https://orcid.org/0009-0007-5159-3343
Abstract
Follicular cholangitis is a rare cause of bile duct inflammation and stenosis, mimicking stricturing malignancies such as cholangiocarcinoma. This condition is considered distinct from follicular cholecystitis, which involves chronic inflammatory and lymphoplasmacytic changes in the gallbladder. We present a case of a woman in her 70s who was incidentally found to have an intrahepatic bile duct stricture in the left lobe of the liver. After surgical management, she was found to have concurrent follicular cholangitis and follicular cholecystitis. This case highlights the similar histopathological features and overlap of the conditions.
Introduction
Follicular cholangitis is a rare, benign inflammatory disorder of the bile ducts. It is characterised histologically by lymphoplasmacytic inflammation and lymphoid follicle proliferation within the mucosal layer of the biliary tree. It may be mistaken for cholangiocarcinoma due to its propensity to cause biliary strictures, and patients may also have elevated tumour markers including carbohydrate antigen 19–9 (CA19–9). Clinical presentations include jaundice, abdominal pain, nausea, pruritus and fever, although many patients are asymptomatic. To the best of the authors’ knowledge, this is the first case to report concurrent follicular cholangitis and follicular cholecystitis.
Case report
A 77-year-old female presented to the emergency department with an acute onset of epigastric pain and fever. This was on a background of ischaemic heart disease with stents, type 2 diabetes mellitus, hypertension and hypercholesterolaemia. There was no personal or family history of lymphoproliferative or autoimmune disease. She had no history of cholelithiasis or malignancy. On examination, she was febrile but haemodynamically stable. She did not appear jaundiced. There was moderate epigastric pain, with no guarding, peritonism or abdominal masses. Blood tests showed an isolated elevation of CA19–9 of 97 (normal <40) with normal carcinoembryonic antigen (CEA), immunoglobulins, liver function tests and inflammatory markers (Table 1). Given her cardiovascular risk, she was initially investigated with a full cardiac workup including a CT aortogram. These investigations demonstrated no acute coronary pathology but incidentally identified biliary lesions and bile duct dilatation in the left hepatic lobe, prompting outpatient follow-up.
Preoperative blood tests
| Full Blood Count | ||
|---|---|---|
| Test | Reference | Value |
| Haemoglobin (g/L) | 110–160 | 117 |
| Hematocrit | 0.3–0.46 | 0.37 |
| White cell count (×109/L) | 4–11 | 10.4 |
| Neutrophils (×109/L) | 2–7.5 | 4.58 |
| Lymphocytes (×109/L) | 1–4 | 4.58 (H) |
| Monocytes (×109/L) | 0–1 | 0.98 |
| Basophils (×109/L) | 0–0.5 | 0.03 |
| Platelets (×109/L) | 150–450 | 250 |
| Electrolytes, Urea and Creatinine | ||
| Sodium (mmol/L) | 135–145 | 142 |
| Potassium (mmol/L) | 3.5–5.5 | 4.6 |
| Chloride (mmol/L) | 95–110 | 110 |
| Bicarbonate (mmol/L) | 20–32 | 24 |
| Urea (mmol/L) | 3.5–9.5 | 9.7 (H) |
| Creatinine (μmol/L) | 45–95 | 70 |
| Estimated glomerular filtration rate (ml/min/1.73 m2) | >59 | 74 |
| Urate (mmol/L) | 0.15–0.4 | 0.31 |
| Calcium (mmol/L) | 2.15–2.55 | 2.51 |
| Phosphate (mmol/L) | 0.8–1.5 | 1.19 |
| Bilirubin total (mmol/L) | 3–15 | 9 |
| Alkaline phosphatase (U/L) | 30–115 | 60 |
| Gamma-glutamyl transferase (U/L) | 5–35 | 30 |
| Lactate dehydrogenase (U/L) | 120–250 | 292 (H) |
| Aspartate aminotransferase (U/L) | 10–35 | 32 |
| Alanine aminotransferase (U/L) | 5–30 | 21 |
| Total Protein (g/L) | 64–83 | 75 |
| Albumin (g/L) | 36–47 | 42 |
| Globulin (g/L) | 23–39 | 33 |
| Inflammatory markers | ||
| C-reactive protein (mg/L) | <5 | 0.9 |
| Erythrocyte sedimentation rate (mm/hr) | 1–35 | 11 |
| Tumour markers | ||
| CA 19–9 (U/A) | <40 | 97 (H) |
| CEA (μg/L) | <5.1 | 2.5 |
| Immunoglobulins | ||
| Immunoglobulin G (g/L) | 6.20–14.40 | 11.81 |
| Immunoglobulin G1 (g/L) | 3.82–9.29 | 5.79 |
| Immunoglobulin G2 (g/L) | 2.42–7.00 | 4.85 |
| Immunoglobulin G3 (g/L) | 0.218–1.761 | 0.571 |
| Immunoglobulin G4 (g/L) | 0.039–0.864 | 0.591 |
| (H): outside of reference range | ||
An endoscopic ultrasound demonstrated biliary stricturing and an 8 mm poorly defined lesion in segments II/III (Fig. 1). A 2 cm, hypoechoic heterogeneous triangular lymph node was identified in the hilum. Cholelithiasis and biliary sludge were present in the gallbladder. An 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan showed heterogeneous non-focal moderately increased FDG uptake throughout segment II/III of the liver with a standardised uptake value maximum (SUVmax) of 5.8 (Fig. 2). No PET-avid gallbladder lesions, radiopaque calculi or other foci suggestive of metastatic or lymphoproliferative disease were identified. A liver magnetic resonance imaging scan demonstrated features suggestive of cholangitis, with a dilated central intrahepatic duct measuring 7 mm. This was most prominent in the left hemiliver where there was associated periportal oedema and a large wedge-shaped area of relative hepatic dysfunction in segments II and IVa. Given the concern for an underlying malignant process, a standard laparoscopic left lateral segmentectomy and cholecystectomy was performed. There were no intraoperative complications.
Endoscopic ultrasound showing an 8 mm poorly defined lesion in segment II/III (arrows).
FDG PET scan showing moderate FDG uptake (SUVmax 5.8) in the central left hepatic lobe (arrow).
The resected liver specimen macroscopically had a prominent bile duct at the centre of the liver segment. The duct appeared to be compressed and was surrounded by a cream-discoloured area measuring 11 × 10 × 9 mm (Fig. 3). Microscopically, the liver sections showed extensive cholangitis involving the small, intermediate and large ducts with circumferential fibrosis and inflammation (Fig. 4). Prominent lymphoid follicles with chronic inflammatory cells involving the inflamed ducts were identified. The lymphoid aggregates showed mixed B and T lymphocytes with a reactive pattern on staining for CD20, CD5, CD3, CD10, Bcl-2, and CD23. Cyclin D1 was negative. No increased numbers of IgG4 or IgM plasma cells were identified. Staining for p53 showed a wild-type nuclear pattern and no loss of SMAD4 nuclear staining was demonstrated. No ductopenia, ductular proliferation or small duct injury was identified to suggest autoimmune cholangitis. ‘Onion skin’ fibrosis and oedema were not present. The resected gallbladder showed microscopic features of follicular cholecystitis (Fig. 5). There was fibromuscular hyperplasia with Rokitansky-Aschoff sinuses indicative of chronic cholecystitis. Prominent lymphoid aggregates were present within the lamina propria. No features of dysplasia or malignancy were seen in the liver or gallbladder.
Compressed intrahepatic bile duct (arrowhead) with a cream discoloured area surrounding the duct.
Prominent lymphoid follicles in the mucosa of a large bile duct.
Prominent lymphoid follicles in the gallbladder mucosa.
The patient’s postoperative stay was initially uncomplicated, and she was discharged within a week of the surgery. However, 2 weeks postoperatively, she developed an insidious onset of fever and abdominal pain. CT imaging showed an abscess in the left perihepatic region. This was drained using CT guidance and the patient was prescribed targeted antibiotic therapy including amoxicillin and clavulanate, allowing for full recovery and discharge after 6 days. The patient returned to all regular activities 6 weeks after the operation and at 7-month follow-up, there was no evidence of recurrent disease.
Discussion
The authors present a rare case of concurrent intrahepatic follicular cholangitis and follicular cholecystitis. Follicular cholangitis and follicular cholecystitis are characterised by lymphoid follicular hypertrophy with prominent lymphoplasmacytic inflammation and stromal fibrosis [1, 2]. Benign conditions that mimic follicular cholangitis include primary sclerosing cholangitis and IgG4-sclerosing cholangitis. Malignant conditions such as cholangiocarcinoma and follicular lymphoma also need to be excluded. In this case, the elevated CA19–9 alongside biliary stricturing heightened concern for a malignant process. CA19–9 is an antigen released from the pancreaticobiliary epithelium in response to inflammation or tissue damage and as such, it may be elevated in both benign and malignant biliary pathology. Ultimately, diagnosis of follicular cholangitis can only be made after histological examination and exclusion of other conditions.
A literature review demonstrated that the mean age of patients with follicular cholangitis was 62 years, and there was a female predominance (Table 2). Patients were often asymptomatic or presented with cholestatic symptoms. Five cases reported an elevated CA19–9, highlighting the limited specificity of this tumour marker in diagnosing follicular cholangitis. Most patients had deranged liver function tests, which were unremarkable in this case. Three cases reported recurrence of biliary strictures and cholangitis. All cases were managed surgically due to concern of an underlying malignant process. Follicular cholecystitis also demonstrates a female predominance and has been reported more frequently in the literature than follicular cholangitis. It has been associated with a variety of pathologies including cholelithiasis, gallbladder neoplasia, gram-negative bacterial infection, and primary sclerosing cholangitis among others [2].
Literature review
| Author | Year | Age/Sex | Presentation | LFTs | CA19–9 | Radiology findings | Surgery | Follow-up |
|---|---|---|---|---|---|---|---|---|
| Aoki et al. [1] | 2003 | 57 F | Asymptomatic | Elevated | Normal | Common hepatic duct lesions and stenosis at the hepatic hilum | Right hepatectomy with bile duct resection | NA |
| Lee et al. [3] | 2005 | 61 M | Intermittent periumbilical pain, scleral icterus, red urine | Elevated as well as lipase and ESR | NA | Luminal narrowing and wall thickening of the right and left hepatic ducts and proximal common hepatic duct. | Resection of extrahepatic and right bile duct, cholecystectomy and hepaticojejunostomy | NA |
| Fujita et al. [4] | 2010 | 44 M | Asymptomatic | Elevated | Normal | Stricture at the hepatic hilum and right bile duct dilatation. | Extended right hepatectomy | Recurrence at 10 months |
| 58F | Asymptomatic | Elevated | Normal | Hilar bile duct stricture | Extended left hepatectomy | Recurrence 2 months post-op and death after 2.5 years from liver failure | ||
| Zen et al. [5] | 2012 | 73 F | Abdominal pain and jaundice | Elevated | Elevated | Right hepatic duct stricture and peripheral duct dilatation | Right hepatectomy | NA |
| 70 M | Asymptomatic | Elevated | Elevated | Left perihilar duct stricture and peripheral duct dilatation | Left hepatectomy | NA | ||
| 42 F | Pruritus, jaundice, portal hypertension | Elevated | Normal | Periductal hilar mass and extrahepatic bile duct stricture | Liver transplant | NA | ||
| Fujii et al. [6] | 2014 | 60s F | Pruritus, fatigue | Elevated | Normal | Biliary stricture involving the hilum as well as the left and right main bile ducts | Left trisegmentectomy | No recurrence at 24 months |
| Saito et al. [7] | 2016 | 69F | Abdominal pain | Elevated | Normal | Stricture of a left intrahepatic biliary duct and dilatation of the peripheral biliary duct | Left hepatectomy | No recurrence at 12 months |
| Chang et al. [8] | 2019 | 60 M | Asymptomatic | Elevated | Normal | Stricture of the B8 duct | Right hepatectomy and caudate lobectomy | No recurrence at 18 months |
| Kosone et al. [9] | 2020 | 70 M | Epigastric discomfort, back pain and jaundice | Elevated | Normal | Stenosis of the middle to upper part of the common bile duct with associated PET uptake | Right hepatic and caudate lobectomy with extrahepatic bile duct resection | No recurrence two and a half years post op |
| Lampropoulou et al. [10] | 2023 | 59 M | Asymptomatic | Elevated | Normal | Stricture of the left hepatic duct and proximal dilatation of the left intrahepatic biliary tree | Left hepatectomy with regional lymph node dissection | No recurrence at 8 months |
| Koneri et al. [11] | 2023 | 77 F | Asymptomatic | Elevated | Normal | Mass in the distal bile duct with common and intrahepatic bile duct dilatation. No PET uptake in the lesion. | Subtotal stomach preserving pancreaticoduodenectomy and lymph node dissection. | No recurrence at 42 months |
| Lee et al. [12] | 2024 | 57 F | Jaundice | Elevated | Elevated | 47 mm thickening of the hilar and proximal segments of the common bile duct. Pericholedochal and portocaval lymphadenopathy. | Extended right hemihepatectomy and hepaticojejunostomy. Regional lymph node dissection. | NA |
| Oura et al. [13] | 2024 | 74 F | Asymptomatic | Elevated | Normal | Left bile duct stenosis and dilatation of B2 and B3 ducts | Extended left hepatectomy | Nо recurrence after 82 months; developed decompensated liver cirrhosis and portal hypertension. |
| Tandon et al. [14] | 2025 | 34F | Abdominal discomfort, menorrhagia | Normal | Normal | Mildly PET-avid oval shaped lesion in the distal common bile duct. | Antegrade CBD excision with ampullectomy | No recurrence after 1 month |
| Fischer et al. [15] | 2026 | 73F | Abdominal pain, nausea, background Langerhans cell histiocytosis | Elevated | Elevated | 16 mm central bile duct lesion causing stenosis of the left hepatic duct | Left hemihepatectomy | 7 months follow up show cholestasis and bile duct dilatation |
| Present case | 2026 | 77 F | Epigastric pain and fever | Normal | Elevated | Biliary stricture and 8 mm lesion in segments II/III | Left lateral segmentectomy | No recurrence at 7 months post-op |
To the best of the authors’ knowledge, we report the first case of concurrent follicular cholangitis and follicular cholecystitis. Follicular cholangitis is a condition that should be considered as a differential diagnosis in localized biliary strictures. This case raises the possibility that follicular cholangitis and follicular cholecystitis may represent a spectrum of the same underlying inflammatory process, rather than distinct entities. The aetiology of these inflammatory processes remains unclear.
Conflicts of interest
None declared.
Funding
None declared.
