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Histopathology of Hereditary Diffuse Gastric Cancer: From Grossing and 3D Microscopy to Immunophenotypic and Molecular Profiling

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Hereditary Gastric and Breast Cancer Syndrome

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Abstract

Hereditary diffuse gastric cancer (HDGC) is one of the three inherited syndromes that affect primarily the stomach, besides gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and familial intestinal gastric cancer (FIGC). HDGC is an autosomal dominant cancer syndrome, caused by germline variants in the CDH1 and CTNNA1 genes and is associated with an increased risk of development of diffuse gastric cancer and lobular breast cancer.

In this chapter, we focus on the pathological spectrum and multiple phenotypes of HDGC from carriers of germline CDH1 variants. Particularly, the chapter will address the following topics: (1) histopathological features of HDGC intramucosal lesions, as detected in prophylactic total gastrectomy specimens, including the presentation of a novel three-dimensional model; (2) recommendations for handling prophylactic total gastrectomy specimens; (3) immunohistochemical and molecular characteristics of HDGC signet ring cell carcinoma foci; (4) macroscopic, endoscopic and histological findings of advanced HDGC; (5) morpho-molecular details distinguishing indolent and aggressive HDGC phenotypes.

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Acknowledgements

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Conflicts of Interest

The authors state that they have no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Pathology, Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal

    Irene Gullo, Carla Oliveira & Fátima Carneiro

  2. Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal

    Irene Gullo, Carla Oliveira & Fátima Carneiro

  3. Ipatimup – Institute of Molecular Pathology and Immunology of the University of Porto/i3S – Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal

    Irene Gullo, José Garcia-Pelaez, Carla Oliveira & Fátima Carneiro

  4. Department of Gastroenterology, Centro Hospitalar Universitário de São João (CHUSJ), Porto, Portugal

    Rui Morais

  5. NIHR BioResource for Translational Research, University of Cambridge, Cambridge, United Kingdom

    Yuchun Ding

Authors
  1. Irene Gullo
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  2. José Garcia-Pelaez
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  3. Rui Morais
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  4. Yuchun Ding
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  5. Carla Oliveira
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  6. Fátima Carneiro
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Corresponding author

Correspondence to Fátima Carneiro .

Editor information

Editors and Affiliations

  1. European Institute of Oncology, University of Milan, Milan, Italy

    Giovanni Corso

  2. European Institute of Oncology, University of Milan, Milan, Italy

    Paolo Veronesi

  3. University of Siena, Siena, Italy

    Franco Roviello

1 Electronic Supplementary Material

Identification of signet ring cell carcinoma foci (yellow areas) in consecutive haematoxylin and eosin sections (MP4 76911 kb)

518851_1_En_9_MOESM2_ESM.mp4

3D reconstruction of signet ring cell carcinoma foci in a stomach section from a carrier of CDH1 germline variant. The green area represents the boundaries of normal gastric mucosa, while red areas represent invasive intramucosal cancer foci. Foci were multiple and at different levels within the same fragment (MP4 7835 kb)

Supplementary Video 9.2

3D reconstruction of signet ring cell carcinoma foci in a stomach section from a carrier of CDH1 germline variant. The green area represents the boundaries of normal gastric mucosa, while red areas represent invasive intramucosal cancer foci. Foci were multiple and at different levels within the same fragment (MP4 7835 kb)

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Gullo, I., Garcia-Pelaez, J., Morais, R., Ding, Y., Oliveira, C., Carneiro, F. (2023). Histopathology of Hereditary Diffuse Gastric Cancer: From Grossing and 3D Microscopy to Immunophenotypic and Molecular Profiling. In: Corso, G., Veronesi, P., Roviello, F. (eds) Hereditary Gastric and Breast Cancer Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-031-21317-5_9

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