Dataset Information

Carcinoma of unknown primary (CUP): an update for histopathologists.

ABSTRACT: Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic cancers in which the site of origin is not identifiable. These carcinomas have a poor outcome due to their late presentation with metastatic disease, difficulty in identifying the origin and delay in treatment. The aim of the pathologist is to broadly classify and subtype the cancer and, where possible, to confirm the likely primary site as this information best predicts patient outcome and guides treatment. In this review, we provide histopathologists with diagnostic practice points which contribute to identifying the primary origin in such cases. We present the current clinical evaluation and management from the point of view of the oncologist. We discuss the role of the pathologist in the diagnostic pathway including the control of pre-analytical conditions, assessment of sample adequacy, diagnosis of cancer including diagnostic pitfalls, and evaluation of prognostic and predictive markers. An integrated diagnostic report is ideal in cases of CUP, with results discussed at a forum such as a molecular tumour board and matched with targeted treatment. This highly specialized evolving area ultimately leads to personalized oncology and potentially improved outcomes for patients.

SUBMITTER: Beauchamp K

PROVIDER: S-EPMC10713813 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Carcinoma of unknown primary (CUP): an update for histopathologists.

Beauchamp Katie K Moran Bruce B O'Brien Timothy T Brennan Donal D Crown John J Sheahan Kieran K Cotter Maura Bríd MB

Cancer metastasis reviews 20230703 4

Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic cancers in which the site of origin is not identifiable. These carcinomas have a poor outcome due to their late presentation with metastatic disease, difficulty in identifying the origin and delay in treatment. The aim of the pathologist is to broadly classify and subtype the cancer and, where possible, to confirm the likely primary site as this information best predicts patient outcome and guides treatment. In this review ...[more]

PMID: 37394540

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Project description:Carcinoma of unknown primary (CUP) is a difficult-to-manage malignancy. Multi-omic profiles and treatment outcome vs. degree of precision matching were assessed. Tumours underwent next-generation sequencing (NGS) [tissue and/or blood-derived cell-free DNA (cfDNA)]. Selected patients had transcriptome-based immune profiling and/or programmed cell death 1 ligand 1 (PD-L1) immunohistochemistry analysis. Patients could be reviewed by a Molecular Tumor Board, but physicians chose the therapy. Of 6497 patients in the precision database, 97 had CUP. The median number of pathogenic tissue genomic alterations was 4 (range, 0-25), and for cfDNA, was 2 (range, 0-9). Each patient had a distinct molecular landscape. Food and Drug Administration (FDA)-approved biomarkers included the following: PD-L1+ ≥ 1%, 30.9% of CUPs tested; microsatellite instability, 3.6%; tumour mutational burden ≥ 10 mutations·Mb-1, 23%; and neurotrophic receptor tyrosine kinase (NTRK) fusions, 0%. RNA-based immunograms showed theoretically druggable targets: lymphocyte activation gene 3 protein (LAG-3), macrophage colony-stimulating factor 1 receptor (CSF1R), adenosine receptor A2 (ADORA2) and indoleamine 2,3-dioxygenase 1 (IDO1). Overall, 56% of patients had ≥ 1 actionable biomarker (OncoKB database). To quantify the degree of matching (tumours to drugs), a Matching Score (MS; roughly equivalent to number of alterations targeted/total number of deleterious alterations) was calculated post hoc. Comparing evaluable treated patients [MS high, > 50% (N = 15) vs. low ≤ 50% (N = 47)], median progression-free survival was 10.4 vs. 2.8 months (95% CI 0.11-0.64; HR 0.27; P = 0.002); survival, 15.8 vs. 6.9 months (95% CI 0.17-1.16; HR 0.45; P = 0.09); and clinical benefit rate (stable disease ≥ 6 months/partial/complete response), 71% vs. 24% (P = 0.003). Higher MS was the only factor that predicted improvement in outcome variables after multivariate analysis. In conclusion, CUPs are molecularly complex. Treatments with high degrees of matching to molecular alterations (generally achieved by individualized combinations) correlated with improved outcomes.

Dataset Information

Carcinoma of unknown primary (CUP): an update for histopathologists.

Publications

Carcinoma of unknown primary (CUP): an update for histopathologists.

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