Aseptic Abscess of the Gallbladder Mimicking Gallbladder Carcinoma after Surgery for Ulcerative Colitis.

A 56-year-old man with acute severe UC had undergone subtotal colectomy and ileal pouch rectal anastomosis 19 years previously. Subsequently, his bowel movements were 10 non-bloody stools per day. Routine colonoscopy indicated proctitis but no pouchitis ( Fig. 1a, b ), and the patient received regular treatment with antidiarrheal agents and oral mesalazine (1,000 mg/day) for rectal inflammation. Computed tomography (CT) performed in August 2021 to investigate epigastric pain revealed no evidence of gallbladder wall thickening ( Fig. 2a ). Colonoscopy shows (a) almost normal mucosa in the ileal pouch, (b) an erosion, small ulcer, and inflammatory polyps in the rectum, (c) friable mucosa and bleeding in the ileal pouch, and (d) an ulcer in the rectum. Contrast-enhanced computed tomography shows (a) no thickening of the gallbladder wall and (b) thickening of the gallbladder wall one year later. In August 2022, he was referred to our department because of a fever (38.0°C), abdominal pain, abdominal fullness, and more than 15 bloody stools per day. He was diagnosed with severe pouchitis [modified pouchitis disease activity index of 12 points ( 1 ), range 0-12 points] based on colonoscopy ( Fig. 1c , d) and abdominal contrast-enhanced CT and was urgently admitted to the hospital. He was started on ciprofloxacin (200 mg every 12 h) and metronidazole (250 mg every 12 h) and underwent mesalazine enema and steroid enema. Ciprofloxacin was discontinued owing to a drug-associated rash. Twelve days after treatment initiation, the fever, abdominal pain, abdominal fullness, and bloody stools had disappeared, and the stool movements had improved to 10 non-bloody stools per day, which was the same as before admission. CT performed on admission revealed localized thickness of the gallbladder wall ( Fig. 2b ), which was diagnosed as a benign tumor of the gallbladder, such as adenomyosis or a polyp, based on magnetic resonance imaging (MRI) ( Fig. 3a , b). The patient had no family history of inflammatory bowel disease (IBD) or gallbladder tumors. No genetic testing was performed. After discharge from the hospital, mesalazine (1,000 mg/day), metronidazole (250 mg every 12 h), mesalazine enema, steroid enema, and antidiarrheal agents were continued, and after 1 month, only oral mesalazine was continued. Magnetic resonance imaging shows (a) thickening of the sac wall with a high signal on T2-weighted images and (b) no accumulation on diffusion-weighted images. One year later (August 2023), an abdominal ultrasonographic examination showed that gallbladder wall thickening had increased. He subsequently underwent contrast-enhanced CT ( Fig. 4 ), MRI ( Fig. 5a-c ), and contrast-enhanced endoscopic ultrasonography (EUS) ( Fig. 6 ). MRI showed gallbladder wall thickening with accumulation at the base of the gallbladder on diffusion-weighted imaging (DWI), while contrast-enhanced EUS showed a 29-mm×17-mm highly echogenic lesion at the base of the gallbladder with early staining in the arterial phase on Sonazoid Ⓡ (GE Healthcare Pharma, Tokyo, Japan). He was suspected to have gallbladder cancer and was admitted to the hospital for cholecystectomy. Contrast-enhanced computed tomography performed one year after the initial hospital admission shows a mass-like wall thickening with contrast effect at the base of the enlarged gallbladder. Magnetic resonance imaging shows (a) increased thickening of the gallbladder wall with an indistinct border between the gallbladder and the liver that is isointense to the liver on T2- weighted imaging. There is (b) high intensity on diffusion-weighted imaging and (c) diffusion limitation on apparent diffusion coefficient mapping. Contrast-enhanced endoscopic ultrasonography shows a 29-mm×17-mm highly echogenic lesion at the base of the gallbladder with early staining in the arterial phase on Sonazoid ® contrast-enhanced endoscopic ultrasonography. The yellow arrowheads indicate the edge of the lesion. On admission, physical and laboratory examinations, including those for tumor markers, showed no abnormal findings ( Table 1 ). In October 2023, he underwent enlarged cholecystectomy and hilar lymph node dissection. A histopathological examination revealed an abscess containing polymorphonuclear neutrophils surrounded by palisading histiocytes in the subserosal layer of the gallbladder wall ( Fig. 7a, b ). There was no atypia in the epithelium of the gallbladder, although there was infiltration of inflammatory cells, mainly lymphocytes. In the combined resected liver tissue, inflammatory cell infiltrate mainly composed of lymphocytes was observed in the portal area, but no findings suggested hepatitis, fibrosis, or cholangitis. Gram, Ziehl-Neelsen, periodic acid-schiff, and Grocott staining were all negative. Postoperatively, he developed paralytic ileus, bile leakage, and an intra-abdominal abscess that resolved with conservative treatment. He is currently under outpatient observation without recurrence of extraintestinal complications including pouchitis and AA. Clinical Variables in the Present Case. PT: prothrombin time, INR: international normalized ratio, APTT: activated partial thromboplastin time, AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase, GGT: gamma-glutamyl transpeptidase, CRP: C-reactive protein, CEA: carcinoembryonic antigen, CA19-9: carbohydrate antigen 19-9, LDH: lactate dehydrogenase Histological examinations show (a) necrotic tissue [Hematoxylin and Eosin (H&E) staining, magnification ×20] with (b) polymorphonuclear leucocytes surrounded by palisading histiocytes (H&E staining, magnification ×200).

Informed consent was obtained from the patient for publication of the case details.

This case highlights two important clinical issues. First, this rare case of gallbladder AA closely mimicked gallbladder carcinoma on various imaging studies. Differential diagnoses for gallbladder wall thickening include acute cholecystitis, chronic cholecystitis, xanthogranulomatous cholecystitis, adenomyomatosis, hepatic causes, and extrinsic inflammatory conditions, such as pancreatitis and pyelonephritis ( 2 ). Intraluminal polypoid lesions include cholesterol polyposis, adenomatous and focal adenomyomatosis, focal xanthogranulomatous cholecystitis, and sludge balls ( 2 ). Tuberculosis and dengue fever have also been reported as causes of gallbladder wall thickening ( 2 ); however, there have been no reports of gallbladder wall thickening due to an AA. To our knowledge, this is the first report of an AA in the gallbladder. Clinically, it is important to distinguish the abovementioned diseases from gallbladder cancer; however, it is not easy to obtain a definitive diagnosis because gallbladder cancer presents with various imaging findings, has nonspecific signs, and mimics the appearance of benign gallbladder diseases. A definitive diagnosis is made using various modalities, such as ultrasonography, EUS, CT, and MRI, with or without contrast media. A wall thickness of ＞10 mm, iso- or hypoechoic wall, increased vascularity, branched or linear intralesional vessels, inhomogeneous enhancement, early hypoenhancement, and involvement of adjacent liver parenchyma are important findings of contrast-enhanced ultrasonography that indicate gallbladder cancer ( 3 ). In addition, heterogeneous arterial phase enhancement is the strongest independent predictor of malignancy, and a dynamic evaluation shows that carcinomas exhibit early contrast loss compared to benign thickening ( 4 ). Findings suggestive of malignancy on contrast-enhanced CT include hyperintense or heterogeneously enhanced walls and homogeneously enhanced walls in all layers ( 5 ). Furthermore, malignancy is suggested by the presence of a two-layered enhancing pattern of the gallbladder walls, hyperenhancement of the inner wall that is more than 2.6 mm thick, faint enhancement of the thin outer wall (less than 3.4 mm), or focal irregular wall thickening ( 6 ). On MRI, gallbladder cancer is typically T1 hypo- to isointense compared with the surrounding liver and heterogeneously T2 iso- to hyperintense to the liver, with heterogeneous enhancement ( 7 ). DWI and apparent diffusion coefficient (ADC) values can help in the diagnosis of malignancy. Gallbladder carcinomas have malignant wall thickening and patchy, heterogeneous, or homogeneous strong diffusion restriction on DWI. In addition, the ADC value is significantly lower in malignant cases than in benign cases ( 8 ). In the present case, contrast-enhanced EUS and CT showed wall thickening with a contrast effect, DWI showed homogeneous intense diffusion restriction, and ADC values were low. Cholecystectomy was performed because gallbladder carcinoma could not be ruled out. Using an ADC value of 1.2×10 -3 mm 2 /s as a cutoff value and considering the other morphological features, the sensitivity and specificity for the identification of malignancy were 76.9% and 84%, respectively ( 9 ). EUS-guided fine-needle aspiration is one of the methods used to obtain a definitive diagnosis; however, its indication is unclear ( 10 ). The diagnosis of AA is still one of the exclusion criteria, and a histological diagnosis is essential if the abscess is differentiated from malignancy. In the present case, it was not possible to perform preoperative histology, including fine-needle aspiration, because the gallbladder was involved. Surgical treatment is used for patients with splenic or intra-abdominal lesions that are difficult to biopsy; therefore, malignancy cannot be ruled out ( 11 - 16 ). Although some patients undergo fluorodeoxyglucose positron emission tomography/CT, the diagnosis of AA remains difficult. If multiple lesions are present in a patient with systemic autoinflammatory disease, it is possible to treat them as AAs. However, if there is a single lesion in a patient with a history of malignant tumor treatment, surgery is necessary, unless malignancy can be completely ruled out by histological examination. Therefore, we believe that our treatment plan for this case is appropriate. When we retrospectively reviewed the CT and MRI findings postoperatively, we found that the mucosal surface was regular, and mild elevation was very similar to submucosal mass-like changes; therefore, it was considered necessary to include a non-epithelial tumor as a differential diagnosis. However, in light of the absence of clinical symptoms such as pain in the right hypochondrium and a fever, the presence of a single lesion, contrast-enhanced EUS findings, and MRI findings, we considered the lesion more likely to be a neoplastic lesion than an abscess. In the present case, it would have been extremely difficult to diagnose AA preoperatively, even from a retrospective perspective. The present case suggests that physicians should be aware of false-positive imaging results and consider aggressive surgical treatment if malignancy cannot be ruled out. Surgery was necessary in the present case; however, we reassessed the selected surgical technique. We consider that it may have been excessive to perform enlarged cholecystectomy and hilar lymph node dissection for a benign disease. An intraoperative frozen section analysis is reportedly useful in diagnosing gallbladder cancer ( 17 ). A frozen section analysis has a sensitivity and specificity of 100% and is considered a reliable tool for determining the extent of resection ( 17 ). This technique reduces the number of single-stage extended cholecystectomies and reduces the surgical difficulty associated with the adhesions encountered in two-stage procedures. In addition, as only one session of general anesthesia is required, this technique is expected to reduce the patient burden and cost. Although no previous report has described the use of a frozen section analysis during surgery for AA and its practicality needs to be studied, we believe that this technique will be useful in avoiding excessive surgery in the future. The second finding was that AA of the gallbladder was present in a patient with UC who had a history of subtotal colectomy. AA is caused by infiltration of polymorphonuclear neutrophils without infection and is reported to be associated with IBD, Behcet's disease, rheumatoid arthritis, spinal arthritis, pyoderma gangrenosum, and recurrent polychondritis ( 18 , 19 ). Andre et al. reported the following findings in a case series of AAs in patients with or without IBD: ( 1 ) deep abscesses on a radiologic examination with neutrophilic features proven by surgical pathology or aspiration when performed; ( 2 ) negative blood cultures and negative serologic tests for bacteria (always including Yersinia enterocolitica ), and, when surgical procedure or aspiration was performed, sterile standard, acid-fast bacillus, and fungal cultures of pus; ( 3 ) failure of antibiotic therapy when prescribed after at least 2 weeks' duration for conventional antibiotic therapy and 3 months' duration for antituberculosis drugs administered for a conventional duration; and ( 4 ) rapid clinical improvement on the day after administration of corticosteroids (at least 1/2 mg/kg of prednisone or equivalent, 1 mg/kg recommended) followed by radiologic improvement after 1 month of corticosteroids, sometimes in combination with immunosuppressive drugs ( 18 ). The present case met the diagnostic criteria of Andre et al. in ( 1 ) the presence of a deep-seated abscess and neutrophil-predominant cellular infiltrate on imaging and ( 2 ) negative results of various culture tests. Furthermore, the lesion was judged to be AA based on characteristic pathological findings and culture results. However, it is extremely difficult to differentiate AAs from malignancy on imaging, and as extended cholecystectomy was performed for diagnostic purposes, it was not possible to prove the ineffectiveness of antibiotic therapy or the efficacy of steroid therapy. Andre et al. reported a case series of AAs classified by IBD complications and found that, in 21 patients with IBD complications, AAs preceded, coexisted with, or followed the diagnosis of IBD, and the pathogenesis of AAs did not always coincide with the development of abscesses and IBD activity ( 18 ). In the present case, the abscess increased in size after the pouchitis and residual proctitis had resolved, which is consistent with the course of AAs associated with IBD. AA is speculated to belong to a spectrum of autoinflammatory multifactorial diseases, but its underlying pathogenesis is not yet understood. Although cases of UC complicated by AA have been reported, only 19 patients with AA concomitant with UC were identified in a search of the PubMed database ( Table 2 ) ( 18 , 20 - 34 ). Most cases developed during medical treatment and correlated with the active stage of colitis, which in the present case may correlate with severe pouchitis and proctitis. However, only two cases developed postoperatively ( 26 ), including the present case. The most common sites of AA are lymphoid organs, such as the spleen and lymph nodes, but AA also occurs in soft tissues close to the body surface, such as the subcutaneous tissue and periosteum, as well as in the kidneys, lungs, and nasal septum. To our knowledge, the present case is the only one of AA in the gallbladder. Summary of Case Reports of Aseptic Abscess in Patients with UC Published in English. AAs can occur in any part of the deep organs. In the present case, there were no imaging findings suggestive of AAs in organs other than the gallbladder, there was no evidence for the implementation of immunosuppressive therapy as prophylactic treatment, and the pouchitis and residual proctitis improved. Therefore, we carefully followed the patient up and determined that no additional treatment was necessary. We encountered a case of AA of the gallbladder that mimicked gallbladder carcinoma, which occurred 19 years after subtotal colectomy and ileal pouch rectal anastomosis following severe pouchitis. AA of the gallbladder is very rare, and it is important to distinguish it from other diseases, such as malignancy.

Gallbladder abscess is an extremely rare type of gallbladder lesion. It is not easy to differentiate between malignant and benign gallbladder tumors on various imaging studies, and the imaging findings of aseptic gallbladder abscesses are unclear. Aseptic abscesses (AAs) are rare complications of ulcerative colitis (UC). However, reports of AA in the gallbladder after total colorectal resection are rare. We herein report a case of AA of the gallbladder that was detected 19 years after subtotal colorectal resection.

The authors state that they have no Conflict of Interest (COI).