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Case Reports
. 2025 Jun 20;17(6):e86451.
doi: 10.7759/cureus.86451. eCollection 2025 Jun.

Cancer of Unknown Primary: A Case Report on the Recognition of Its Clinical Entity and Standard of Care Management

Affiliations
Case Reports

Cancer of Unknown Primary: A Case Report on the Recognition of Its Clinical Entity and Standard of Care Management

Alexander Lazzaro et al. Cureus. .

Abstract

Cancer of unknown primary (CUP) is a distinct and well-established clinical entity that encompasses a heterogeneous group of histologically proven cancers that present unique diagnostic and therapeutic challenges. This case describes a male patient in his late 60s who presented with nonspecific gastrointestinal complaints. A comprehensive workup, including clinical evaluation and various biochemical, imaging, and invasive histopathologic tests, led to the diagnosis of CUP following consultation with medical oncology specialists. A decision was made to forgo further invasive molecular tissue sampling in search of a primary malignant process in favor of initiating systemic chemotherapy. The patient possessed an unfavorable set of prognostic signs. Rapid clinical deterioration occurred the day after treatment initiation. A goals of care conversation led to a transition towards comfort measures only care, and the patient ultimately passed away. This case highlights the importance of non-oncologically trained providers recognizing CUP as its own entity to facilitate standard of care management. Future research is needed to establish benefits in clinical trials looking at molecular tumor profiling and site-specific therapies for this rare malignancy.

Keywords: cancer of unknown origin; cytokeratins; diagnostic mystery; immunohistochemistry (ihc); metastatic adenocarcinoma of unknown primary.

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Conflict of interest statement

Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Abdominal CT scan on presentation
Cross-sectional computed tomography (CT) image of the abdomen showing large-volume ascites (yellow arrow), mesenteric adenopathy in the right lower quadrant (green), and peritoneal thickening and nodularity (red). No abnormalities appreciated in intra-abdominal and intra-pelvic organs. Contiguous axial 1.25 mm images were obtained from the lung bases to the greater trochanters with 100 cc Isovue 370 intravenous contrast in the portal venous phase. Coronal, sagittal, and 3D maximum intensity projection (MIP) reconstructions were obtained.
Figure 2
Figure 2. National Comprehensive Cancer Network® (NCCN®)-recommended diagnostic workup for cancer of unknown primary
As a diagnosis of exclusion, a thorough initial evaluation and workup must be conducted to diagnose cancer of unknown primary. This should commence with a complete history and physical as a first line, followed by biochemical and imaging modalities, then histologic testing and immunophenotyping, and consideration of molecular profiling. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Occult Primary V.2.2025 [10]. © 2024 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.

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