There are no specific blood tests that can diagnose cholangiocarcinoma by themselves. Serum levels of carcinoembryonic antigen (CEA) and CA19-9 are often elevated, but are not sensitive or specific enough to be used as a general screening tool. However, they may be useful in conjunction with imaging methods in supporting a suspected diagnosis of cholangiocarcinoma.

Ultrasound of the liver and biliary tree is often used as the initial imaging modality in patients with suspected obstructive jaundice. Ultrasound can identify obstruction and ductal dilatation and, in some cases, may be sufficient to diagnose cholangiocarcinoma. Computed tomography (CT) scanning may also play an important role in the diagnosis of cholangiocarcinoma.

Upon discovery of a liver tumor, the main issue in the workup is to determine whether the tumor is benign or malignant. Many imaging modalities are used to aid in the diagnosis of malignant liver tumors. For the most common of these, hepatocellular carcinoma (HCC), these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.

Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders..

Many imaging modalities are used to aid in the diagnosis of primary liver cancer. For HCC these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.

Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders.

Ultrasonography of liver tumors involves two stages: detection and characterization. Tumor detection is based on the performance of the method and should include morphometric information (three axes dimensions, volume) and topographic information (number, location specifying liver segment and lobe/lobes). The specification of these data is important for staging liver tumors and prognosis. Tumor characterization is a complex process based on a sum of criteria leading towards tumor nature definition. Often, other diagnostic procedures, especially interventional ones are no longer necessary. Tumor characterization using the ultrasound method will be based on the following elements: consistency (solid, liquid, mixed), echogenicity, structure appearance (homogeneous or heterogeneous), delineation from adjacent liver parenchyma (capsular, imprecise), elasticity, posterior acoustic enhancement effect, the relation with neighboring organs or structures (displacement, invasion), vasculature (presence and characteristics on Doppler ultrasonography and contrast-enhanced ultrasound (CEUS).

Prevention of cancers can be separated into primary, secondary, and tertiary prevention. Primary prevention preemptively reduces exposure to a risk factor for liver cancer. One of the most successful primary liver cancer preventions is vaccination against hepatitis B. Vaccination against the hepatitis C virus is currently unavailable. Other forms of primary prevention are aimed at limiting transmission of these viruses by promoting safe injection practices, screening blood donation products, and screening high-risk asymptomatic individuals. Aflatoxin exposure can be avoided by post-harvest intervention to discourage mold, which has been effective in west Africa. Reducing alcohol abuse, obesity, and diabetes would also reduce rates of liver cancer. Diet control in hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.

Secondary prevention includes both cure of the agent involved in the formation of cancer (carcinogenesis) and the prevention of carcinogenesis if this is not possible. Cure of virus-infected individuals is not possible, but treatment with antiviral drugs such as interferon can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.

Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of chemotherapy drugs and antiviral drugs.

Because of their location, these tumors tend to become symptomatic late in their development and therefore are not usually resectable at the time of presentation. This is variable as, due to obstruction, jaundice may present early and compel the patient to seek help. Complete resection of the tumor offers hope of long-term survival, and of late there has been renewed interest in liver transplantation from deceased donors along with add on therapy. Prognosis remains poor.

Approximately 15,000 new cases of liver and biliary tract carcinoma are diagnosed annually in the United States, with roughly 10% of these cases being Klatskin tumors. Cholangiocarcinoma accounts for approximately 2% of all cancer diagnoses, with an overall incidence of 1.2/100,000 individuals. Two-thirds of cases occur in patients over the age of 65, with a near ten-fold increase in patients over 80 years of age. The incidence is similar in both men and women.

Biochemical markers include a normal GGT for PFIC-1 and -2, with a markedly elevated GGT for PFIC-3. Serum bile acid levels are grossly elevated. Serum cholesterol levels are typically not elevated, as is seen usually in cholestasis, as the pathology is due to a transporter as opposed to an anatomical problem with biliary cells.

While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children..

The two biggest risk factors for ovarian carcinoma are age and family history.

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. A high-contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, so a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis.

Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood to distant sites, tissues, or organs.

In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma "in situ", and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas).

In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options.

Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis of the malignancy.

The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon and bladder cancer staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.

The UICC/AJCC TNM systems are most often used. For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used.

A number of liver function tests (LFTs) are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products. serum proteins, serum albumin, serum globulin,

alanine transaminase, aspartate transaminase, prothrombin time, partial thromboplastin time.

Imaging tests such as transient elastography, ultrasound and magnetic resonance imaging can be used to examine the liver tissue and the bile ducts. Liver biopsy can be performed to examine liver tissue to distinguish between various conditions; tests such as elastography may reduce the need for biopsy in some situations.

Dermatofibrosarcoma protuberans is diagnosed with a biopsy, when a portion of the tumor is removed for examination. In order to ensure that enough tissue is removed to make an accurate diagnosis, the initial biopsy of a suspected DFSP is usually done with a core needle or a surgical incision.

The disease is typically progressive, leading to fulminant liver failure and death in childhood, in the absence of liver transplantation. Hepatocellular carcinoma may develop in PFIC-2 at a very early age; even toddlers have been affected.

Anti-viral medications are available to treat infections such as hepatitis B. Other conditions may be managed by slowing down disease progression, for example:

- By using steroid-based drugs in autoimmune hepatitis.

- Regularly removing a quantity of blood from a vein (venesection) in the iron overload condition, hemochromatosis.

- Wilson’s disease, a condition where copper builds up in the body, can be managed with drugs which bind copper allowing it to be passed from your body in urine.

- In cholestatic liver disease, (where the flow of bile is affected due to cystic fibrosis) a medication called ursodeoxycholic acid (URSO, also referred to as UDCA) may be given.

Because of its rarity, there have been no randomized clinical trials of treatment of GCCL, and all information available derives from small retrospective institutional series or multicenter metadata.

Giant-cell lung cancers have long been considered to be exceptionally aggressive malignancies that grow very rapidly and have a very poor prognosis.

Many small series have suggested that the prognosis of lung tumors with giant cells is worse than that of most other forms of non-small-cell lung cancer (NSCLC), including squamous cell carcinoma, and spindle cell carcinoma.

The overall five-year survival rate in GCCL varies between studies but is generally considered to be very low. The (US) Armed Forces Institute of Pathology has reported a figure of 10%, and in a study examining over 150,000 lung cancer cases, a figure of 11.8% was given. However, in the latter report the 11.8% figure was based on data that included spindle cell carcinoma, a variant which is generally considered to have a less dismal prognosis than GCCL. Therefore, the likely survival of "pure" GCCL is probably lower than the stated figure.

In the large 1995 database review by Travis and colleagues, giant-cell carcinoma has the third-worst prognosis among 18 histological forms of lung cancer. (Only small-cell carcinoma and large-cell carcinoma had shorter average survival.)

Most GCCL have already grown and invaded locally and/or regionally, and/or have already metastasized distantly, and are inoperable, at the time of diagnosis.

The diagnosis of SCLC, TC and AC can be made by light microscopy without the need for special tests in most cases, but for LCNEC it is required to demonstrate NE differentiation by immunohistochemistry or electron microscopy.

Chronic liver diseases like chronic hepatitis, chronic alcohol abuse or chronic toxic liver disease may cause

- liver failure and hepatorenal syndrome

- fibrosis and cirrhosis of liver

Cirrhosis may also occur in primary biliary cirrhosis. Rarely, cirrhosis is congenital.

Diagnosis is made by an assessment of symptoms, physical exam, and medical history, in conjunction with blood tests, a liver biopsy, and imaging. Diagnosis is often made following investigation of prolonged jaundice that is resistant to phototherapy and/or exchange transfusions, with abnormalities in liver enzyme tests. Ultrasound or other forms of imaging can confirm the diagnosis. Further testing may include radioactive scans of the liver and a liver biopsy.

PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out:

- serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months;

- cholangiography demonstrating biliary strictures or irregularity consistent with PSC; and,

- liver biopsy consistent with PSC (if available).

Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its non-invasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.

Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear anti-neutrophil cytoplasmic antibodies; however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20%-50% of PSC patients and, likewise, are not specific for the disease but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).

Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent.

The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation non-anastomotic biliary strictures, and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, response to treatment, and risks of disease progression.

The differential diagnoses are extensive and include: Alagille syndrome, alpha-1-antitrypsin deficiency, Byler disease (progressive familial intrahepatic cholestasis), Caroli disease, choledochal cyst, cholestasis, congenital cytomegalovirus disease, congenital herpes simplex virus infection, congenital rubella, congenital syphilis, congenital toxoplasmosis, cystic fibrosis, galactosemia, idiopathic neonatal hepatitis, lipid storage disorders, neonatal hemochromatosis, and total parenteral nutrition-associated cholestasis.

Genetic changes are very high in SCLC and LCNEC, but usually low for TC, intermediate for AC.

Malignant neoplasm of liver and intrahepatic bile ducts. The most frequent forms are metastatic malignant neoplasm of liver)

- liver cell carcinoma

- hepatocellular carcinoma

- hepatoma

- cholangiocarcinoma

- hepatoblastoma

- angiosarcoma of liver

- Kupffer cell sarcoma

- other sarcomas of liver

Benign neoplasm of liver include hepatic hemangiomas, hepatic adenomas, and focal nodular hyperplasia (FNH).