Gallbladder Adenocarcinoma Responds to Chemo-Immunotherapy in Young Patient Without Gallstones

A 30-year-old female with gallbladder carcinoma achieved complete metabolic resolution of metastases after three cycles of combined chemo-immunotherapy, according to a case report. The patient presented with a two-week history of upper abdominal pain radiating to the back, bloating, and excessive gas.

Laboratory evaluation showed markedly elevated carcinoembryonic antigen (CEA) at 269.26 ng/mL (normal in nonsmokers: <3 ng/mL, normal in smokers: <5.0 ng/mL) and carbohydrate antigen 19-9 (CA 19-9) at 2.8 U/mL (normal: ≤37 U/mL). MRI demonstrated a polypoidal gallbladder fundal mass without evidence of gallstones. Ultrasound identified an irregular, heterogeneous echogenic mass with ill-defined margins in the fundal region of the gallbladder, measuring approximately 3.3 × 3.8 cm.

The patient underwent laparoscopic cholecystectomy, and histopathology confirmed biliary-type adenocarcinoma and evidence of metastasis. Postoperatively, she was diagnosed with stage IV disease and started on systemic therapy with pembrolizumab, gemcitabine, and cisplatin. After three cycles, PET/CT revealed complete metabolic resolution of metastases, with normalization of tumor markers.

The patient presented with GBC without a history of cholelithiasis or family history. She had a past medical history of diabetes mellitus, hypercholesterolemia, and hypothyroidism, and was currently on medications including metformin, semaglutide, atorvastatin, levothyroxine, vitamin supplementation, and antifungal therapy. Surgical history was notable for keloid removal from the neck and chest wall.

On examination, her vital signs were stable and within normal limits (temperature, 36.5°C; blood pressure, 122/81 mmHg; heart rate, 82 beats/minute; respiratory rate, 18 breaths/minute). Abdominal examination revealed tenderness in the upper abdomen with tympanic percussion and normal bowel sounds. There was no palpable organomegaly, no rebound tenderness, no guarding, and no lymphadenopathy.

Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis, often diagnosed incidentally or at an advanced stage. With a five-year survival rate of less than 10% in advanced stages, gallbladder carcinoma is known for its aggressive nature, poor prognosis, and late presentation. GBC is the most common malignancy of the biliary tract, but it only accounts for 1-2% of gastrointestinal cancers worldwide.

The global incidence rate of GBC is approximately 1.2 per 100,000 people, with 122,469 new cases recorded worldwide in 2022. High prevalence is reported in Northern India, South America, and East Asia, while cases remain relatively uncommon in the Middle East, including the United Arab Emirates (UAE). According to the UAE National Cancer Registry of 2023, there were 56 reported cases of gallbladder and other biliary tract cancers, comprising 16 cases among UAE citizens and 40 among non-citizens. The crude incidence rate per 100,000 is 0.7 for females, 0.4 for males, and 0.5 overall. Despite low incidence, GBC demonstrates a high mortality-to-incidence ratio (~87%), indicating the importance of early diagnosis and surgical intervention.

Cholelithiasis is the most significant risk factor, occurring in 85% of GBC patients, with a 10-fold increased risk for larger stones (>3 cm). Chronic inflammation, recurrent cholecystitis, and the presence of gallbladder polyps, especially large adenomatous types, and genetic predispositions also contribute to malignant transformation. Unfortunately, symptoms are rather nonspecific, mimicking benign gastrointestinal or hepatobiliary conditions. As a result, GBC is often discovered incidentally after cholecystectomy.