The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Zhuravlev A.S.

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, 2—4 Bolshaya Pirogovskaya St., Moscow, Russian Federation, 119991

Carcinoma with unknown primary site: Morphological diagnosis

Authors:

Zhuravlev A.S.

More about the authors

Read: 18096 times


To cite this article:

Zhuravlev AS. Carcinoma with unknown primary site: Morphological diagnosis. Russian Journal of Archive of Pathology. 2019;81(2):51‑58. (In Russ.)
https://doi.org/10.17116/patol20198102151

Recommended articles:
Cardiac myxoma: biological features, morphology, differential diagnosis. Russian Journal of Archive of Pathology. 2024;(6):74-81
Quality control of immu­nohistochemical studies: compulsory duty or urgent need?. Russian Journal of Archive of Pathology. 2025;(2):43-52
Soli­tary fibrous tumor of the kidney. Russian Journal of Archive of Pathology. 2025;(3):77-81
Differential Diagnosis of Perianal Skin Neoplasms. Russian Journal of Clinical Dermatology and Vene­reology. 2024;(6):673-678
Clinical Case of HIV-Associated Kaposi’s Sarcoma. Russian Journal of Clinical Dermatology and Vene­reology. 2024;(6):782-786

References:

  1. Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G; ESMO Guidelines Committee. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl.5):v133-v138. https://doi.org/10.1093/annonc/mdm049
  2. NCCN Practice Guidelines in Oncology. Occult primary (Cancer of Unknown Primary [CUP]). 2016. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines_nojava.asp
  3. Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012;379(9824):1428-1435. https://doi.org/10.1016/s0140-6736(11)61178-1
  4. Lampe I, Santin G. Metastatic carcinoma in neck of unknown primary site; salvage by radiation treatment. Univ Hosp Bull. 1946; 12(11):106.
  5. Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R, Greco FA. Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon research institute. J Clin Oncol. 2013;31(2):217-223. https://doi.org/10.1200/jco.2012.43.3755
  6. Greco FA, Lennington WJ, Spigel DR, Hainsworth JD. Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology. J Natl Cancer Inst. 2013;105(11):782-789. https://doi.org/10.1093/jnci/djt099
  7. Hainsworth JD, Greco FA. Gene expression profiling in patients with carcinoma of unknown primary site: from translational research to standard of care. Virchows Archiv.2014;464(4):393-402. https://doi.org/10.1007/s00428-014-1545-2
  8. Pentheroudakis G, Golfinopoulos V, Pavlidis N. Switching benchmarks in cancer of unknown primary: from autopsy to microarray. Eur J Cancer. 2007;43(14):2026-2036. https://doi.org/10.1016/j.ejca.2007.06.023
  9. Marchevsky AM, Gupta R, Balzer B. Diagnosis of metastatic neoplasms: a clinicopathologic and morphologic approach. Arch Pathol Lab Med. 2010;134(2):194-206. https://doi.org/10.1043/1543-2165-134.2.194
  10. Cerezo L, Raboso E, Ballesteros AI. Unknown primary cancer of the head and neck: a multidisciplinary approach. Clin Transl Oncol. 2011;13(2):88-97. https://doi.org/10.1007/s12094-011-0624-y
  11. Löffler H, Puthenparambil J, Hielscher T, Neben K, Krämer A. Patients with cancer of unknown primary: a retrospective analysis of 223 patients with adenocarcinoma or undifferentiated carcinoma. Dtsch Arztebl Int. 2014;111(27-28):481-487. https://doi.org/10.3238/arztebl.2014.0481
  12. Nottebaert M, Exner GU, von Hochstetter AR, Schreiber A. Metastatic bone disease from occult carcinoma: a profile. Int Orthop. 1989;13(2):119-123. https://doi.org/10.1007/bf00266372
  13. Sheahan K, O’Keane JC, Abramowitz A, Carlson JA, Burke B, Gottlieb LS, O`Brien MJ. Metastatic adenocarcinoma of an unknown primary site. A comparison of the relative contributions of morphology, minimal essential clinical data and CEA immunostaining status. Am J Clin Pathol. 1993;99(6):729-735. https://doi.org/10.1093/ajcp/99.6.729
  14. Nafussi AA. Tumor diagnosis 2Ed: practical approach and pattern analysis (Hodder Arnold Publication). CRC Press. 2005.
  15. Lin F, Liu H. Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med. 2014;138(12):1583-1610. https://doi.org/10.5858/arpa.2014-0061-ra
  16. Herbst J, Jenders R, McKenna R, Marchevsky A. Evidence-based criteria to help distinguish metastatic breast cancer from primary lung adenocarcinoma on thoracic frozen section. Am J Clin Pathol. 2009;131(1):122-128. https://doi.org/10.1309/ajcpf42avkhgdrze
  17. Vincent T, DeVita J, Lawrence TS, Rosenberg SA, DePinho RA, Weinberg RA. DeVita, Hellman, and Rosenberg’s cancer: principles & practice of oncology. 10th ed. Lippincott Williams & Wilkins. 2014.
  18. Conner JR, Hornick JL. Metastatic carcinoma of unknown primary: diagnostic approach using immunohistochemistry. Adv Anat Pathol. 2015;22(3):149-167. https://doi.org/10.1097/pap.0000000000000069
  19. DeYoung BR, Wick MR. Immunohistologic evaluation of metastatic carcinomas of unknown origin: an algorithmic approach. Semin Diagn Pathol. 2000;17(3):184-193.
  20. Handorf CR, Kulkarni A, Grenert JP, Weiss LM, Rogers WM, Kim OS, Monzon FA, Halks-Miller M, Anderson GG, Walker MG, Pillai R, Henner WD. A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. Am J Surg Pathol. 2013;37(7):1067-1075. https://doi.org/10.1097/pas.0b013e31828309c4
  21. Lin F, Prichard J, Liu H, et al. (eds.). Handbook of practical immunohistochemistry: frequently asked questions. New York (NY): Springer, 2011.
  22. Dabbs DJ. Diagnostic immunohistochemistry: theranostic and genomic applications. 4th ed. Philadelphia: Churchill Livingstone; 2014.
  23. Kandalaft PL, Gown AM. Practical applications in immunohistochemistry: carcinomas of unknown primary site. Arch Pathol Lab Med. 2016;140(6):508-523. https://doi.org/10.5858/arpa.2015-0173-cp
  24. Oien KA, Dennis JL. Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to molecular profiling. Ann Oncol. 2012;23(Suppl.10):x271-x277. https://doi.org/10.1093/annonc/mds357
  25. Ordonez NG. Broad-spectrum immunohistochemical epithelial markers: a review. Hum Pathol. 2013;44(7):1195-1215. https://doi.org/10.1016/j.humpath.2012.11.016
  26. Agaimy A, Specht K. Metastatic malignant melanoma with complete loss of differentiation markers (undifferentiated/dedifferentiated melanoma): analysis of 14 patients emphasizing phenotypic plasticity and the value of molecular testing as surrogate diagnostic marker. Am J Surg Pathol. 2016;40(2):181-191. https://doi.org/10.1097/pas.0000000000000527
  27. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13(9):962-972. https://doi.org/10.1038/modpathol.3880175
  28. Heim-Hall J, Yohe SL. Application of immunohistochemistry to soft tissue neoplasms. Arch Pathol Lab Med. 2008;132(3):476-489.
  29. Taweevisit M, Isarakul P, Chaipipat M, Keetacheeva K, Wattanasirmkit V, Shuangshoti S. Cytokeratin 7 and 20 as immunohistochemical markers in identification of primary tumors in craniospinal metastases: do they have a significant role? Neuropathology. 2003;23(4):271-274. https://doi.org/10.1046/j.1440-1789.2003.00511.x
  30. Dennis JL, Hvidsten TR, Wit EC, Komorowski J, Bell AK, Downie I, Mooney J, Verbeke C, Bellamy C, Keith WN, Oien KA. Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clin Cancer Res. 2005;11(10):3766-3772. https://doi.org/10.1158/1078-0432.ccr-04-2236
  31. Miller RT. Immunohistochemistry in the diagnosis of metastatic carcinoma of unknown primary origin. In: Paper presented at Proceedings of the American Academy of Oral and Maxillofacial Pathology Annual Meeting. San Juan, Puerto Rico. 30.04.2011. Accessed 30.04.2011. Available at: http://www.aaomp.org/annual-meeting/ docs/2011_CE5_Miller--Met%20ca%20Final%20Handout.pdf.
  32. Weidner N, Cote RJ, Saul Suster, Weiss LM. Modern surgical pathology. 2nd ed. Saunders Elsevier. 2009;48-70.
  33. Park SY, Kim BH, Kim JH, Lee S, Kang GH. Panels of immunohistochemical markers help determine Primary sites of metastatic adenocarcinoma. Arch Pathol Lab Med. 2007;131(10):1561-1567.
  34. Bellizzi AM. Assigning site of origin in metastatic neuroendocrine neoplasms: a clinically significant application of diagnostic immunohistochemistry. Adv Anat Pathol. 2013;20(5):285-314. https://doi.org/10.1097/pap.0b013e3182a2dc67
  35. Sangoi AR, Ohgami RS. PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. Mod Pathol. 2011;24(3):412-424. https://doi.org/10.1038/modpathol.2010.176
  36. Spigel DR, Hainsworth JD. Neuroendocrine carcinoma of unknown primary site. Semin Oncol. 2009;36(1):52-59. https://doi.org/10.1053/j.seminoncol.2008.10.003
  37. Li Z, Yuan J, Wei L, Zhou L, Mei K, Yue J, Gao H, Zhang M, Jia L, Kang Q, Huang X, Cao D. SATB2 is a sensitive marker for lower gastrointestinal well-differentiated neuroendocrine tumors. Int J Clin Exp Pathol. 2015;8(6):7072-7082. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525934
  38. Pereira TC, Share SM, Magalhães AV, Silverman JF. Can we tell the site of origin of metastatic squamous cell carcinoma? An immunohistochemical tissue microarray study of 194 cases. Appl Immunohistochem Mol Morphol. 2011;19(1):10-14. https://doi.org/10.1097/pai.0b013e3181ecaf1c
  39. Compton AM, Moore-Medlin T, Herman-Ferdinandez L, Clark C, Caldito GC, Wang XI, Thomas J, Abreo FW, Nathan CO. Human papillomavirus in metastatic lymph nodes from unknown primary head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. 2011;145(1):51-57. https://doi.org/10.1177/0194599811400385
  40. Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA. 2001;98(24):13790-13795. https://doi.org/10.1073/pnas.191502998
  41. Monzon FA, Koen TJ. Diagnosis of metastatic neoplasms: molecular approaches for identification of tissue of origin. Arch Pathol Lab Med. 2010;134(2):216-224. https://doi.org/10.5858/arpa.2013-0157-ra
  42. Moran S, Martínez-Cardús A, Sayols S, Musulén E, Balañá C, Estival-Gonzalez A, Moutinho C, Heyn H, Diaz-Lagares A, de Moura MC, et al. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol. 2016;17(10):1386-1395. https://doi.org/10.1016/s1470-2045(16)30297-2
  43. Centeno BA, Bloom G, Chen DT, Chen Z, Gruidl M, Nasir A, Yeatman TY. Hybrid model integrating immunohistochemistry and expression profiling for the classification of carcinomas of unknown primary site. J Mol Diagn. 2010;12(4):476-486. https://doi.org/10.2353/jmoldx.2010.090197
  44. Nystrom SJ, Hornberger JC, Varadhachary GR, Hornberger RJ, Gutierrez HR, Henner DW, Becker SH, Amin MB, Walker MG. Clinical utility of gene-expression profiling for tumor-site origin in patients with metastatic or poorly differentiated cancer: impact on diagnosis, treatment, and survival. Oncotarget. 2012;3(6):620-628. https://doi.org/10.18632/oncotarget.521
  45. Gracia A, Balañá C, Kaskens L, Chiavenna S, Matias-Guiu X, Rubio-Rodríguez D, Rubio-Terrés C, Iglesias L, Esteller M. Economic analysis of epicup, an epigenetic test to predict the tissue of origin in cancer of unknown primary site, The usa payors perspective. Value Health. 2015;18(7):A356. https://doi.org/10.1016/j.jval.2015.09.670
  46. Ross JS, Wang K, Gay L, Otto GA, White E, Iwanik K, Palmer G, Yelensky R, Lipson DM, et al. Comprehensive genomic profiling of carcinoma of unknown primary site: new routes to targeted therapies. JAMA Oncol. 2015;1(1):40-49. https://doi.org/10.1001/jamaoncol.2014.216

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.