Adenocarcinoma of unknown primary site is 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 workup is to identify subsets of patients with a more favorable clinicopathologic subtype and likely better outcome.
Systemic chemotherapy is the mainstay of treatment for the overwhelming majority of patients.
Rare subgroups may be candidates for targeted or immune therapies based on results of next-generation sequencing or other biomarkers predictive of response.
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
- family history of cancer
Other diagnostic factors
- personal history of previous cancer
- history of smoking
- palpable mass
- symptoms of postobstructive pneumonia
- neurologic pain or weakness
- cervical chain adenopathy
- constitutional symptoms
- history of heavy alcohol consumption
- age >60 years
1st investigations to order
- CT chest/abdomen/pelvis
- 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)
- gene expression profiling (GEP)
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
- Squamous or neuroendocrine carcinoma of unknown primary
- Cancer of unknown primary: ESMO clinical practice guideline for diagnosis, treatment and follow-up
- NCCN clinical practice guidelines in oncology: occult primary
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