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Histopathology. 2019 May 2. doi: 10.1111/his.13892. [Epub ahead of print]

Colorectal metastasis to the gallbladder mimicking a primary gallbladder malignancy: histopathological and molecular characteristics.

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Department of Pathology, Radboud university medical center, Nijmegen, The Netherlands.
Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Department of Pathology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.



Outcomes of colorectal cancer (CRC) treatment and survival have steadily improved over the past decades, accompanied by an increased risk of developing second primary tumours and metastatic tumours at unusual sites. Metastatic CRC can show mucosal colonization, thereby mimicking a second primary tumour. This potential confusion could lead to incorrect diagnosis and consequently inadequate treatment of the patient. The aim of this study was to differentiate between metastatic CRC and a second primary (gallbladder cancer, GBC) using a combination of standard histopathology and molecular techniques.


Ten consecutive patients with both CRC and GBC were identified in our region using the Dutch national pathology archive (PALGA). Two patients served as negative controls. Histology of GBC was reviewed by nine pathologists. A combination of immunohistochemistry, microsatellite analysis, genome-wide DNA copy number analysis and targeted somatic mutation analysis was used to aid in differential diagnosis. In two patients, CRC and GBC were clonally related, as confirmed by somatic mutation analysis. For one case, this was confirmed by genome wide DNA copy number analysis. However, in both cases, pathologists initially considered the GBC as a second primary tumour.


Metastatic CRC displaying mucosal colonization is often misinterpreted as a second primary tumour. A combination of traditional histopathology and molecular techniques, improves this interpretation, and lowers the risk of inadequate treatment. This article is protected by copyright. All rights reserved.


clonality; colorectal cancer; gallbladder cancer; metastasis; next generation sequencing


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