Gallbladder and Biliary Tract Pathology Study Guide

Gallbladder Pathology and Biliary Tract Pathology Video

Gallbladder and biliary tract pathology includes:

Biliary atresia
Gallstones
Biliary colic
Acute cholecystitis
Chronic cholecystitis
Ascending cholangitis
Gallstone ileus
Gallbladder carcinoma

Biliary Atresia

Biliary atresia is due to failure of biliary atresia to develop or early destruction of extrahepatic biliary tree.

Biliary atresia results in biliary obstruction within the initial three months of life.

Biliary atresia presents with jaundice.

Biliary atresia may progress to cirrhosis.

Operative view of complete extrahepatic biliary atresia. Biliary atresia. Chardot C - Orphanet journal of rare diseases (2006). Not Altered. CC.
Histological analyses of livers from biliary atresia patients and control. (a) HE and (b) Masson's trichrome staining. Forkhead box A3 attenuated the progression of fibrosis in a rat model of biliary atresia: Disease. Not altered. CC.

Gallstones

Gallstones are also called cholelithiasis.

The gallbladder contains solid, rounded stones because of precipitation of cholesterol (cholesterol stones) or bilirubin (bilirubin stones) in bile.

Gallstones may be due to:

Supersaturation of cholesterol or bilirubin
Reduced phospholipids (e.g. lecithin) or bile acids (usually enhance solubility)
Stasis

Cholesterol stones (yellow) are the most prevalent type (ninety percent), particularly in the West.

Gallstones are typically radiolucent (10 percent of gallstones are radiopaque because of associated calcium).

Risk factors for the development of gallstones include:

Higher weight
Female
Fertile
Age (40 years or older)
High levels of estrogen (women, obesity, many pregnancies, and oral contraceptives)
Clofibrate use
Native American ancestry
Crohn’s disease
Cirrhosis

Bilirubin makes up the pigmented bilirubin stones.

Bilirubin stones are normally radiopaque.

Risk factors specific to bilirubin stones include:

Extravascular hemolysis (increased bilirubin in bile)
Biliary tract infection (e.g. E. coli, Ascaris lumbricoides, and Clonorchis sinensis)

A common roundworm called Ascaris lumbricoides infects people worldwide, especially in places with poor sanitation (through fecal-oral transmission).

The biliary tract is infected by the endemic Clonorchis sinensis (Chinese liver fluke), which raises the risk of gallstones, cholangitis, and cholangiocarcinoma.

Gallstones are generally asymptomatic.

Complications of bilirubin stones include:

Biliary colic
Acute cholecystitis
Chronic cholecystitis
Ascending cholangitis
Gallstone ileus
Gallbladder cancer

Gallstones. Biliary sludge and gallstones. There is borderline thickening of the gallbladder wall. Mikael Häggström, M.D. Not altered. CC0
Gallstones. Gallstones as seen on plain X-ray James Heilman, MD - Not altered. CC BY-SA 3.0
Gallstones. Large gallstone as seen on CT James Heilman, MD - Not altered. CC BY-SA 4.0
Gallstones. The large, yellow stone is largely cholesterol, while the green-to-brown stones are mostly composed of bile pigments Emmanuelm Not altered. CC BY 3.0
Gallstones. Large gallstone. Haitham Alfalah - Not altered. CC BY 3.0
Gallstones. X-ray microtomograph of a gallstone. - Not altered. CC BY-SA 3.0
Chronic Cholecystitis. Abdominal ultrasonography showing gallstones, wall thickening and fluid around the gall bladder Mikael Häggström, M.D. Not altered. CC0
Gallstones. Numerous small gallstones made up largely of cholesterol George Chernilevsky, Not altered. CC BY-SA 4.0
Gross morphological features of patient gallstones employed in this study.A) Representative image of a group of gallstones retrieved from a single patient (GS 2) demonstrating consistent size and visual appearance. B) Cross section of gallstone (GS 1) and C) Cross section of gallstone (GS 4), revealing heterogeneous appearance throughout a single gallstone. D) The sectioning procedure was attempted on 4 patient gallstones of varying size and visual appearance. Gallstone sample GS 1 was selected for use in biofilm analysis experiments based on the success of the sectioning technique and having characteristics consistent with gallstones containing a high percentage of cholesterol. Visualization of extracellular matrix components within sectioned Salmonella biofilms on the surface of human gallstones. Marshall JM, Flechtner AD, La Perle KM, Gunn JS - PloS one (2014). Not Altered. CC.
Biliary Colic. A 1.9 cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis as seen on ultrasound. There is 4 mm gall bladder wall thickening. James Heilman, MD. Not altered. CC BY-SA 3.0

Biliary Colic

Biliary colic presents with right upper quadrant pain that comes and goes is brought on by the gallbladder contracting against a stone that is stuck in the cystic duct.

If the stone passes, the symptoms of biliary colic subside.

Acute pancreatitis or obstructive jaundice may be caused by common bile duct blockage.

Biliary Colic. A 1.9 cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis as seen on ultrasound. There is 4 mm gall bladder wall thickening. James Heilman, MD. Not altered. CC BY-SA 3.0

Acute Cholecystitis

Acute cholecystitis is inflammation of the gallbladder wall.

Acute cholecystitis may be due to an impacted stone in the cystic duct that causes inflammation, bacterial overgrowth (E. coli), and dilatation with pressure ischemia.

Symptoms of acute cholecystitis include:

Right upper quadrant pain that radiates to the right scapula
Fever
Leukopenia (low white blood cell count)
Nausea
Vomiting

Lab findings in acute cholecystitis show a high level of serum alkaline phosphatase (from duct injury).

If acute cholecystitis is not treated there is a chance for gall bladder rupture.

Acute Cholecystitis. Acute cholecystitis as seen on ultrasound. The closed arrow points to gallbladder wall thickening. Open arrow points to stones in the GB James Heilman, MD - Not altered. CC BY-SA 3.0
Acute Cholecystitis. Acute cholecystitis as seen on CT James Heilman, MD. Not altered. CC BY-SA 4.0
Acute Cholecystitis. Acute cholecystitis with gallbladder wall thickening, a large gallstone, and a large gallbladder James Heilman, MD. Not altered. CC BY-SA 4.0
Acute Cholecystitis. Gross examination of gallbladder cholesterolosis, with yellow streaks of cholesterol deposition. K C Geetika, Talwar OP. Not altered. CC BY 4.0
Acute Cholecystitis. Histopathology of eosinophilic cholecystitis K C Geetika, Talwar OP. Not altered. CC BY 4.0
Acute Cholecystitis. Histopathology of acute gangrenous cholecystitis, showing necrosis, neutrophils and partially sloughed off mucosa. Mikael Häggström, M.D. -Not altered. CC0
Acute Cholecystitis. Gross examination of gallbladder carcinoma, with a prominent nodule. K C Geetika, Talwar OP -Not altered. CC BY 4.0

Chronic Cholecystitis

Chronic cholecystitis is chronic inflammation of the gallbladder.

Chronic cholecystitis may be the result of long-term cholelithiasis-related chemical irritation, with or without concurrent episodes of acute cholecystitis.

Chronic cholecystitis is characterized by the gallbladder mucosa herniating into the skeletal wall (Rokitansky-Aschoff sinus).

Symptoms of chronic cholecystitis include:

Right upper quadrant ache, particularly after eating
Fatigue

Porcelain gallbladder is a complication of late stage chronic cholecystitis.

Porcelain gallbladder is a shrunken, hard gallbladder because of chronic inflammation, fibrosis, and dystrophic calcification.

Porcelain gallbladder findings vastly increases the risk for carcinoma of the gallbladder.

Cholecystectomy is the recommended course of action for chronic cholecystitis, especially if a porcelain gallbladder is present.

Chronic Cholecystitis. Abdominal ultrasonography showing gallstones, wall thickening and fluid around the gall bladder Mikael Häggström, M.D. Not altered. CC0
iNOS expression in gallbladder mucosa of chronic cholecystitis with H.pylori infection (A) and without H. pylori infection (B) (×100). A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. Zhou D, Guan WB, Wang JD, Zhang Y, Gong W, Quan ZW - PloS one (2013). Not Altered. CC.

Ascending Cholangitis

Ascending cholangitis is a bacterial infection of the bile ducts.

Ascending cholangitis is typically brought on by an escalating gram-negative intestinal infection.

Symptoms of ascending cholangitis include:

Stomach discomfort
Jaundice
Sepsis

There is a higher prevalence of choledocholithiasis (stone in biliary ducts) in ascending cholangitis.

Ascending Cholangitis. Cholangiogram through a nasobiliary drain showing the common bile duct in black (diagonally from top left to bottom right in the center) with an interruption in the contour due to a large gallstone. Samir. Not altered. CC BY-SA 3.0
Ascending Cholangitis. Duodenoscopy image of ampulla of Vater with pus extruding from it, indicative of cholangitis. Released into public domain on consent of patient -- Samir. Not altered. CC BY SA 3.0

Gallstone Ileus

Gallstone ileus occurs when the small bowel is obstructed by a gallstone.

A predisposition to gallstone ileus may occur because of fistula formation between the small bowel and gallbladder as a result of cholecystitis.

Gallstone ileus. Prashanth Saddala. Not altered. CC.
Gallstone ileus. Prashanth Saddala. Not altered. CC.
Gallstone ileus. Prashanth Saddala. Not altered. CC.

Gallbladder Carcinoma

Gallbladder carcinoma is a malignant lesion of the gallbladder.

The glandular epithelium that lines the gallbladder wall is where gallbladder carcinoma develops.

Risk factors for gallbladder carcinoma include:

Gallstones
Acute cholecystitis
Chronic cholecystitis
Porcelain gallbladder

An older woman with cholecystitis is the classic type of individual susceptible to gallbladder carcinoma.

Gallbladder carcinoma has a poor prognosis.

Gallbladder Carcinoma. Gallbladder adenocarcinoma histopathology KGH. Not altered. CC BY-SA 3.0
Gallbladder Carcinoma. Incidentally discovered gallbladder cancer (adenocarcinoma) following a cholecystectomy. Not altered. CC BY-SA 3.0
Gallbladder Carcinoma. Gallbladder adenocarcinoma lymphatic invasion histopathology . Not altered. CC BY-SA 3.0
Immunohistochemical analysis of expression of P-gp and GST-π in GBC tissues. (A) Negative expression of P-gp; (B) Positive expression of P-gp was observed in gallbladder carcinoma. The majority of positive cells were located on the surface of the mucosa; C) Negative expression of GST-π in gallbladder carcinoma; (D) Positive expression of GST-π in gallbladder carcinoma (magnification, ×20). Arrows denote positive cells. P-gp, P-glycoprotein; GST-π, glutathione S-transferase π; GBC, gallbladder carcinoma. Clinical significance of P-glycoprotein and glutathione S-transferase π expression in gallbladder carcinoma. Ma QJ, Zhang YC, Shi JS, Li GC - Experimental and therapeutic medicine (2014). Not Altered. CC.
Expression of MK1 and RegIV in the benign and malignant lesions of gallbladder. EnVision immunohistochemistry, original magnification x200. MK1 and RegIV positive reaction was mainly localized in the cell membrance and/or cytoplasm. A, MK1 positive expression in peri-tumor tissue with moderate atypical hyperplasia. B, MK1 positive expression in highly differentiated gall bladder adenocarcinoma. C, RegIV positive expression in polyp with severe atypical hyperplasia. D, RegIV positive expression in moderately differentiated gall bladder adenocarcinoma. Expression of MK-1 and RegIV and its clinicopathological significances in the benign and malignant lesions of gallbladder. Yang L, Lan S, Liu J, Yang Z - Diagnostic pathology (2011). Not Altered. CC.
CD109 expression is restricted in squamous cell/adenosquamous carcinomas of the gallbladder. Immunohistochemistry of CD109 on normal gallbladder tissue, adenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma of the gallbladder. Arrows refer to CD109 positive cells. Magnification: 200X. CD109 is a novel marker for squamous cell/adenosquamous carcinomas of the gallbladder. Dong F, Lu C, Chen X, Guo Y, Liu J - Diagnostic pathology (2015). Not Altered. CC.
Histopathologically demonstrated the primary gallbladder adenosquamous carcinoma and splenic tumor.Representative histological images of (A) the primary gallbladder adenosquamous carcinoma and (B) the splenic metastasis (hematoxylin–eosin stain, ×40). Both had features consistent with adenosquamous carcinoma. Surgical resection of splenic metastasis from the adenosquamous gallbladder carcinoma: A case report. Utsumi M, Aoki H, Kunitomo T, Mushiake Y, Kanaya N, Yasuhara I, Arata T, Katsuda K, Tanakaya K, Takeuchi H - International journal of surgery case reports (2016). Not Altered. CC.
Patient case MRI and FNA of liver lesion. (a) MRI of the abdomen showed a bulky gallbladder tumor measuring 5.6 cm with direct extension into the liver, innumerable hepatic and periportal nodal metastases which exerted mass effect on the cystic duct, and peripancreatic and right diaphragmatic nodal involvement. (b) Ultrasound-guided biopsy of a metastatic liver lesion shows small and fragile epithelioid cells with little cytoplasm and fine chromatin. Abundant apoptotic bodies and mitotic figures were seen consistent with small cell carcinoma. Small Cell Carcinoma of the Gallbladder: Case Report and Comprehensive Analysis of Published Cases. Carrera C, Kunk P, Rahma O - Journal of oncology (2015). Not Altered. CC.