Granular necrosis: a distinctive form of cell death in malignant tumours

Hemamali Samaratunga, Brett Delahunt, John R. Srigley, Daniel M. Berney, Liang Cheng, Andrew Evans, Bungo Furusato, Katia R.M. Leite, Gregory T. MacLennan, Guido Martignoni, Holger Moch, Chin Chen Pan, Gladell Paner, Jae Ro, Michelle Thunders, Toyonori Tsuzuki, Thomas Wheeler, Theodorus van der Kwast, Murali Varma, Sean R. WilliamsonJohn W. Yaxley, Lars Egevad

Research output: Contribution to journalReview article

Abstract

Foci of necrosis are frequently seen in malignant tumours and may be due to a variety of causes. Different types of necrosis are given various names based upon their morphological features and presumed pathogenesis, such as coagulative, liquefactive and fibrinoid necrosis. Here, we propose the term ‘granular necrosis’ (GN) for a specific form of tumour necrosis characterised by the presence of well-defined necrotic foci being sharply demarcated from adjacent viable tumour. A constant feature is loss of architecture resulting in an amorphous necrotic mass containing granular nuclear and cytoplasmic debris, without an associated neutrophilic infiltrate. There is usually extensive karyorrhexis, which in larger tumours is more prominent at the periphery. These foci are often microscopic but may range up to several millimetres or larger in size. This distinctive form of necrosis has been erroneously given a variety of names in the literature including coagulative necrosis and microscopic necrosis, which on the basis of the aforementioned gross and microscopic findings is inappropriate. It is apparent that this is a specific form of necrosis, hence the descriptive term ‘granular necrosis’ that differentiates this form of necrosis from other types. The presence of GN is recognised as occurring in a variety of tumour types, being commonly seen in renal cell carcinoma, where it has been shown to have independent prognostic significance. In some epithelial and stromal tumours of the uterus, the presence of GN also has prognostic significance and is a defining feature for the differentiation of uterine leiomyoma and leiomyosarcoma. The pathogenesis of GN is unresolved. It does not show the features of apoptosis and in recent studies has been shown to have some of the molecular changes associated with necroptosis.

Original languageEnglish (US)
Pages (from-to)507-514
Number of pages8
JournalPathology
Volume52
Issue number5
DOIs
StatePublished - Aug 2020

Keywords

  • Carcinoma
  • granular necrosis
  • high grade
  • necrosis
  • pathogenesis
  • prognosis
  • sarcoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Samaratunga, H., Delahunt, B., Srigley, J. R., Berney, D. M., Cheng, L., Evans, A., Furusato, B., Leite, K. R. M., MacLennan, G. T., Martignoni, G., Moch, H., Pan, C. C., Paner, G., Ro, J., Thunders, M., Tsuzuki, T., Wheeler, T., van der Kwast, T., Varma, M., ... Egevad, L. (2020). Granular necrosis: a distinctive form of cell death in malignant tumours. Pathology, 52(5), 507-514. https://doi.org/10.1016/j.pathol.2020.06.002