Common sites of CRC metastasis are the surrounding lymph nodes, liver, and lung [1]. Pancreatic metastasis caused by CRC is rare [2–5], although there are some reports [10, 11]. Up to 80% of isolated pancreatic metastases originate from renal tumors [12]. Metastatic pancreatic cancer accounts for about 2% of all pancreatic tumors [3].
We indexed CRC, pancreas, and metastasis in PubMed from 2010 to 2021 and identified 16 cases (Table 2) [10, 13–27]. There were nine males and seven females, with an average age of 64.8 ± 10.3 years, of which 13 cases were metachronous metastasis, and three were simultaneous metastasis. Nine primary tumors originated from the rectum, four from the sigmoid colon, two from the ascending colon, and one from the cecum. The median interval from the first colon tumor resection to the diagnosis of metastatic pancreatic cancer was 50.5 + 28.8 months, excluding three simultaneous metastases. There were 13 cases of metachronous metastasis (81.2%), of which only one received chemotherapy. The final survival was not recorded (Table 2); however, the overall survival with metastatic pancreatic cancer who underwent surgery was the shortest at 17 months. The longest was 64.8 months, and the average survival was 39.6 ± 18.7 months.
Pancreatic cancer is often occult because of its relatively low incidence. Pancreatic lesions are often found on physical examination. Signs and symptoms include abdominal pain, abdominal distention, jaundice, weight loss, loss of appetite, and abnormal blood glucose. Pancreatic metastases are as challenging to identify as primary pancreatic cancer. Most cases are discovered late [6, 7, 28]. Diagnosis often requires biopsy cytology or intraoperative and post-resection pathological examinations [8]
In the present case, our preoperative diagnosis depended on CT and tumor markers, while the final diagnosis depended on postoperative histopathology and immunohistochemistry. The preoperative enhanced CT revealed a slightly low-density shadow in the pancreas and was thought to represent metastatic pancreatic cancer. This disease should be differentiated from pancreatic cancer, and CT often shows localized masses with low or low mixed density, lack of blood supply, dilation of the pancreatic duct, and adjacent vascular invasion [28]. The second differential diagnosis is a solid pseudopapillary tumor of the pancreas; on imaging, the density of these solid tumors is uneven, composed of a mixture of solid and cystic components. On a plain CT scan, the solid component is hypodense or isodensity, while the cystic component is liquid low-density shadow; on the enhanced scan, the solid component is mildly enhanced in the arterial phase, moderately heterogeneously enhanced in the venous and delayed phases. The cystic component does not appear on the enhanced scan [29]. The third differential diagnosis is non-functional pancreatic neuroendocrine tumors, most of which are asymptomatic. CT often reveals large tumors with uneven tumor density, accompanied by calcified nodules or liquefaction and necrosis [30].
Our conjecture was confirmed by postoperative pathological histological examination and immunohistochemistry. Pathology and immunohistochemistry were consistent with adenocarcinoma, intestinal cancer metastasis, negative intravascular tumor thrombus, negative nerve invasion, and absence of lymph node metastasis in ten lymph nodes around the pancreas. Histological markers were as follows: CDX-2 (+), villin (+), CK20(+), CK7(-), CK19(+), Ki-67(+) 60%, and SATB2(+).
The pathology and immunohistochemistry of the colon provided by the patient's family indicated that the differentiated adenocarcinoma in the ileocecal part was mucinous adenocarcinoma and ulcerative. Other markers were as follows: P-gp(-), ToPoII(+), MLH1(+), MSH2(+), MSH6(+), PMS2(+), GST-π(+), CEA(+), CD56(-), CDX-2(+), and CK-20(+). The pathological and immunohistochemical indications of lung metastases were as follows: (left upper lobe) invasive or metastatic adenocarcinoma was considered lung metastasis of CRC, measuring 1.8 cm × 1.8 cm × 1.5 cm. CK20(+), CK7(-) TTF-1(-), napsinA(-), CDX-2(+), and villin(+). Colon-derived immune markers are CK20, CDX2, and villin, while CK7 is derived from the lung or pancreas and is not expressed in gastrointestinal tumors. CK20 and CDX2 are primarily expressed in gastrointestinal tumors and rarely in pancreatic cancer, but they lack specificity [31–33]. Our histopathological examinations revealed that the origins of lung cancer and pancreatic cancer were both from the colon (Fig. 5). We analyzed the gene mutation spectrum of three tumor sites. We found that CRC oncogenes appeared at all three sites (KRAS, APC, and TP53)[34], suggesting a common histopathological origin. It is not clear how colon cancer metastasizes to the pancreas. Because the lymph nodes near the pancreas lesion were negative, cancer cells from the colon may have traveled to the pancreas through the bloodstream, and this was presumed to be the most probable pathway.
Pancreatic metastasis cancer is primarily treated with chemotherapy and surgery [35, 36]. In Hung's retrospective analysis of 329 secondary pancreatic tumor resection cases, only 17 cases of pancreatic metastases after colon cancer were found. The most extended interval of postoperative pancreatic metastases was 287 months, the 5-year survival was 24.6%, and the 5-year median survival was 24.0% [37]. Blanco-Fernández et al. found that surgery for pancreatic metastases from renal cell carcinoma improved survival [38]. Chikhladze et al. studied surgical and non-surgical treatment of pancreatic metastases and found that surgery improved survival [39]. Surgical resection of transferred liver metastases confers benefits in colon cancer liver metastasis studies [40, 41]. Because there are few cases of colon cancer with pancreatic metastasis, there is no unified treatment standard. When comparing pancreatic metastases in other sites, surgery combined with postoperative chemotherapy is considered effective. The chemotherapy standard for colon cancer is oxaliplatin combined with capecitabine, and the second option is capecitabine single-drug chemotherapy[42]. We continued capecitabine as single-drug chemotherapy because the patient refused oxaliplatin intravenous chemotherapy. As of this report, the patient had recovered well, the CEA decreased to normal, and no tumor recurrence was observed on postoperative review.
In conclusion, pancreatic metastasis from colon cancer is rare and may be misdiagnosed as primary pancreatic cancer. For space-occupying lesions of the pancreas, such as those with a previous history of CRC and a recent CEA elevation, metastasis of CRC to the pancreas should be suspected. The final diagnosis relies on histopathology and immunohistochemistry. We believe that a comprehensive NGS analysis of metastatic tumors can improve the differential diagnosis of metastatic tumors. As the case is rarely reported worldwide, there is a lack of consensus regarding treatment; however, surgery combined with postoperative chemotherapy is effective.