A common clinical entity, comprising 2% to 4% of all incident cancers worldwide.
Untreated, prognosis is poor, with a median survival between 3 and 4 months.
A key goal in the diagnostic work-up is to identify subsets of patients with a more favourable clinico-pathological subtype and likely better outcome.
Systemic chemotherapy is the mainstay of treatment. Supportive therapies control pain and other symptoms.
Adenocarcinoma of unknown primary site (AUP) is the major subgroup in the common clinical entity of cancer of unknown primary site (CUP). It is defined as metastatic adenocarcinoma for which the primary site is undetectable at presentation, despite thorough physical exam and laboratory and radiographic investigation.
History and exam
Key diagnostic factors
- bone pain
- FHx of cancer
Other diagnostic factors
- personal hx of previous cancer
- hx of smoking
- palpable mass
- symptoms of post-obstructive pneumonia
- neurological pain or weakness
- cervical chain adenopathy
- constitutional symptoms
- hx of heavy alcohol consumption
- age >60 years
- black ancestry
1st investigations to order
- CT (chest, abdomen, pelvis)
- MRI of breast
- transvaginal ultrasound
- diagnostic paracentesis
- upper aerodigestive panendoscopy (for patients with isolated cervical adenopathy)
Investigations to consider
- colonoscopy (for patients with resectable liver metastases)
- light microscopy, with haematoxylin and eosin (H&E) staining
- immunohistochemical (IHC) markers
- oestrogen and progesterone receptor status
- serum tumour markers
- positron emission tomography (PET)
- gene expression profiling
identification of primary site pending
>1 metastasis: favourable clinico-pathological subtype not identified
>1 metastasis: women with isolated axillary lymphadenopathy (likely primary: breast)
>1 metastasis: women with peritoneal carcinomatosis (likely primary: ovarian)
>1 metastasis: with neuroendocrine features
>1 metastasis: poorly differentiated adenocarcinoma of the midline
>1 metastasis: likely prostate primary
Ross C. Donehower, MD, FACP
Division of Medical Oncology
Johns Hopkins University School of Medicine
RCD declares that he has no competing interests.
Dr Ross C. Donehower would like to gratefully acknowledge Dr David Cosgrove and Dr Hatim Hussain, previous contributors to this monograph. DC and HH declare that they have no competing interests.
Nikhil Khushalani, MD
Department of Medicine
Roswell Park Cancer Institute
NK declares that he has no competing interests.
Zelig Tochner, MD
Children's Hospital of Philadelphia
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
JS declares that he has no competing interests.
- Squamous or neuroendocrine carcinoma of unknown primary
- NCCN clinical practice guidelines in oncology: occult primary
- NCCN Clinical Practice Guidelines in Oncology: occult primary
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