Report of a case with T1a gallbladder poorly differentiated adenocarcinoma, solid type, which developed into lymph node metastases
© Takano et al. 2015
Received: 31 August 2015
Accepted: 2 November 2015
Published: 16 November 2015
We experienced a case with gallbladder carcinoma growing limited to the mucosa (T1a), which developed massive lymphatic vessel spread and lymph node metastases.
A 72-year-old man was referred to our hospital for the swelling of his gallbladder during a routine ultrasound sonography checkup. We diagnosed the patient with gallbladder carcinoma with lymph node metastasis according to the radiographic findings and performed the open cholecystectomy and lymph node dissection. A histological examination showed poorly differentiated adenocarcinoma, solid type, and the tumor was limited to the mucosa. The number of lymphatic vessels was increased in the tumor and peritumor areas, and cancer cells were observed in the lymphatic vessels, which were detected via D2-40 immunohistochemistry. A careful histological examination and follow-up is required for T1a gallbladder carcinoma.
The prognosis of gallbladder carcinoma is poor. The 5-year survival rate of surgical resection was reported to be 40 % . However, patients with T1a gallbladder carcinoma (GC) are considered to be curable by cholecystectomy without lymph node dissection [2, 3], and no evidence has shown that the lymph node dissection improves the prognosis of T1a GC [4–6]. Furthermore, the frequency of lymph node metastases of T1a GC was reported to be 0–2.5 % [6, 7].
However, we experienced a case with gallbladder carcinoma growing limited in the mucosa developed massive lymphatic vessel spread and lymph node metastases.
We herein report the rare case of lymph node metastases in a patient with GC and discuss the considerations for the etiology of lymph node metastases in this case.
A 72-year-old man was referred to our hospital for the swelling of his gallbladder which was indicated during a routine ultrasound sonography checkup. He had been previously treated for hypertension, diabetes mellitus, and a cerebral infarction. He had no family history of cancer. There were no physical abnormalities on this admission. The laboratory data indicated a slight elevation of γ-GTP at 119 IU/l, but no other abnormal findings. The values of tumor markers were within the normal ranges; CEA, 2.6 ng/ml and CA19-9, 29.3 U/ml.
According to these findings, we diagnosed the patient with gallbladder carcinoma with lymph node metastasis and performed open cholecystectomy and lymph node dissection of the hepatoduodenal ligament. An analysis of intraoperative frozen sections revealed tumor invasion to the cystic duct; therefore, we additionally resected the extrahepatic bile duct and regional lymph nodes. The concentration of biliary amylase was not elevated at 196 IU/l.
Although a frozen section of the cystic duct indicated tumor invasion, the tumor invasion into the distal bile duct and perineural invasion were not seen.
The patient was administered gemcitabine (1000 mg/m2/biweekly) and S1 (100 mg/every other day) as an adjuvant therapy. However, lymph node metastases occurred in the paraaortic and supraclavicular regions, 10 months after the operation. We subsequently added radiation therapy for both regions and continued gemcitabine and S1 for 2 years.
The frequency of lymph node metastases by tumor invasion is as follows: T1a, the tumor invaded into the mucosa 0–2.5 %; T1b, the tumor invaded into muscularis 5–16 %; T2, the tumor invaded into the perimuscular connective tissue 9–30 %; T3, the tumor perforated into the serosa 39–72 %; and T4, directly invaded into other organs 67–80 % .
The wall of the gallbladder is composed of three layers: mucosa, muscularis, and serosa. There is no muscularis mucosa or submucosa . Tumors in the mucosa easily invade the muscular layer and subserosa. The specific structure of the gallbladder wall might be one of the reasons why T1a GC led to lymph node metastases.
The histological grade is strongly related to the prognosis of gallbladder carcinoma. The frequency of lymph node metastases is higher in high nuclear grade tumors or poorly differentiated adenocarcinomas .
The specific histological finding in the present case was that lymphatic vessels were observed in the tumor. This finding suggests that cytokines are produced in the tumor tissues which induced the lymphatic vessels. Recent reports have indicated that vascular endothelial growth factor C and D induced neoplastic lymph angiogenesis and were related to lymph node metastasis in several cancers, including gallbladder carcinoma [14–16].
Because a lymph node metastasis was suspected according to the preoperative evaluations in this case, we initially diagnosed the patient with T2 gallbladder carcinoma and performed lymph node dissection. If a case would be incidentally diagnosed as T1a gallbladder carcinoma, the additional lymph node dissection was not performed according to the guidelines.
We have experienced a case with T1a gallbladder carcinoma developed lymph node metastases. Therfore, even in T1a gallbladder carcinoma, a careful histological examination and follow-up is required.
Written informed consent was obtained from the patient for publication of this case and any accompanying images. A copy of the written consent is available for review by the Editorial-in-Chief of this journal.
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