Top

Published in:

01-01-2021 | Metastasis | Review

Carcinoma of unknown primary with hepatic metastases: a need of judicious and contemplative diagnostic algorithm

Authors: Vikram Sai Shivaji, Joseph Charles Wilson, Noemi L. Schmidt, Orpheus Kolokythas, Neeraj Lalwani

Published in: Abdominal Radiology | Issue 1/2021

Abstract

Carcinoma of Unknown Primary presenting primarily as hepatic metastases encompasses a dismal subgroup of tumors with a median survival of 5.9 months. Adenocarcinoma is the most common histological subtype identified upon biopsy and the primary tumor remains undetectable in the majority of cases despite extensive workup. It is important to have a validated and standardized algorithm to follow these tumors to avoid unnecessary tests, as the wishes and health status of the patient represent the principal concerns. The purpose of this paper is to briefly review the current literature on carcinoma of unknown primary with hepatic metastases and propose a standardized diagnostic approach.

Pavlidis N, Fizazi K (2005) Cancer of unknown primary (CUP). Critical Reviews in Oncology/Hematology 54 (3):243–250. https://doi.org/10.1016/j.critrevonc.2004.10.002CrossRefPubMed

K. Fizazi FAG (2015) Cancer of Unknown Primary Site: ESMP Clinical Practice Guidelines for diagnosis, treatment and follow up. Annals of Oncology 26 (supplement 5):v133–v138CrossRef

Levi F, Te VC, Erler G, Randimbison L, La Vecchia C (2002) Epidemiology of unknown primary tumours. European Journal of Cancer 38 (13):1810–1812. https://doi.org/10.1016/S0959-8049(02)00135-1CrossRefPubMed

Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M, Rouesse J (1988) Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. Arch Intern Med 148 (9):2035–2039

Tothill RW, Kowalczyk A, Rischin D, Bousioutas A, Haviv I, van Laar RK, Waring PM, Zalcberg J, Ward R, Biankin AV, Sutherland RL, Henshall SM, Fong K, Pollack JR, Bowtell DDL, Holloway AJ (2005) An Expression-Based Site of Origin Diagnostic Method Designed for Clinical Application to Cancer of Unknown Origin. Cancer Research 65 (10):4031. https://doi.org/10.1158/0008-5472.CAN-04-3617CrossRefPubMed

Ferté C, Penel N, Bonneterre J, Adenis A (2010) Individual Life Expectancy Estimation Using Validated Prognostic Scores for Patients with Cancer of Unknown Primary. Oncology 78 (2):87–93. https://doi.org/10.1159/000306137CrossRefPubMed

Hogan BA, Thornton FJ, Brannigan M, Browne TJ, Pender S, O’Kelly P, Lyon SM, Lee MJ (2002) Hepatic Metastases from an Unknown Primary Neoplasm (UPN): Survival, Prognostic Indicators and Value of Extensive Investigations. Clinical Radiology 57 (12):1073–1077. https://doi.org/10.1053/crad.2002.1085CrossRefPubMed

Hess KR, Abbruzzese MC, Lenzi R, Raber MN, Abbruzzese JL (1999) Classification and Regression Tree Analysis of 1000 Consecutive Patients with Unknown Primary Carcinoma. Clinical Cancer Research 5 (11):3403PubMed

Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P (1994) Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. Journal of Clinical Oncology 12 (6):1272–1280. https://doi.org/10.1200/JCO.1994.12.6.1272CrossRefPubMed

10.

Ayoub JP, Hess KR, Abbruzzese MC, Lenzi R, Raber MN, Abbruzzese JL (1998) Unknown primary tumors metastatic to liver. Journal of Clinical Oncology 16 (6):2105–2112. https://doi.org/10.1200/JCO.1998.16.6.2105CrossRefPubMed

11.

Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1 (1):27–31. https://doi.org/10.1038/nm0195-27CrossRefPubMed

12.

Klein CA (2009) Parallel progression of primary tumours and metastases. Nat Rev Cancer 9 (4):302–312. https://doi.org/10.1038/nrc2627CrossRefPubMed

13.

Naresh KN (2002) Do metastatic tumours from an unknown primary reflect angiogenic incompetence of the tumour at the primary site?—a hypothesis. Medical Hypotheses 59 (3):357–360. https://doi.org/10.1016/S0306-9877(02)00221-9CrossRefPubMed

14.

Van’t Veer LJ, Weigelt B (2003) Road map to metastasis. Nature Medicine 9:999. https://doi.org/10.1038/nm0803-999bCrossRefPubMed

15.

Varadhachary GR, Abbruzzese JL, Lenzi R (2004) Diagnostic strategies for unknown primary cancer. Cancer 100 (9):1776-1785. https://doi.org/10.1002/cncr.20202CrossRefPubMed

16.

Veer LVJ WB (2003) Road map to metastases. Nature medicine

17.

K. N (2002) Do metastatic tumors from an unknown primary reflect angiogenic incompetence of the tumor at primary site?- a hypothesis. Medical Hypothesis 59(3):357–360CrossRef

18.

Abbruzzese JL, Abbruzzese MC, Lenzi R, Hess KR, Raber MN (1995) Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. Journal of Clinical Oncology 13 (8):2094–2103. https://doi.org/10.1200/jco.1995.13.8.2094CrossRefPubMed

19.

Varadhachary GR, Raber MN (2014) Cancer of Unknown Primary Site. New England Journal of Medicine 371 (8):757–765. https://doi.org/10.1056/NEJMra1303917CrossRef

20.

Pentheroudakis G, Pavlidis N (2010) Cancer of unknown primary site: 20 questions to be answered. Annals of Oncology 21 (suppl_7):vii303–vii307. https://doi.org/10.1093/annonc/mdq278

21.

Vikeså J, Møller AKH, Kaczkowski B, Borup R, Winther O, Henao R, Krogh A, Perell K, Jensen F, Daugaard G, Nielsen FC (2015) Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin. BMC Cancer 15 (1):151. https://doi.org/10.1186/s12885-015-1128-xCrossRefPubMedPubMedCentral

22.

Lazaridis G, Pentheroudakis G, Fountzilas G, Pavlidis N (2008) Liver metastases from cancer of unknown primary (CUPL): A retrospective analysis of presentation, management and prognosis in 49 patients and systematic review of the literature. Cancer Treatment Reviews 34 (8):693–700. https://doi.org/10.1016/j.ctrv.2008.05.005CrossRefPubMed

23.

Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P (1994) Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol 12 (6):1272–1280. https://doi.org/10.1200/jco.1994.12.6.1272CrossRefPubMed

24.

Pouessel D, Culine S, Becht C, Ychou M, Romieu G, Fabbro M, Cupissol D, Pinguet F (2004) Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site. Cancer 100 (6):1257–1261. https://doi.org/10.1002/cncr.20100CrossRefPubMed

25.

Trivanović D, Petkovic M, Stimac D (2009) New Prognostic Index to Predict Survival in Patients with Cancer of Unknown Primary Site with Unfavourable Prognosis. Clinical Oncology 21 (1):43–48. https://doi.org/10.1016/j.clon.2008.09.007CrossRefPubMed

26.

Pavlidis N, Khaled H, Gaafar R (2015) A mini review on cancer of unknown primary site: A clinical puzzle for the oncologists. Journal of Advanced Research 6 (3):375–382. https://doi.org/10.1016/j.jare.2014.11.007CrossRefPubMed

27.

Seve P, Ray-Coquard I, Trillet-Lenoir V, Sawyer M, Hanson J, Broussolle C, Negrier S, Dumontet C, Mackey JR (2006) Low serum albumin levels and liver metastasis are powerful prognostic markers for survival in patients with carcinomas of unknown primary site. Cancer 107 (11):2698–2705. https://doi.org/10.1002/cncr.22300CrossRefPubMed

28.

Ariza A, Balana C, Concha A, Hitt R, Homet B, Matilla A, Alba E (2011) Update on the diagnosis of cancer of unknown primary (CUP) origin. Clin Transl Oncol 13 (7):434–441. https://doi.org/10.1007/s12094-011-0679-9CrossRefPubMed

29.

Pavlidis N, Fizazi K (2005) Cancer of unknown primary (CUP). Crit Rev Oncol Hematol 54 (3):243–250. https://doi.org/10.1016/j.critrevonc.2004.10.002CrossRefPubMed

30.

Karsell PR, Sheedy PF II, O’Connell MJ (1982) Computed tomography in search of cancer of unknown origin. JAMA 248 (3):340–343CrossRef

31.

Pavlidis N, Briasoulis E, Hainsworth J, Greco FA (2003) Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 39 (14):1990–2005. https://doi.org/10.1016/s0959-8049(03)00547-1CrossRefPubMed

32.

Varadhachary GR, Karanth S, Qiao W, Carlson HR, Raber MN, Hainsworth JD, Greco FA (2014) Carcinoma of unknown primary with gastrointestinal profile: immunohistochemistry and survival data for this favorable subset. Int J Clin Oncol 19 (3):479–484. https://doi.org/10.1007/s10147-013-0583-0CrossRefPubMed

33.

Culine S, Kramar A, Saghatchian M, Bugat R, Lesimple T, Lortholary A, Merrouche Y, Laplanche A, Fizazi K (2002) Development and Validation of a Prognostic Model to Predict the Length of Survival in Patients With Carcinomas of an Unknown Primary Site. Journal of Clinical Oncology 20 (24):4679–4683. https://doi.org/10.1200/JCO.2002.04.019CrossRefPubMed

34.

Varadhachary GR (2007) Carcinoma of unknown primary origin. Gastrointestinal Cancer Research: GCR 1 (6):229–235PubMed

35.

Spigel DR, Hainsworth JD, Greco FA (2009) Neuroendocrine carcinoma of unknown primary site. Semin Oncol 36 (1):52–59. https://doi.org/10.1053/j.seminoncol.2008.10.003CrossRefPubMed

36.

Bar-Eli M, Abbruzzese JL, Lee-Jackson D, Frost P (1993) p53 gene mutation spectrum in human unknown primary tumors. Anticancer Res 13 (5A):1619–1623PubMed

37.

Briasoulis E, Tsokos M, Fountzilas G, Bafaloukos D, Kosmidis P, Samantas E, Skarlos D, Nicolaides C, Pavlidis N (1998) Bcl2 and p53 protein expression in metastatic carcinoma of unknown primary origin: biological and clinical implications. A Hellenic Co-operative Oncology Group study. Anticancer Res 18 (3B):1907–1914

38.

Taylor MB, Bromham NR, Arnold SE (2012) Carcinoma of unknown primary: key radiological issues from the recent National Institute for Health and Clinical Excellence guidelines. The British Journal of Radiology 85 (1014):661–671. https://doi.org/10.1259/bjr/75018360CrossRefPubMedPubMedCentral

39.

Pavlidis N, Briasoulis E, Hainsworth J, Greco FA (2003) Diagnostic and therapeutic management of cancer of an unknown primary. European Journal of Cancer 39 (14):1990–2005. https://doi.org/10.1016/S0959-8049(03)00547-1CrossRefPubMed

40.

Patel CM, Sahdev A, Reznek RH (2011) CT, MRI and PET imaging in peritoneal malignancy. Cancer Imaging 11 (1):123–139. https://doi.org/10.1102/1470-7330.2011.0016CrossRefPubMedPubMedCentral

41.

El Rassy E, Kattan J, Pavlidis N (2019) A new entity of abdominal squamous cell carcinoma of unknown primary. European Journal of Clinical Investigation. https://doi.org/10.1111/eci.13111CrossRefPubMed

42.

Pattani KM, Goodier M, Lilien D, Kupferman T, Caldito G, Cherie-Ann ON (2011) Utility of Panendoscopy for the Detection of Unknown Primary Head and Neck Cancer in Patients with a Negative PET/CT Scan. Ear, Nose and Throat Journal 90 (8):E16–E20. https://doi.org/10.1177/014556131109000818CrossRef

43.

Randall DA, Johnstone PA, Foss RD, Martin PJ (2000) Tonsillectomy in diagnosis of the unknown primary tumor of the head and neck. Otolaryngol Head Neck Surg 122 (1):52–55. https://doi.org/10.1016/s0194-5998(00)70143-4CrossRefPubMed

44.

Orel SG, Weinstein SP, Schnall MD, Reynolds CA, Schuchter LM, Fraker DL, Solin LJ (1999) Breast MR Imaging in Patients with Axillary Node Metastases and Unknown Primary Malignancy. Radiology 212 (2):543–549. https://doi.org/10.1148/radiology.212.2.r99au40543CrossRefPubMed

45.

Olson JA, Jr., Morris EA, Van Zee KJ, Linehan DC, Borgen PI (2000) Magnetic resonance imaging facilitates breast conservation for occult breast cancer. Ann Surg Oncol 7 (6):411–415CrossRef

46.

Canale S, Vilcot L, Ammari S, Lemery M, Bidault F, Balleyguier C, Caramella C, Dromain C (2014) Whole body MRI in paediatric oncology. Diagnostic and Interventional Imaging 95 (6):541–550. https://doi.org/10.1016/j.diii.2013.11.002CrossRefPubMed

47.

Lauenstein TC, Goehde SC, Herborn CU, Treder W, Ruehm SG, Debatin JF, Barkhausen J (2002) Three-Dimensional Volumetric Interpolated Breath-Hold MR Imaging for Whole-Body Tumor Staging in Less Than 15 Minutes: A Feasibility Study. American Journal of Roentgenology 179 (2):445–449. https://doi.org/10.2214/ajr.179.2.1790445CrossRefPubMed

48.

Lauenstein TC, Goehde SC, Herborn CU, Goyen M, Oberhoff C, Debatin JF, Ruehm SG, Barkhausen J (2004) Whole-Body MR Imaging: Evaluation of Patients for Metastases. Radiology 233 (1):139–148. https://doi.org/10.1148/radiol.2331030777CrossRefPubMed

49.

Eustace S, Tello R, Decarvalho V, Carey J, Melhem E, Yucel EK (1998) Whole body turbo STIR MRI in unknown primary tumor detection. Journal of Magnetic Resonance Imaging 8 (3):751–753. https://doi.org/10.1002/jmri.1880080336CrossRefPubMed

50.

Hainsworth JD, Greco FA (1993) Treatment of Patients with Cancer of an Unknown Primary Site. New England Journal of Medicine 329 (4):257–263. https://doi.org/10.1056/NEJM199307223290407CrossRef

51.

Liu Y (2019) FDG PET/CT for metastatic squamous cell carcinoma of unknown primary of the head and neck. Oral Oncology 92:46–51. https://doi.org/10.1016/j.oraloncology.2019.03.014CrossRefPubMed

52.

Kennel T, Garrel R, Costes V, Boisselier P, Crampette L, Favier V (2019) Head and neck carcinoma of unknown primary. European Annals of Otorhinolaryngology, Head and Neck Diseases. https://doi.org/10.1016/j.anorl.2019.04.002CrossRefPubMed

53.

De Miguel AC, Cid RP, Trufero JM, Bernad IP, Urquizu LC, Cubero JH, Torres AA (2015) Gene expression profiling and its use in adenocarcinomas of unknown primary origin: A case report. Oncology Letters 10 (4):2657–2661. https://doi.org/10.3892/ol.2015.3572CrossRef

54.

Varadhachary GR, Talantov D, Raber MN, Meng C, Hess KR, Jatkoe T, Lenzi R, Spigel DR, Wang Y, Greco FA, Abbruzzese JL, Hainsworth JD (2008) Molecular Profiling of Carcinoma of Unknown Primary and Correlation With Clinical Evaluation. Journal of Clinical Oncology 26 (27):4442–4448. https://doi.org/10.1200/JCO.2007.14.4378CrossRefPubMed

55.

Spigel DR, Greco FA, Hainsworth JD, Lennington WJ (2013) Molecular Profiling Diagnosis in Unknown Primary Cancer: Accuracy and Ability to Complement Standard Pathology. JNCI: Journal of the National Cancer Institute 105 (11):782-790. https://doi.org/10.1093/jnci/djt099

56.

Su AI, Welsh JB, Sapinoso LM, Kern SG, Dimitrov P, Lapp H, Schultz PG, Powell SM, Moskaluk CA, Frierson HF, Hampton GM (2001) Molecular Classification of Human Carcinomas by Use of Gene Expression Signatures. Cancer Research 61 (20):7388PubMed

57.

Hannouf MB, Winquist E, Mahmud SM, Brackstone M, Sarma S, Rodrigues G, Rogan PK, Hoch JS, Zaric GS (2017) The Potential Clinical and Economic Value of Primary Tumour Identification in Metastatic Cancer of Unknown Primary Tumour: A Population-Based Retrospective Matched Cohort Study. PharmacoEconomics-Open 2 (3):255–270. https://doi.org/10.1007/s41669-017-0051-2CrossRefPubMedCentral

58.

Bloom G, Yang IV, Boulware D, Kwong KY, Coppola D, Eschrich S, Quackenbush J, Yeatman TJ (2004) Multi-platform, multi-site, microarray-based human tumor classification. The American Journal of Pathology 164 (1):9–16. https://doi.org/10.1016/S0002-9440(10)63090-8CrossRefPubMedPubMedCentral

59.

Varadhachary G (2013) New Strategies for Carcinoma of Unknown Primary: The Role of Tissue-of-Origin Molecular Profiling. Clinical Cancer Research 19 (15):4027. https://doi.org/10.1158/1078-0432.CCR-12-3030CrossRefPubMed

60.

Greco FA, Oien K, Erlander M, Osborne R, Varadhachary G, Bridgewater J, Cohen D, Wasan H (2011) Cancer of unknown primary: progress in the search for improved and rapid diagnosis leading toward superior patient outcomes. Annals of Oncology 23 (2):298–304. https://doi.org/10.1093/annonc/mdr306CrossRefPubMed

Title: Carcinoma of unknown primary with hepatic metastases: a need of judicious and contemplative diagnostic algorithm
Authors: Vikram Sai Shivaji
Joseph Charles Wilson
Noemi L. Schmidt
Orpheus Kolokythas
Neeraj Lalwani
Publication date: 01-01-2021
Publisher: Springer US
Keyword: Metastasis
Published in: Abdominal Radiology / Issue 1/2021
Print ISSN: 2366-004X
Electronic ISSN: 2366-0058
DOI: https://doi.org/10.1007/s00261-020-02630-3

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Carcinoma of unknown primary with hepatic metastases: a need of judicious and contemplative diagnostic algorithm

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2021

The Poké Ball sign in mature ovarian cystic teratoma

Correction to: Transjugular intrahepatic portosystemic shunt placement: portal vein puncture guided by 3D/2D image registration of contrast-enhanced multi-detector computed tomography and fluoroscopy

3.0 T MRI IVIM-DWI for predicting the efficacy of neoadjuvant chemoradiation for locally advanced rectal cancer

The role of interventional radiology in the pre-liver transplant patient

Stratification of cystic renal masses into benign and potentially malignant: applying machine learning to the bosniak classification

Radiomics of hepatocellular carcinoma

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page