Cancer of unknown primary origin
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Differentiating Cancer of Unknown Primary Origin from other Diseases |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Roukoz A. Karam, M.D.[2], Maria Fernanda Villarreal, M.D. [3]
Synonyms and keywords: Occult cancer; CUP; Metastases of unknown primary origin; Unknown primary origin neoplasm; Cancers of unknown primary site; Neoplasms of unknown primary site; Carcinoma of unknown primary; Cancer of unknown origin; Cancer of unknown primary; Unknown primary tumors; UPT; Metastatic malignant neoplasms
Overview
Cancer of unknown primary origin or CUP is the diagnosis of metastatic cancer when the anatomic site of origin remains unidentified. Cancer of unknown primary origin is common, and it accounts for 2–5% of all cancers. Cancer of unknown primary origin may be classified according to pathology findings into 4 groups: adenocarcinomas, poorly differentiated carcinomas, squamous cell carcinomas, and carcinomas with neuroendocrine differentiation. The majority of patients with cancer of unknown primary origin may be initially asymptomatic. Early clinical features include fatigue, weight-loss, and loss of appetite. If left untreated, the majority of patients with cancer of unknown primary origin may progress to develop multiple organ failure, heart failure, and death. The treatment for cancer of unknown primary origin will depend on several factors, such as: metastatic origin, biopsy findings, patients age, and performance status. The 5-year survival of patients with cancer of unknown primary origin is less than 2%.
Pathophysiology
- The exact pathogenesis of cancer of unknown primary origin is not fully understood.
- Cancer of unknown primary, like other cancers, arises from one cell that has managed to escape regulation and produces a tumor at a certain site (the site of origin) and consequently metastasizes to other parts of the body.
- It is thought that the site of origin of CUP remains unknown due to one of the following theories:[1]
- Remaining small and undetectable clinically
- Disappearing after metastasizing
- Elimination by body's defense
- It remains unknown whether cancers of unknown primaries are genetically or phenotypically distinct from metastasis with known origins.[1]
Diagnosis
Diagnostic Criteria
- The diagnosis of cancer of unknown primary origin is made when the following diagnostic criteria are met: tissue biopsy indicating malignancy and all known primary origins of cancer are ruled out.
- The search of the primary tumor's anatomical location has proven to be very challenging and costly; nevertheless, it is pursued with focus on the types of tumors that might benefit from efficient and targeted treatment.[2][3]
- The initial approach may vary on a case-by-case basis; however, the diagnosis is made after histopathological and clinical testing:[4]
- The histopathological examination of the tissue includes microscopic evaluation followed by immunohistochemical analysis.
- Clinical diagnostic tests must be exhausted in order to aid in identifying the primary origin and this includes:[5]
- Detailed medical history and full physical exam
- Complete blood count
- Liver function tests
- Electrolytes
- Urinalysis
- Fecal occult blood
- Chest radiography
- Chest, abdominal, and pelvic CT scan (depending on the case)
Symptoms
- Cancer of unknown primary origin may be asymptomatic.
- Symptoms of cancer of unknown primary origin may include the following:[1]
Physical Examination
- Patients with cancer of unknown primary origin usually appear cachexic.
- There are no remarkable findings in the physical examination of these patients; the presentation is variable and depends on many factors including the primary tumor's origin and extent of organs involved.[1]
Laboratory Findings
- There are no specific diagnostic laboratory findings associated with cancer on unknown primary origin; however, certain abnormal laboratory findings may help in locating the primary origin of the tumor.
Electrocardiogram
- There are no ECG findings associated with cancer of unknown primary origin.
X-ray
- A chest x-ray is a prerequisite in the diagnosis of cancer of unknown primary; however, it's value is of less significance when it comes to locating the primary tumor or differentiating it from a metastatic lesion.[6]
- A mammography may be helpful in the identification of the primary origin of the tumor in women presenting with metastatic adenocarcinoma.[7]
Echocardiography or Ultrasound
- There are no specific echocardiography or ultrasound findings associated with cancer of unknown primary origin. However, a testicular or breast ultrasound may be helpful in the localization of the primary origin of the tumor in certain cases.[5]
CT scan
- CT scan may be helpful in the diagnosis of cancer of unknown primary origin. It is considered one of the most valuable diagnostic tools in the search for the primary origin of the tumor.
- CT scanning has provided a 20% increase in diagnostic accuracy relative to other imaging modalities.[8]
MRI
- There are no MRI findings associated with cancer of unknown primary origin. However, a breast MRI may be helpful in the detection of the tumor's primary origin in females with isolated axillary lymphadenopathy and suspected primary breast carcinoma.[9]
Other Imaging Findings
- There are no other imaging findings associated with cancer of unknown primary origin.
Other Diagnostic Studies
- Other diagnostic studies for cancer of unknown primary that may help establish the origin of the tumor include:
- Tumor markers such as αFP, βHCG, CA125, CA 27.29, CA 19.9, and CEA[10]
- Diagnostic tonsillectomy[11]
- Gastrointestinal endoscopy, ENT panendoscopy (which is a combination of laryngoscopy, esophagoscopy, and bronchoscopy), proctoscopy, and colposcopy[12][13]
Treatment
Medical Therapy
- There is no treatment for cancer of unknown primary origin; the mainstay of therapy is supportive care.[14]
- The treatment for cancer of unknown primary origin will depend on several factors, such as metastatic origin, biopsy findings, patients age, and performance status.
- Medical therapy for cancer of unknown primary origin should be adjusted on an individual basis and according to well-defined clinicopathologic subsets.[14]
- The table below summarizes different types of medical therapy strategies for cancer of unknown primary origin.
| Treatment for cancer of unknown primary origin Adapted from the European Society of Medical Oncology[14] | |
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| Sub-type | Proposed treatment |
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Poorly differentiated carcinoma, predominately nodal disease |
Platinum based combination chemotherapy |
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Peritoneal carcinomatosis in female |
Platinum based chemotherapy |
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Isolated axillary nodal metastases in female |
Identical to breast cancer with similar nodal involvement |
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Irradiation for N1-N2 disease. | |
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Liver, bone, or multiple-site metastases of adenocarcinoma |
Low toxicity chemotherapy of palliative orientation or best supportive care are acceptable |
Surgery
- Surgical intervention is not recommended for the management of cancer of unknown primary origin.
Prevention
- There are no primary preventive measures available for cancer of unknown primary origin.[14]
- There is no evidence that follow-up of asymptomatic patients is needed.[14]
References
- ↑ 1.0 1.1 1.2 1.3 Varadhachary GR (2007). "Carcinoma of unknown primary origin". Gastrointest Cancer Res. 1 (6): 229–35. PMC 2631214. PMID 19262901.
- ↑ Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M; et al. (1988). "Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients". Arch Intern Med. 148 (9): 2035–9. PMID 3046543.
- ↑ Briasoulis E, Pavlidis N (1997). "Cancer of Unknown Primary Origin". Oncologist. 2 (3): 142–152. PMID 10388044.
- ↑ Collado Martín R, García Palomo A, de la Cruz Merino L, Borrega García P, Barón Duarte FJ, Spanish Society for Medical Oncology (2014). "Clinical guideline SEOM: cancer of unknown primary site". Clin Transl Oncol. 16 (12): 1091–7. doi:10.1007/s12094-014-1244-0. PMC 4239766. PMID 25392080.
- ↑ 5.0 5.1 Bugat R, Bataillard A, Lesimple T, Voigt JJ, Culine S, Lortholary A, Merrouche Y, Ganem G, Kaminsky MC, Negrier S, Perol M, Laforêt C, Bedossa P, Bertrand G, Coindre JM, Fizazi K (2003). "Summary of the Standards, Options and Recommendations for the management of patients with carcinoma of unknown primary site (2002)". Br. J. Cancer. 89 Suppl 1: S59–66. doi:10.1038/sj.bjc.6601085. PMC 2753014. PMID 12915904.
- ↑ Nystrom JS, Weiner JM, Wolf RM, Bateman JR, Viola MV (1979). "Identifying the primary site in metastatic cancer of unknown origin. Inadequacy of roentgenographic procedures". JAMA. 241 (4): 381–3. PMID 758556.
- ↑ Abbruzzese JL, Abbruzzese MC, Lenzi R, Hess KR, Raber MN (1995). "Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin". J Clin Oncol. 13 (8): 2094–103. doi:10.1200/JCO.1995.13.8.2094. PMID 7636553.
- ↑ Karsell PR, Sheedy PF, O'Connell MJ (1982). "Computed tomography in search of cancer of unknown origin". JAMA. 248 (3): 340–3. PMID 7087129.
- ↑ Olson JA, 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): 411–5. PMID 10894136.
- ↑ Molina R, Bosch X, Auge JM, Filella X, Escudero JM, Molina V; et al. (2012). "Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site". Tumour Biol. 33 (2): 463–74. doi:10.1007/s13277-011-0275-1. PMID 22161237.
- ↑ Tytor M, Olofsson J (1986). "Cervical lymph node metastases with occult primary". Clin Otolaryngol Allied Sci. 11 (6): 463–7. PMID 3815873.
- ↑ Mousseau M, Schaerer R, Lutz JM, Ménégoz F, Faure H, Swiercz P (1991). "[Hepatic metastasis of unknown primary site]". Bull Cancer. 78 (8): 725–36. PMID 1932839.
- ↑ Lefebvre JL, Coche-Dequeant B, Van JT, Buisset E, Adenis A (1990). "Cervical lymph nodes from an unknown primary tumor in 190 patients". Am J Surg. 160 (4): 443–6. PMID 2221252.
- ↑ 14.0 14.1 14.2 14.3 14.4 Briasoulis E, Tolis C, Bergh J, Pavlidis N (2005). "ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cancers of unknown primary site (CUP)". Ann. Oncol. 16 Suppl 1: i75–6. doi:10.1093/annonc/mdi804. PMID 15888766.