With estimated incidence rates of 3 per 100,000 individuals in the United States, gallbladder carcinoma is rarely encountered in clinical practice [1]. Still, it encompasses up to 90% of all neoplastic processes arising from the biliary tree [1] [2]. Risk factors are increasing age, female gender, certain ethnic (native American ancestry) and geographic predispositions (southeast Asia has a significantly higher incidence rate compared to the rest of the world), the presence of gallstones and chronic inflammation, as well as parasitic infections, congenital abnormalities of the biliary tract, and genetics [1] [2] [3] [4] [5]. The 5-year survival rate of patients suffering from gallbladder carcinoma from the time of diagnosis is less than 5% [3], and the poor overall prognosis occurs due to two reasons. Firstly, the gallbladder lacks a serosal layer at the site where it is in contact with the liver, thus allowing rapid dissemination and metastatic spread of the tumor [3]. And secondly, the clinical presentation is often nonspecific and mimics other more common pathologies of the biliary tree (cholelithiasis, cholecystitis, other abdominal tumors, etc.) [1] [2] [4] [5] [6] [7]. Right upper quadrant abdominal pain, fever, jaundice, nausea, vomiting, pruritus, anorexia, and weight loss are the most important complaints in the literature when it comes to gallbladder carcinoma [1] [2] [4] [6] [8].

• Weight Loss

  A 45-year-old woman came to us with complaints of flatulent dyspepsia associated with weight loss and anorexia. [ncbi.nlm.nih.gov]

  […] a malignant neoplasm of the bile reservoir, characterized by anorexia, nausea, vomiting, weight loss, progressively worsening right upper quadrant pain, and eventually jaundice. Tumors of the gallbladder are predominantly adenocarcinomas. [medical-dictionary.thefreedictionary.com]

  Most patients are asymptomatic until the disease is advanced but presenting symptoms include abdominal pain (usually in the upper right quadrant), nausea, vomiting, jaundice, anorexia and weight loss. [orpha.net]

  Other symptoms include right upper quadrant pain, weight loss and anorexia. Over 90% of cases of gallbladder cancer are adenocarcinomas, with the majority related to chronic inflammatory metaplasia and dysplasia 15. [radiopaedia.org]

• Painless Jaundice

  Of note, Courvoisier's law states that in the presence of a palpably enlarged gallbladder which is nontender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones. [en.wikipedia.org]

• Soft Tissue Mass

  Skull x-ray revealed a well circumscribed soft tissue mass over a lytic bone defect in the frontal region. [ncbi.nlm.nih.gov]

• Abdominal Pain

  A 72-year-old woman presented with postprandial abdominal pain and was found to have a mass in the body of the gallbladder with direct liver invasion. Histological examination showed an adenosquamous carcinoma with an infiltrate of benign OGCs. [ncbi.nlm.nih.gov]

  Most patients are asymptomatic until the disease is advanced but presenting symptoms include abdominal pain (usually in the upper right quadrant), nausea, vomiting, jaundice, anorexia and weight loss. [orpha.net]

  Right upper quadrant abdominal pain, fever, jaundice, nausea, vomiting, pruritus, anorexia, and weight loss are the most important complaints in the literature when it comes to gallbladder carcinoma. [symptoma.com]

• Abdominal Mass

  Suspect cancer if patients have an unexplained extrahepatic biliary obstruction or abdominal mass. Diagnose cancers by imaging, beginning with ultrasonography, followed by MRCP. [merckmanuals.com]

  An abdominal mass: An enlarged gallbladder may indicate gallbladder cancer. An enlarged gallbladder is caused by a blockage of the bile ducts. [verywell.com]

• Jaundice

  A 52-year-old woman presented with right upper quadrant pain and obstructive jaundice. [ncbi.nlm.nih.gov]

• Biliary Colic

  Cancer of the gallbladder is a rare gastrointestinal (GI) tract pathology that must be diagnosed by clinical tests as its symptoms overlap with those of other GI tract conditions, such as biliary colic and gallstones. [news-medical.net]

  Pain may resemble that of biliary colic (reflecting biliary obstruction) or may be constant and progressive. Sepsis (secondary to acute cholangitis), although unusual, may be induced by endoscopic retrograde cholangiopathy (ERCP). [merckmanuals.com]

  […] they are diagnosed and treated at an advanced stage. 1,2 The neoplasm most frequently affects the fundus and body of the gallbladder and along with its non-specific, late clinical presentation which is comparable to other more common disorders–such as biliary [elsevier.es]

• Hepatomegaly

  Ultrasound of the abdomen revealed hepatomegaly with thick-walled gallbladder with multiple stones and a mass at the fundus, but normal uterus and ovary. [ncbi.nlm.nih.gov]

  Other features include fatigue, acholic stool, a palpable mass, hepatomegaly, or a distended gallbladder (Courvoisier sign, with distal cholangiocarcinoma). [merckmanuals.com]

• Gallbladder Enlargement

  Gallbladder cancer symptoms include: • Nausea and vomiting • Abdominal pain • Jaundice • Gallbladder enlargement • Abdominal swelling • Weight loss • Loss of appetite Who Gets Gallbladder Cancer The American Cancer Society’s estimates for gallbladder [cancertutor.com]

• Eruptions

  The eruptions with pruritus resolved within 1 wk after the operation. This is the first report, to our knowledge, of coincident biliary malignancy and erythroderma. [ncbi.nlm.nih.gov]

• Dermatitis

  Although exfoliative dermatitis (erythroderma) secondary to malignancy is commonly associated with lymphomas or leukemias, coincident gastrointestinal (GI) malignancy and erythroderma is rare. [ncbi.nlm.nih.gov]

• Subcutaneous Nodule

  A 42-year-old woman presented with multiple subcutaneous nodules over the abdominal wall, anterior chest wall, back and in bilateral breasts. Fine needle aspiration cytology (FNAC) of these nodules revealed metastatic adenocarcinoma. [ncbi.nlm.nih.gov]

• Dark Urine

  If you have gallbaldder cancer, you may have some of the following symptoms: feeling sick vomiting pain in the upper right side of the abdomen (tummy) which can come and go your skin and the white of your eyes are yellowed (jaundice) dark urine pale coloured [global.ihi.com]

Because of the very low survival rate of patients with gallbladder carcinoma, physicians must raise clinical suspicion toward a malignant disorder in the presence of nonspecific abdominal complaints. A detailed patient history and a complete physical examination, which will assess the course and progression of symptoms, but also their potential origin (through abdominal inspection and palpation), are vital steps in the workup. Laboratory tests are of limited benefit in the raising suspicion toward gallbladder carcinoma [4] [8]. Serum tumor markers, however, mainly carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), are frequently elevated in this patient group, suggesting their important role in the workup [9] [10]. Imaging studies are the cornerstone in making the diagnosis. Various techniques are recommended, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (particularly high-resolution), positron emission tomography (fludeoxyglucose (FDG)-PET and PET-CT), endoscopic ultrasonography (EUS), and magnetic resonance cholangiopancreatography (MRCP) [1] [2] [6] [7]. A large space-occupying mass in the gallbladder that is frequently infiltrating the liver is a typical finding, while asymmetric and extensive gallbladder wall thickening is also an important sign used to discriminate this tumor from other etiologies [1] [2]. Once the initial diagnosis is made, often through high-resolution US, CT, or MRI (all used to assess nodal or metastatic spread as well), EUS is vital in determining the exact stage of the tumor, as it provides the ability to perform a biopsy (through fine-needle aspiration) and subsequent histopathological examination [3] [11].

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