Kiyotaka Hosoda, Akira Shimizu, Koji Kubota,Tsuyoshi Notake, Hikaru Hayashi, Koya Yasukawa, KentaroUmemura, Atsushi Kamachi,Takamune Goto, Hidenori Tomida, Shiori Yamazaki， Yuri Narusawa,NaokoAsano, Takeshi Uehara,Yuji Soejima

Abstract

Key Words: Gallbladder; Malignant lymphoma; Burkitt’s lymphoma; Gallbladder cancer;Lymphadenopathy; Case report

INTRODUCTION

Malignant lymphoma of the gallbladder is extremely rare[1 -4 ]. In almost all cases of this malignancy, patients are diagnosed as having gallbladder adenocarcinoma or cholecystitis at the time of surgery, and preoperative diagnosis is extremely difficult.Although several reports have documented malignant lymphomas of the gallbladder,most of these malignancies are diffuse large B-cell lymphomas and mucosa-associated lymphoid tissue-type lymphomas (MALTomas)[2 ,4 ,5 ], and only two reports have previously documented Burkitt’s lymphoma of the gallbladder[6 ,7 ]. Herein, we report the case of a patient with Burkitt’s lymphoma of the gallbladder mimicking gallbladder adenocarcinoma.

CASE PRESENTATION

Chief complaints

An 83 -year-old man with no abdominal complaints was found to have a gallbladder tumor along with periportal lymph node enlargement and was admitted to our institution for further investigation.

History of present illness

The tumor was detected during contrast-enhanced computed tomography (CT)performed for a detailed examination of hypertension.

History of past illness

The patient had a history of cerebral artery stenosis and paroxysmal atrial fibrillation.

Personal and family history

No personal and family history.

Physical examination

Abdominal examination revealed no palpable mass or tenderness.

Laboratory examinations

Laboratory examinations performed upon admission revealed mild to moderate renal dysfunction (creatinine: 1 .21 mg/dL) and slightly elevated levels of serum carcinoembryonic antigen and serum soluble interleukin 2 receptor (6 .1 ng/mL and 635 IU/mL,respectively). Other laboratory data were within normal limits.

Imaging examinations

A contrast-enhanced abdominal CT scan revealed two irregular and highly contrastenhanced masses at the neck and body of the gallbladder as well as periportal lymph node enlargement, measuring 30 mm × 20 mm in diameter and consistent with gallbladder cancer lymph node metastasis (Figure 1 ). Magnetic resonance imaging revealed that the tumor signal was hypointense on T1 -weighted imaging and hyperintense on T2 -weighted and diffusion-weighted imaging (Figure 2 ). Positron emission tomography (PET) revealed increased18 F-fluorodeoxyglucose uptake in the tumor (Figure 3 ). Endoscopic ultrasonography (EUS) showed a heterogeneous echoic mass extending into the lumen, but it did not infiltrate the serosa (Figure 4 ).

FINAL DIAGNOSIS

The final diagnosis was gallbladder adenocarcinoma with lymph node metastasis.

TREATMENT

On the basis of these findings, the patient underwent bile duct resection with gallbladder bed resection and periportal lymph node dissection. The surgical findings revealed the gallbladder tumor was relatively softer than ordinary gallbladder cancers.The swollen lymph node was firm but did not invade the portal vein. However, the patient developed severe aspiration pneumonia and bile leakage after the surgery,which were treated conservatively. The patient was discharged 2 mo after the surgery.

OUTCOME AND FOLLOW-UP

Histologic examination revealed periportal lymphadenopathy and two tumors at the neck and body of the gallbladder, measuring 27 mm × 20 mm and 20 mm × 18 mm in diameter, respectively. Histological findings also showed monotonous lymphoid cells with hemophagocytosis by macrophages. Immunohistochemical staining for markers showed the presence of CD10 , BCL6 , and c-Myc and the absence of BCL2 . The Ki-67 index was ＞ 80 % (Figure 5 ). Therefore, the patient was finally diagnosed as having Burkitt’s lymphoma. Although the surgical margin was pathologically negative,recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on PET-CT immediately after discharge. Thus, he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide,doxorubicin, vincristine, and prednisone.

DISCUSSION

Malignant lymphoma of the gallbladder is a rare form of gallbladder malignancy,which accounts for 0 .1 %-0 .2 % of all gallbladder cancers[1 -3 ]. In previous reports, most of these malignancies were documented to be diffuse large B-cell lymphomas and MALTomas[2 ,4 ], and only two reports had documented Burkitt’s lymphoma of the gallbladder[6 ,7 ]. Compared to previous cases, the present case yielded some interesting clinical and imaging findings.

Table 1 Diagnostic criteria for gastrointestinal malignant lymphoma

Figure 1 A contrast-enhanced abdominal computed tomography scan shows two irregular and highly contrast-enhanced masses(arrowheads and arrow) at the neck and body of the gallbladder as well as periportal lymph node enlargement, which is consistent with gallbladder cancer lymph node metastasis. A: Axial section image in the early phase showing neck of the gallbladder; B: Axial section image in the delayed phase showing neck of the gallbladder in the delayed phase; C: Coronal sectional image showing body of the gallbladder.

First, this is potentially the first reported case of “primary” gallbladder Burkitt’s lymphoma. According to the diagnostic criteria of primary gastrointestinal lymphoma(Table 1 ) defined by Dawson et al[8 ] and Lewin et al[9 ], the previous two cases were diagnosed as “secondary” gallbladder Burkitt’s lymphoma because they included extra-gallbladder lesions, such as duodenal, hepatic, or central nervous system lesions.In contrast, in the present case, the tumor was localized in the gallbladder and a periportal lymph node. Although no gastrointestinal symptoms were observed because the primary site was the gallbladder, other criteria were fulfilled. Therefore,the patient was diagnosed as having “primary” gallbladder Burkitt’s lymphoma, and the case was considered novel.

Figure 2 Magnetic resonance imaging reveals a hypointense tumor signal. A: T1 -weighted imaging (arrowheads); B: A hyperintense signal on T2 -weighted imaging (arrowheads); C: Diffusion-weighted imaging (arrowheads).

Figure 3 Endoscopic ultrasonography shows a heterogeneous echoic mass (arrows) with internal partially low echo (arrowheads). The mass extends into the lumen but does not infiltrate the serosa.

Second, gallbladder Burkitt’s lymphoma can present as a localized disease that mimics gallbladder cancer. The imaging features of malignant lymphoma were reported by Onoet al[3 ], who reported that high-grade malignant lymphomas showed solid and bulky masses or irregular wall thickening. In addition, because Burkitt’s lymphoma is a highly aggressive and rapidly progressive disease, some extranodal sites are generally involved at the time of diagnosis[10 ] and tumor localization around the primary lesion is rare[11 ]. In this case, the malignancy was localized in the body of the gallbladder and a periportal lymph node. Since these findings were consistent with the imaging findings of gallbladder adenocarcinoma, we could not confirm a preoperative diagnosis of malignant lymphoma.

Unfortunately, the patient had lymphoma recurrence 2 mo after the surgery because the introduction of chemotherapy had to be delayed owing to postoperative complications. Burkitt’s lymphoma is a highly aggressive disease, but it is highly sensitive to chemotherapy. Therefore, chemotherapy has the highest priority in the treatment of Burkitt’s lymphoma[10 ], and we should have introduced chemotherapy as soon as possible after the surgery. If we had been aware of the possibility of gallbladder malignant lymphoma, we could have avoided the extended procedure and could have initiated chemotherapy at the appropriate time.

Figure 4 Histologic examination. A: Periportal lymphadenopathy and two tumors at the neck and body of the gallbladder, measuring 27 mm × 20 mm and 20 mm × 18 mm in diameter, respectively; B: Histological findings reveal monotonous lymphoid cells with hemophagocytosis by macrophages; C-E:Immunohistochemical staining for markers shows the presence of CD10 (C), BCL6 (D), and c-Myc (E) and the absence of BCL2 ; F: The Ki-67 index is ＞ 80 %. The white scale bars represent 1 mm.

Although the accurate preoperative diagnosis of gallbladder malignant lymphoma is quite difficult[2 ,12 ], some previous reports[3 ,12 ,13 ] have suggested the possibility of a precise preoperative diagnosis based on imaging findings. Specifically, Onoet al[3 ]showed that the signal intensity of the gallbladder wall on T2 -weighted imaging is more hypointense in malignant lymphoma than in carcinoma. In addition, Katoet al[12 ] reported the usefulness of an internal partially low echo in distinguishing malignant lymphoma from carcinoma. On a retrospective review of the present case,although no obvious differences were observed in the intensity of T2 -weighted imaging when compared to that of gallbladder cancers, EUS revealed an internal partially low echo of the tumor. Furthermore, in this case, a discrepancy existed in that no serosal invasion was observed despite the size of the tumor and presence of lymphadenopathy. We think this might be a characteristic finding that distinguishes gallbladder malignant lymphoma from carcinoma.

Figure 5 Positron emission tomography reveals increased 18 F-fluorodeoxyglucose uptake at the superior pancreaticoduodenal lymph nodes and hepatic radical margin. A: Superior pancreaticoduodenal lymph nodes; B: Hepatic radical margin.

Nevertheless, a biopsy examination seems the best diagnostic technique in the present case, considering the possibility of malignant lymphoma, and hence, biopsy should be planned for patients with the above imaging findings.

CONCLUSION

Burkitt’s lymphoma can occur in the gallbladder. Therefore, this disease should be considered in the differential diagnosis of a gallbladder tumor, and biopsy can be useful in facilitating the early introduction of chemotherapy in cases with suggestive imaging findings.