Summary
Definition
History and exam
Key diagnostic factors
- bone pain
- family history of cancer
Other diagnostic factors
- jaundice
- ascites
- personal history of previous cancer
- history of smoking
- pain
- palpable mass
- symptoms of postobstructive pneumonia
- neurologic pain or weakness
- headaches
- seizures
- cervical chain adenopathy
- constitutional symptoms
- depression
- delirium
- history of heavy alcohol consumption
- hepatomegaly
- hemoptysis
Risk factors
- age >60 years
Diagnostic investigations
1st investigations to order
- CT chest/abdomen/pelvis
- mammography
- MRI of breast
- transvaginal ultrasound
- diagnostic paracentesis
- direct laryngoscopy with or without esophagoscopy and bronchoscopy
Investigations to consider
- light microscopy, with hematoxylin and eosin (H&E) staining
- positron emission tomography (PET)/CT
- immunohistochemical (IHC) markers
- estrogen and progesterone receptor status
- serum tumor markers
- next-generation sequencing (NGS)
Emerging tests
- gene expression profiling (GEP)
Treatment algorithm
identification of primary site pending
multiple metastases: favorable clinicopathologic subtype not identified
multiple metastases: women with isolated axillary lymphadenopathy (likely primary: breast cancer)
multiple metastases: women with papillary adenocarcinoma of the peritoneal cavity (likely primary: ovarian cancer)
multiple metastases: poorly differentiated carcinoma with neuroendocrine features (likely primary: small cell lung cancer)
multiple metastases: well-differentiated neuroendocrine tumors
multiple metastases: adenocarcinoma with colorectal immunohistochemistry (likely primary: colorectal cancer)
multiple metastases: poorly differentiated carcinoma of the mediastinum or retroperitoneum in males <40 years
blastic bone metastases with immunohistochemistry/serum prostate-specific antigen (likely primary: prostate cancer)
single metastatic lesion
oligometastatic disease
Contributors
Authors
Michael S. Lee, MD
Associate Professor
Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
University of Texas MD Anderson Cancer Center
Houston
TX
Disclosures
MSL has consulted for Pfizer, Bayer, Delcath, and Imvax. His institution has received research funding from Amgen, Exelixis, Bristol-Myers Squibb, Pfizer, Rafael Pharmaceuticals, EMD Serono, Genentech/Roche, Merck, Arcus, and Shanghai EpiMab Biotherapeutics. MSL is the author of a number of papers cited in this topic.
Acknowledgements
Dr Michael S. Lee would like to gratefully acknowledge Dr Ross C. Donehower, Dr David Cosgrove, and Dr Hatim Hussain, previous contributors to this topic.
Disclosures
RCD, DC, and HH declare that they have no competing interests.
Peer reviewers
Nikhil Khushalani, MD
Assistant Professor
Department of Medicine
Roswell Park Cancer Institute
Buffalo
NY
Disclosures
NK declares that he has no competing interests.
Zelig Tochner, MD
Associate Professor
Radiation Oncology
Children's Hospital of Philadelphia
Philadelphia
PA
Disclosures
ZT declares that he has no competing interests.
Justin Stebbing, MA, MRCP, MRCPath, PhD
Consultant Medical Oncologist/Senior Lecturer
Department of Medical Oncology
Imperial College/Imperial Healthcare NHS Trust
Charing Cross Hospital
London
UK
Disclosures
JS declares that he has no competing interests.
Differentials
- Squamous or neuroendocrine carcinoma of unknown primary
More DifferentialsGuidelines
- Cancer of unknown primary: ESMO clinical practice guideline for diagnosis, treatment and follow-up
- NCCN clinical practice guidelines in oncology: occult primary
More Guidelines
Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer