2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary

doi:10.1007/s12094-018-1899-z

Review

. 2018 Nov;20(11):1361-1372.

doi: 10.1007/s12094-018-1899-z. Epub 2018 May 28.

2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary

F Losa¹, L Iglesias², M Pané³, J Sanz⁴, B Nieto⁵, V Fusté⁶, L de la Cruz-Merino⁷, Á Concha⁸, C Balañá⁹, X Matías-Guiu¹⁰

Affiliations

¹ Medical Oncology Department, Institut Català d'Oncologia ICO-Hospitalet/Hospital de Sant Joan Despí, Moisès Broggi, Sant Joan Despí, Carrer de Jacint Verdaguer, 90, 08970, Sant Joan Despí, Barcelona, España. ferran.losa@sanitatintegral.org.
² Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
³ Pathology Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
⁴ Pathology Department, Hospital Clínico San Carlos, Madrid, Spain.
⁵ Medical Oncology Department, Hospital Universitario de León, León, Spain.
⁶ Pathology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁷ Medical Oncology Department, Hospital Universitario Virgen Macarena, Seville, Spain.
⁸ Pathology Department, Hospital Universitario A Coruña, La Coruña, Spain.
⁹ Medical Oncology Department, Institut Català d'Oncologia, Badalona, Barcelona, Spain.
¹⁰ Pathology Department, Hospital Universitario Arnau de Vilanova de Lleida y Hospital Universitari de Bellvitge, IRBLLEIDA, IDIBELL, CIBERONC, L'Hospitalet de Llobregat, Barcelona, Spain.

PMID: 29808414
PMCID: PMC6182632
DOI: 10.1007/s12094-018-1899-z

Review

2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary

F Losa et al. Clin Transl Oncol. 2018 Nov.

. 2018 Nov;20(11):1361-1372.

doi: 10.1007/s12094-018-1899-z. Epub 2018 May 28.

Authors

F Losa¹, L Iglesias², M Pané³, J Sanz⁴, B Nieto⁵, V Fusté⁶, L de la Cruz-Merino⁷, Á Concha⁸, C Balañá⁹, X Matías-Guiu¹⁰

Affiliations

¹ Medical Oncology Department, Institut Català d'Oncologia ICO-Hospitalet/Hospital de Sant Joan Despí, Moisès Broggi, Sant Joan Despí, Carrer de Jacint Verdaguer, 90, 08970, Sant Joan Despí, Barcelona, España. ferran.losa@sanitatintegral.org.
² Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
³ Pathology Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
⁴ Pathology Department, Hospital Clínico San Carlos, Madrid, Spain.
⁵ Medical Oncology Department, Hospital Universitario de León, León, Spain.
⁶ Pathology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
⁷ Medical Oncology Department, Hospital Universitario Virgen Macarena, Seville, Spain.
⁸ Pathology Department, Hospital Universitario A Coruña, La Coruña, Spain.
⁹ Medical Oncology Department, Institut Català d'Oncologia, Badalona, Barcelona, Spain.
¹⁰ Pathology Department, Hospital Universitario Arnau de Vilanova de Lleida y Hospital Universitari de Bellvitge, IRBLLEIDA, IDIBELL, CIBERONC, L'Hospitalet de Llobregat, Barcelona, Spain.

PMID: 29808414
PMCID: PMC6182632
DOI: 10.1007/s12094-018-1899-z

Abstract

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.

Keywords: Biopsy; Cancer of unknown primary; Chemotherapy; Diagnosis; Histopathology; Immunohistochemistry; Molecular pathology; Prognosis.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

The authors declare that, when writing and revising the text, they did not know the names of the pharmaceutical companies that provided financial support for this project, so this support has not influenced the content of this article.

Ethical approval

The study has been performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments. This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

Figures

**Fig. 1**
Advisable minimum IHC panel. *IHC* immunohistochemistry

**Fig. 2**
Summary of proposed management of cancer of unknown primary

**Fig. 3**
SEAP diagnostic algorithm. Sample material should be obtained by imaging or surgical techniques, preferably in the form of a core-needle, incisional or excisional biopsy. In the pathology department, optimal use of the material should be ensured. This may mean separating fragments into different paraffin blocks to save material for future use, if necessary. Tests should then be done using a basic immunohistochemical panel, according to morphology, and an advanced immunohistochemical panel, based on information obtained from the basic panel, clinical features, and microscopy findings. The recommended number of stains is approximately 7. The aim is to preserve material for possible use of a molecular platform

See this image and copyright information in PMC

Cited by

Pelvic squamous cell carcinoma of unknown primary origin with hydronephrosis and ureteral stricture: A case report.
Meng W, Gao Y, Pan L, Zhao G, Chen Q, Bai L, Zheng R. Meng W, et al. Medicine (Baltimore). 2024 Jan 26;103(4):e37057. doi: 10.1097/MD.0000000000037057. Medicine (Baltimore). 2024. PMID: 38277516 Free PMC article.
Pelvic metastatic squamous cell carcinoma of unknown primary site: A case report and brief literature review.
Zhu QZ, Li HJ, Li YQ, Yu XH, Shu KY. Zhu QZ, et al. Medicine (Baltimore). 2023 Dec 29;102(52):e36796. doi: 10.1097/MD.0000000000036796. Medicine (Baltimore). 2023. PMID: 38206704 Free PMC article. Review.
Local Treatment Efficacy for Single-Area Squamous Cell Carcinoma of the Unknown Primary Site.
Kurita T, Yunokawa M, Tanaka Y, Okamoto K, Kanno M, Fusegi A, Omi M, Netsu S, Nomura H, Tonooka A, Kanao H. Kurita T, et al. Curr Oncol. 2023 Oct 20;30(10):9327-9334. doi: 10.3390/curroncol30100674. Curr Oncol. 2023. PMID: 37887574 Free PMC article.
The Elusive Primary: Metastatic Adenocarcinoma of the Breast Presenting Solely as a Hard Sternal Mass.
Mohd Omar R, Ismail IA, Md Yasin M, Ahmad Affandi K, Hasbullah HH, Mohamad Ali ND. Mohd Omar R, et al. Am J Case Rep. 2023 Aug 23;24:e940594. doi: 10.12659/AJCR.940594. Am J Case Rep. 2023. PMID: 37608536 Free PMC article.
Carcinoma of unknown primary (CUP): an update for histopathologists.
Beauchamp K, Moran B, O'Brien T, Brennan D, Crown J, Sheahan K, Cotter MB. Beauchamp K, et al. Cancer Metastasis Rev. 2023 Dec;42(4):1189-1200. doi: 10.1007/s10555-023-10101-6. Epub 2023 Jul 3. Cancer Metastasis Rev. 2023. PMID: 37394540 Free PMC article. Review.

See all "Cited by" articles

References

1. Pavlidis N, Fizazi K. Cancer of unknown primary (CUP) Crit Rev Oncol Hematol. 2005;54:243–250. doi: 10.1016/j.critrevonc.2004.10.002. - DOI - PubMed
1. Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012;379:1428–1435. doi: 10.1016/S0140-6736(11)61178-1. - DOI - PubMed
1. Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G, et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v133–v138. doi: 10.1093/annonc/mdv305. - DOI - PubMed
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Occult Primary (Cancer of Unknown Primary [CUP]) Version 1.2018–November 9, 2017. https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf. Accessed 2 Jan 2018.
1. Greco FA, Hainsworth J. Cancer of unknown primary site. Cancer: principles and practice of oncology. Philadelphia: Lippincott Williams and Wilkins; 2011.

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- Genetic Alliance

[1] Pavlidis N, Fizazi K. Cancer of unknown primary (CUP) Crit Rev Oncol Hematol. 2005;54:243–250. doi: 10.1016/j.critrevonc.2004.10.002. - DOI - PubMed

[2] Pavlidis N, Fizazi K. Cancer of unknown primary (CUP) Crit Rev Oncol Hematol. 2005;54:243–250. doi: 10.1016/j.critrevonc.2004.10.002. - DOI - PubMed

[3] Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012;379:1428–1435. doi: 10.1016/S0140-6736(11)61178-1. - DOI - PubMed

[4] Pavlidis N, Pentheroudakis G. Cancer of unknown primary site. Lancet. 2012;379:1428–1435. doi: 10.1016/S0140-6736(11)61178-1. - DOI - PubMed

[5] Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G, et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v133–v138. doi: 10.1093/annonc/mdv305. - DOI - PubMed

[6] Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G, et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v133–v138. doi: 10.1093/annonc/mdv305. - DOI - PubMed

[7] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Occult Primary (Cancer of Unknown Primary [CUP]) Version 1.2018–November 9, 2017. https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf. Accessed 2 Jan 2018.

[8] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Occult Primary (Cancer of Unknown Primary [CUP]) Version 1.2018–November 9, 2017. https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf. Accessed 2 Jan 2018.

[9] Greco FA, Hainsworth J. Cancer of unknown primary site. Cancer: principles and practice of oncology. Philadelphia: Lippincott Williams and Wilkins; 2011.

[10] Greco FA, Hainsworth J. Cancer of unknown primary site. Cancer: principles and practice of oncology. Philadelphia: Lippincott Williams and Wilkins; 2011.

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed