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Adenocarcinoma of unknown primary site

Last reviewed: 30 Jun 2025
Last updated: 30 Jul 2025

Summary

Definition

History and exam

Key diagnostic factors

  • pain (e.g., abdomen, chest, bone)
  • family history of cancer
  • constitutional symptoms
Full details

Other diagnostic factors

  • jaundice
  • symptoms of post-obstructive pneumonia
  • haemoptysis
  • ascites
  • cervical chain adenopathy
  • personal history of previous cancer
  • history of smoking
  • palpable mass
  • neuropathic pain or weakness
  • headaches
  • seizures
  • delirium
  • history of heavy alcohol consumption
  • hepatomegaly
Full details

Risk factors

  • age >60 years
Full details

Diagnostic investigations

1st investigations to order

  • full blood count
  • comprehensive metabolic panel
  • CT chest/abdomen/pelvis
  • MRI
  • biopsy (pathological assessment)
  • immunohistochemistry (IHC) tests
Full details

Investigations to consider

  • fecal occult blood test
  • lactate dehydrogenase
  • urinalysis
  • 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT
  • breast imaging (mammography, MRI, ultrasound)
  • transvaginal ultrasound
  • paracentesis
  • endoscopy
  • direct laryngoscopy with or without oesophagoscopy and bronchoscopy
  • serum tumour markers
  • genetic biomarker testing
Full details

Emerging tests

  • tissue of origin testing

Treatment algorithm

INITIAL

identification of primary site pending

ACUTE

unfavourable subtype: multiple metastases and/or without a likely primary site

favourable subtype: women with isolated axillary lymphadenopathy (likely breast primary)

favourable subtype: women with peritoneal carcinomatosis of a serous papillary adenocarcinoma (likely ovarian primary)

favourable subtype: poorly differentiated carcinoma with neuroendocrine features (likely small cell lung cancer primary)

favourable subtype: well-differentiated neuroendocrine tumours (likely neuroendocrine primary)

favourable subtype: adenocarcinoma with colorectal immunohistochemistry (likely colorectal primary)

favourable subtype: poorly differentiated carcinoma of the mediastinum or retroperitoneum in males <40 years (likely testicular primary)

favourable subtype: blastic bone metastases with immunohistochemistry/serum prostate-specific antigen (likely prostate primary)

favourable subtype: single metastatic lesion

favourable subtype: 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.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: occult primary [internet publication].Full text

Krämer A, Bochtler T, Pauli C, et al. Cancer of unknown primary: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Mar;34(3):228-46.Full text  Abstract

National Institute for Health and Care Excellence. Metastatic malignant disease of unknown primary origin in adults: diagnosis and management. Apr 2023 [internet publication].Full text

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
  • Adenocarcinoma of unknown primary site images
  • Differentials

    • Squamous or neuroendocrine carcinoma of unknown primary
    More Differentials
  • Guidelines

    • NCCN clinical practice guidelines in oncology: head and neck cancers
    • NCCN clinical practice guidelines in oncology: occult primary
    More Guidelines
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