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Metastatic Cancer With Unknown Primary Site Clinical Presentation

  • Author: Winston W Tan, MD, FACP; Chief Editor: Wafik S El-Deiry, MD, PhD  more...
 
Updated: Apr 01, 2016
 

History

Because most patients with malignant neoplasms of unknown origin have fairly advanced-stage disease, the constitutional symptoms of malaise, weakness, fatigue, and weight loss are present in nearly all patients.

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Physical

The clinical presentation of cancer of unknown primary origin is extremely variable, and depends on the extent and type of organ involvement. Most patients present with multiple areas of involvement in multiple visceral sites, the most common being lung, bone, lymph nodes, and liver. A detailed physical examination should be conducted, and should include head and neck, rectal, testicular, pelvic, and breast examinations.

Patients have early dissemination of their cancer without symptoms at the primary site. Nevertheless, clinical manifestations may suggest the primary site, as follows:

  • Ascites should lead to evaluation for a gastrointestinal or an ovarian primary.
  • An axillary mass in a female should lead to evaluation for breast cancer[4, 5]
  • Cervical lymphadenopathy should lead to a thorough otolaryngologic examination[6]
  • Signs consistent with brain metastasis should lead to a search for a lung, breast, or kidney primary
  • Apparent bone metastasis should lead to evaluation for prostate, breast, lung, renal, or thyroid primary
  • A testicular mass should lead to measurement of tumor markers such as beta–human chorionic gonadotropin (beta-HCG) and alpha-fetoprotein (AFP)
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Contributor Information and Disclosures
Author

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman of Education, Division of Hematology/Oncology, Mayo Clinic Florida

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, Texas Medical Association, American Society of Clinical Oncology, Philippine Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Nasir Shahab, MD 

Nasir Shahab, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Surabhi Amar, MD Fellow, Department of Internal Medicine, Division of Hematology/Oncology, Mayo Clinic Jacksonville

Surabhi Amar, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Benjamin Movsas, MD 

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology

Disclosure: Nothing to disclose.

Chief Editor

Wafik S El-Deiry, MD, PhD Rose Dunlap Professor of Medicine, Chief, Division of Hematology and Oncology, Penn State Hershey Medical Center

Wafik S El-Deiry, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Clinical Investigation, American Society of Gene and Cell Therapy

Disclosure: Nothing to disclose.

Additional Contributors

Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for Physician Leadership, European Society for Medical Oncology, Association of Clinical Research Professionals, American Federation for Clinical Research, Eastern Cooperative Oncology Group, Society for Immunotherapy of Cancer, American Medical Informatics Association, American College of Physicians, American Federation for Medical Research, American Medical Association, American Society of Hematology, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Acknowledgements

Michael Perry, MD, MS, MACP† Former Nellie B Smith Chair of Oncology Emeritus, Former Director, Division of Hematology and Medical Oncology, Former Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

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CT scan of neck with contrast. The arrows indicate metastatic lymphadenopathy. Image courtesy of Head and Neck Cancer-Multidisciplinary Approach, Davidson, BJ.
Table. Immunohistochemical markers for cancers of unknown primary
Primary MarkerPrimary Tumor TypeAdditional Markers
CK7- /CK 20 +Colorectal cancer and merkel cell carcinomaCEA and CDX-2  (for GI malignancy)
CK 7 +/CK 20 -Lung,breast, thyroid, endometrial, cervical, pancreas, and cholangiocarcinomaTTF-1 (lung, thyroid)



ER, PR (breast)



GCDFP-15 (gynecologic)



CK- 19 (pancreas)



Ck+7/ CK 20+Urothelial, ovarian, pancreas, cholangiocarcinomaUrothelin (genitourinary) 



WT-1 (ovarian, mesothelial)



CK = cytokeratin; CEA = carcinoembryonic antigen; TTF1 = thyroid transcription factor 1; ER = estrogen receptor; PR = progesterone receptor; GCDFP-15  = gross cystic disease fluid protein–15; WT-1 = Wilms tumor gene 1; PSA = prostate specific antigen
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