Primary Non-Hodgkin's Lymphoma of the Gallbladder: A Population-based Analysis

Discussion

Primary lymphomas of the gallbladder are extremely rare, representing around 0.1-0.2% of all malignant tumors of the gallbladder (6). Data on clinical characteristics, optimal management and outcomes of these tumors is extremely limited. Mitropoulos et al. identified 11 cases of PNHL-GB reported in the English literature and observed that these patients present a median age of 68 years with equal gender distribution. The most common-presenting complaint among these patients was abdominal pain (7). The largest dataset to date was provided by Mani et al., who described their single-Institution series of 13 patients with primary gallbladder lymphoma. In addition, they also performed a comprehensive review of the literature and summarized previously reported cases (6). They observed that these cancers were primarily noted in females and most patients presented with symptoms mimicking cholecystitis. In their series, DLBCL was the most common histological variant, followed by EMZL and FL, respectively. Patients with DLBCL and EMZL were older (mean age 75.8 years) at the time of diagnosis versus other lymphoma subtypes (mean age 47 years) and were more likely to present with gallstones.

Our study represents the largest series of patients with PNHL-GB. We observed that this cancer predominantly affects white males, usually in the seventh decade of life. Most patients have loco-regional disease at the time of diagnosis. We also observed certain differences amongst different histological subtypes of PNHL-GB. In addition, we noted that patients with DLBCL had lower overall survival compared to FL and EMZL. Furthermore, patients who underwent resection survived longer than those who did not receive surgery (both for the whole patient cohort and after stratification by stage). Finally, our results demonstrate that patients who received adjuvant RT appeared to survive longer than those who received surgery alone.

The results of this study are very similar to previously reported studies of other primary GI non-Hodgkin lymphomas. The largest dataset of patients with primary GI non-Hodgkin lymphomas was reported by Shannon et al who analyzed 16,129 patients using the SEER database (3). They observed that primary GI NHL primarily affects white males, and the majority of cases are diagnosed after 65 years of age. DLBCL was the most common histological variant, followed by FL. In their series, the gastric location was the most common site and included 49.7% of identified cases, while 28.5% occurred in the small intestine and 16.4% in the large intestine. Among patients for whom staging information was available, 44.3% had localized disease (vs. 67% in our series). Overall median survival was 25 months with a 5-year survival rate of 35.6% (vs. 42 months and 40% in our patients). In their series, female gender and follicular cell histology were associated with improved survival. None of these factors had effect on survival in our small analysis of gallbladder lymphoma patients. They noted higher survival in patients who received adjuvant RT vs. resection alone (median 69 months vs. 36 months, respectively), possibly indicating a role of adjuvant RT in primary GI lymphomas.

We also summarized PNHL-GB cases previously described in the literature (Table IV) (6-20). We found that most cases of PNHL-GB are diagnosed incidentally in cholecystectomy specimens (7). Few case reports have described the use of fine-needle aspiration as a potential preoperative diagnostic tool (21). In addition, certain radiological features have been observed with different histological subtypes that can aid in preoperative diagnosis. For example, high-grade lymphomas such as DLBCL manifest as a bulky solid mass within the gallbladder or marked irregular wall thickening, whereas, low-grade variants such as FL tend to produce slight thickening of the gallbladder wall (22, 23). Peri-portal lesions and para-aortic lesions are also commonly noted in these patients. In addition, CT or MRI findings of homogenous submucosal thickening of gallbladder wall with a preserved mucosal surface are also described as being suggestive of a lymphoma (21).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1.

Kaplan–Meier survival curve for overall survival by (a) DLBCL vs. FL/EMZL histology (median survival 13 months vs. 53 months, p=0.034); b): surgical resection vs. no resection (median survival 42 months vs. 2 months, p=0.015).

Currently, there are no guidelines for the management of gallbladder lymphomas. Single-case experiences report good long-term outcomes with cholecystectomy alone for lesions limited to the gallbladder (24, 25). There are very limited data on the role of adjuvant therapies in the treatment of gallbladder lymphoma (7, 17). In our series, we observed that patients who underwent resection demonstrated better outcomes compared to those who did not undergo surgical resection. In addition, patients who received adjuvant RT appeared to have superior long-term survival than those who underwent resection alone. However, due to the small number of patients in the comparison groups, we cannot derive any conclusions about the role of resection and adjuvant RT in this group of patients. In addition, most cases with gallbladder lymphomas are diagnosed on cholecystectomy specimens post-resection. Hence, identifying a role of adjuvant modalities post-resection is important for these cases.

We encountered certain limitations associated with using a population-based data registry including the retrospective nature of the study and limited information on some data points including clinical presentation, diagnostic modalities (radiology, CD markers), tumor size, grade, type of surgery (open vs. laparoscopic, simple vs. extended resections) and modified Ann Arbor staging for GI lymphomas. Moreover, since chemotherapy and immunotherapy data is not available in the SEER database, it is difficult to analyze their role in the long-term survival of these patients. Additionally, it could not be ascertained whether these cases were diagnosed incidentally or before surgery. Despite all these limiting factors, the most important benefit of this database is that we were able to analyze a large number of patients with such a rare disease, which is usually not possible through single-institution series. Using the information available in the SEER database, we are the first to report characteristics and survival outcomes of patients with PNHL-GB.