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Year : 2018  |  Volume : 14  |  Issue : 6  |  Page : 1325-1329

Importance of routine histopathological examination of a gallbladder surgical specimen: Unexpected gallbladder cancer

Department of General Surgery, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey

Date of Web Publication28-Nov-2018

Correspondence Address:
Oguzhan Dincel
Yeni Mah. 26294 sk. Elif Kent Sitesi B Blok No: 2, Adiyaman
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.187301

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 > Abstract 

Introduction: Cholecystectomy performed for benign diseases of the gallbladder is important for the diagnosis of gallbladder cancer. This is done by pathological examination of the removed specimens for patients with no detected or suspected complications before surgery. Although some centers undertake selective approaches for histopathological examination of gallbladder specimens, many centers perform this examination routinely. In our study, we investigated results of pathological examinations carried out on cholecystectomy specimens, in respect to unexpected cases of gallbladder cancer.
Methods: We reviewed cholecystectomy cases performed for benign diseases of gallbladder from January 2012 to February 2016 by investigating pathological specimens from the gallbladder. We evaluated demographical properties and their association with the pathological diagnosis and frequency of unexpected gallbladder cancer cases. We reported additional treatment and survival information of the malignancy cases after surgery.
Results: We reviewed 1294 cases of cholecystectomy, and the mean patient age was 47.5 ± 14.3 years. The most frequent diagnosis was chronic cholecystitis (92.3%), and it was more prevalent among younger patients and female sex (P < 0.0001). Five patients (0.4%) were determined to have gallbladder cancer, and the mean age of these cases was 65.6 ± 18.2 years. Two cases were Stage 2, two cases were Stage 3B, and one case was Stage 3A. There was no T1 or Tis tumor.
Conclusion: Routine histopathological examination of gallbladder is significant with respect to the determination of additional interventions at the postoperative period required for cancer cases coincidentally diagnosed.

Keywords: Cancer staging, cholecystectomy, histopathology, unexpected gallbladder cancer

How to cite this article:
Dincel O, Goksu M, Hatipoglu HS. Importance of routine histopathological examination of a gallbladder surgical specimen: Unexpected gallbladder cancer. J Can Res Ther 2018;14:1325-9

How to cite this URL:
Dincel O, Goksu M, Hatipoglu HS. Importance of routine histopathological examination of a gallbladder surgical specimen: Unexpected gallbladder cancer. J Can Res Ther [serial online] 2018 [cited 2020 Jun 1];14:1325-9. Available from: http://www.cancerjournal.net/text.asp?2018/14/6/1325/187301

 > Introduction Top

Histopathological examination of gallbladder specimens is an important step toward the confirmation of clinical and radiological diagnosis.[1] In addition, it has judicial significance,[2] and most of the surgical units mandate routine examination of the specimen.[3] However, the necessity to carry out pathological examination for all gallbladder specimens collected during operation is a subject of question.[1],[4] For all benign lesions and early Stage T1 malignancies of gallbladder, simple cholecystectomy is regarded as an adequate treatment.[5] Therefore, no additional treatment or intervention is required apart from the simple cholecystectomy.

Suspicious or malignant states can be detected early via imaging of gallbladder before surgery or intraoperative exploration. However, the pathological examination of surgery specimens would help to determine an exact diagnosis.[4] Such evaluation and the use of pathology unit facilities should be considered while discussing whether routine examination is necessary.[1],[3],[6],[7]

Unexpected gallbladder cancer is generally diagnosed after the examination of specimens obtained from cholecystectomy performed due to preliminary diagnoses of benign diseases of gallbladder. Its frequency among all cholecystectomy cases has been reported between 0.23 and 3.30%. Early diagnosis for these aggressive cancers is very important; however, the prognosis and outcomes are still not fully understood.[8],[9]

In this study, we retrospectively reviewed pathological reports of the specimens obtained from open or laparoscopic cholecystectomy due to benign diseases of the gallbladder. We emphasize the importance of the examination of all cholecystectomy specimens and suggest a referral of all cases reported as primary gallbladder cancer.

 > Methods Top

The study protocol was approved by the internal review board. We retrospectively reviewed the data of all patients that underwent cholecystectomy (open or laparoscopic) between January 2012 and February 2016 for benign diseases of gallbladder. One patient that was diagnosed with gallbladder cancer before surgery (both clinically and radiologically) was not included in the study. During the operation of all cases included, none of the specimens had any suspicious signs, and all of the specimens were sent to the pathology unit for routine examination purposes.

Demographical data such as age-sex, operation findings, pathology results, stage of cancer cases, and their survival data were noted. Pathology reports were obtained for all patients. Classification of cases was done based on the pathology results. We examined the distribution of pathological diagnoses, effect of age and sex on this distribution, and the prevalence of cancer cases. For five patients that were reported as gallbladder cancer, additional information was obtained from medical oncology unit.

Pathological examination results were categorized as cholecystitis, cholesterolosis, nonspecific pathologies (adenomyomatosis, hyperplasia, polyp, metaplasia, and dysplasia), and malignancy. Each category was analyzed for age and sex distribution.

Statistical analyses

Statistical analyses were carried out using SPSS version 22.0 (IBM, Armonk, NY, USA). Continuous variables with a normal distribution are expressed as the mean ± standard deviation. Categorical variables are expressed as frequencies and percentages. Fisher's exact test and Chi-square test were used to compare nonparametric variables. The Student's t-test was used to compare two groups of parametric variables with a normal distribution, and ANOVA test was used to compare more than two groups. Statistical results are presented at a confidence interval of 95.0. A P < 0.05 was considered statistically significant.

 > Results Top

A total of 1294 patients were examined during the study period. The mean age of patients was 47.5 ± 14.3 years, ranging between 16 and 91 years. Of all the patients, 1018 were female, and 276 were male, with a female/male ratio of 3.7.

Indications for operation were biliary colic (n = 908, 70.1%), chronic cholecystitis (n = 297, 23.0%), acute cholecystitis (n = 55, 4.3%), and other benign diseases of gallbladder other than cholelithiasis such as polyp and adenomyomatosis (n = 34, 2.6%). The number of cholecystectomy cases performed with laparoscopy, open surgery, and conversion to open surgery were 1248 (96.4%), 14 (1.0%), and 32 (2.4%), respectively.

[Table 1] shows distribution of the study patients according to categories and their evaluation. Analysis of cholecystitis category shows that chronic cholecystitis is the most frequent pathology (92.3%), and patient age in this group (46.9 ± 14.2) was younger in comparison to other groups (P < 0.0001). As for sex distribution, female sex was more frequent among cases of chronic cholecystitis (female/male = 4.1/1.0).
Table 1: Histopathological diagnoses and demographic information of patients

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There was no age difference between patients with (n = 201, 15.5%) and without cholesterolosis (P = 0.660). However, there was a preponderance of female sex among cases of cholesterolosis, with a female:male ratio of 6.7:1.0 (P = 0.001).

In the category that includes nonspecific diagnoses other than malignancy, the mean age of patients with metaplasia (n = 39, 3.0%) and dysplasia (n = 8, 0.6%) were 49.6 ± 14, and 56.9 ± 14.9 years, respectively. We found age difference in general evaluation between the groups (P = 0.015). However, we did not find difference in statistical analysis on individual basis. In addition, there was no difference in terms of sex distribution (P = 0.201).

There was age difference between patients with or without malignancy (P = 0.005); however, there was no difference regarding sex distribution (P = 1.000). Patients with malignant disease (65.6 ± 18.2 years) were older than those without a malignant disease (47.4 ± 14.3 years).

Among patients with malignant disease, two had Stage 2 (T2N0) disease while others had Stage 3A (T3N0), Stage 3B (T2N1), and Stage 3B (T2N1) disease, respectively. Due to difficulty in exploration, laparoscopy was converted to open surgery in three patients. Expanded resection was considered in one patient, but could not be performed due to poor general condition. This patient died 3 weeks later. One of two patients that had expanded surgery died 30 months later and the other died 10 months later. Expanded surgery could not be performed in the other two patients because consent was not approved for additional intervention. One of these patients died 10 months later, and the other one died 6 months later. [Table 2] summarizes properties and outcomes of patients with malignant disease.
Table 2: Characteristics and follow-up of patients with malignant disease

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 > Discussion Top

Although rare, gallbladder cancer is the fifth most frequent malignant tumor of gastrointestinal system. The disease has an aggressive course and is especially observed among elderly population. It is more frequent at the seventh decade, and 2–3 times more common among women compared to men. Unless pathological examination of the material obtained with cholecystectomy performed for benign diseases of the gallbladder is reported as early stage cancer, prognosis of gallbladder cancer is poor.[10],[11],[12] Approximately, 0.23–3.30% of cases that undergo cholecystectomy for benign diseases are determined to have gallbladder cancer.[6],[8],[11],[13],[14] In our study, the frequency of unexpected gallbladder cancer was 0.4%. However, the prevalence of gallbladder cancer varies according to geographical regions including the incidental ones.[3] It is possible to see varying results at different studies because its prevalence is higher in Asian countries and Northern India in comparison to western countries.[15]

Gallbladder cancer is rare in Northern Europe and North America.[16] The highest prevalence, according to the World Health Organization's 2008 data, was reported in Japan as 15.7 per 100,000.[17] A cause for the varying incidence rates can be inaccurate patient selection with regard to symptoms related to biliary tract. Therefore, the rare and unexpected diagnosis is an important issue for clinicians.[8]

Chronic inflammation, infection, and stones are currently believed to be the causes of malignant conversion in gallbladder epithelia.[18] Various studies have long been reporting the association between gallbladder cancer, and the chronic inflammation caused by gallstones.[19],[20] Gallstones are detected in 54–97% of gallbladder cancer cases. Prolonged chronic inflammation caused by gallstones should be taken into account for this association.[21] Nonetheless, inflammation at the gallbladder wall is usually not a specific sign as it can also be seen in chronic inflammatory diseases.[13]

With 92.3% frequency, chronic cholecystitis is the most common pathology among the diseases associated with unexpected gallbladder cancer, and our results are consistent with this knowledge.[3],[22] Deng et al.[4] also found an association between cancer and acute cholecystitis. In our study, pathological examination revealed malignancy in four patients who had a preliminary diagnosis of chronic cholecystitis, and one patient who had a preliminary diagnosis of acute cholecystitis.

Two important carcinogenesis models exist. These are Metaplasia-dysplasia-carcinoma and adenocarcinoma. Several studies have reported associations between pyloric metaplasia and dysplasia, pyloric metaplasia and cancer, and also intestinal metaplasia and pyloric metaplasia, dysplasia, and cancer.[23],[24] In this study, dysplasia-cancer association was detected in only one case of cancer.

The histopathological examination of specimens that are removed due to diseases of gallbladder as clinically considered benign or not has been a subject of debate. There are different approaches in general surgery practice regarding inspection of the specimens during operation and sending the specimen to pathology.[25] In India and other developed countries, there are diverse reports about the usefulness of this practice because the number of incidentally detected cancer cases is not so high.[13]

In countries where the prevalence is high, it is advised to send the specimens to pathology, because it is only possible to detect the disease at its treatable early stage via histopathological examination. The value of examining gallbladder specimens has been questioned, giving rise to selective applications. Selective pathology is defined as the macroscopic evaluation of the gallbladder during the operation, and it has been on the front for a couple of years. One of the reports disputed routine pathological examination of gallbladder specimens and recommended selective examination.[5]

Dix et al.[6] recommended the same approach and stated that routine histopathological examination did not provide any additional benefit to the patient, surgeon, or the pathologist. Darmas et al.[26] stated selective examination would reduce the workload of pathology unit without putting the safety of patient at risk.

Mittal et al.[27] detected abnormal macroscopic appearance in 47.0% of 1312 cases of cholecystectomy that they performed. In that study, all 13 cancer cases were from among those which had the abnormal appearance of the specimen. As a result, they recommended pathological examination for cases that have such abnormal appearance.

Chin et al.[28] reported that age and sex differences did not have any effect on the histopathological examination results of cholecystectomy specimens, and as a result, they recommended a selective approach. On the other hand, some authors on the opposite opinion state selective approach may be dangerous and is far from being scientific.[29]

One study from Malaysia emphasized the importance of histopathological examination of gallbladder specimens and noted that it is necessary to examine the specimens even in the absence of clinical or macroscopical suspicion.[30] Diagnosis of all cancer cases in our study was confirmed with histopathological examination, and there was no report of observation of a suspicious macroscopic sign intraoperatively.

The majority of unexpected primary gallbladder cancers are expected to be at the early stage of the disease. Deng et al.[4] showed 64.0% of cancer cases were T1a or T1b. However, one meta-analysis study reported only 42.4% of unexpected cancer cases were Stage Tis or T1 in histopathological examination.[7] Kalita et al.[13] reported 14 of 25 tumor cases were Stage T2. Cholecystectomy is an appropriate treatment for benign disease of gallbladder and even early Stage T1 lesions.[6] However, none of our patients had early stage disease as described in literature (Tis or T1). Two of our patients were Stage 2 (T2N0), two cases were Stage 3B (T2N1), and one case was Stage 3A (T3N0). None of these cases were found to have any suspicious sign either with preoperative imaging studies or during their operation. Due to difficulty in exploration of Stage 3A and 3B cases (better to say suspicion of tumor in this case), their surgery was converted to open. For two cases, expanded surgery was performed with a second operation; however, one case survived for 10 months, and the other case survived for 30 months.

 > Conclusion Top

There are different opinions in the literature about the examination of gallbladder specimens. The selective approach may be performed at regions where the prevalence of gallbladder cancer is low. However, the routine examination may be performed at regions where prevalence is high. In our study, all of the patients that are found to have gallbladder cancer had advanced disease. Simple cholecystectomy was not sufficient, and they required additional interventions. To detect these cases, we believe routine examination is necessary for all gallbladder specimens even in the absence of macroscopically suspicious signs, which was the case in our patients.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

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Deng YL, Xiong XZ, Zhou Y, Shrestha A, Li FY, Cheng NS. Selective histology of cholecystectomy specimens – Is it justified? J Surg Res 2015;193:196-201.  Back to cited text no. 4
Taylor HW, Huang JK. ‘Routine’ pathological examination of the gallbladder is a futile exercise. Br J Surg 1998;85:208.  Back to cited text no. 5
Dix FP, Bruce IA, Krypcyzk A, Ravi S. A selective approach to histopathology of the gallbladder is justifiable. Surgeon 2003;1:233-5.  Back to cited text no. 6
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  [Table 1], [Table 2]


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