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.

Metastatic Colon Cancer Presenting as Gallbladder Perforation: Highlighting the Diagnostic Challenges and Clinical Implications

“…8,9 Specific markers, such as CK20 and CDX2, are commonly used to confirm colorectal origin. 2,10 Although gallbladder tumors typically exhibit positivity for both CK7 and CK20, the presence of CK7-negative/CK20-positive cells with CDX2 positivity is indicative of a possible colorectal primary origin. 10 Treatment decisions for metastasis to the gallbladder from the colon depend on various factors and require a multidisciplinary approach.…”

“…1 Of note also is the fact that in approximately 25% of patients with CRC, metastatic disease is present upon presentation (stage IV), and another 18% of individuals develop metastases metachronously after the initial CRC has been treated. 2 Metastatic CRC (mCRC) primarily arises in the liver and lungs. Rare metastatic locations include the gallbladder in 0.8% of cases.…”

Comprehensive clinicopathological and genomic profiling of gallbladder cancer reveals actionable targets in half of patients

“…IHC was performed essentially as described previously 37 with standard chromogenic horseradish peroxidase-diaminobenzidine (HRP-DAB) detection method using the semiautomated LabVision Autostainer (Immunologic, Duiven, the Netherlands). IHC was performed both to aid in histological subtyping of GBC (EMA, MUC2, MUC5AC, MUC6, CK7, CK20, and p63), to validate NGS results and to screen for a selection of potential therapeutic targets in a large cohort of patients (PD-L1, HER2, Pan-TRK and p53).…”

Unraveling Neuroendocrine Gallbladder Cancer: Comprehensive Clinicopathologic and Molecular Characterization

“…Immunohistochemistry (IHC) was performed on 4-µm whole-slide FFPE sections semiautomated using the Lab Vision Autostainer (Immunologic, Duiven, the Netherlands) for MUC2, MUC5AC, MUC6, and TTF-1 essentially as described before 13 or fully automated using Tissue-Tek Genie (Sakura Finetek, Torrance, CA) for chromogranin A, CD56, CK7, CK20, Ki-67, EMA (MUC1), p53, and synaptophysin with ready-to-use reagents. Details of antibodies are listed in the Data Supplement.…”