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

Tessa J J de Bitter, Ragna L A van der Linden, Shannon van Vliet, Fieke Weren, Daoud Sie, Bauke Ylstra, Hans C van der Linden, Nikki Knijn, Marjolijn J L Ligtenberg, Rachel S van der Post, Femke Simmer, Iris D Nagtegaal

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aims: Outcomes of colorectal cancer (CRC) treatment and survival have steadily improved during the past decades, accompanied by an increased risk of developing second primary tumours and metastatic tumours at unusual sites. Metastatic CRC can show mucosal colonisation, 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. Methods and results: 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, genomewide 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 genomewide DNA copy number analysis. However, in both cases, pathologists initially considered the GBC as a second primary tumour. Conclusions: Metastatic CRC displaying mucosal colonisation 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.

Original languageEnglish
Pages (from-to)394-404
Number of pages11
JournalHistopathology
Volume75
Issue number3
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

de Bitter, Tessa J J ; van der Linden, Ragna L A ; van Vliet, Shannon ; Weren, Fieke ; Sie, Daoud ; Ylstra, Bauke ; van der Linden, Hans C ; Knijn, Nikki ; Ligtenberg, Marjolijn J L ; van der Post, Rachel S ; Simmer, Femke ; Nagtegaal, Iris D. / Colorectal metastasis to the gallbladder mimicking a primary gallbladder malignancy : histopathological and molecular characteristics. In: Histopathology. 2019 ; Vol. 75, No. 3. pp. 394-404.
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title = "Colorectal metastasis to the gallbladder mimicking a primary gallbladder malignancy: histopathological and molecular characteristics",
abstract = "Aims: Outcomes of colorectal cancer (CRC) treatment and survival have steadily improved during the past decades, accompanied by an increased risk of developing second primary tumours and metastatic tumours at unusual sites. Metastatic CRC can show mucosal colonisation, 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. Methods and results: 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, genomewide 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 genomewide DNA copy number analysis. However, in both cases, pathologists initially considered the GBC as a second primary tumour. Conclusions: Metastatic CRC displaying mucosal colonisation 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.",
keywords = "clonality, colorectal cancer, gallbladder cancer, metastasis, next-generation sequencing",
author = "{de Bitter}, {Tessa J J} and {van der Linden}, {Ragna L A} and {van Vliet}, Shannon and Fieke Weren and Daoud Sie and Bauke Ylstra and {van der Linden}, {Hans C} and Nikki Knijn and Ligtenberg, {Marjolijn J L} and {van der Post}, {Rachel S} and Femke Simmer and Nagtegaal, {Iris D}",
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year = "2019",
month = "1",
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doi = "10.1111/his.13892",
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de Bitter, TJJ, van der Linden, RLA, van Vliet, S, Weren, F, Sie, D, Ylstra, B, van der Linden, HC, Knijn, N, Ligtenberg, MJL, van der Post, RS, Simmer, F & Nagtegaal, ID 2019, 'Colorectal metastasis to the gallbladder mimicking a primary gallbladder malignancy: histopathological and molecular characteristics' Histopathology, vol. 75, no. 3, pp. 394-404. https://doi.org/10.1111/his.13892

Colorectal metastasis to the gallbladder mimicking a primary gallbladder malignancy : histopathological and molecular characteristics. / de Bitter, Tessa J J; van der Linden, Ragna L A; van Vliet, Shannon; Weren, Fieke; Sie, Daoud; Ylstra, Bauke; van der Linden, Hans C; Knijn, Nikki; Ligtenberg, Marjolijn J L; van der Post, Rachel S; Simmer, Femke; Nagtegaal, Iris D.

In: Histopathology, Vol. 75, No. 3, 01.01.2019, p. 394-404.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Colorectal metastasis to the gallbladder mimicking a primary gallbladder malignancy

T2 - histopathological and molecular characteristics

AU - de Bitter, Tessa J J

AU - van der Linden, Ragna L A

AU - van Vliet, Shannon

AU - Weren, Fieke

AU - Sie, Daoud

AU - Ylstra, Bauke

AU - van der Linden, Hans C

AU - Knijn, Nikki

AU - Ligtenberg, Marjolijn J L

AU - van der Post, Rachel S

AU - Simmer, Femke

AU - Nagtegaal, Iris D

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aims: Outcomes of colorectal cancer (CRC) treatment and survival have steadily improved during the past decades, accompanied by an increased risk of developing second primary tumours and metastatic tumours at unusual sites. Metastatic CRC can show mucosal colonisation, 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. Methods and results: 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, genomewide 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 genomewide DNA copy number analysis. However, in both cases, pathologists initially considered the GBC as a second primary tumour. Conclusions: Metastatic CRC displaying mucosal colonisation 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.

AB - Aims: Outcomes of colorectal cancer (CRC) treatment and survival have steadily improved during the past decades, accompanied by an increased risk of developing second primary tumours and metastatic tumours at unusual sites. Metastatic CRC can show mucosal colonisation, 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. Methods and results: 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, genomewide 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 genomewide DNA copy number analysis. However, in both cases, pathologists initially considered the GBC as a second primary tumour. Conclusions: Metastatic CRC displaying mucosal colonisation 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.

KW - clonality

KW - colorectal cancer

KW - gallbladder cancer

KW - metastasis

KW - next-generation sequencing

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U2 - 10.1111/his.13892

DO - 10.1111/his.13892

M3 - Article

VL - 75

SP - 394

EP - 404

JO - Histopathology

JF - Histopathology

SN - 0309-0167

IS - 3

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