Skip to main content

Tumors of Unknown Primary

  • Chapter
  • First Online:
Essentials of Anatomic Pathology

Abstract

Not so long ago, “Anaplastic Tumor” ranked among the top ten most common diagnoses in pathology departments around the World. That this is no longer true is in large measure attributable to the widespread use of IHC methods for the diagnosis of very poorly differentiated or anaplastic malignant tumors, whether as metastases or apparent primary lesions. In effect, IHC stains provide a sensitive method for the demonstration of characteristic cell products or structural proteins (antigens) that allow identification of cell lineage when morphologic features alone cannot do so. This chapter provides a concise and practical approach for the application of IHC methods to facilitate the diagnosis of tumors of unknown origin. Screening approaches employing selected panels of stains are described for common broad categories of tumors (carcinomas, sarcomas, lymphomas, etc.), together with “second-tier” stains to home in on a more specific diagnosis. Emphasis is on an efficient practical approach, that is both economical (using the minimum number of stains) and rapid (requiring of the least number of additional staining runs). For rapid reference many of the IHC stains and stain panels are presented in summary tables, without further detail of the typical patterns of reactivity of each antibody. However, all of the antibodies (stains) described in this chapter have been discussed previously in; further details may be found by recourse to individual organ and issue specific chapters throughout the book.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

SUGGESTED READING

General

  • Chu PG, Weiss LM. Keratin Expression in human tissues and neoplasms. Histopathol 2002;40:403–439.

    Article  CAS  Google Scholar 

  • Dabbs, DJ (ed). Diagnostic immunohistochemistry. Philadelphia, Churchill Livingston, 2006.

    Google Scholar 

  • Nadji M, Nassiri M, Morales AR (eds). Efficient Tumor Immunohisto­chemistry: A Differential Diagnosis-driven Approach. Chicago, ASCP Press, 2006.

    Google Scholar 

  • Taylor CR, Cote RJ (eds). Immunomicroscopy: A Diagnostic Tool for the Surgical Pathologist. 3rd ed., Philadelphia, Saunders, 2006.

    Google Scholar 

Unknown Tumor

  • Al-Nafussi A, Wong NA. Intra-abdominal spindle cell lesions: a review and practical aids to diagnosis. Histopathol 2001;38:387–402.

    Article  CAS  Google Scholar 

  • Anderson GG, Weiss LM. Determining tissue of origin for metastatic cancers: meta-analysis and literature review of immunohistochemistry performance. Appl Immunohistochem Mol Morphol 2010;18:3–8.

    Google Scholar 

  • Antonescu CR. The role of genetic testing in soft tissue sarcoma. Histopathol 2006;48:13–21.

    Article  CAS  Google Scholar 

  • Bahrami A, Truong LD, Ro JY.Undifferentiated tumor: true identity by immunohistochemistry. Arch Pathol Lab Med 2008;132:326–348.

    PubMed  Google Scholar 

  • Becher MW, Abel TW, Thompson RC, Weaver KD, Davis LE. Immunohistochemical analysis of metastatic neoplasms of the central nervous system. J Neuropathol Exp Neurol 2006;65:935–944.

    Article  PubMed  CAS  Google Scholar 

  • Bender RA, Erlander MG. Molecular classification of unknown primary cancer. Semin Oncol 2009;36:38–43.

    Article  PubMed  CAS  Google Scholar 

  • Cheng L. Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer 2004;101:2006–2010.

    Google Scholar 

  • Cheng L, Sung MT, Cossu-Rocca P, et al. OCT4: Biological functions and clinical applications as a marker of germ cell neoplasia. J Pathol 2007; 211:1–9.

    Google Scholar 

  • Cheuk W, Kwan MY, Suster S, Chan JK. Immunostaining for thyroid transcription factor 1 and cytokeratin 20 aids the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinomas. Arch Pathol Lab Med 2001;125:228–231.

    PubMed  CAS  Google Scholar 

  • Chu PG, Weiss LM. Keratin expression in human tissues and neoplasm. Histopathol 2002;40:403–439.

    Article  PubMed  CAS  Google Scholar 

  • Coindre JM. Immunohistochemistry in the diagnosis of soft tissue tumours. Histopathol 2003;43:1–16.

    Article  CAS  Google Scholar 

  • 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;11:3766–3772.

    Article  PubMed  CAS  Google Scholar 

  • Gown AM, Yaziji H. Immunohistochemical analysis of ­carcinomas of unknown primary site. Pathol Case Rev 1999;4:250–259.

    Article  Google Scholar 

  • Heim-Hall J, Yohe SL. Application of immunohistochemistry to soft tissue neoplasms. Arch Pathol Lab Med 2008;132:476–489.

    PubMed  Google Scholar 

  • Krishnan C, George TI, Arber DA. Bone marrow metastases: a survey of nonhematologic metastases with immunohistochemical study of metastatic carcinomas. Appl Immunohistochem Mol Morphol 2007;15:1–7.

    Article  PubMed  Google Scholar 

  • Lagendijk JH, Mullink H, van Diest PJ, Meijer GA, Meijer CJ. Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry; differential diagnosis between colonic and ovarian carcinomas as primary sited. Hum Pathol 1998;29:491–497.

    Article  PubMed  CAS  Google Scholar 

  • Lagendijk JH, Mullink H, van Diest PJ, Meijer GA, Meijer CJ. Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach. J Clin Pathol 1999;52:283–290.

    Article  PubMed  CAS  Google Scholar 

  • Oien KA. Pathologic evaluation of unknown primary cancer. Semin Oncol 2009;36:8–37.

    Article  PubMed  CAS  Google Scholar 

  • Park SY, Kim KH, Kim JH, Lee S, Kang GH. Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. Arch Pathol Lab Med 2007;131:1561–1567.

    PubMed  CAS  Google Scholar 

  • Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol 2008;33:626–632.

    Google Scholar 

  • Tot T. Review: Cytokeratins 20 and 7 as biomarkers: usefulness in discriminating primary from metastatic adenocarcinoma. Eur J Cancer 2002;38:758–763.

    Article  PubMed  CAS  Google Scholar 

  • Varadhachary GR, Abbruzzese JL, Lenzi R. Diagnostic strategies for unknown primary cancer. Cancer 2004;100:1776–1785.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Klipfel, N., Simental-Pizarro, R., Taylor, C.R. (2011). Tumors of Unknown Primary. In: Cheng, L., Bostwick, D. (eds) Essentials of Anatomic Pathology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6043-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-6043-6_3

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-6042-9

  • Online ISBN: 978-1-4419-6043-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics