Gall bladder, a foregut organ is very common organ to be affected by many pathological diseases which include wide spectrum of the lesions from congenital ones to cholelithiasis, inflammatory or pre-malignant and malignant lesions [1] . It is one of the most common organs to be resected [2]. 

Gall bladder is a pear shaped structure lying on the visceral surface of right lobe of liver [3]. Histologically, it is lined by the tall columnar epithelium bathed with mucus which separates the mucosal cells from the bile. It has three layers namely mucosa, muscularis and adventitia [4].

Cholelithiasis is the commonest etiology throughout the world. There is variation in the prevalence of cholelithiasis according to the age, sex and ethnicity [5]. In India, the prevalence of cholelithiasis is between 2- 29% while in Northern India, it is more prevalent that’s why Northern India is known to be as stone belt. Cholelithiasis is a multifactorial disease [6], more prevalent in fatty fertile females of forty years until menopause but can occur in children and males also. Additional factors include age, genetic susceptibility, obesity, insulin resistance, alcohol consumption, increased triglyceride level, pregnancy and various drugs [7] .

Ascorbic acid and Calcium consumption of unsaturated fats and dietary fibres have the protective effect. Most of the patients are asymptomatic while some present with biliary colic or it’s complications, commonest being the chronic cholecystitis, others are muscle hypertrophy, cholesterolosis, fibrosis and hyperplasia of mucus glands [8]. Gall bladder dyskinesia resulting in bile stasis is considered as the main pathology responsible for gall stone formation. Three factors namely mucus, calcium and lipid act together to promote the nucleation of the stones[9].

Stones are categorized as cholesterol stones, pigment stones and the mixed stones according to their composition [10] . These can be identified easily by their morphology e.g. cholesterol stones are single, oval and yellowish in color, pigmented stones are usually multiple and they are small in size and black colored. Mixed stones are multiple, multifaceted and can be of variable size [11].

Gall stones are responsible for the irritation of the columnar epithelium and is the main underlying cause for a number of histopathological changes like acute and chronic cholecystitis, cholesterolosis and pre-neoplastic conditions like metaplasia and dysplasia, ultimately culminating into the neoplasia [12] . That’s why, patients with cholelithiasis need proper surveillance as most of the carcinoma of gall bladder are found in association of the stones [13] .

As the most of the patients are asymptomatic, gall bladder carcinoma is often diagnosed late incidentally on histopathological examination accounting for the grave prognosis. Carcinoma gall bladder accounts for only 3% of all gastrointestinal malignancies. It is seen in patients of age more than 50 years and also more prevalent in females like other gall bladder pathologies. As it is diagnosed frequently in late stage, it has 5 year survival rate of only 1-5%. Most carcinomas are adenocarcinoma (approximately 84%), rest include adenosquamous, squamous and other rarer type of carcinoma [14] . Thus the present study was aimed to find out the histological changes in gall bladder and their association with various types of stones.

The present histopathological study was a prospective study which includes a detailed analysis of all cholecystectomy specimens presenting at the Department of Pathology, Shadan Institute of Medical Sciences, Teaching Hospital and Research Center.

Inclusion Criteria: All the cases with a clinical diagnosis of chronic cholecystitis, irrespective of age and sex were included in this study.

Exclusion Criteria: All the cases of malignant gallbladder lesions were excluded from this study.

The cases were drawn from Clinical Department of the hospital attached to Medical College. The age and sex of the patient, site of biopsy and other relevant clinical data were recorded. Patients of all ages were considered for the present study. The tissue samples were received in 10% buffered formalin and processed and 200 specimens were studied grossly and histologically. Multiple sections were taken from the larger specimens and the smaller ones fully submitted for processing by paraffin embedding. Appropriate number of sections of 4-5 micron thick tissue sections were cut and stained routinely with Hematoxylin and Eosin (H&E). There was no inter-observer variability in any of the cases. Ethical committee approval was acquired and the consent from the patients was taken in the clinical surgical department before the surgical procedure.

Statistical Analysis

Data regarding various etiologies of gallbladder lesions was collected and analyzed using statistical tools. Chi-square test will find association between spectrums of lesions. SPSS will be used for statistical analysis

A total of 180 gall bladder specimens were studied for their histopathological characteristics.

Table 1: Distribution of Age

In table 1, the age range of the patients varied from 20 to 80 years, with the majority of cases (60%) occurring in the 41-60 years age group.

In table 2, a female predominance was noted, with 135 cases (75%) being females and 45 cases (25%) being males, resulting in a male-to-female ratio of approximately 1:3.

Table 2: Distribution of Gender

The lesions were classified into non-neoplastic and neoplastic categories, with further sub-classifications as detailed below.

Table 3: Symptoms of patients

The most common presenting symptoms included Right upper quadrant abdominal pain (85%) followed by Dyspepsia (65%), Nausea/vomiting (40%) and Fever in cases of acute cholecystitis and empyema (20%).

Table 4: Histopathological Spectrum of Gall Bladder Lesions (n=180)

Table 5: Histopathological Analysis

The distribution of lesions in this study non-neoplastic lesions being predominant. However, the proportion of xanthogranulomatous cholecystitis (11.1%) and carcinoma (3.9%) is slightly higher, likely due to increased awareness and detailed histopathological examination. Chronic cholecystitis is the most prevalent lesion, emphasizing the importance of early diagnosis and management to prevent complications. Neoplastic lesions, though less frequent, carry significant clinical implications, highlighting the need for vigilant screening in at-risk populations (older adults, metabolic syndrome).

Table 6: Study of Histopathological Spectrum of Lesions of Gall Bladder (n=180) with the inclusion of age group distribution

Gall stone diseases are the major cause of morbidity and mortality throughout the world. The prevalence of the disease varies with age, sex, geographic area and the ethnic groups. The trend of the disease has changed in thelast couple of decades due to the change in the dietary habits, migration of people and environmental insults. [15] In our study, the mean age of the patients was 44 years. We observed maximum (50.9%) number of patients in 31-50 years age group, equally distributed in each decade. This was in concordance with the studies of Kaur et al in a total of 384 patients in which 196 (52%) were of age group between 31-50 years. [15] However in study by Thamilselvi et al maximum number of patients were in 51 to 60 years of age which is higher in comparison to our study. In this study, we observed female predominance i.e. male: female was 1:8.3 that is similar with the previous studies. [16]

Inter play of female sex hormones (progesterone and estrogens) and its metabolic effects along with the sedentary lifestyle is said to be responsible for the high incidence of gall stones in females. [17] Gall stones are generally responsible for various forms of cholecystitis and associated lesions i.e. hyperplasia, metaplasia, dysplasia and carcinoma of the gallblader. [18] However, in 5 % to 10% of the cases, cholecystitis occurs without calculus. [19] In India, the incidence of calculus disease and its relationship with chronic cholecystitis varies from North to South India.

We observed nearly similar frequency of chronic calculus cholecystitis as seen in other North Indian studies by Mohan et al and Goyal et al. [20] Depending upon the colour, shape and size, the gall stones are classified into mixed (brownish yellow), cholesterol (yellow and white) and pigmented stones (dark brown and black). [21] In the present study, mixed stones were the most common type. This was correlated with the previous studies by Mohan et al, Mathur et al and Gopal Krishnan et al. The various lesions noted with gall stones include acute cholecystitis, chronic cholecystitis with associated epithelial and stromal alterations, chronic activecholecystitis, dysplasia and carcinoma. [22]

In present study, 1.8% of gall bladder lesions were due to acute cholecystitis which is quite close to the figures in the study by Thamilselviet al. Chronic cholecystitisis is associated with cholelithiasis in more than 90 % of the cases. In the present study, we observed chronic cholecystitis in 94.2% cases which is concordant with the observations made by Stanchu et al. [23] In this study in majority of specimens, cholesterolosis was found to be associated with cholesterol stones followed by mixed stones.

The incidence of chronic calculus cholecystitis was found to be 57.76% with female preponderance and mostly in third decade. Our study strongly recommends routine histopathological examination of all cholecystectomy specimens for the detection of various variants of chronic cholecystitis and also of incidental carcinoma of gall bladder which helps in their treatment and prognosis The histopathological spectrum of gallbladder lesions in gallstone disease included chronic cholecystitis and associated variety of mucosal alterations and lesions like cholesterosis, metaplasia, dysplasia and carcinoma. Commonest stones were mixed type and were more frequently associated with premalignant lesions. Frequency of Incidental gallbladder carcinoma detection was 0.6% and these were more commonly associated with pigment type of stones. Carefully planned studies to learn the etiopathogenesis of cholelithiasis will go a long way in preventing

1. Dattal DS, Kaushik R, Gulati A, Sharma VK. Morphological spectrum of gall bladder lesions and their correlation with cholelithiasis. Int J Res Med Sci 2017;5:840-6.
2. Shukla HS, Sirohi B, Behari A et al. ICMR consensus document for the management of gall bladder cancer. Indian Journal of Medical and Paediatric Oncology 2015; 36(2):79-84.
3. Siddiqui FG, Memon AA and Ahmad. Routine histopathology of gallbladder after elective cholecystectomy for gallstones: waste of resources or a justified act? BMC Surgery. 2013; 13:26.
4. Devi B, Shetty J, Bose V. Histopathological Spectrum of Diseases in Gallbladder. National Journal of Laboratory Medicine. 2017; 6(4): 6-9.
5. Goyal S, Singla S, Duhan A. Correlation between gallstones characteristics and gallbladder mucosal changes: A retrospective study of 313 patients. Clin Cancer Investig J. 2014;3:157-61.
6. Selvi T, Sinha P, Subramaniam PM, Konapur PG, Prabha CV.A clinicopathological study of cholecystitis with special reference to analysis of cholelithiasis. International Journal of Basic Medical Science 2011; 2(2):68-72.
7. Awasthi N. A retrospective histopathological study of cholecystectomies. Int J Health Allied Sci. 2015;4:203-06.
8. Memon W, Khanzada TW, Samad A, Kumar B. Histopathological spectrum of gallbladder specimen after cholecystectomy. Pak J Med Sci 2011; 27:533-56.
9. Nigam M, Ranwaka R, Nigam B, Singh M, Devpura T P. Prevalance of carcinoma in symptomatic gallstone disease-A study following cholecystectomy. JEMDS 2013;25(2):4554-58.
10. Narendra GN, Gautam K. A spectrum of benign gallbladder diseases and their laparoscopic management: An experience of 100 patients. IJHRMLP 2015; 1(2): 25-31.
11. Arathi N, Awasthi S, Kumar A. Pathological profile of 11cholecystectomies at a teritiary centre. Natl J Med Dent Res. 2013;2(1):28-38.
12. Estrado RL, Brown NM, James CE: Chronic follicular cholecytitis: radiological, pathological and surgical aspects. Br J Surg 1960; 48:205.
13. Mohan H, Punia RP S, Dhawan SB, Ahal S, Sekhon MS. Morphological spectrum of gallstone disease in 1100 cholecystectomies in North India Indian Journal of Surgery, 2005; 67(3), 140-142
14. Sharma,Basu, Agarwal, Mishra. Gall Bladder disease in Gorakhpur region. Indian Journal Of Gastroenterology 1985:4(4):123-124
15. Guzman-Valdivia G. Xanthogranulomatous cholecystitis: 15 years Experience. World Journal of Surgery. 2004; 28(3):254-257.
16. Dixit VK, Parakash A, Gupta A et al. Xanthogranulatous Cholecystitis. Digestive Diseases and sciences 1998;43 (5) :122-125
17. Fox H, Mainwaring AR: Eosinophillic infiltration of gall bladder. Gastroenterology 1972; 63:1049- 1052.
18. Dabbs DJ. Eosinophilic and lymphoesinophilic cholecystitis. Am J SurgPathol 1993; 17: 497-501.
19. Durate I, Llanos O, Domke H, Harz C, Valdivieso V. Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution and probability of detection in routine histologic samples. Cancer 1993;72:1878-84.
20. Akritidis N, Mantzios G, Pappas G. Gallbladder adenomyomatosis presenting as fever of unknown origin: a case report. Hepatogastroenterology 2001; 48(37):112-
21. Indian Council for medical research (ICMR). Annual report of population based cancer registries of National Cancer Registry programme9 1996). New Delhi, ICMR publication, pg 18.
22. Pandey M, Pathak K, Gautam A et al. Carcinoma of the Gallbladder: A Retosepctive Review of 99 cases. Digestive Diseases and Sciences. 2001;46 (6): 1145-1151.
23. Esendagli G, Akarca FG, Balci S et al.A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods:A Multicentre Study Turk Patoloji Derg 2018; 34:41-48.