcoholism and diabetes, and Mallory bodies are only present in diabetic patients if alcoholism or obesity complicates the condition. In addition, case studies on diseases in which Mallory bodies have been identified, along with pharmacological side effects and experimental induction of Mallory bodies by various antimitotic and oncogenic chemicals, are presented. Mallory bodies occur only sporadically in abetalipoproteinemia, von Gierke's disease and focal nodular hyperplasia and during hepatitis due to calcium antagonists or perhexiline maleate. Other conditions and clinical drug side effects are still putative. Finally, a variety of experimental drugs have been developed that cause Mallory body formation, but markedly different cell dynamics and metabolic pathways may raise questions about the relevance of such animal models for human Mallory body formation. In conclusion, the Mallory body is indicative but not pathognomonic of alcohol involvement. A discussion on theories of development and pathological significance transcending the clinical frameworks will be presented in a future paper.

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The Neoplastic Cell

Cheville¹

2009

Ultrastructural Pathology the Comparative Cellular Basis of Disease

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Intriguing Case Globular Cytoplasmic Inclusion Bodies in a Metastatic Hepatocellular Carcinoma of the Iliac Bone

Cited by 7 publications

References 13 publications

Analysis of Intracytoplasmic Hyaline Bodies in a Hepatocellular Carcinoma

Analysis of Intracytoplasmic Hyaline Bodies in a Hepatocellular Carcinoma

The mallory body: Morphological, clinical and experimental studies (part 1 of a literature survey)

The Neoplastic Cell

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