Hyperplastic Cholecystoses

Published on 09/08/2015 by admin

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 Adenomyomatosis: Mural GB wall thickening due to formation of intramural diverticula (Rokitansky-Aschoff sinuses) with smooth muscle and epithelial proliferation

image Cholesterolosis: Deposition of foamy, cholesterol-laden histiocytes in subepithelium of GB

IMAGING

• Adenomyomatosis

image US: Focal, segmental, or diffuse wall thickening with anechoic intramural spaces, intramural echogenic foci ± acoustic shadowing, “comet tail” artifacts, & twinkle artifact
image MR: High-signal cystic spaces (with curvilinear arrangement) on T2WI/MRCP within focally or diffusely thickened GB wall (string of beads or pearl necklace sign)
image CT: Segmental/diffuse GB wall thickening (may present as fundal enhancing soft tissue nodule)

– Cystic nonenhancing spaces within thickened GB wall
• Cholesterolosis

image US: Multiple small (< 10 mm) nonshadowing iso-/hyperechoic polyps with “comet tail” & twinkle artifact
image MR: Small, round polyps with intermediate T1/T2 signal
image CT: Usually imperceptible

CLINICAL ISSUES

• Virtually always asymptomatic, but may very rarely present with RUQ pain
• Almost always an incidental finding with no significance

image Must be correctly differentiated from malignancy based on imaging appearance
image Adenomyomatosis may rarely require cholecystectomy if symptomatic or if imaging findings are equivocal and there is concern for GB carcinoma
image Cholesterol polyps may be resected when large or when growth is documented
image
(Left) Schematic drawing of adenomyomatosis illustrates a thickened gallbladder (GB) wall with multiple intramural cystic spaces image.

image
(Right) Ultrasound of an elderly woman with right upper quadrant pain shows tiny echogenic foci image within the anterior wall of the GB and posterior “comet tail” artifacts image. This appearance is likely caused by reverberation of the ultrasound pulse within cholesterol crystals in the GB subepithelium.
image
(Left) Ultrasound image demonstrates diffuse thickening of the GB wall with numerous foci of “comet tail” artifact image, classic for adenomyomatosis. Note the presence of a gallstone image, found in 90% of cases.

image
(Right) Color Doppler ultrasound demonstrates “twinkle” artifact image associated with the echogenic reflectors within the thickened GB wall. “Comet tail” and twinkle artifacts are due to reverberation within cholesterol deposited within epithelial penetrations (Rokitansky-Aschoff sinuses).

TERMINOLOGY

Synonyms

• Cholesterolosis: Strawberry gallbladder (GB), cholesterol polyp
• Adenomyomatosis: GB diverticulosis, cholecystitis glandularis proliferans, adenomyomatous hyperplasia

Definitions

• Idiopathic, nonneoplastic, and noninflammatory proliferative disorder that results in GB wall thickening

image Subclassified into 2 entities
image Adenomyomatosis

– Mural GB wall thickening due to exaggeration of normal luminal epithelial folds and formation of intramural diverticula (Rokitansky-Aschoff sinuses) in conjunction with smooth muscle and GB epithelial proliferation
image Cholesterolosis

– Deposition of foamy, cholesterol-laden histiocytes in subepithelium of GB
– Numerous small accumulations (strawberry GB) or larger polypoid deposit (cholesterol polyp)

IMAGING

General Features

• Best diagnostic clue

image Adenomyomatosis

– Focal (typically fundal) or diffuse GB wall thickening with intramural cystic spaces containing echogenic foci and “comet tail” artifacts
image Cholesterolosis

– Echogenic GB polyps with associated “comet tail” artifact
• Location

image Cholesterolosis: Superficial GB wall (epithelium)
image Adenomyomatosis: Deep GB wall (muscular layer)

– Fundal (most common), segmental mid-body (“hourglass” configuration of GB), or diffuse
• Size

image Cholesterol polyps typically 5-10 mm

CT Findings

• Adenomyomatosis

image Segmental or diffuse GB wall thickening

– May present as fundal enhancing soft tissue nodule
image Cystic nonenhancing spaces (Rokitansky-Aschoff sinuses) within thickened GB wall (usually within fundal mass)

– Cystic spaces most important feature to differentiate adenomyomatosis from GB carcinoma
– Ancillary findings favoring adenomyomatosis: Smooth borders without evidence of biliary ductal dilatation, hepatic invasion, or regional adenopathy
image Often brisk wall enhancement post contrast
• Cholesterolosis: Subepithelial cholesterol and small cholesterol polyps usually imperceptible on CT

MR Findings

• Cholesterolosis

image Small, round, intraluminal polyps juxtaposed against low T1WI signal and high T2WI signal bile

– Nodules are homogeneous and of intermediate signal intensity on both T1WI and T2WI
– Nodules are directly attached to GB wall
• Adenomyomatosis

image T1-hypointense foci within thickened GB wall corresponding to bile-filled intramural diverticula

– Occasionally T1-hyperintense due to inspissated bile/debris within Rokitansky-Aschoff sinuses
image T2WI/MRCP high signal cystic spaces (with a curvilinear arrangement) within focally or diffusely thickened GB wall (string of beads or pearl necklace sign)
image Cystic spaces show no enhancement on T1WI C+ images
image Diffusion weighted imaging (DWI) not a reliable means of distinguishing cancer from adenomyomatosis
• MR is highly accurate (> 90%) in differentiation of adenomyomatosis from GB carcinoma

Ultrasonographic Findings

• Grayscale ultrasound

image Adenomyomatosis

– Focal, segmental, or diffuse wall thickening

image Focal or localized form the most common, usually affecting GB fundus
image Segmental form causes annular thickening of GB wall, resulting in strictures: Annular thickening in GB mid body results in “hourglass” appearance
image Diffuse form results in wall thickening of entire GB
– Anechoic intramural spaces (Rokitansky-Aschoff sinuses) within thickened portions of GB wall
– Intramural echogenic foci ± acoustic shadowing or reverberation (“comet tail”) artifacts

image Echogenic foci correspond to small intramural diverticula containing sludge, stones, cholesterol, or papillary projections
image Leads to “diamond ring” appearance (echogenic foci surrounded by anechoic cystic spaces)
– US has sensitivity of 80% and specificity of 86% for diagnosis of adenomyomatosis
image Cholesterolosis

– Multiple small (< 10 mm) nonshadowing iso- to hyperechoic nonmobile polyps
– “Comet tail” artifact posterior to echogenic foci (cholesterol) within GB wall
– No associated posterior acoustic shadowing
– Background GB wall is usually normal thickness
• Color Doppler

image Adenomyomatosis

– Twinkle artifact posterior to echogenic foci within intramural diverticula

image Rapidly fluctuating mixture of Doppler signals (red and blue pixel) caused by strongly reflecting granular interface and narrow band of intrinsic US machine noise
image May imitate turbulent flow but corresponding flat Doppler spectrum confirms noise
image Twinkle artifacts usually more prominent at low color Doppler frequencies
– Unlike malignancy, no color Doppler vascularity within regions of wall thickening
image Cholesterolosis

– Twinkle artifact caused by focal cholesterol deposits within GB wall

Radiographic Findings

• Oral cholecystogram

image Adenomyomatosis: “Pearl necklace” GB with multiple contrast-filled intramural diverticula

Imaging Recommendations

• Best imaging tool

image Adenomyomatosis: Ultrasound, MR/MRCP

– High-resolution, high-frequency transducer helpful for optimal visualization of GB fundus (most common location for adenomyomatosis)
image Cholesterolosis: Ultrasound

DIFFERENTIAL DIAGNOSIS

Chronic Cholecystitis

• Small contracted GB with generalized wall thickening and gallstones, but no mural “comet tail” artifact

Gallbladder Carcinoma

• Most frequently presents as polypoid mass > 2 cm or irregular, asymmetric GB wall thickening
• Frequently associated with regional adenopathy, biliary ductal obstruction, and hepatic invasion
• Usually internal Doppler color flow vascularity
• No intramural cystic spaces or “comet tail”/twinkle artifacts
• Segmental or focal forms of adenomyomatosis may be difficult to distinguish from GB cancer
• High association with cholelithiasis

Xanthogranulomatous Cholecystitis

• Inflammatory process with accumulation of lipid-laden macrophages and inflammatory cells within GB wall
• Results from rupture of Rokitansky-Aschoff sinuses and extravasation of bile into GB wall → xanthoma formation
• Gallstones present in all cases
• GB wall thickening with intramural hypodense nodules/bands and pericholecystic inflammation/fluid

Adenomatous Polyp

• Benign solitary polyp most often measuring 5-15 mm

image Risk of malignancy relates to polyp size
• No “comet tail” or twinkle artifact

Phrygian Cap

• Normal variant with folding of GB fundus, which might mimic focal fundal adenomyomatosis with cystic spaces

PATHOLOGY

General Features

• Etiology

image Idiopathic and acquired, but exact etiology not understood

– Adenomyomatosis postulated to be related to chronic mechanical obstruction of GB or chronic GB inflammation
– Cholesterolosis postulated to be related to altered hepatic cholesterol synthesis or abnormal cholesterol transport out of mucosa
• Associated abnormalities

image Gallstones in up to 90% of cases of adenomyomatosis and 50% of cases of cholesterolosis

– Highest association with segmental form of adenomyomatosis
image Coexistence of GB carcinoma with adenomyomatosis (especially segmental form) questioned, but now generally not considered to be premalignant

Gross Pathologic & Surgical Features

• Focal/diffuse GB wall thickening without inflammatory changes
• Adenomyomatosis: Herniation of bile-containing cystic spaces (Rokitansky-Aschoff sinuses) into GB muscularis propria
• Cholesterolosis: Yellow deposits in GB (“strawberry” GB)

Microscopic Features

• Adenomyomatosis

image Mural thickening secondary to overgrowth of mucosa and smooth muscle proliferation
image Exaggerated Rokitansky-Aschoff sinuses (intramural diverticula)
image Does not involve adenomatous changes
• Cholesterolosis

image Abnormal deposit of triglycerides, cholesterol, and cholesterol esters in mucosa
image Villus-like mucosal protrusions; may coalesce into polyps

– Nodular form: 2/3 of cases, nodules < 1 mm, “strawberry” GB
– Polypoid form: 1/3 of cases, solitary or multiple

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Virtually always asymptomatic, but may very rarely present with RUQ pain

Demographics

• Gender

image Adenomyomatosis more common in females (F:M = 3:1)
image No gender predilection in cholesterolosis
• Epidemiology

image Adenomyomatosis identified in 2-9% of resected GBs
image Cholesterolosis prevalence of 9-26% in cholecystectomy specimens

– Cholesterol polyps account for 60-90% of all GB polyps

Natural History & Prognosis

• Usually incidental finding of no clinical importance
• Must be correctly differentiated from malignancy based on imaging appearance

Treatment

• Adenomyomatosis: No treatment in asymptomatic patients where diagnosis is certain

image Cholecystectomy if symptomatic or if imaging findings are equivocal and there is concern for GB carcinoma
• Cholesterol polyps: Although benign, nonspecific appearance often prompts intervention; may be resected when large or when growth documented

image Management strategies (surveillance and size threshold for resection) are controversial
• Management of GB polyps

image Most useful predictor of risk of malignancy is size

– > 18-20 mm: Almost always malignant → CT or EUS for preoperative staging → open cholecystectomy
– 10-20 mm: Risk of malignancy 43-77% → open or laparoscopic cholecystectomy
– 5-10 mm: Very low risk of malignancy → follow-up imaging in 3, 6, 12 months & yearly afterward to prove stability (no consensus on frequency of imaging)
– < 5 mm: Extremely low risk of malignancy → possibly follow-up imaging in 6 & 12 months (no consensus)
image Cholecystectomy is recommended when GB polyp associated with cholelithiasis, primary sclerosing cholangitis (PSC), or when patient is symptomatic (regardless of size of polyp)

DIAGNOSTIC CHECKLIST

Consider

• Differentiate focal or segmental forms of adenomyomatosis from GB malignancy

Image Interpretation Pearls

• Look for “comet tail” reverberation artifacts on US within thickened GB wall
image
(Left) Ultrasound of a patient with vague abdominal pain shows annular wall thickening image of the mid body of the GB. Note the presence of intramural diverticula and echogenic foci image in this pathologically confirmed example of segmental adenomyomatosis.

image
(Right) MRCP in the same patient shows an “hourglass” deformity image of the GB and several adjacent intramural diverticula image. Common bile duct dilatation image and clinical suspicion of intermittent choledocholithiasis prompted cholecystectomy.
image
(Left) Ultrasound of an elderly woman shows an incidental, partially cystic mass arising from the GB fundus image. Echogenic foci within the lesion are associated with “comet tail” artifact, characteristic of adenomyomatosis.

image
(Right) Ultrasound shows “comet tail” artifact image and several minute, echogenic GB polyps image. Pathology showed cholesterolosis and hyperplastic (cholesterol) polyps.
image
(Left) Axial CECT demonstrates tiny internal cystic spaces image within a thickened portion of the GB fundus.

image
(Right) Coronal MIP MRCP in the same patient demonstrates multiple cystic spaces image in the GB fundus corresponding to the findings on CT. Both the CT and MR appearance is classic for adenomyomatosis, a benign finding that does not require follow-up or treatment.
image
Transverse sonogram of a patient with adenomyomatosis shows a thickened gallbladder wall image and multiple echogenic foci with “comet tail” reverberation artifacts image.

image
Axial CECT demonstrates thickening of the GB fundus image with multiple tiny cystic spaces, characteristic of adenomyomatosis.
image
Axial CECT demonstrates a curvilinear arrangement of tiny cystic spaces around the margins of the thickening GB fundus image, the so-called pearl necklace sign, characteristic of adenomyomatosis.
image
Coronal MIP MRCP image demonstrates a cluster of T2 hyperintense cysts image at the GB fundus, a classic appearance for focal fundal adenomyomatosis.
image
This axial CECT is of an 86-year-old man with confirmed fundal adenomyomatosis image. The cystic regions within the mass are thought to represent dilated Rokitansky-Aschoff sinuses.
image
Axial CECT of a 50-year-old woman with diffuse adenomyomatosis shows cystic spaces within a markedly thickened GB wall image. Although the features are characteristic of adenomyomatosis, a cholecystectomy was performed due to suggestion of hepatic invasion at CT image.
image
Axial T2WI MR was performed in a 44-year-old woman who underwent evaluation for a suspected hemangioma of the liver, but had no clinical symptoms of gallbladder disease. Note the segmental focal thickening of the gallbladder fundus image, consistent with fundal adenomyomatosis.
image
ERCP demonstrates focal narrowing (“hourglass” deformity) image, multiple intramural diverticula image, and gallstones image.
image
Ultrasound of a 51-year-old man with vague right upper quadrant pain shows multiple echogenic foci image and subtle “comet tail” artifacts within a cystic-appearing GB fundal mass image. Fundal adenomyomatosis may be mistaken at ultrasound for adjacent duodenum.
image
MRCP of the same patient shows a fundal mass containing high-signal foci image within dilated Rokitansky-Aschoff sinuses. This MR “string of pearls” sign is characteristic of fundal adenomyomatosis.

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