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Metastatic Melanoma

8/26/19 : Dr. Mendez presents a case of an elderly gentleman who presented with painless jaundice, generalized weakness and fatigue ultimately diagnosed with metastatic melanoma.





1. What are the main components of liver biochemistries?

  • AST and ALT are present in hepatocytes (though can vary with other confounding injuries). AST is found in cardiac muscle, skeletal muscle, kidney, and brain. ALT levels do correlate to degree of abdominal adiposity. Elevated AST/ALT in the appropriate setting may indicate hepatocellular damage

  • Alk phos is found in the liver and bones. Elevated levels of alk phos result typically from inflammation of the biliary tree or bile flow abnormalities. This can either be fractionated to determine source, or measured simultaneously with GGT to diagnose cholestasis

  • Tests of hepatic synthetic function include albumin and PT/INR


2. What is the approach to patients with abnormal liver biochemistries?

  • As per usual, start with history and physical. Looking to identify risk factors for liver disease (hepatotoxins? risk for viral hepatitis? other diseases that are risks?)

  • PE to look for clues to etiology as well as signs of chronic liver disease (muscle wasting? spider nevi? ascites? lymphadenopathy? Increased JVP?). This guides further testing.

  • Classify liver test abnormalities - hepatocellular, cholestatic, or isolated hyperbilirubinemia. If both are elevated, characterize by the predominant abnormality. Can further classify based on timeline: acute (less than 6 weeks), subacute (6wks - 6 months), or chronic (>/= 6 mo.).


3. Hepatocellular pattern: disproportionate elevation in AST/ALT compared to alk phos, serum bili may be elevated, synthetic function may be abnormal

  • Viral hepatitis

  • Alcohol/drugs: AST:ALT ration is often 2:1 with elevated GGT

  • Toxins

  • Autoimmune

  • Wilson disease: can also have AST>ALT, accompanied by coombs-negative hemolytic anemia

  • Ischemia: Budd Chiari or ischemic hepatitis

  • Congestive hepatopathy

  • NASH


4. Cholestatic pattern: disproportionate elevation in alk phos compared with AST/ALT, serum bili may be elevated, synthetic function may be abnormal



--Extrahepatic:

  • Choledocholithiasis

  • Malignant obstruction

  • Biliary strictures

  • Infections

--Intrahepatic

  • Drugs/toxins

  • PBC/PSC

  • Pregnancy

  • TPN

  • Infiltrative diseases (amyloid, sarcoid, TB)

  • Metastatic carcinoma

--Testing: usually starts with RUQ ultrasound to evaluate for extrahepatic cholestasis and look at hepatic parenchyma. Next steps depend on what is seen - if US shows acute obstruction (stone or malignancy), ERCP should be considered. If cholestasis is more chronic or pts are high risk, could consider MRCP or CT.

In patients with intrahepatic cholestasis, AMA, ANA, anti-smooth muscle antibodies should be checked. Viral hepatitis panels, MRCP can also help to evaluate. Liver biopsy should be obtained if all testing is nonconfirmatory.


5. Isolated hyperbili: elevated bili in the setting of normal AST/ALT and Alk phos

--Unconjugated

  • Increased production (hemolysis, wilson disease)

  • Impaired uptake (heart failure, drugs)

  • Impaired conjugation (Crigler-Najjar, gilbert, hyperthyroidism)

--Conjugated

  • A variety of genetic disorders

  • Choledocholithiasis

  • Intrinsic and extrinsic tumors

  • PSC

  • AIDs cholangiopathy


6. What is the differential for metastases to the liver?

Triphasic CT (non-contrast, arterial and portal venous phases) can help differentiate among lesions in the liver.

-Lesions from the colon, stomach and pancreas usually show lower attenuation

-Neuroendocrine tumors, renal cell carcinoma, breast carcinoma, melanoma and thyroid carcinoma are more rapidly enhancing on arterial phase of enhancement


7. Learning points about melanoma:


Staging and breslow depth are most important in prognosis and management.

-Stage 0: in situ, treat with surgical removal

-Stage 1: <1mm

-Stage 2: 1-2mm

-Stage 3: one or more lymph nodes involved

-Stage 4: advanced to distant body area


In metastatic melanoma, BRAF mutation can predict a therapeutic response.

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