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Gallbladder adenoma with focal adenocarcinoma
S. Ciurea, E. Matei, P. Petrisor, L. Luca, Mirela Boros, V. Herlea, I. Popescu (Chirurgia, 103 (3): 359-362)
Polypoid lesions of the gallbladder (PLGs) are discovered in 5% of all patients submitted to an abdominal ultrasound (US) (1). The majority are cholesterol "polyps" (pseudo-polyps). Rarely, these lesions are benign or malignant neoplasms (2-5).
Case presentation
A 52-year old patient was referred to our center on 22.02.2008 from the Center of Internal Medicine and Nephrology - Fundeni, where he was treated for bilateral polycystic kidney disease (adult form) and obesity. His past surgical history was remarkable for multiple extraperitoneal nephrolithotomies for recurrent renal lithiasis (in 1997, 1998 and 2000) and left inguinal hernia repair in 2005.
In December 2007 the patient was admitted in the Center of Internal Medicine and Nephrology for intermittent, mild, right upper abdominal quadrant pain, associated with nausea. Gallbladder (GB) lithiasis was suspected and an ultrasound (US) examination was performed (fig. 1), which revealed a distended GB with a slightly thickened wall; on the liver wall of the GB a sessile 20 mm protrusive mass was discovered, suggestive for a polyp.
For more details, a contrast CT scan was performed (fig. 2), showing a distended GB with a long axis of 9.8 cm and a nodular endoluminal procident mass of 20/17 mm, attached to the anterosuperior wall of the corpus. The tumor had well delineated borders; it was spontaneously isodense with the liver parenchyma, iodophilic. The thickness of the adjacent GB wall was 4 mm.
Figure 1A
Figure 1B
Figure 2
The patient was referred to the Center of General Surgery and Liver Transplantation on 22.02.2008. Due to the patient's preference for a minimal invasive procedure (after having multiple surgeries), a laparoscopic cholecystectomy with partial resection of the GB bed was performed. A careful dissection, without perforation, was performed and the GB was successfully retrieved in a laparoscopic pouch. The specimen (fig. 3) was submitted to a frozen section histo-pathological examination which showed a tubulopapillary adenoma with moderate-severe dysplasia and in-situ carcinoma foci, with structural preservation of the polyp base.
The patient had an uneventful postoperative course and was discharged in the second postoperative day. Scheduled postoperative controls were planned.
The final histological result (fig. 4) confirmed the data offered by the frozen-section examination. On immunohistochemical examination tumor cells were positive for CEA, CK7+ and CK20+.
Figure 3
Figure 4
PLGs are relatively frequent (incidence between 1 and 5.6%), usually being discovered incidentally by US or CT (1, 6, 7). The majority is represented by cholesterol pseudopolyps. True polypoid neoplasms, most of them adenomas, represent 4.3-33% of all PLGs (6, 8-10).
GB adenomas can be single or multiple, sessile or pedunculated, with a mulberrylike appearance and are inserted mostly at the level of the distal half of the GB.
At the moment of diagnosis, GB adenomas present at least moderate dysplasia and can be categorized as: tubular, papillary and tubulopapillary. GB adenomas can show different kinds of metaplasia: gastric foveolar, intestinal (with calyx cells, with Paneth cells or with endocrine cells) and pyloric (11-13). On immunohistochemical examination, the glandular epithelium of the GB adenomas is cytokeratin 7 positive (CK7+); in areas of intestinal and pyloric metaplasia, focal positivity for cytokeratin 20 (CK20+) is present. Epithelial tumoral markers like the epithelial membrane antigen (EMA), Ber-EP4 and carcinoembryonic antigen (CEA) are frequently positive (13).
Malignant transformed GB adenomas (4.5-7.6% of all PLGs) (2,14) probably represent just a small percentage of GB cancers (around 1% (6)), most GB cancers developing from dysplastic mucosa, without a precursor adenoma (15, 16).
Different studies (2,9,14,17,18) have identified clinical elements associated with a high probability for a malignant polyp:
· A reduced number of polyps (less than 3).
· The size of the PLG - a quarter of PLGs larger than 10 mm and most of the polyps larger than 18 mm are malignant.
· The sessile pattern.
· Age over 50.
PLGs are usually asymptomatic. Symptoms may appear when GB lithiasis is associated.
Ultrasonography is the imaging of choice in order to establish the diagnosis. Endoscopic ultrasonography, duplex color US and contrast-enhanced harmonic gray scale ultrasonography may markedly improve the accuracy of the differential diagnosis of gallbladder polyps.
Spiral computerized tomography and positron emission tomography are recommended when there is suspicion of malignancy and for a better assessment of locoregional extension and staging (metastases, lymph node enlargement).
A conservative approach is indicated in selected cases (multiple small polyps - which usually are asymptomatic, cholesterol polyps) with serial US follow-up (every 6 months) to identify the change in size, suggestive for malignant transformation.
The treatment of PLGs (cholecystectomy) is required in symptomatic cases, in cases with associated GB lithiasis or when a malignant transformation is suspected. Shinkai even recommends cholecystectomy for less than 3 polyps, regardless of their size (14).
Laparoscopic cholecystectomy is the treatment of choice (19, 20) but in cases with suspected malignancy some authors advocate the open procedure (rather than a laparoscopic approach), to avoid the risk of spillage and the potential for peritoneal and port-site seeding (18). Kubota and colleagues (3) recommend laparoscopic cholecystectomy with full-thickness dissection for polyps between 10 and 18 mm and open cholecystectomy for polyps greater than 18 mm.
The frozen-section examination is mandatory to reveal the malignant transformation and manage the surgical procedure according to the stage of the disease. In stages IA or IB, the cholecystectomy is considered adequate (the incidence of lymph nodes metastases is 10%) (21); in stage II extended cholecystectomy is recommended, suited for GB carcinoma (IV-V segmentectomy, loco-regional lymph node dissection and resection of common bile duct).
In conclusion, GB adenoma polyps are rare lesions, usually asymptomatic, requiring a comprehensive workup in order to establish the correct therapeutic approach. There are clinical and imagistic elements suggesting malignization, therefore frozen-section examination is mandatory.

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