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Year : 2019  |  Volume : 3  |  Issue : 2  |  Page : 45-47

Sporadic synchronous triple primary cancers in elderly female: Microsatellite instability high resectable colon cancer, epidermal growth factor receptor-mutated metastatic lung cancer, and neuroendocrine tumor of appendix

1 Department of Medical Oncology, Rajiv Gandhi Cancer Hospital and Research Institute, Delhi, India
2 Department of Nuclear Medicine, Rajiv Gandhi Cancer Hospital and Research Institute, Delhi, India
3 Department of Radiodiagnosis, Rajiv Gandhi Cancer Hospital and Research Institute, Delhi, India
4 Department of Radiodiagnosis, Christian Medical College and Hospital, Vellore, Tamil Nadu, India

Date of Web Publication18-Sep-2019

Correspondence Address:
Dr. Ankush Jajodia
Rajiv Gandhi Cancer Hospital and Research Institute, Sector 5, Rohini - 110 085, Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/oji.oji_19_19

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Colorectal cancer and lung cancer are the most common malignancies in the world. However, not all pulmonary nodules in a case of colon cancer are considered as metastasis, especially with features suggestive of limited colon disease without any nodal or liver involvement. The morphology of the pulmonary nodules is also an important consideration before subjecting the patient to another invasive procedure, as solitary pulmonary nodule with irregular margins, suggestive of another primary lesion. We describe a case of a patient with colon cancer, nonsmall cell lung cancer with single bone lesion, and neuroendocrine tumor of appendix. Initially suspected to be a case of metastatic colon cancer, the patient was later diagnosed as epidermal growth factor receptor-mutant metastatic pulmonary adenocarcinoma, with localized microsatellite instability high phenotype colon cancer.

Keywords: Colon cancer, lung cancer, neuroendocrine tumor, triple primary cancer

How to cite this article:
Goyal S, Botra S, Sharma M, Gupta M, Koyyala VP, Jajodia A, Sarangi PK. Sporadic synchronous triple primary cancers in elderly female: Microsatellite instability high resectable colon cancer, epidermal growth factor receptor-mutated metastatic lung cancer, and neuroendocrine tumor of appendix. Oncol J India 2019;3:45-7

How to cite this URL:
Goyal S, Botra S, Sharma M, Gupta M, Koyyala VP, Jajodia A, Sarangi PK. Sporadic synchronous triple primary cancers in elderly female: Microsatellite instability high resectable colon cancer, epidermal growth factor receptor-mutated metastatic lung cancer, and neuroendocrine tumor of appendix. Oncol J India [serial online] 2019 [cited 2021 Dec 5];3:45-7. Available from: https://www.ojionline.org/text.asp?2019/3/2/45/266979

  Introduction Top

Colorectal cancer is the third most common cancer diagnosed in males and the second most common in females around the world.[1] Liver is the most common site of metastasis from colonic cancer, with lung being the second most common site of metastasis.[2] Pulmonary metastases from colon cancer are usually multiple, however in 10% of cases the metastasis can be single or can be a synchronous tumors of Lung and Colon.[3],[4],[5] Hence, not all lesions in the lung in a patient with colon cancer are metastasis, and it is important to differentiate between primary lung lesion and the metastasis. Development of metastasis is a concern for both clinicians and the patients as it changes the staging and further management. This is report of a case of colorectal cancer with a lesion in the lung, initially considered to be a metastatic disease, which was later diagnosed as a case primary of the lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation.

  Case Report Top

A 63-year-old woman with multiple medical comorbidities presented with a history of lower abdominal pain, anorexia, weight loss, and constipation on and off for 2 months. She was a nonsmoker, with no other addictions. She had no family history of malignancy. She had a medical history of diabetes, hypertension, and hypothyroidism, well controlled on medication. She also had a surgical history of hysterectomy for menorrhagia and dysfunctional uterine bleeding. On physical evaluation, she had mild pallor and distended abdomen. Other physical examinations were normal.

Routine parameters were within normal limits, except mild microcytic hypochromic anemia. Ultrasound of the abdomen revealed distended bowel loops with loaded colon with fecal matter. Contrast-enhanced computed tomography (CECT) scan revealed asymmetric concentric mural wall thickening in the ascending colon causing luminal irregularity. The thickening is also involving the adjacent base of appendix with dilated mildly thick-walled appendicular lumen. Colonoscopy showed an ascending colonic growth. Multiple biopsies were taken. Biopsy from the colonic growth revealed moderately differentiated adenocarcinoma. CECT scan of the chest was suggestive of a right middle lobe lobulated nodular lesion with few other subcentimetric lung nodules. Positron emission tomography (PET) scan showed metabolically active colon lesion, lung lesion, and a solitary bone lesion in D11 vertebra [Figure 1], [Figure 2], [Figure 3]. Biopsy of the right lung was nonsmall cell carcinoma, i.e., adenocarcinoma. However, immunohistochemistry (IHC) was positive for thyroid transcription factor-1 and negative for special AT-rich sequence-binding protein 2, making a diagnosis of primary lung adenocarcinoma. EGFR mutation analysis detected L858R mutation in exon 21. ALK rearrangement testing by IHC was negative. In view of metastatic lung primary, she was started on tyrosine kinase inhibitor with tablet erlotinib for the lung primary and underwent a right hemicolectomy in view of an ascending colonic mass. Histopathology of the surgical specimen revealed moderately differentiated adenocarcinoma, with no regional lymph nodal metastasis (0/22 LN), pT3N0 (according to the AJCC 7th ed.ition). The surgical specimen also showed the presence of incidental primary Neuroendocrine tumor (NET) of appendix, which was not visible on Preoperative PET scan. The NET was grade 1 with 1 mitosis per 10 HPF and Ki-67 of 1%. IHC was done and positive for chromogranin and synaptophysin. MSI testing by IHC on colon Specimen revealed the loss of PMS2 nuclear expression. In view of high MSI phenotype and other low-risk features, and completely resected appendiceal NET, the patient was not planned for adjuvant chemotherapy and is on follow-up with oral first-generation anti-EGFR tyrosine kinase, erlotinib for primary lung cancer. Review PET scan after 3 months showed good partial response to the lung lesion with persistent bony lesion without any abdominal disease. After 1 year of follow-up, the patient has no recurrence of colon cancer with continued response to erlotinib.
Figure 1: Cecum and proximal ascending colon showing metabolically active circumferential wall thickening (maximum standardized uptake value 11.0) extending to involve ileocecal region. Perilesional fat stranding is noted. Multiple enlarged and subcentimeter metabolically active pericolic lymph nodes are seen in the adjacent mesentery (maximum standardized uptake value 2.7)

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Figure 2: Right lung middle lobe showing a metabolically active soft tissue lesion with irregular margins (1.4 × 1.2, maximum standardized uptake value 3.3). Minimal right pleural effusion is seen

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Figure 3: Fused positron emission tomography–computed tomography images showing metabolically active sclerotic lesion in D11 vertebra (maximum standardized uptake value 6.8)

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  Discussion Top

Lung cancer and colon cancer are two of the most common malignancies around the world.[6] Smoking is considered to be common risk factor for both cancers; however, this patient was a nonsmoker. Multiple primary cancer is referred to the occurrence of two or more cancers in a patient, either simultaneously (synchronous) or with some time interval. If this interval is >6 months, it is said to be metachronous. The incidence of multiple tumors varies from 0.7% to 11.7%. The combined presence of synchronous primary tumors of COlon and Lung are very rare with the incidence reported to e less than 0.1%.[4] There are a few criteria which help distinguish between multiple primary tumor and metastatic disease: (a) the two tumors must be distinct from each other, (b) they must have their distinct features of malignancy and histology, and (c) the possibility of one being metastasis from the other must be ruled out.

The main reason for differentiating primary from a secondary tumor is that plan of management and intent of therapy changes. Common genetic alterations usually underlie cancers in multiple organs, but a common genetic alteration involving these three neoplasms has not been described in literature. Quint et al. described few clues to differentiate the pulmonary nodules as primary or metastatic. The metastatic tumors are usually multiple and distributed in both lungs, particularly with smooth margins. The primary lesions are usually solitary pulmonary nodule, with spiculated margins.[7] As in this case, the patient had radiological morphology matching the description, along with no nodal involvement, intra-abdominal metastasis, or liver metastasis. Diagnosing and treating the multiple primary cancer are difficult. Surgical resection is a possibility if both tumors are early cancers but may not be possible in a widespread disease. However, treating each of these cancers according to the respective guidelines may help achieve a better outcome. In this case, after diagnosis of a primary EGFR-mutant lung adenocarcinoma, she underwent surgery for colon cancer with curative intent. With her MSI high phenotype and early-stage colon cancer with no adverse features, she did not need any further chemotherapy. She is currently under close clinical follow-up with palliative treatment for lung cancer.

  Conclusion Top

Lung and colon cancers are the most common cancers around the globe. It can occur as a synchronous primary and must be differentiated from metastatic disease. The management and the intent may change completely. Not all lung nodules in a diagnosed case of colon cancer are considered metastasis, especially solitary pulmonary nodule with speculated margins and in the absence of intra-abdominal metastasis. This is to highlight the fact that in all cases of suspicion radiologically, diagnostic tissue biopsy should be considered to rule out synchronous primaries, both or at least one of which may be treated with curative intent.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.  Back to cited text no. 1
Tsikitis VL, Malireddy K, Green EA, Christensen B, Whelan R, Hyder J, et al. Postoperative surveillance recommendations for early stage colon cancer based on results from the clinical outcomes of surgical therapy trial. J Clin Oncol 2009;27:3671-6.  Back to cited text no. 2
Peng YF, Gu J. Synchronous colorectal and lung cancer: Report of three cases. World J Gastroenterol 2008;14:969-73.  Back to cited text no. 3
Yun HR, Yi LJ, Cho YK, Park JH, Cho YB, Yun SH, et al. Double primary malignancy in colorectal cancer patients – MSI is the useful marker for predicting double primary tumors. Int J Colorectal Dis 2009;24:369-75.  Back to cited text no. 4
Chiang JM, Yeh CY, Changehien CR, Chen JS, Tang R, Tsai WS, et al. Clinical features of second other-site primary cancers among sporadic colorectal cancer patients – A hospital-based study of 3,722 cases. Hepatogastroenterology 2004;51:1341-4.  Back to cited text no. 5
Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, et al. Global surveillance of cancer survival 1995-2009: Analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 2015;385:977-1010.  Back to cited text no. 6
Quint LE, Park CH, Iannettoni MD. Solitary pulmonary nodules in patients with extrapulmonary neoplasms. Radiology 2000;217:257-61.  Back to cited text no. 7


  [Figure 1], [Figure 2], [Figure 3]


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