HISTOPATHOLOGICAL SPECTRUM OF GALL BLADDER LESIONS IN A TERTIARY CARE HOSPITAL IN THE - PowerPoint Presentation

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HISTOPATHOLOGICAL SPECTRUM OF GALL BLADDER LESIONS IN A TERTIARY CARE HOSPITAL IN THE MALWA BELT: A HOSPITAL BASED STUDY

DR. NIDHI BANSAL, MD PATHOLOGY,

DR. ARNAV KR. ROYCHOUDHURY, MD PATHOLOGY

ASSISTANT PROF., DEPT. OF PATHOLOGY

ADESH INSTITUTE OF MEDICAL SCIENCES &

RESEARCH, BATHINDA, PUNJAB

INDIA

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INTRODUCTION

The

gall bladder is one of the most frequently resected organs in the gastrointestinal tract with a varied spectrum of diseases affecting it ranging from both inflammatory and non-inflammatory lesions to invasive as well as non-invasive neoplastic lesions

.

Cholelithiasis is one of the most common disorder affecting 10-20% of adult populations in developed countries1. In India cholelithiasis is more prevalent in north as compared to south affecting 10-20% of the population 1,2.

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Non

neoplastic lesions includes acute on chronic cholecystitis, chronic calculous cholecystitis, gangrenous cholecystitis, eosinophilic cholecystitis, xanthogranulomatous cholecystitis, cholesterol polyp,

cholesterolosis

, empyema, choledochal cyst, metaplasia and focal mucosal hyperplasia.

Neoplastic conditions includes inflammatory pseudotumor, adenocarcinoma and neuroendocrine carcinoma

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Cholecystitis associated with cholelithiasis is a common disease particularly found in fertile and fatty females in their forties, however it can also affect males and children. This condition has increased in the past two decades due to increase intake of unhealthy fat rich food, lack of exercise, obesity and sedentary

lifestyle.

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MATERIALS & METHODS

The study was conducted at Department of Pathology at Adesh Institute of Medical Sciences, Bathinda for a period of 6 months from April 2017 to October 2017.

Histopathology reports were analyzed for different histopathological lesions in relation to age and gender. Data regarding age, gender, pre-cholecystectomy ultrasound or CT findings for any suspicion of carcinoma or mass gall bladder was obtained from the request forms of the patients while subsequent histopathology results of the gall bladder specimens were retrieved from computer of the concerned histopathology section. The data was entered into and analyzed by Microsoft Excel software.

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REVIEW OF LITERATURE

Literature is filled with evidence to support a more selective policy towards histopathological examination. Multiple series have confirmed the safety, efficacy and rationality of sending macroscopically abnormal specimens for histopathology while not missing a single case of invasive adenocarcinoma of

gallbladder.

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Darmaset

al reported incidental gallbladder carcinoma in 0.3 % i.e. in only four of 1452 patients for whom cholecystectomy specimens were examined over a period of 5 years, all four of whom demonstrated mass on gross examination of the cholecystectomy specimen and two of those showed pre-operative suspicions of malignancy

.

Bazouaet

al analyzed 2890 cholecystectomy specimens which showed malignancy in 10 cases, all of which had demonstrated thick-walled gallbladders on gross examination and in two of which suspicious mass had been

apparent.

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An Indian study showed 610 (46.5%) cholecystectomy specimens showing macroscopic abnormalities in the form of thickening, mucosal ulcerations or polypoidal lesions. Malignancy was found in 13 of these 610 cholecystectomy specimens with macroscopic abnormalities. None of the cholecystectomy specimens without macroscopic abnormalities were found to have gallbladder

carcinoma.

In a prospective comparative study by Romero-González et al it was concluded that it was safe not to send almost half (46%) of cases for histopathology by considering pre-operative, intra-operative and post-operative evidence pointing towards malignancy

.

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Primary GB carcinoids are extremely rare. The first case of a carcinoid tumor of the GB was reported in 1929, and 43 cases of carcinoid tumors have been

repord

till date. Approximately half of the reported cases of GB carcinoid tumors appear to be endocrine cell

carcinomas.

At present, 278 cases of GB NETs are reported in the Surveillance, Epidemiology, and End Results (SEER) database. Only five well-differentiated NETs are registered in SEER, indicating that the entity of “benign” NET is very rare in the

GB.

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Neuroendocrine cells derive from local multipotent gastrointestinal stem cells rather than, as initially guessed, by migration by the neural crest. GB NETs may develop from endocrine cells induced by intestinal metaplasia of the body and fundus as well as from preexisting endocrine cells in the neck of the

GB.

The age at presentation of GB NETs ranges from 38 to 81 years, and there is a markedly higher incidence in

women.

Carcinoid syndrome is very rare (<1%),and most GB carcinoids are diagnosed incidentally during a histological examination of GB specimens at autopsy, after cholecystectomy for acute or chronic cholecystitis, or after surgery for another suspected

biliary

pathology.

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EPIDEMIOLOGY & RISK FACTORS

The pathogenesis of gallbladder cancer is likely multifactorial, with no single causative factor being identified.

Risk factors for gallbladder cancer can be divided into four broad categories as annotated in the following list including-

Patient demographics

Gallbladder

abnormalities

(3) Patient exposures

(4)

Infections

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PATHOGENESIS

GB epithelium progresses from dysplasia to carcinoma in situ to invasive carcinoma

• Area of dysplasia and carcinoma in situ is often missed in routine cholecystectomy specimens as there are no associated gross characteristics that would target an area for histological sections.

• Carcinoma in situ may appear within the Rokitansky

aschoff

sinuses and often mistaken for invasive carcinoma

Rate of progression of precursor lesions to invasive carcinoma

has estimated around 15 years

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Risk factors for the development of gallbladder cancer are listed as follows:

(1) Demographic factors

:

Advanced age (b) Female gender (c) Obesity

(d) Geography: South American, Indian, Pakistani, Japanese, and Korean

(e) Ethnicity: Caucasians, Southwestern Native American, Mexican, and American

(f) Genetic predisposition

(

2) Gallbladder pathologies/abnormalities:

(a) Cholelithiasis (b) Porcelain gallbladder (c) Gallbladder polyps

(d) Congenital biliary cysts (e) Pancreaticobiliary anomalies

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(3)

Exposures

:

(a) Heavy metals

(b) Medications: methyldopa, OCP, isoniazid, and estrogen

(c) Smoking

(4)

Infections

:

(a) Salmonella

(b) Helicobacter

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Demographic Factors

A striking geographical variability is observed in the prevalence of gallbladder carcinoma worldwide.

Regions reporting a high incidence of gallbladder cancer include Delhi, India (21.5/100,000), La Paz, Bolivia (15.5/100,000), South Karachi, Pakistan (13.8/100,000), and Quito, Ecuador (12.9/100,000) [1]. High rates are reported in Chile (27/100,000), Poland (14/100,000).

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Northern India, Korea, Japan, and central/eastern Europe including Slovakia, Czech Republic, and Slovenia have also reported a higher prevalence than the worldwide

average.

By contrast, gallbladder cancer is rare in the western world (USA, UK, Canada, Australia, and New Zealand) with incidence rates of 0.4–0.8 in men and 0.6–1.4 in women per

100,000.

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International Comparison of AAR with that of PBCRs in India GALL BLADDER (ICD-10: C23-C24)(Courtesy: Three-Year Report of the PBCRs: 2012-2014)

Males

Bio

Bio

Province in Chile had the highest AAR (11.3) internationally.

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International Comparison of AAR with that of PBCRs in India GALL BLADDER (ICD-10: C23-C24)(Courtesy: Three-Year Report of the PBCRs: 2012-2014)

Females

Valdivia in Chile had the highest AAR (25.1) internationally

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RESULTS & OBSERVATIONS

A total of 141 patients who had undergone cholecystectomy during the above mentioned six months were taken into the study.

Among these patients, majority (75.8%) were female and only 24.1% were male.

The age of the patients ranged from 20 to 85 years. Non-neoplastic lesions (93.6%) constitute the majority of the cholecystectomy specimens followed by few cases of neoplastic lesions (6.38%).

Benign tumors contributed 22.2%, whereas Malignant tumors comprised of 77.7% of all the neoplastic lesions.

Among all the cholecystectomy specimens the carcinoma gall bladder contributed 4.96% of all cases. Details of the histopathological findings with number of cases are shown in Table 1.

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Histopathological observations from all the submitted cholecystectomy specimens showed

Cholecystitis

as the most common benign non-neoplastic lesion comprising of 83 cases (58.8%) with

Chronic Calculous Cholecystitis

being the major contributor, 70 cases ( 49.64%) followed by 7 cases (4.96%) of acalculous cholecystitis, 3 cases (2.12%) of granulomatous cholecystitis and 1 case (0.71%) each of acute-on-chronic cholecystitis, eosinophilic cholecystitis and xanthogranulomatous cholecystitis.

Cholesterolosis

presented as the 2nd most common benign lesion comprising of

32 cases (22.69%) of all cholecystectomy specimens. Hyperplasia constituted 6

cases (4.25%) followed by 5 cases (3.54%) of metaplasia.

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Fig. 1.

Chronic calculous cholecystitis

showing cuboidal to columnar lining epithelium with Rokitansky

aschoff

sinuses and chronic inflammatory infiltrate infiltrating into the serosa.

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LESION

NO. OF CASES

PERCENTAGES

Acute on chronic cholecystitis

1

0.71%

Chronic calculous cholecystitis

70

49.64%

Chronic acalculous cholecystitis

7

4.96%

Gangrenous cholecystitis

3

2.12%

Eosinophilic cholecystitis

1

0.71%

Xanthogranulomatous cholecystitis

1

0.71%

Cholesterolosis

32

22.69%

Empyema

1

0.71%

Cholesterol polyps

3

2.12%

Choledochal cyst

1

0.71%

Mucosal hyperplasia

6

4.25%

Metaplasia

5

3.54%

Inflammatory pseudotumor

2

1.41%

Adenocarcinoma gall bladder

5

3.54%

Neuroendocrine carcinoma

2

1.41%

 TOTAL

 141

 100% 

Table

1: Details of the histopathological findings with number of cases

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A

B

B

Fig. 2.

Cholesterolosis

showing collection of foamy macrophages in the lamina propria (H & E 4x, 40x)

B

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Fig. 3. Showing

Intestinal metaplasia

in gall bladder lining epithelium. ( H&E 10x)

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A

B

Fig. 4. Showing

Eosinophilic Cholecystitis

(H & E 4x, 40x)

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Fig.5. Showing

Xanthogranulomatous Cholecystitis

(H&E 10x)

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Fig.6.

Choledochal

cyst

showing lining epithelium. Sub-epithelium shows presence of mixed inflammatory infiltrate along with

cuboidal

lined glands. ( H&E,10x, 40x)

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Fig.7(a).

Inflammatory Pseudotumor

showing benign looking spindle cells admixed with

fibro-

collagenous

tissue and lymphocytes (H&E 10x)

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Fig.7 (b).

Inflammatory

Pseudotumour

showing

myofibroblastic

cells admixed with

lymphocytes

(H&E 40X)

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Fig. 8.

Adenocarcinoma Gall Bladder

Showing malignant glands infiltrating into the wall ( H&E 10x)

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Fig.9.

Adenocarcinoma

Showing malignant cells with vesicular nuclei and prominent nucleoli. Few mitotic figures are also seen (H&E 40x)

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Fig.10.

Neuroendocrine carcinoma

Showing organoid pattern (H&E 10x)

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Fig.

11.

Neuroendocrine tumor

showing tumor cells with vesicular nucleus having salt n pepper chromatin (H&E 40x)

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Incidence of gall bladder premalignant and malignant lesions have been shown in table 2.

Age wise distribution of gall bladder histopathological lesions with special reference to pre-malignant (hyperplasia, metaplasia) and malignant lesions are being shown in table 3.

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LESION

MALE

FEMALE

BENIGN TUMOR

2(40%)

3(60%)

PREMALIGNANT

6(54.54%)

5(45.45%)

MALIGNANT

3(42.85%)

4(57.1%)

Table 2: Incidence of gall bladder premalignant and malignant lesions

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AGE GROUPS (YEARS)

HYPERPLASIA

METAPLASIA

INFLAMMATORY PSEUDOTUMOR

ADENOCARCINOMA

NEURO

ENDOCRINE CARCINOMA

OVERALL

20-29

1(16.7%)

-

-

1(20%)

-

2(10%)

30-39

3(50%)

-

-

1(20%)

-

4(20%)

40-49

-

3(60%)

-

-

-

3(15%)

50-59

-

2(40%)

1(50%)

-

1(50%)

4(20%)

60-69

2(33.3%)

-

1(50%)

2(40%)

1(50%)

6(30%)

70-79

-

-

-

1(20%)

-

1(5%)

80-89

-

-

-

-

-

0(0%)

TOTAL

6(100%)

5(100%)

2(100%)

5(100%)

2(100%)

20(100%)

Table 3: Age wise distribution of gall bladder histopathological lesions with special reference to pre-malignant (hyperplasia, metaplasia) and malignant lesions

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DISCUSSION

Gallbladder disease is the most common surgical disorder that requires elective surgery, either open or laparoscopic cholecystectomy. The specimens are received in each histopathology laboratory, where they are evaluated for various pathological lesions. The estimated prevalence of the disease in India is reported to be between 2% and 29%

.

The present study was conducted on 141 cholecystectomy specimens to determine the histopathological spectrum of gallbladder disease. Histopathology is the gold standard for diagnosis and planning of future treatment regimens.

In our present study, the age of the patients ranged from 20 to 85 years. Maximum number of patients was in the fourth decade of their life. Male to female ratio was 1:3.1 in the present study which was in concordance with the studies conducted by Mohan et

al

and Siddique et

al.

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The high incidence of gall bladder disease in females are because of the sedentary life styles and female sex hormones which expose the females to the formation of

gallstones.

Chronic cholecystitis was the most common diagnostic entity comprising of 115 (81.5%) cases which included various histopathological spectrum like Chronic calculous cholecystitis, chronic acalculous cholecystitis,

cholesterolosis

, gangrenous cholecystitis, eosinophilic cholecystitis and xanthogranulomatous cholecystitis.

The findings of our study was in concordance to the studies conducted by Siddiqui et al

and

Thamil

Selvi

et al

and who also reported chronic cholecystitis as the most common histopathological finding in their study as well.

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Xanthogranulomatous cholecystitis is a rare form of chronic cholecystitis which mimics gallbladder cancer although it is not cancerous. It was first discovered and reported in the medical literature in 1976 by J.J. McCoy, Jr., and

colleagues.

Our study showed gangrenous cholecystitis in 3 (2.12%) cases which was similar to the findings of the study conducted by Nidimusili et

al

and

Kayyali

et

al.

Gangrenous cholecystitis is the end result of gall bladder inflammation that starts from vascular compromise and progresses to ischemia, necrosis and ultimately perforation of the gall bladder wall. Diabetes mellitus, associated cardiovascular diseases, and advanced age are some of the key factors that causes increase in the probability of gangrenous

cholecystitis

.

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CONCLUSIONIn present study we have studied total 141 cases of gall bladder lesion during the period of six months in

Adesh

Institute of Medical Sciences & Research,

Bathinda

.

Out of 141 cases non neoplastic lesions account for 93.6% (132 cases), while 9 cases of neoplastic lesions

accponted

for 4.96% of all the gall bladder lesions .

Out of 141 cases most common lesion is chronic

calculous

cholecystitis

accounting for 49.64% (70 cases).

Female were predominantly affected in present study with 75.8% cases.

Most of the non neoplastic lesions of the gall bladder lesions were common in 3rd, 4th and 5th decades of life.

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Neoplastic lesions of the gall bladder are common in 5th,6th and 7th decades of life. Benign tumors contributed 22.2% whereas malignant tumors contributed 77.7% of all the neoplastic lesions Adenocarcinoma of gall bladder occurs after 5th decade of life contributing to 5 cases (3.54%)

To conclude it is evident that g

all bladder lesions were common indication for surgical intervention and pathological evaluation. Most of them were inflammatory lesions with

cholelithiasis

, however thorough examination is important as these lesions may progress to fatal malignancies.

The

histopathological

study of gall bladder is the most convenient method for diagnosis of various lesions of gall bladder especially neoplastic condition like adenoma and adenocarcinoma, their staging, and proper management of the various conditions.

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REFERENCES

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Mhamunkar

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THANK YOU धन्यवाद

GRAZIE