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Carcinoma of Unknown Primary
Brian L. Bones, MD; Paige Bennett, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Diagnostic Checklist

        TERMINOLOGY

        • Definitions

          • Biopsy-proven neoplastic lesion, or high clinical suspicion of malignancy, for which primary site has not been identified
            • Cancer of unknown primary or occult primary tumor are umbrella terms for all neoplastic types often used interchangeably
            • Carcinoma of unknown primary is specific term for neoplasms of epithelial origin
              • Adenocarcinoma of unknown primary specific to tissue of glandular epithelial origin such as breast, prostate, and lower gastrointestinal cancers
              • Squamous cell carcinoma of unknown primary specific to tissue of epidermoid origin such as skin, head and neck, esophagus, and lung
              • Neuroendocrine carcinoma of unknown primary specific to ubiquitous tissue that typically performs an endocrine function such as carcinoid, medullary thyroid, small cell lung cancer, and islet cell tumors of the pancreas

        INITIAL DIAGNOSTIC WORK-UP

        • History and Pathology

          • CT/MR Evaluation

            • F-18 FDG PET/CT

              IMAGING

              • F-18 FDG PET/CT Findings

                • F-18 FDG PET/MR Findings

                  • Gallium68-DOTATATE PET/CT

                    DIFFERENTIAL DIAGNOSIS

                    • Primary Malignancy Sites Detected by F-18 FDG PET/CT

                      • False-Positive Interpretations

                        • False-Negative Interpretations

                          PATHOLOGY

                          • General Features

                            CLINICAL ISSUES

                            • Presentation

                              • Demographics

                                • Natural History & Prognosis

                                  DIAGNOSTIC CHECKLIST

                                  • Consider

                                    • Initial Diagnostic Evaluation

                                      • Supplemental Diagnostic Evaluations in Addition to Clinical Evaluation

                                        • Specific Malignancies to Evaluate for Depending on Lesion Pathology and Site

                                          • Specific Recommendations to Aid Interpretation

                                            Selected References

                                            1. Gődény M et al: Impact of 3T multiparametric MRI and FDG-PET-CT in the evaluation of occult primary cancer with cervical node metastasis. Cancer Imaging. 16(1):38, 2016
                                            2. Riaz S et al: Diagnostic Accuracy of 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in the Evaluation of Carcinoma of Unknown Primary. Mol Imaging Radionucl Ther. 25(1):11-8, 2016
                                            3. Ruhlmann V et al: Hybrid imaging for detection of carcinoma of unknown primary: A preliminary comparison trial of whole-body PET/MRI versus PET/CT. Eur J Radiol. 85(11):1941-1947, 2016
                                            4. Yu X et al: Advantages and disadvantages of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of unknown primary. Oncol Lett. 12(5):3785-3792, 2016
                                            5. Hofman MS et al: Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 35(2):500-16, 2015
                                            6. Kim KW et al: Cancer of unknown primary sites: what radiologists need to know and what oncologists want to know. AJR Am J Roentgenol. 200(3):484-92, 2013
                                            7. Ettinger DS et al: NCCN Clinical Practice Guidelines Occult primary. J Natl Compr Canc Netw. 9(12):1358-95, 2011
                                            8. Fizazi K et al: Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 22 Suppl 6:vi64-8, 2011
                                            9. Kwee TC et al: FDG PET/CT in carcinoma of unknown primary. Eur J Nucl Med Mol Imaging. 37(3):635-44, 2010
                                            10. McMahon CJ et al: Lymphatic metastases from pelvic tumors: anatomic classification, characterization, and staging. Radiology. 254(1):31-46, 2010
                                            11. Kwee TC et al: Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol. 19(3):731-44, 2009
                                            12. Pavlidis N et al: Carcinoma of unknown primary (CUP). Crit Rev Oncol Hematol. 69(3):271-8, 2009
                                            Related Anatomy
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                                            Related Differential Diagnoses
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                                            References
                                            Tables

                                            Tables

                                            KEY FACTS

                                            • Terminology

                                              • Imaging

                                                • Diagnostic Checklist

                                                  TERMINOLOGY

                                                  • Definitions

                                                    • Biopsy-proven neoplastic lesion, or high clinical suspicion of malignancy, for which primary site has not been identified
                                                      • Cancer of unknown primary or occult primary tumor are umbrella terms for all neoplastic types often used interchangeably
                                                      • Carcinoma of unknown primary is specific term for neoplasms of epithelial origin
                                                        • Adenocarcinoma of unknown primary specific to tissue of glandular epithelial origin such as breast, prostate, and lower gastrointestinal cancers
                                                        • Squamous cell carcinoma of unknown primary specific to tissue of epidermoid origin such as skin, head and neck, esophagus, and lung
                                                        • Neuroendocrine carcinoma of unknown primary specific to ubiquitous tissue that typically performs an endocrine function such as carcinoid, medullary thyroid, small cell lung cancer, and islet cell tumors of the pancreas

                                                  INITIAL DIAGNOSTIC WORK-UP

                                                  • History and Pathology

                                                    • CT/MR Evaluation

                                                      • F-18 FDG PET/CT

                                                        IMAGING

                                                        • F-18 FDG PET/CT Findings

                                                          • F-18 FDG PET/MR Findings

                                                            • Gallium68-DOTATATE PET/CT

                                                              DIFFERENTIAL DIAGNOSIS

                                                              • Primary Malignancy Sites Detected by F-18 FDG PET/CT

                                                                • False-Positive Interpretations

                                                                  • False-Negative Interpretations

                                                                    PATHOLOGY

                                                                    • General Features

                                                                      CLINICAL ISSUES

                                                                      • Presentation

                                                                        • Demographics

                                                                          • Natural History & Prognosis

                                                                            DIAGNOSTIC CHECKLIST

                                                                            • Consider

                                                                              • Initial Diagnostic Evaluation

                                                                                • Supplemental Diagnostic Evaluations in Addition to Clinical Evaluation

                                                                                  • Specific Malignancies to Evaluate for Depending on Lesion Pathology and Site

                                                                                    • Specific Recommendations to Aid Interpretation

                                                                                      Selected References

                                                                                      1. Gődény M et al: Impact of 3T multiparametric MRI and FDG-PET-CT in the evaluation of occult primary cancer with cervical node metastasis. Cancer Imaging. 16(1):38, 2016
                                                                                      2. Riaz S et al: Diagnostic Accuracy of 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in the Evaluation of Carcinoma of Unknown Primary. Mol Imaging Radionucl Ther. 25(1):11-8, 2016
                                                                                      3. Ruhlmann V et al: Hybrid imaging for detection of carcinoma of unknown primary: A preliminary comparison trial of whole-body PET/MRI versus PET/CT. Eur J Radiol. 85(11):1941-1947, 2016
                                                                                      4. Yu X et al: Advantages and disadvantages of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of unknown primary. Oncol Lett. 12(5):3785-3792, 2016
                                                                                      5. Hofman MS et al: Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation. Radiographics. 35(2):500-16, 2015
                                                                                      6. Kim KW et al: Cancer of unknown primary sites: what radiologists need to know and what oncologists want to know. AJR Am J Roentgenol. 200(3):484-92, 2013
                                                                                      7. Ettinger DS et al: NCCN Clinical Practice Guidelines Occult primary. J Natl Compr Canc Netw. 9(12):1358-95, 2011
                                                                                      8. Fizazi K et al: Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 22 Suppl 6:vi64-8, 2011
                                                                                      9. Kwee TC et al: FDG PET/CT in carcinoma of unknown primary. Eur J Nucl Med Mol Imaging. 37(3):635-44, 2010
                                                                                      10. McMahon CJ et al: Lymphatic metastases from pelvic tumors: anatomic classification, characterization, and staging. Radiology. 254(1):31-46, 2010
                                                                                      11. Kwee TC et al: Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol. 19(3):731-44, 2009
                                                                                      12. Pavlidis N et al: Carcinoma of unknown primary (CUP). Crit Rev Oncol Hematol. 69(3):271-8, 2009