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Early Metastatic Cancer of Unknown Primary Origin at Presentation: A Clinical Study of 302 Consecutive Autopsied Patients

Early Metastatic Cancer of Unknown Primary Origin at Presentation: A Clinical Study of 302... Abstract • We studied 302 consecutive autopsied patients who presented with carcinoma of unknown primary origin. The most frequent metastatic sites were the nodes, lung, and bone. The primary site was identified while patients were alive in 27% and at autopsy in 57%; the site remained unidentified in 16%. The pancreas (26.5%), lung (17.2%), kidney (4.6%), and colorectum (3.6%) were the most frequent primary sites, but the reliability of diagnostic tests used in the search for this site was disappointing. Survival was identical in patients whose primary site was discovered while alive, at autopsy, or remained unknown. The number of metastases at presentation was the major prognostic factor. Analysis of autopsy data demonstrated that patients with carcinoma of unknown primary origin pursue a different course than expected when the primary site is the first manifestation of the disease. On the basis of these results and the results of other modern series, we suggest an approach consisting of a limited initial workup but with greater emphasis on modern histochemistry studies and immunohistopathologic and other kinetic and morphologic parameters to understand the patient tumor characteristics better and base the clinical management on an individual basis. (Arch Intern Med 1988;148:2035-2039) References 1. Holmes FF, Fouts TL: Metastatic cancer of unknown primary site. Cancer 1970;26:816-820.Crossref 2. Nystrom JS, Weiner JM, Wolf RM, et al: Identifying the primary site in metastatic cancer of unknown origin. JAMA 1979;241:381-383.Crossref 3. Osteen RT, Kopf G, Wilson RE: In pursuit of the unknown primary. Am J Surg 1978;135:494-498.Crossref 4. Didolkar MS, Fanous N, Elias EG, et al: Metastatic carcinomas from occult primary tumors: A study of 254 patients. Ann Surg 1977; 186:625-630.Crossref 5. Moertel CG: Adenocarcinoma of unknown origin. Ann Intern Med 1979;91:646-647.Crossref 6. Greco FA, Oldham RK, Fer MF: The extragonadal germ cell cancer syndrome. Semin Oncol 1982;9:448-455. 7. Snyder RD, Mavligit GM, Valdivieso M: Adenocarcinoma of unknown primary site: A clinico-pathological study. Med Pediatr Oncol 1979;6:289-294.Crossref 8. Cancer statistics 1984. CA 1984;34:1. 9. Peto R, Pike MC, Armitage P, et al: Design and analysis of randomized clinical trials requiring prolonged observation of each patient: Analysis and example. Br J Cancer 1977;35:1-39.Crossref 10. Albers CA, Johnson RH, Mansberger AR: The management of patients with metastatic cancer from an unknown primary site. Am Surg 1981;47:162-166. 11. McMillan JH, Levin E, Stephens RM: Computed tomography in the evaluation of metastatic adenocarcinoma from an unknown primary site. Radiology 1982;143:143-146.Crossref 12. Neumann KH, Nystrom JS: Metastatic cancer of unknown origin: Nonsquamous cell type. Semin Oncol 1982;9:427-434. 13. Clary CF, Michel RP, Wang NS, et al: Metastatic carcinoma: The lung as the site for the clinically undiagnosed primary. Cancer 1983;51:362-366.Crossref 14. Altman E, Cadman E: An analysis of 1539 patients with cancer of unknown primary site. Cancer 1986;57:120-124.Crossref 15. Karsell PR, Sheedy PF, O'Connell J: Computed tomography in search of cancer of unknown origin. JAMA 1982;248:340-343.Crossref 16. Sakahara H, Endo F, Nakajima K, et al: Serum Ca 19.9 concentrations and computed tomography findings in patients with pancreatic carcinoma. Cancer 1986;57:1324-1326.Crossref 17. Rosenblatt MB, Lisa JR, Trinidad S: Pitfalls in the clinical and histologic diagnosis of bronchogenic carcinoma. Dis Chest 1966;49:396-404.Crossref 18. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma: Analysis of 1000 autopsied cases. Cancer 1950;3:74-85.Crossref 19. End Results Section, Biometry Branch, National Cancer Institute : End Results in Cancer , US Dept of Health, Education, and Welfare publication 4. Government Printing Office, 1972. 20. Gilbert HA, Kagan AR: Metastases: Incidence, detection and evaluation without histologie confirmation , in Weiss L (ed): Fundamental Aspects of Metastasis . New York, Elsevier Science Publishing Co Ine, 1976, pp 385-405. 21. Nissenblatt MJ: The CUP syndrome (carcinoma unknown primary). Cancer Treat Rev 1981;8:211-224.Crossref 22. Cassiere SG, McLain DA, Emory WB, et al: Metastatic carcinoma of the pancreas simulating primary bronchogenic carcinoma. Cancer 1980;46:2319-2321.Crossref 23. Greenberg BE, Young JM: Pulmonary metastases from occult primary sites resembling bronchogenic carcinoma. Dis Chest 1958;33:496-505.Crossref 24. Koch M, McPherson TA: Carcinoembryonic antigen levels as an indicator of primary site in metastatic disease of unknown origin. Cancer 1981;48:1242-1244.Crossref 25. Tubiana M, Schlumberger M, Rougier R, et al: Long-term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer 1985;55:794-804.Crossref 26. Jesse RH, Perez CA, Fletcher GH: Cervical lymph nodes metastasis of unknown primary cancer. Cancer 1973;31:854-859.Crossref 27. Copeland EM, McBride CM: Axillary metastases from unknown primary sites. Ann Surg 1973;178:25-27. 28. Nelson RB: Chemotherapy of metastatic adenocarcinoma of unknown origin. JV Engl J Med 1980;303:498. 29. Woods RL, Fow RM, Tattersall MHN, et al: Metastatic adenocarcinomas of unknown primary site: A randomized study of two combination chemotherapy regimens. TV Engl J Med 1980;303:87-89.Crossref 30. Indupalli SR, Bedikian AY, Bodey GP: Adenocarcinoma of unknown primary origin: Impact of chemotherapy on survival. South Med J 1981;74:1431-1435.Crossref 31. McKeen E, Smith F, Haidak D, et al: Fluorouracil (F), Adriamycin (A), and mitomycin-C (M), FAM, for adenocarcinoma of unknown origin (AUO), abstracted. Proc Am Soc Clin Oncol , 1980, No. (C-154) , p 358. 32. Fiore JJ, Kelsen DP, Gralla RJ, et al: Adenocarcinoma of unknown primary origin: Treatment with vindesine and doxorubicin. Cancer Treat 1985;69:591-594. 33. Ruddon RW: Tumor markers in the recognition and management of poorly differentiated neoplasms and cancers of unknown primary. Semin Oncol 1982;9:416-426. 34. Mackay B, Ordoner NG: The role of the pathologist in the evaluation of poorly differentiated tumors. Semin Oncol 1982;9:396-415. 35. Gatter KG, Mason DY: The use of monoclonal antibodies for histopathologic diagnosis of human malignancy. Semin Oncol 1982;9:517-525. 36. Kiang DT, Kennedy BJ: Estrogen receptor assay in the differential diagnosis of adenocarcinomas. JAMA 1977;238:32-34.Crossref 37. Salmon SE, Hamburger AW, Soehnlen B, et al: Quantitation of differential sensitivity of human tumor stem cells to anticancer drugs. N Engl J Med 1978;298:1321-1327.Crossref 38. Weisenthal LM, Marsden JA, Dill PL, et al: A novel dye exclusion method for testing in vitro chemosensitivity of human tumors. Cancer Res 1983;43:749-757. 39. Meyer JS: Potential value of cell kinetics in management of cancers of unknown origin. Semin Oncol 1982;9:513-516. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Early Metastatic Cancer of Unknown Primary Origin at Presentation: A Clinical Study of 302 Consecutive Autopsied Patients

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Publisher
American Medical Association
Copyright
Copyright © 1988 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1988.00380090101024
Publisher site
See Article on Publisher Site

Abstract

Abstract • We studied 302 consecutive autopsied patients who presented with carcinoma of unknown primary origin. The most frequent metastatic sites were the nodes, lung, and bone. The primary site was identified while patients were alive in 27% and at autopsy in 57%; the site remained unidentified in 16%. The pancreas (26.5%), lung (17.2%), kidney (4.6%), and colorectum (3.6%) were the most frequent primary sites, but the reliability of diagnostic tests used in the search for this site was disappointing. Survival was identical in patients whose primary site was discovered while alive, at autopsy, or remained unknown. The number of metastases at presentation was the major prognostic factor. Analysis of autopsy data demonstrated that patients with carcinoma of unknown primary origin pursue a different course than expected when the primary site is the first manifestation of the disease. On the basis of these results and the results of other modern series, we suggest an approach consisting of a limited initial workup but with greater emphasis on modern histochemistry studies and immunohistopathologic and other kinetic and morphologic parameters to understand the patient tumor characteristics better and base the clinical management on an individual basis. (Arch Intern Med 1988;148:2035-2039) References 1. Holmes FF, Fouts TL: Metastatic cancer of unknown primary site. Cancer 1970;26:816-820.Crossref 2. Nystrom JS, Weiner JM, Wolf RM, et al: Identifying the primary site in metastatic cancer of unknown origin. JAMA 1979;241:381-383.Crossref 3. Osteen RT, Kopf G, Wilson RE: In pursuit of the unknown primary. Am J Surg 1978;135:494-498.Crossref 4. Didolkar MS, Fanous N, Elias EG, et al: Metastatic carcinomas from occult primary tumors: A study of 254 patients. Ann Surg 1977; 186:625-630.Crossref 5. Moertel CG: Adenocarcinoma of unknown origin. Ann Intern Med 1979;91:646-647.Crossref 6. Greco FA, Oldham RK, Fer MF: The extragonadal germ cell cancer syndrome. Semin Oncol 1982;9:448-455. 7. Snyder RD, Mavligit GM, Valdivieso M: Adenocarcinoma of unknown primary site: A clinico-pathological study. Med Pediatr Oncol 1979;6:289-294.Crossref 8. Cancer statistics 1984. CA 1984;34:1. 9. Peto R, Pike MC, Armitage P, et al: Design and analysis of randomized clinical trials requiring prolonged observation of each patient: Analysis and example. Br J Cancer 1977;35:1-39.Crossref 10. Albers CA, Johnson RH, Mansberger AR: The management of patients with metastatic cancer from an unknown primary site. Am Surg 1981;47:162-166. 11. McMillan JH, Levin E, Stephens RM: Computed tomography in the evaluation of metastatic adenocarcinoma from an unknown primary site. Radiology 1982;143:143-146.Crossref 12. Neumann KH, Nystrom JS: Metastatic cancer of unknown origin: Nonsquamous cell type. Semin Oncol 1982;9:427-434. 13. Clary CF, Michel RP, Wang NS, et al: Metastatic carcinoma: The lung as the site for the clinically undiagnosed primary. Cancer 1983;51:362-366.Crossref 14. Altman E, Cadman E: An analysis of 1539 patients with cancer of unknown primary site. Cancer 1986;57:120-124.Crossref 15. Karsell PR, Sheedy PF, O'Connell J: Computed tomography in search of cancer of unknown origin. JAMA 1982;248:340-343.Crossref 16. Sakahara H, Endo F, Nakajima K, et al: Serum Ca 19.9 concentrations and computed tomography findings in patients with pancreatic carcinoma. Cancer 1986;57:1324-1326.Crossref 17. Rosenblatt MB, Lisa JR, Trinidad S: Pitfalls in the clinical and histologic diagnosis of bronchogenic carcinoma. Dis Chest 1966;49:396-404.Crossref 18. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma: Analysis of 1000 autopsied cases. Cancer 1950;3:74-85.Crossref 19. End Results Section, Biometry Branch, National Cancer Institute : End Results in Cancer , US Dept of Health, Education, and Welfare publication 4. Government Printing Office, 1972. 20. Gilbert HA, Kagan AR: Metastases: Incidence, detection and evaluation without histologie confirmation , in Weiss L (ed): Fundamental Aspects of Metastasis . New York, Elsevier Science Publishing Co Ine, 1976, pp 385-405. 21. Nissenblatt MJ: The CUP syndrome (carcinoma unknown primary). Cancer Treat Rev 1981;8:211-224.Crossref 22. Cassiere SG, McLain DA, Emory WB, et al: Metastatic carcinoma of the pancreas simulating primary bronchogenic carcinoma. Cancer 1980;46:2319-2321.Crossref 23. Greenberg BE, Young JM: Pulmonary metastases from occult primary sites resembling bronchogenic carcinoma. Dis Chest 1958;33:496-505.Crossref 24. Koch M, McPherson TA: Carcinoembryonic antigen levels as an indicator of primary site in metastatic disease of unknown origin. Cancer 1981;48:1242-1244.Crossref 25. Tubiana M, Schlumberger M, Rougier R, et al: Long-term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer 1985;55:794-804.Crossref 26. Jesse RH, Perez CA, Fletcher GH: Cervical lymph nodes metastasis of unknown primary cancer. Cancer 1973;31:854-859.Crossref 27. Copeland EM, McBride CM: Axillary metastases from unknown primary sites. Ann Surg 1973;178:25-27. 28. Nelson RB: Chemotherapy of metastatic adenocarcinoma of unknown origin. JV Engl J Med 1980;303:498. 29. Woods RL, Fow RM, Tattersall MHN, et al: Metastatic adenocarcinomas of unknown primary site: A randomized study of two combination chemotherapy regimens. TV Engl J Med 1980;303:87-89.Crossref 30. Indupalli SR, Bedikian AY, Bodey GP: Adenocarcinoma of unknown primary origin: Impact of chemotherapy on survival. South Med J 1981;74:1431-1435.Crossref 31. McKeen E, Smith F, Haidak D, et al: Fluorouracil (F), Adriamycin (A), and mitomycin-C (M), FAM, for adenocarcinoma of unknown origin (AUO), abstracted. Proc Am Soc Clin Oncol , 1980, No. (C-154) , p 358. 32. Fiore JJ, Kelsen DP, Gralla RJ, et al: Adenocarcinoma of unknown primary origin: Treatment with vindesine and doxorubicin. Cancer Treat 1985;69:591-594. 33. Ruddon RW: Tumor markers in the recognition and management of poorly differentiated neoplasms and cancers of unknown primary. Semin Oncol 1982;9:416-426. 34. Mackay B, Ordoner NG: The role of the pathologist in the evaluation of poorly differentiated tumors. Semin Oncol 1982;9:396-415. 35. Gatter KG, Mason DY: The use of monoclonal antibodies for histopathologic diagnosis of human malignancy. Semin Oncol 1982;9:517-525. 36. Kiang DT, Kennedy BJ: Estrogen receptor assay in the differential diagnosis of adenocarcinomas. JAMA 1977;238:32-34.Crossref 37. Salmon SE, Hamburger AW, Soehnlen B, et al: Quantitation of differential sensitivity of human tumor stem cells to anticancer drugs. N Engl J Med 1978;298:1321-1327.Crossref 38. Weisenthal LM, Marsden JA, Dill PL, et al: A novel dye exclusion method for testing in vitro chemosensitivity of human tumors. Cancer Res 1983;43:749-757. 39. Meyer JS: Potential value of cell kinetics in management of cancers of unknown origin. Semin Oncol 1982;9:513-516.

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Sep 1, 1988

References

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