Portsite metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor: a case report

Abstract

Port site metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor is rare. To the best of our knowledge, there are only four such cases reported worldwide. We report a woman in her 70s with cholecystitis who underwent laparoscopic cholecystectomy. Intraoperative laparoscopic exploration did not reveal an abdominal tumor, and postoperative gallbladder pathology did not suggest malignancy. However, 11 months later, she developed an incisional mass in the epigastric port site. In another 6 months, magnetic resonance imaging revealed an abdominal wall tumor. Therefore, she underwent radical resection of the subcutaneous tumor, and postoperative pathology revealed adenocarcinoma. However, no primary tumor was found after systemic imaging examination.

Introduction

Laparoscopic cholecystectomy (LC) is the best treatment for cholecystitis. ¹ However, port sites are among the most common sites of metastasis after LC for incidentally detected gallbladder cancer (iGBC). ² Approximately 10.3% of iGBC patients develop port site metastasis (PSM) after LC. ³ There are several suggested causes, namely trocar injuries, intraoperative tumor perforation, specimen extraction without using a bag, reduced immunity, and leakage of carbon dioxide (CO₂) around the port leading to tumor cell accumulation at the port site (chimney effect).^3–5

PSM after LC with an unknown primary tumor is rare. The following is a brief summary of the case: a woman in her 70s who underwent LC for calculous cholecystitis 17 months earlier was diagnosed with unprovoked PSM in the epigastrium.

Case report

History

The reporting of this case conforms to the CARE guidelines. ⁶ We obtained written informed consent for publication from the patient. We also obtained patient consent for treatment. All patient details have been deidentified. The need to obtain ethical approval was waived because this was a retrospective study.

A woman in her 70 s was diagnosed with calculous cholecystitis at another center. At that time, tumor marker concentrations, namely carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), alpha fetoprotein (AFP), and cancer antigen (CA) 125, were within normal limits. The patient underwent laparoscopic cholecystectomy at that center. The gallbladder did not rupture during the operation and was successfully extracted from the epigastric port in a protective bag. Postoperative pathology revealed “chronic calculous cholecystitis accompanied by adenomatous hyperplasia and mild dysplasia of the gallbladder glands”. Approximately 11 months after the surgery, the patient found a subcutaneous hard mass measuring approximately 2 cm in diameter in the previous incision at the epigastric port site. The mass gradually increased in size in the subsequent 6 months, which was when she came to our center for further treatment. She had a history of hypertension, hyperlipemia, and diabetes, but no family history of cancer.

Physical examination

The mass was located in the epigastric port site and measured approximately 6 cm in size, with a hard texture, poor mobility, mild tenderness, and no local skin redness, swelling, or exudation.

Laboratory and imaging examinations

Laboratory tests revealed a total bilirubin concentration of 9.8 µmol/L, alanine aminotransferase concentration of 17 U/L, leukocyte count of 10.6 × 10⁹/L, neutrophilic granulocyte percentage of 78.7%, C-reactive protein concentration of 5.7 mg/L, AFP of 2.3 µg/L, CEA of 25 µg/L, CA 19-9 of <2 kU/L, and CA 125 of 22.9 kU/L. The results of occult blood testing of the urine and stool were negative. Abdominal contrast-enhanced magnetic resonance imaging (MRI) revealed a hypervascular mass that was ill-defined and measured 52 mm × 61 mm in the upper abdominal wall (Figure 1a–d) and splenic hemangioma. Preoperative gastrointestinal endoscopy was not performed because abdominal contrast-enhanced MRI did not reveal an abdominal tumor. We assessed that the mass could be completely resected; therefore, fine-needle aspiration cytology or biopsy was not performed preoperatively.

Figure 1.

Contrast-enhanced MR imaging of the abdominal wall tumor. a: arterial phase; b: venous phase; c: T2WI; d: sagittal view and e: resected specimen showing that the tumor invaded the muscle tissue and parietal peritoneum.

Diagnosis

The diagnosis was a portsite mass.

Treatment

The patient underwent extended excision of the subcutaneous tumor. Intraoperatively, we found that the tumor had spread to the muscle tissue and parietal peritoneum (Figure 1e). Rapid intraoperative pathology demonstrated adenocarcinoma with negative-margin (R0) resection. Postoperative pathology indicated the following: highly differentiated adenocarcinoma measuring 7 × 6 × 3 cm, invading the muscle tissue and parietal peritoneum. Immunohistochemistry revealed the following: cytokeratin 7 (CK7) (+), CK19 (+), CK20 (+), MUC5AC (+), Ki-67 (+) at 20%, CDX2 (±), special AT-rich binding protein 2 (SATB2) (−), PAX8 (−), Wilms’ tumor 1 (WT-1) (−), estrogen receptor (ER) (−), and MUC2 (−) (Figure 2). Positron emission tomography-computed tomography (PET-CT) and gastrointestinal endoscopy were performed and revealed no neoplastic lesions elsewhere in the body. Gallbladder histopathology was performed again, in our center, and no tumor foci were found. After the operation, the patient’s CEA concentration decreased gradually. We suggested chemotherapy, but the patient firmly refused. The CEA concentration (11 µg/L) was elevated at the final follow-up. Speculating that she might have developed tumor recurrence, we recommended periodic follow-up MRI; however, the patient refused.

Figure 2.

HE staining (a) and immunohistochemical staining (b–f) (×200). a: the adenocarcinoma invaded muscle tissue; b: CK7 (+); c: CK19 (+); d: CK20 (+); e: Ki-67 (+) at 20% and f: MUC5AC (+).

Discussion

PSM is common after oncological surgery; however, PSM after LC with an unknown primary tumor is unusual.^7–10 To our knowledge, there are only four such cases reported worldwide,^7–10 and we compared these cases with ours (Table 1). Among the five cases, four patients were women and most were older people, with a mean age of 60.8 years. The longest time between LC surgery and the discovery of PSM was 28 months, while the shortest was 6 months. The PSM sites varied and did not exclusively involve the incision from which the specimen was extracted. Yildirim et al.’s case had a history of kidney transplantation, and the patient underwent continuous immunosuppressive therapy. The time between LC surgery and PSM was the shortest in Yildirim et al.’s case. Additionally, PSMs were found in all of the port sites. Therefore, decreased immunity may be an important factor in the development of PSM. Intraoperative gallbladder rupture or the absence of a protective bag may also be mechanisms underlying the development of PSM. Therefore, gallbladder rupture should be avoided, and a protective bag should be used when extracting specimens. In our case, the gallbladder remained intact with a protective bag during extraction through the epigastric port, and no tumor foci were found in the second gallbladder histopathology. As no other primary tumor was found, we hypothesized that the port site tumor originated from the gallbladder. Gallbladder microcarcinoma likely exfoliated and seeded the incision during LC (chimney effect), which may lead to PSM. Two previous cases had a significant increase in CEA concentration; tumor marker concentrations were not mentioned in the remaining three case reports (Table 1). All cases reported a pathological result of adenocarcinoma with an unknown primary tumor.

Table 1.

Five cases of PSM after LC with an unknown primary tumor

Author, year	Sex	Age (years)	Interval to PSM (months)	PSM site	Tumor marker concentrations	Pathology and immunohistochemistry	Survival after LC (months)
10 Yildirim S, 2006	female	52	6	all four port sites	not given	adenocarcinoma; mucicarmine+	24
7 Polychronidis A, 2008	male	75	11	periumbilical port site; right subcostal port site	CEA: 150 µg/L	well differentiated adenocarcinoma; mtp53+, CD31+	35
Janusz H, 2009	female	57	23	periumbilical port site; right subcostal port site	not given	tubular adenocarcinoma; CK19+, CK20+	>33
9 Rao S, 2014	female	45	28	epigastric port site	not given	papillary adenocarcinoma	>28
Current case	female	70s	11	epigastric port site	CEA: 25 µg/L	well differentiated adenocarcinoma; CK7+, CK19+, CK20+, Ki-67±, MUC5AC+	>17

PSM, port site metastasis; LC, laparoscopic cholecystectomy; CEA, carcinoembryonic antigen; mtp53, mutant-type protein 53; CD, cluster of differentiation; CK, cytokeratin.

PSM is easily misdiagnosed as a hypertrophic scar in an incision after surgery for benign disease. Therefore, if there is a mass at port site after LC, especially with a sudden elevation in tumor marker concentrations, the possibility of PSM should be considered. PSM must also be differentiated from Sister Mary Joseph’s nodule, which is an umbilical lesion caused by abdominal malignant tumors. ¹¹ The primary mechanism of Sister Mary Joseph’s nodule formation may be related to the anatomy of the umbilicus, which is a relatively weak depression. In the present case, the patient's tumor was located in the epigastric port site; therefore, Sister Mary Joseph’s nodule could be excluded. Additionally, in this case, we must reflect on the fact that preoperative biopsy was not performed. If there had been a pathological report for preoperative needle biopsy, this could have guided the next treatment.

Conclusion

PSM after LC may be related to decreased immunity, the absence of a protective bag during specimen extraction, intraoperative gallbladder rupture, and the chimney effect of CO₂. The possibility of PSM should be considered when a patient develops a mass at a port site after LC.

Research Data

Research Data for Portsite metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor: a case report

Research Data for Portsite metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor: a case report by Jun Lu, Weijiang Zhou and Lixin Zhou in Journal of International Medical Research