Single pancreatic and multiple hepatic metastases developing 6 years after left hemicolectomy for colon cancer: A case report

Abstract

A 50-year-old woman presented with a pancreatic tumor and multiple hepatic tumors identified via computed tomography (CT). The patient had undergone surgical resection for colon cancer 6 years earlier, followed by resection of a metastatic lung tumor 3 years ago. In the current presentation, primary pancreatic cancer with metastatic hepatic tumors was initially suspected. However, the possibility of previously resected colon cancer metastasizing to the pancreas also had to be considered. CT findings alone could not make this distinction. Therefore, endoscopic ultrasound-guided fine-needle aspiration was performed. Histopathological examination of the pancreatic tumor indicated adenocarcinoma, with features similar to those of the previously resected colon cancer. Immunohistochemical staining was negative for cytokeratin 7 but positive for cytokeratin 20, caudal-type homeobox 2, and special AT-rich sequence-binding protein 2. These findings indicated a pancreatic metastasis of colonic origin. In addition, a percutaneous ultrasound-guided biopsy of one of the hepatic tumors had histopathological findings that were similar to those of the pancreatic tumor. Hence, the patient was diagnosed with pancreatic and hepatic metastases from the previously resected colon cancer. Chemotherapy was initiated after this diagnosis.

Introduction

Pancreatic metastases account for approximately 2% of all malignant pancreatic neoplasms¹⁾. Renal cell carcinoma is the most common primary origin of pancreatic metastases, accounting for 61.7% of all cases, followed by colon cancer at 7.8%²⁾. Imaging findings, including those from computed tomography (CT), ultrasonography, endoscopic ultrasonography (EUS), and endoscopic retrograde cholangiopancreatography (ERCP), for pancreatic metastases of colon cancer include well-demarcated masses, compressive stenosis of the main pancreatic duct, and goblet-like interruption of the main pancreatic duct caused by tumor invasion or obstruction. However, these findings are not specific to metastatic colon cancer^3,4).

In cases with a solitary pancreatic tumor, it is challenging to differentiate between primary pancreatic cancer and pancreatic metastasis based only on the findings of imaging modalities such as CT or EUS, as the findings can be identical⁵⁾. In some cases, the definitive diagnosis of pancreatic metastasis may be made only after surgical resection⁶⁾. In addition, pancreatic metastatic tumors often occur in the context of systemic metastatic disease, indicating that chemotherapy may be a more appropriate treatment option than surgical resection. Therefore, histological evaluation plays an essential role in the diagnosis of patients with pancreatic tumors, especially those with a history of malignancy.

Herein, we report the case of a patient presenting with a single pancreatic tumor and multiple hepatic tumors 6 years after undergoing colectomy for colon cancer.

Case report

A 50-year-old female presented with a single pancreatic mass and multiple hepatic masses on CT. She had a history of colectomy for colon cancer and subsequent right lower lobectomy for a related metastatic lesion (Figs. 1a, 1b). At the current presentation, a 20-mm, poorly demarcated and hypovascular tumor was observed around the junction of the head and body of the pancreas (Fig. 2a) with an upstream dilated pancreatic duct (Fig. 2b). In addition, hypodense liver lesions with peripheral ring enhancement in segments 3 and 8 were observed on CT (Fig. 2c).

Six years ago, at 44 years of age, the patient had undergone laparoscopic-assisted left hemicolectomy for descending colon cancer. She had been pathologically diagnosed with pType 2, 15×10 mm, moderately differentiated tubular adenocarcinoma, pT2 (muscularis propria), int, INFb, ly0, v2, pN0, PM0, DM0, pStage I. Three years after the hemicolectomy, at 47 years of age, she underwent right lower lobectomy for pulmonary metastasis of colon cancer. The pathological diagnosis was 14×10 mm, PUL0, Ly0, V0, surgical margin negative. Thereafter, follow-up included blood tests every 3 months and CT scans every 6 months.

Three years after her lobectomy, tumor markers that were previously within normal ranges were elevated: carcinoembryonic antigen, 29.0 ng/mL and carbohydrate antigen 19-9, 44.2 U/mL. Considering the solitary nature of the pancreatic tumor, primary pancreatic cancer with hepatic metastases was initially suspected. However, we could not rule out the possibility of pancreatic and hepatic metastases of the previously resected colon cancer. We performed EUS-guided fine-needle aspiration (EUS-FNA) to obtain specimens of the pancreatic lesions for pathological evaluation. EUS revealed a 20-mm heterogeneous hypoechoic mass at the junction of the pancreatic head and body (Fig. 3a). EUS-FNA was performed from the duodenal side using a 22-gauge aspiration needle (Fig. 3b). Rapid on-site evaluation was conducted, and three passes were performed⁷⁾. Hematoxylin and eosin (H&E) staining of the EUS-FNA specimen indicated adenocarcinoma with histological features similar to those of the previously resected colon cancer and pulmonary metastasis (Fig. 4a). Immunohistochemical staining was negative for cytokeratin 7 (CK7), positive for cytokeratin 20 (CK20) and caudal-type homeobox 2 (CDX2), and weakly positive for special AT-rich sequence-binding protein 2 (SATB2) (Figs. 4b-4e). These findings strongly indicated that the pancreatic tumor had metastasized from the colon.

Percutaneous ultrasound-guided biopsy was performed on one of the hepatic tumors. The results of histopathological examination of the hepatic tumor, including immunohistochemical staining, were similar to those of the pancreatic tumor. To confirm the diagnosis, additional immunohistochemical staining was conducted on the previously resected specimens of the colon cancer and pulmonary metastasis. The results were negative for CK7, positive for CK20 and CDX2, and weakly positive for SATB2, similar to the results of immunohistochemical staining for the pancreatic and hepatic tumors.

Based on these pathological findings, the patient was definitively diagnosed with pancreatic and hepatic metastasis of colon cancer. To select the most appropriate chemotherapy, we conducted cancer gene analysis of the previously resected lung specimen, and found that it had a mutation in the rat sarcoma viral oncogene but not in the B-Raf proto-oncogene, serine/threonine kinase. Furthermore, it was not classified as a microsatellite instability-high cancer. A standard first-line chemotherapy regimen for colon cancer comprising capecitabine, oxaliplatin, and bevacizumab was initiated. Seven months after initiating chemotherapy, the pancreatic and hepatic tumors slightly shrank. However, 8 months after initiating chemotherapy, a second-line regimen of capecitabine, irinotecan, and bevacizumab was initiated owing to the development of neuropathy. Eighteen months after the second-line chemotherapy regimen, disease progression with enlarged hepatic metastases and emergence of new pulmonary metastases was noted, and a third-line regimen of trifluridine/tipiracil was initiated. At 2 years after initiation of the first-line chemotherapy regimen, the patient received the third-line chemotherapy.

Fig. 1.

Prediagnostic imaging findings prior to pancreatic tumor detection

(a) Colonoscopy performed 6 years before diagnosing the pancreatic tumor revealed an elevated lesion in the descending colon. The tumor was surgically resected and diagnosed as a moderately differentiated tubular adenocarcinoma with invasion into the muscularis propria. Lymphatic invasion was not observed. However, venous invasion was present.

(b) Three years after colectomy, a pulmonary metastasis in the right lower lobe (yellow arrowhead) was surgically resected. At that time, abdominal CT revealed no evidence of pancreatic or hepatic tumors.

CT, computed tomography

Fig. 2.

Contrast-enhanced CT findings at the time of pancreatic tumor diagnosis

(a) In the arterial phase, a 20-mm, poorly enhanced, irregularly shaped mass was identified at the junction of the pancreatic head and body (yellow arrowheads).

(b) In the equilibrium phase, dilation of the main pancreatic duct distal to the pancreatic tumor was observed (white arrowhead).

(c) In the arterial phase, multiple hypodense masses with peripheral ring-shaped enhancement were observed in both hepatic lobes (red arrowheads).

CT, computed tomography

Fig. 3.

EUS findings during EUS-FNA

(a) Dual imaging showing the B-mode (left) and power Doppler mode (right). A hypoechoic mass with an irregular internal structure was observed at the junction of the pancreatic head and body from the gastric lumen (yellow arrowheads).

(b) Under real-time convex EUS, a 22-gauge FNA needle (white arrowheads) was used to puncture the pancreatic mass.

EUS, endoscopic ultrasonography;FNA, fine-needle aspiration

Fig. 4.

Histopathological findings of the EUS-FNA specimen

(a) Hematoxylin and eosin staining confirmed the diagnosis of adenocarcinoma.

(b) Immunohistochemical staining showing that the tumor cells did not express cytokeratin 7.

(c) Immunohistochemical staining revealing that the tumor cells had strong positivity for cytokeratin 20.

(d) Immunohistochemical staining showing that the tumor cells had strong positivity for caudal-type homeobox 2.

(e) Immunohistochemical staining revealing that the tumor cells had weak positivity for the special AT-rich sequence-binding protein 2.

EUS-FNA, endoscopic ultrasonography-guided fine-needle aspiration

Discussion

This report describes the case of a patient with a pancreatic metastatic tumor that developed 6 years after colon cancer surgery. The patient could not be diagnosed via CT imaging alone; hence, histopathological analysis of the pancreatic specimens was conducted via EUS-FNA, which was essential in confirming the diagnosis. In addition to H&E staining, immunohistochemical staining enabled the definitive diagnosis of pancreatic metastasis of colon cancer. Furthermore, histopathological comparison of the pancreatic and hepatic lesions with the previously resected primary colon cancer and subsequent pulmonary metastatic lesion specimens helped determine the appropriate treatment strategy, which is a key point of this report.

It is often challenging to distinguish pancreatic metastatic tumors from primary pancreatic cancer. Metastatic lesions are occasionally identified during postoperative surveillance CT and confirmed after surgical resection. EUS-FNA has become a widely used method for obtaining specimens of pancreatic lesions for their histopathological diagnosis based on H&E staining, which has a sensitivity and specificity of >90%^8,9). The diagnostic accuracy of EUS-FNA coupled with histopathological analysis via H&E staining for metastatic pancreatic tumors is as high as 89%¹⁰⁾. Furthermore, recent advancements in immunohistochemical analysis have facilitated the identification of the origin of tumors. To date, 18 cases of colon cancer-derived pancreatic metastasis diagnosed using EUS-FNA with H&E and immunohistochemical staining have been reported (Table 1)^5,11-20).

Immunohistochemical staining patterns can help differentiate pancreatic metastases from primary pancreatic cancer. Previous studies have reported that CK7 is expressed in only 5% of colon cancer cases and in 92% of pancreatic cancer cases, whereas CK20 is expressed in 100% of colon cancer cases and 62% of pancreatic cancer cases²¹⁾. In addition, CDX2, a well-known marker of cancers of gastrointestinal origin, is positive in 99% of colon cancer cases and only 32% of pancreatic cancer cases²²⁾. These findings are in accordance with those of our case, which was negative for CK7 and positive for CK20 and CDX2. Furthermore, we also evaluated SATB2 expression in a planned manner. SATB2 is a nuclear matrix-associated transcription factor that is selectively expressed in glandular epithelial cells of the lower gastrointestinal tract. In colon cancer cases, SATB2 expression analysis has a reported sensitivity of approximately 95% and a specificity of 88%²³⁾. Notably, SATB2 is rarely expressed in noncolon adenocarcinomas, including those originating from the pancreas, stomach, and prostate. In contrast, CK20 and CDX2 expression analyses are widely used as they have a high sensitivity for colon cancer at 95% and 95%-100%, respectively. Both of these markers, however, are also expressed in noncolon adenocarcinomas, such as pancreatic, gastric, and ovarian tumors, resulting in lower specificity of approximately 70%-80%^21,22). SATB2 expression analysis provides superior specificity in this context and has proven to be especially useful in distinguishing colon cancer metastasis from primary pancreatic cancer. Furthermore, the combination of SATB2 and CK20 identifies 98% of colon cancer cases²³⁾. However, there are no reports describing SATB2 staining in EUS-FNA specimens of pancreatic metastases. In our case, all specimens, including those obtained via EUS-FNA, liver biopsy, and previous surgical specimens, were positive for SATB2. These findings, in combination with other immunohistochemical markers, strongly indicated a colonic origin. Therefore, the assessment of CK7, CK20, CDX2, and SATB2 in EUS-FNA specimens is potentially valuable in diagnosing pancreatic tumors in patients with a history of colon cancer.

Colon cancer with pancreatic metastases is often an indicator of widespread systemic disease and is associated with a poor prognosis. The prognosis of pancreatic metastases from unresectable colon cancer is unclear. The mean overall survival of patients with unresectable advanced-stage or recurrent colon cancer who underwent chemotherapy with capecitabine, oxaliplatin, and bevacizumab, which was initially used in our case, is 21.36 months²⁴⁾. However, in palliative cases, it is approximately 8 months²⁵⁾. In our case, the patient survived for >2 years after the initiation of chemotherapy.

Pancreatic metastases from colon cancer are challenging to distinguish from primary pancreatic cancer based only on imaging modalities such as CT and EUS. Therefore, in patients with a history of colon cancer who present with a pancreatic tumors, EUS-FNA with immunohistochemical staining is important for an accurate diagnosis and selecting an appropriate treatment regimen.

Table 1.

Clinical characteristics of pancreatic metastases from colorectal cancers diagnosed using EUS-FNA

EUS-FNA, endoscopic ultrasound-guided fine-needle aspiration;Ref, reference;M, male;F, female;ADC, adenocarcinoma;CK, cytokeratin;CDX, caudal-related homeodomain protein;SATB2, special AT-rich sequence-binding protein 2;NA, not available

Acknowledgments

The authors would like to express their deep appreciation to all the endoscopy medical staff and ward staff at Japanese Red Cross Society Fukushima Hospital for their assistance with the endoscopic procedures and care of this patient.

Conflict of interest

The authors declare no conflicts of interest.

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