metastatic cancer of unknown primary
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Epidemiology
- 5-10% of cancers presenting to oncologist
Pathology
- 60% have adenocarcinoma
- 35% have poorly differentiated carcinoma
Immunophenotype
- adrenal carcinoma:
- breast adenocarcinoma:
- cholangiocarcinoma, primary:
- colorectal adenocarcinoma:
- endocervical carcinoma: CEA +, AE1/AE3 +,
- endometrial carcinoma: CEA -,
- epithelioid hemangioendothelioma:
- CD31 +, CD34 +, factor VIII +, CAM5.2 -/+, CEA -
- hepatocellular carcinoma (except fibrolamellar):
- lung squamous cell carcinoma: 34betaE12 +, CK7 -, CK20 -
- lung adenocarcinoma:
- lung small cell carcinoma: CAM5.2 +, AE1/AE3 +, TTF1 +
- mesothelioma: CEA -, CK7 +, ber-EP4 -
- pancreatic adenocarcinoma: CEA +, AE1/AE3 +, CK20 +, CK7 +
- prostate adenocarcinoma: CEA -,
- renal adenocarcinoma:
- thyroid follicular carcinoma:
- thyroglobulin +, TTF1 +, vimentin +
- rare CD45 membrane staining may be seen in undifferentiated & neuroendocrine carcinomas
History
- smoking
- asbestos exposure
- abdominal pain
- family history of breast cancer, ovarian cancer, colon cancer
- inflammatory bowel disease (colon carcinoma)
- hepatitis or cirrhosis (hepatocellular carcinoma)
- removal of skin lesions (melanoma)
Physical examination
- lymph nodes
- thyroid
- skin
- prostate (men)
- breasts, pelvic examination (women)
- rectum
Laboratory
- stool evaluation for occult blood
- urinalysis
- complete blood count (CBC)
- liver function tests
- serum prostate-specific antigen (men)
- presence of tumor markers is rarely diagnostic
- serum beta chorionic gonadotropin (beta-hCG)
- serum alpha-fetoprotein (AFP)
- serum carcinoembryonic antigen (CEA)
- serum CA-125 (women)
- not useful for diagnosis or prognosis[4]
- may be useful in montoring response to therapy
- CA-19-9, CA-15-3 rarely useful
- multigene expression profiles not recommended[4]
- biopsy (see biopsy of metastatic cancer of unknown primary)
Radiology
- chest X-ray
- abdominal & pelvic computed tomography (CT)
- mammography (women)
- magnetic resonance imaging (MRI) of breast
- women with cancer in axillary lymph nodes but non-diagnostic mammogram
- CT of head & neck
- enlarged cervical lymph nodes
- PET scan (positron-emission tomography)
- has not been shown to impyyrove outcomes
- not recommended[4]
- contrast radiography of GI tract not routine
Differential diagnosis
- axillary lymphadenopathy in women*
- obtain MRI of breast
- if positive, treat according to breast cancer stage
- if negative, treat as stage 2 breast cancer
- isolated cervical lymphadenopathy
- obtain upper endoscopy, bronchoscopy, laryngoscopy
- if negative, treat with chemotherapy & radiation as for head & neck cancer
- isolated inguinal lymphadenopathy
- anorectal, genital & perirectal examination
- if negative, lymph node resection of local radiation therapy
- peritoneal carcinomatosis & ascites
- treat as ovarian cancer
- cytoreductive surgery & chemotherapy
- midline non-adenocarcinoma of the mediastinum or retroperitoneum
- obtain serum alpha-fetoprotein & serum beta-chorionic gonadotropin
- testicular exam & testicular ultrasound
- treat with platinum-based chemotherapy for germ cell tumors
* NEJM knowledge+ seems to endorse fine needle aspiration followed by a core biopsy
Management
- establish diagnosis with sufficient histologic specimen
- biopsy most accessible site
- open biopsy preferred to fine needle aspiration (FNA)
- FNA unsatisfactory for lymph node biopsy
- special consideration is given to treatable malignancies
- germ cell cancer
- choriocarcinoma
- head & neck carcinoma
- breast cancer
- ovarian cancer
- exhaustive search for primary tumor has not been shown to improve outcomes[4]
- treat tumor based on histology & prognostic factors[4]
- special cases: presentations that dictate specific workups & therapies
- squamous cell carcinoma in a cervical node
- suggests head & neck cancer
- upper GI endoscopy, bronchoscopy, laryngoscopy[4]
- treatment:
- radical neck dissection
- radiotherapy +/- chemotherapy
- carcinoma in axillary nodes (female)
- suggests breast cancer
- obtain MRI of breasts[4]
- treatment
- peritoneal carcinomatosis & ascites (female)
- poorly differentiated cancer, predoinantly midline
- men age < 50, lung or retroperitoneal or mediastinal mass or lymph nodes, elevated serum beta-hCG or serum AFP
- suggests germ cell tumor (extragonadal)
- cisplatin/VP-16-based chemotherapy
- bony metastases (male)
- suggests prostate cancer
- digital rectal examination & serum prostate-specific antigen
- tumor stained for prostate-specific antigen (PSA) expression
- androgen blockade: leuprolide plus flutamide
- adenocarcinoma, liver metastases, elevated CEA
- suggests gastrointestinal malignancy
- upper endoscopy & colonoscopy if evidence of gastrointestinal bleeding
- with resection of detected tumor(s)
- 5-fluorouracil
- regardless of serum CEA level, if localized to the abdomen, treat as gastrointestinal malignancy[4]
- isolated inguinal lymphadenopathy
- unknown primary with disease mostly below the diaphragm, treat as gastrointestinal cancer
- unknown primary with disease mostly above the diaphragm, treat as lung cancer[4]
- disseminated adenocarcinoma of unknown primary has unfavorable prognosis regardless of degree of diffentiation
- aggressive treatment with platinum-based chemotherapy[4]
- squamous cell carcinoma in a cervical node
- some patients may benefit from radiation or chemotherapy
- supportive care
- prognosis: poor prognostic indicators
- failure to find treatable neoplasm
- older age
- adenocarcinoma
- multiple metastases
- multiple comorbidities
- low performance status
- hospice/palliative care appropriate for poor prognosis
More general terms
More specific terms
Additional terms
References
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 614-618
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 677
- ↑ Dabbs. Diagnostic Immunohistochemistry. Churchill-Livingstone, 2002. chapter 7; p171
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16. 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2021.
- ↑ Hainsworth JD, Fizazi K. Treatment for patients with unknown primary cancer and favorable prognostic factors. Semin Oncol. 2009 Feb;36(1):44-51 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19179187
- ↑ Pavlidis N, Pentheroudakis G. Cancer of unknown primary site: 20 questions to be answered. Ann Oncol. 2010 Oct;21 Suppl 7:vii303-7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20943633
- ↑ Hainsworth JD, Spigel DR, Litchy S, Greco FA. Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. J Clin Oncol. 2006 Aug 1;24(22):3548-54. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16877720
- ↑ Pavlidis N. Cancer of unknown primary: biological and clinical characteristics. Ann Oncol. 2003;14 Suppl 3:iii11-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12821533
- ↑ Spigel DR, Hainsworth JD, Greco FA. Neuroendocrine carcinoma of unknown primary site. Semin Oncol. 2009 Feb;36(1):52-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19179188
- ↑ Petrakis D, Pentheroudakis G, Voulgaris E, Pavlidis N. Prognostication in cancer of unknown primary (CUP): development of a prognostic algorithm in 311 cases and review of the literature. Cancer Treat Rev. 2013 Nov;39(7):701-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23566573
- ↑ Varadhachary GR Carcinoma of unknown primary: focused evaluation. J Natl Compr Canc Netw. 2011 Dec;9(12):1406-12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22157558
- ↑ Fizazi K, Greco FA, Pavlidis N et al. ESMO Guidelines Committee. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v133-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26314775
Fizazi K, Greco FA, Pavlidis N et al. ESMO Guidelines Working Group. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011 Sep;22 Suppl 6:vi64-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21908507 - ↑ National Cancer Institute Carcinoma of Unknown Primary - Health Professional Version https://www.cancer.gov/types/unknown-primary/hp