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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 27  |  Issue : 2  |  Page : 144-146

Carcinoma of unknown primary: An early cancer with metastasis for epidemiological purposes?


1 Department of Hospital Cancer Registry, Dr. B Borooah Cancer Institute, Gopinath Nagar, Guwahati, India
2 Department of Pathology, Dr. B Borooah Cancer Institute, Gopinath Nagar, Guwahati, India
3 Department of Head and Neck Oncology, Dr. B Borooah Cancer Institute, Gopinath Nagar, Guwahati, India

Date of Web Publication19-Nov-2013

Correspondence Address:
Manigreeva Krishnatreya
Room No. 32, OPD Block, Dr. B Borooah Cancer Institute, Guwahati - 781 016
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-4958.121596

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  Abstract 

Background: The data set of carcinoma of unknown primary (CUP) is not used for analyzing the burden and pattern of cancer in a given population. Aim: A retrospective analysis of the cancer registry data was done to see whether CUP can be utilized in the analysis of the burden of cancer in a given population. Materials and Methods: The data of CUP were obtained from the records of a hospital cancer registry of a regional cancer center from January 2010 to December 2011. The cases of CUP considered for the analysis were histologically confirmed malignancies with unknown primary. Results: CUP accounted for 4.5% of all cancers in our analysis. Squamous carcinoma was the major histological type (58%), with the following clinical entities observed in our analysis: CUP of the lymph nodes in 62.4%, of the liver in 21.2%, of the bone in 8.8%, of the peritoneal cavity in 2.7%, of the lung in 1.9%, of the pleural effusion in 1.4%, of the brain in 0.5%, of the ovary in 0.53%, and to the skin in 0.2% patients. The occurrence of CUP in relative proportion for both males and females showed that the majority (60%) of the clinical entity of CUP was seen at the supraclavicular lymph nodes, where a large proportion of cancers were of the head and neck region. Conclusion: The data of CUP to the regional lymph nodes in the head and neck region, though not specific, can be taken into account for the estimation of burden of head and neck cancer in populations with a high incidence of head and neck cancers, which will prevent the underestimation of actual burden of head and neck cancers of the population for advocacy and policy making by the health planners.

Keywords: Carcinoma, Epidemiology, Metastasis, Unknown primary


How to cite this article:
Krishnatreya M, Kataki AC, Sharma JD, Das K. Carcinoma of unknown primary: An early cancer with metastasis for epidemiological purposes?. J Med Soc 2013;27:144-6

How to cite this URL:
Krishnatreya M, Kataki AC, Sharma JD, Das K. Carcinoma of unknown primary: An early cancer with metastasis for epidemiological purposes?. J Med Soc [serial online] 2013 [cited 2019 Dec 13];27:144-6. Available from: http://www.jmedsoc.org/text.asp?2013/27/2/144/121596


  Introduction Top


Carcinoma of unknown primary (CUP) is defined as a metastatic tumor, when the demonstrable site of the primary origin cannot be identified, [1] which should be based on the clinical history, complete physical examination, routine laboratory tests, imaging, radio-metabolic techniques, and a careful review of the histology. The data set of CUP in cancer registries is not used for analyzing the burden and pattern of cancer in a given population. In the early 1970s, it was of the view that the diagnosis of CUP could only be made if the primary tumor was not found at autopsy. [2] The hypothesis for the origin of CUP has been postulated in two groups by Stella et al. [3] The first suggests that CUP is a heterogeneous group of site-specific tumors that share the properties of the small primary from which it derives, and the second regards CUP as a distinct entity with a specific genetic asset. Currently, immunohistochemistry (IHC) is often the only standard method by which a probable origin of the primary can be postulated. Retrospective analysis of the cancer registry data was done to see whether CUP can be utilized in the analysis of burden of cancer in a population.


  Materials and Methods Top


In this retrospective analysis, the data of CUP were obtained from the records of a hospital cancer registry of regional cancer center for a period from January 2010 to December 2011. The cases of CUP that were considered for the analysis were histologically confirmed malignancies with unknown primary, based on clinical history, complete physical examination, laboratory tests, imaging techniques, and histopathologic or cytological examination of tissues with IHC staining, whenever required, as per the case records of the patients. All the CUP cases were diagnosed after a single attempt with clinical, radiological, and histo-/cytopathological examination including IHC analysis at the time of diagnosis, though they were reviewed for the diagnosis of CUP at the beginning of their treatment. The protocol followed for the diagnosis of CUP is same for all the cases at our center. The cases of CUP in this analysis were classified and coded according to the International Statistical Classification of Diseases (ICD) of the World Health Organization, 10 th revision (from C77.0-9 to C78-79) and the International Classification of Disease for Oncology (ICD-O-3), 3 rd revision (C80.9). The data were entered onto the hospital-based cancer registry data management software version 1.0 (HBCRDM1.0) developed by the National Cancer Registry Program of Indian Council of Medical Research. The data were exported to MS Excel spreadsheet for the calculation and analysis of the results. All the cases of CUP were analyzed for its relative proportion to cancers of known origin/sites, gender distribution, mean age of males and females with CUP, the occurrence of CUP at different anatomical sites, and different histological types of CUP. Statistical formula for mean has been employed to calculate the average age of the patients with CUP.


  Results Top


During the period from January 2010 to December 2011, a total of 12,285 patients were registered at our cancer registry, including old and new cases. In our series, out of 12,285 cancer patients, 554 patients had CUP. Out of all CUPs, 416 (75.0%) were males and 138 (24.9%) were female patients. The average age of patients presenting with CUP was 56.8 years in males and 50.6 years in females. CUP represents a heterogeneous group of malignancies with a unique clinical behavior. The following clinical entities were observed in our analysis: CUP of the lymph nodes in 346 (62.4%), CUP of the liver in 118 (21.2%), CUP of the bone in 49 (8.8%), CUP to the peritoneal cavity as ascites in 15 (2.7%), CUP of the lungs in 11 (1.9%), CUP as malignant pleural effusion in 8 (1.4%), CUP of the brain in 3 (0.5%), CUP of the ovary in 3 (0.53%), and CUP to the skin in 1 (0.2%) patient. CUPs were divided into two broad groups based on their histopathology and IHC analysis for the differentiation of their histological types, the differentiated group, and the poorly differentiated malignancy. The common histology types amongst the differentiated group of CUP were squamous carcinoma in 301 (57.5%), adenocarcinoma in 200 (38.3%), neuroendocrine carcinoma in 8 (1.5%), and spindle cell carcinoma in 8 (1.5%) patients. Specific tumor histology that presented as CUP was small cell carcinoma in 3 (0.5%) cases and malignant melanoma in 1 (0.2%) case out of all CUPs. In 33 (6%) patients, the differentiated histology of secondary or metastatic site was not established because of poor patient compliance, and the histological diagnosis remained as poorly differentiated carcinoma only. Out of metastasis to lymph nodes with unknown primary, vast majority was seen in the lymph nodes of the neck [331 (59.7%)]. Also, 65% males and 44% females with clinical CUP [Figure 1] had regional spread to the lymph nodes of the head and neck without any obvious primary, and in only 13 (2.3%) cases out of all CUPs to the lymph nodes, the spread was seen in other lymphatic sites such as mediastinum, axillary, inguinal, or abdominal.
Figure 1: Distribution of carcinoma of unknown primary in relative proportion for males and females

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  Discussion Top


CUP accounts for 2-5% of all cancers. [4] In this series, CUP accounted for 4.5% of all cancers and this proportion (4.5%) of CUP has been observed in the absence of a positron emission tomogram (PET) scan facility in our center, which is needed for aiding in the diagnosis of CUP. This might also suggest that PET scan may not be always helpful in significantly lowering the proportion of CUP diagnosis, given a high number of head and neck cancer in the given population, and PET has been recommended specially in the evaluation of post radiotherapy head and neck patients, [5] though the role of PET with fused CT scan is better than PET alone for the detection and anatomic localization of head and neck tumors. [6] The occurrence of CUP in relative proportion for both males and females showed that majority of CUP is seen at the head and neck lymph nodes. Briasoulis et al. have observed in a certain population group that CUP commonly occurs in a single site such as the liver, bone, and the lungs. [7] However, in our series, in a different population at risk, the CUP mostly presented at the head and neck lymph node, and it accounted for 59.7% of all CUPs in the absence of a primary origin or with a probable occult primary in epithelial lining of head and neck region. In our registry, out of all the cases of malignancies, 4054 (33%) patients were cancers of the head and neck epithelial origin. In metastasis to liver, lung, peritoneal cavity, and bones with occult primary, the probability of the origin of primary could be from multiple organs; but in the regional lymphatic metastasis of the head and neck, in 90% of metastasis, the putative origin is from the epithelial lining of the head and neck. [8] The combined proportion of CUP to the regional lymph nodes of head and neck and cancers of head and neck epithelial origin will contribute to a substantial number of cancer cases in our population. High age-adjusted incidence rate (AAR) for cancers of the head and neck region is seen in our population due to the prevalence of consumption of tobacco in both smokeless and smoke forms. [9] In the present analysis, percentage distribution of CUP to the regional lymph nodes of the head and neck region was similar in its distribution to the epithelial head and neck cancers for both males and females. With the advent of newer technology, the ability to predict the primary site of tumor origin in CUP is improving rapidly and the vital issue is concerning the biology that drives early occult metastatic spread. In CUP, the biological behavior of early metastasis may be due to escaping of clinical detection of the primary when the secondary or metastasis is apparent, or the primary may disappear after seeding the metastasis due to elimination of the primary by body's immune mechanism. [4] The study of chromosomal and molecular abnormalities is beyond the scope of this current retrospective analysis and, hence, cannot be discussed here.

The pattern of occurrence for CUP can be summarized by our findings based on the known cancer site distribution in a population at risk. The pattern of CUP is similar to that of known cancer site distribution in a population group, and the same risk factors are probably involved for development of known cancer site malignancies as well as CUP in the head and neck region. There is a study which has highlighted the importance of pinpointing the magnitude of head and neck cancer burden, so as to augment the National Cancer Registry Program, considering the high AAR of head and neck cancers across the country and in the South-East Asian region. [10],[11]

It can be concluded from this retrospective study that CUP to the regional lymph nodes of head and neck is a subset of occult or small primary with early distant metastasization because the burden of CUP as a clinical entity resembles known cancer site distribution in the given population. The data of CUP to the regional lymph nodes in the head and neck region, though not specific, can be taken into account for the estimation of burden of head and neck cancer in populations with a high incidence of head and neck cancers, which will prevent the underestimation of actual burden of head and neck cancers of the population for advocacy and policy making by the health planners.

 
  References Top

1.Abbruzzese JL, Lenzi R, Raber MN, Pathak S, Frost P. The biology of unknown primary tumors. Semin Oncol 1993;20:238-43.  Back to cited text no. 1
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2.Holmes FF, Fouts TL. Metastatic cancer of unknown primary site. Cancer 1970;26:816-20.  Back to cited text no. 2
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3.Stella G, Senetta R, Cassenti A, Ronco M, Cassoni P. Cancers of unknown primary: Current perspective and future therapeutic strategies. J Transl Med 2012;10:12.  Back to cited text no. 3
    
4.Vardhachary GR. Carcinoma of Unknown Primary Origin. Gastrointest Cancer Res 2007;1:229-35.  Back to cited text no. 4
    
5.McGuirt WF, Greven K, William D, Keyes JW Jr, Watson N, Cappellari JO, et al. PET scanning in head and neck oncology: A review. Head Neck 1998;20:208-15.  Back to cited text no. 5
    
6.Schöder H, Yeung HW, Gonen M, Kraus D, Larson SM. Head and neck cancer: Clinical usefulness and accuracy of PET/CT image fusion. Radiology 2004;231:65-72.  Back to cited text no. 6
    
7.Briasoulis E, Pavlidis N. Cancer of unknown primary origin. Oncologist 1997;2:142-52.  Back to cited text no. 7
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8.Stell P, Maran A. Head and Neck Surgery. In: Watkinson JC, Gaze MN, Wilson JA, editors Metastatic neck disease. 4 th ed. New Delhi: Butterworth-Heinemann; 2000. p. 197-213.  Back to cited text no. 8
    
9.Sanghvi LD, Rao DN, Joshi S. Epidemiology of head and neck cancers. Semin Surg Oncol 1989;5:305-9.  Back to cited text no. 9
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10.Patel JA, Shah FG, Kothari JM, Patel KD. Prevalence of head and neck cancers in Ahmedabad, Gujarat. Indian J Otolaryngol Head Neck Surg 2009;61:4-10.  Back to cited text no. 10
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11.Mehanna H. Head and neck cancer-Part 1: Epidemiology, presentation, and prevention. BMJ 2010;341:c4684.  Back to cited text no. 11
    


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