Occult scar carcinoma of the lung with overt liver metastases and high serum CA 19-9 levelsYY Lin1, SF Cho2
1 Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/jpgm.JPGM_145_19
Source of Support: None, Conflict of Interest: None
Lung cancer is well known as one of the most lethal malignancies due to difficulty in early diagnosis and high potential of distal metastases. We report a 73-year-old male with medical history of pulmonary tuberculosis and chronic cough who presented for evaluation of weight loss of 6 kg (from 61 kg to 55 kg) over the past 6 weeks. On physical examination, no obvious abnormality was observed. Chest X-ray showed post-tuberculosis fibrotic lesion in the left lung field [Figure 1]a. However, laboratory investigations revealed significantly elevated serum levels of carbohydrate antigen 19-9 (Ca 19-9)(38,070.19 U/mL) and carcinoembryonic antigen (CEA) (4,398 ng/ml). Colonoscopy and esophagogastroduodenoscopy showed no obvious tumor lesion. Abdominal ultrasonography revealed multiple hypoechoic lesions in the liver suggestive of metastases. Contrast enhanced computed tomography (CT) of chest and abdomen revealed postinflammatory fibrosis and pleural nodular thickening at upper and lingual lobes of left lung [Figure 1]b, as well as metastatic liver tumors. To further investigate the origin of the malignancy, whole body positron emission tomography/computed tomography (PET/CT) was performed, which revealed heterogeneously high grade of fluorodeoxyglucose (FDG) avidity exactly in the site of suspected postinflammatory fibrosis with maximal standardized uptake value (SUVmax) of 6.5 [Figure 1]c as well as the thickening of left pleura found on the previous CT scan, with SUVmax value of 9.1 [Figure 1]C1. Moreover, multiple lymph nodes with reactive FDG avid in periaortal or subaortal area were also observed [Figure 1]d. The patient underwent video-assisted thoracoscopic surgery, and wedge resection and a pleural biopsy were performed. Histopathological examination revealed poorly differentiated adenocarcinoma [Figure 2]a. Immunohistochemical study of the tumor cells showed positive for CK7 [Figure 2]b, TTF-1 [Figure 2]c and CA19-9 [Figure 2]d. A liver specimen was analyzed retrospectively, and an immunohistochemical study was positive for CK7 [Figure 2]B1 and TTF-1 [Figure 2]C1. In addition, a strong expression of CA19-9 [Figure 2]D1 was found. Genetic examination was negative for mutation of epidermal growth factor receptor. The patient was started on recommended systemic chemotherapy and followed up regularly.
The initial suspected diagnosis of this patient tended towards a primary malignancy of the gastrointestinal tract because of metastases in the liver; which was supported by extremely high levels of CEA and CA19-9. However PET/CT study indicated possibility of primary lung cancer after it revealed high FDG avidity in areas where the initial CT findings were suggestive of fibrocavitary opacity with fibrosis and thickened pleura. Our experience in investigating this patient reiterates the superiority of PET/CT over conventional CT scan in detecting the origin of malignancy because the former incorporates both anatomic and functional evaluations. For a suspicious lesion with normal or near normal anatomic structure on CT scan, PET/CT can further distinguish cancer cells from normal cells based on higher metabolic activity in cancer cells. Due to its higher sensitivity, previous studies have also stated that PET/CT scan is a better tool to investigate the origin of a malignancy than conventional CT scan.,
Although PET/CT provided important information in this case, there were still some other clues implicating the lung as the primary malignancy. The patient had other known risk factors for developing lung cancer such as being a long-term smoker; and past history of receiving drug therapy for his rheumatoid arthritis  and having pulmonary tuberculosis. Moreover, immunohistochemical study to evaluate expression of cytokines, such as cytokerotin-7 and cytokerotin-20 provided additional information.
Our patient had very high CA 19-9 level at diagnosis. CA 19-9 is also called sialylated Lewis(a) antigen which is a mucus glycoprotein commonly present in high amounts in adenocarcinomas of the colon, pancreas, and stomach. With respect to its association with cancer, a growing amount of data suggested that its carbohydrate structure is the ligand for E-selectin. In addition, sialylated Lewis(a) and sialylated Lewis(x) are believed to have important roles in selectin-mediated adhesion of cancer cells to vascular endothelium. This process is believed to be closely associated with hematogenous spread of cancers. CA 19-9 is also found in the glands of bronchi and bronchioles. It is our postulation that in the present case the primary lung malignant lesion had a high predilection for metastasizing which explains the high serum CA 19-9 levels.
In conclusion, this case reiterates the importance of doing a whole body PET/CT scan study to identify an occult primary malignant lesion.
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[Figure 1], [Figure 2]