—  SPECIALTY CONFERENCE HANDOUT  —

Liver Pathology
Thursday, February 16, 2006 - 7:30 PM
Centennial I




Moderator:

Mary Kay Washington
Vanderbilt University Medical Center
Nashville, TN


Disclosure: The speakers have indicated they have nothing to disclose.


Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view

Case 1

Submitted by:
Cynthia Behling
University of California
San Diego, CA

Clinical Summary:

The patient is currently a 9 year old obese Hispanic boy who had initially been referred to hepatology clinic at the age of 4 when hepatomegaly was discovered by his pediatrician during a well care visit. A liver biopsy was performed and showed steatosis . Etiologies of liver disease other than steatosis were excluded. No specific treatment was initiated except for dietary counseling and discussion of healthy lifestyle.

The patient continued to receive care from his pediatrician but recently returned to hepatology for followup of his liver condition, because of excess weight and a concern for the development of diabetes.

Past Medical History
The patient was born at 8 months gestation after an uneventful prenatal course. He weighed 5 lbs 4 oz at birth. Developmental milestones were met. When he was initially referred to hepatology at the age of 4, he was noted to be "overweight". The patient has mild asthma. His dietary intake is notable for 2-3 regular sodas per day, candy, fried cheese snacks and ice cream on a daily basis, fast food meals twice a week large portion sizes and 4-5 hours of television viewing per day. He does not regularly exercise.

Family history
The patient's father is morbidly obese and has hypertension and type 2 diabetes. The patient's mother is in good health. Maternal and paternal relatives have diabetes, hypertension, high cholesterol.

Medications
Inhaled albuterol PRN

Review of Systems
Non contributory

Physical Exam
At the time of his return to Heptology Clinic at the age of 9, the patient weighed 55.7 kg and measured 135 cm in height. BMI was 30.56. The remainder of the physical exam was normal except for the presence of severe acanthosis nigricans around the neck and in the axilla bilaterally.

LABS
Significant laboratory abnormalities include ALT 383, AST 257, GGT 171. Fasting glucose was 92.

A second liver biopsy was performed. On the basis of the results, the patient was eligible for and consented to be part of an NIH sponsored treatment trial and is currently enrolled in the trial.

Both liver biopsies are included for review.


Case 1 - Figure 1 - First biopsy, low power view of Masson stain.

Case 1 - Figure 2 - First biopsy, portal tracts.

Case 1 - Figure 3 - First biopsy, high power view of central vein on Masson stain.



Case 1 - Figure 4 - Second biopsy, low power view of Masson stain.

Case 1 - Figure 5 - Second biopsy, low power view of Masson stain.

Case 1 - Figure 6 - Second biopsy, high power view of portal tract.



Case 1 - Figure 7 - Second biopsy, Masson stain of portal tract.

Case 1 - Figure 8 - Second biopsy, portal inflammatory infiltrate.

Case 1 - Figure 9 - Second biopsy, Masson stain of central vein.




Case 2

Submitted by:
Charles Lassman
University of California
Los Angeles, CA

Clinical Summary:

The patient is a 22 year old woman, G3P1, s/p C-section for full-term pregnancy, transferred to UCLA Medical center with deep jaundice and acute liver failure. There was no prior history of liver disease. She was approximately 38 weeks gravid when she noted ankle swelling, and when elevated blood pressure was detected. There was no pruritus and no alteration in mental status. She presented to a local Medical Center (1 week prior to transfer) with an approximately a 1-week history of increasing jaundice. Upon admission, she was noted to be deeply jaundice and anemic. The fetus was bradycardic. A STAT C-section was performed, and the baby has reportedly been doing well post-delivery.

Following delivery, she developed hypotension and was transferred to the ICU for close monitoring. There, she was given PRBC's and FFP for anemia and coagulopathy. She remained afebrile. On post-operative day #1, she was noted to be somewhat lethargic. Her serum bilirubin continued to rise, though her transaminases remained low. She developed progressive thrombocytopenia to 43,000. She was started on IV antibiotics. Over the subsequent days, her coagulopathy progressed with increasing jaundice requiring supportive transfusions. Her renal function progressively worsened. She also developed increasing abdominal distention and discomfort. Paracentesis revealed bloody fluid without obvious infection. In view of her worsening clinical picture, she was transferred for a higher level of care. The clinical differential diagnosis included acute fatty liver of pregnancy vs. HELLP. After transfer, coagulopathy worsened, renal function deteriorated, encephalopathy developed, and the bilirubin continued to rise. The AST and ALT remained mildly elevated. The patient underwent orthotopic liver transplantation approximately 2 after initial presentation and one week after C-section.

  OLT-14 days OLT-7days OLT - 1day
AST 51 81 87
ALT 38 32 41
Total bili 20.7 34.3 41.5
Alk phos 333 252 173
HCT 30.5    
PLTS 75    
WBC 11.7 30.6  


Case 2 - Figure 1 - Low power view of explanted liver.

Case 2 - Figure 2 - Portal tract.

Case 2 - Figure 3 - Medium power view of central vein and portal tracts.



Case 2 - Figure 4 - High power view of portal tracts showing cholangiolar cholestasis.

Case 2 - Figure 5 - High power view of portal tract.

Case 2 - Figure 6 - Medium power view of central vein.



Case 2 - Figure 7 - High power view showing canalicular cholestasis.

Case 2 - Figure 8 - High power view of portal tract.

Case 2 - Figure 9 - Low power view of reticulin stain.



Case 2 - Figure 10 - Portal structures on reticulin stain.

Case 2 - Figure 11 - Centrilobular area on reticulin stain.



Case 2 - Figure 12 - Low power, Masson stain.

Case 2 - Figure 13 - High power, Masson stain.




Case 3

Submitted by:
Raouf E. Nakhleh
Mayo Clinic
Jacksonville, FL

Clinical Summary:

A 60yo Caucasian male with end-stage liver disease secondary to alcohol use undergoes liver transplantation. At the time of transplant, the patient had refractory ascites requiring a TIPS procedure a year prior. The native liver weight was 1210gm and was diffusely nodular. Near the hilum a prominent 1.2cm tan nodule was present and is seen on the slides.


Case 3 - Figure 1 - Low power view of 1.2 cm parenchymal nodule

Case 3 - Figure 2 - Variable cellularity within the nodule

Case 3 - Figure 3 - The nodule is well circumscribed, with a pushing border



Case 3 - Figure 4 - Variation in cell size and density within the nodule

Case 3 - Figure 5 - Rounded cells with eosinophilic cytoplasm and peripheral clearing

Case 3 - Figure 6 - Higher power view of epithelioid cells



Case 3 - Figure 7 - Cells containing fat are focally present.

Case 3 - Figure 8 - High power view of lesional cells.

Case 3 - Figure 9 - High power view of cells showing cytoplasmic clearing.



Case 3 - Figure 10 - High power view of spindle cells

Case 3 - Figure 11 - Immunohistochemical stain for HMB-45 shows diffuse positivity within the nodule.

Case 3 - Figure 12 - HMB 45. A granular cytoplasmic staining pattern is present in a majority of the lesional cells.



Case 3 - Figure 13 - Immunohistochemical stain for actin shows patchy staining within the nodule.

Case 3 - Figure 14 - Actin. Epithelioid and spindle cells within the nodule are immunoreactive for actin.




Case 4

Submitted by:
David Kleiner
National Institutes of Health
Bethesda, MD

Clinical Summary:

The patient is a 23 year old man with a history of recurrent pulmonary, hepatic and bone infections since young childhood. These infections have required repeated hospitalizations and chronic administration of antibiotics and antifungals. This time he was admitted for investigation of sinusitis and during the work-up was noted to have an elevated liver associated enzymes (Alkaline phosphatase 866 (range 37-116), ALT 52 (range 6-41), AST 37 (range 9-34) and total bilirubin of 0.6 mg/dL). Imaging using ultrasound, CT and MRI showed multiple hepatic lesions consistent with abscesses. A CT guided aspirate grew Staph. aureus and Strep. mitis. He was started on Ceftriaxone, Vancomycin and Rifampin and discharged, but returned one week later with right upper quadrant pain, fatigue and chills. He was taken to surgery where drains were placed and wedge resections of liver were performed. One of the specimens was a wedge of liver measuring 7 x 4.5 x 3 cm. Sectioning revealed multiple small firm white nodules measuring up to 0.4 cm, but no frank abscesses. Hemorrhage and fibrosis was noted on one edge of the specimen. The section submitted for review was selected from an area without obvious gross parenchymal lesions.


Case 4 - Figure 1 - Hepatic abscess from one of the other liver specimens submitted on this patient (10x, H&E)

Case 4 - Figure 2 - Low power overview of hepatic parenchyma (4x, H&E)

Case 4 - Figure 3 - Low power overview of hepatic parenchyma (4x, H&E)



Case 4 - Figure 4 - One of numerous collections of pigmented macrophages (40x, H&E)

Case 4 - Figure 5 - Scattered granulomas were seen. This one may have been located in or near a portal area (20x, H&E)

Case 4 - Figure 6 - Another example of the granulomatous inflammation (20x, H&E)



Case 4 - Figure 7 - Central vein with inflammation (40x, H&E)

Case 4 - Figure 8 - Portal area with obliterated duct (10x, H&E)



Case 4 - Figure 9 - Large duct with inflammation (10x, H&E)

Case 4 - Figure 10 - Small duct with periductal fibrosis and inflammation (40x, H&E)




Case 5

Submitted by:
John Hart
University of Chicago
Chicago, IL

Clinical Summary:

This 57-year-old male was diagnosed with chronic HBV hepatitis in 1991. Laboratory evaluation at that time revealed a positive serum HBsAg test but a negative HBeAg test. A liver biopsy in 1994 documented the presence of cirrhosis. An abdominal ultrasound examination and CT scan performed in 1998 revealed two nodules that were more than 4 cm in greatest dimension, as well as several smaller lesions. None of the lesions was regarded as radiographically diagnostic of hepatocellular carcinoma. The serum AFP at that time was 30 ng/ml. A percutaneous needle biopsy of the largest nodule was read as atypical macroregenerative nodule (borderline lesion). The patient was treated with Lamivudine and followed with serial MRI examinations and serum AFP levels. The two large lesions remained essentially unchanged and the serum AFP level remained stable.

On 4/3/01 the patient underwent orthotopic liver transplantation. Examination of the explanted native liver revealed cirrhosis with six distinct nodules, including 6.0 cm and 5.0 cm masses. Sections revealed that two of the smaller lesions (3.5 and 3 cm) were well-differentiated hepatocellular carcinomas. There were also two macroregenerative nodules. Sections of the two largest lesions were more difficult to precisely classify. A section from the largest mass is submitted for your review. The patient has had no evidence of recurrent hepatocellular carcinoma in the post-transplant period, with last follow-up on 3/6/05.


Case 5 - Figure 1 - Interface between largest nodule and adjacent liver.

Case 5 - Figure 2 - Reticulin stain showing interface between nodule and adjacent liver.

Case 5 - Figure 3 - Medium power view of nodule.



Case 5 - Figure 4 - Non-triadal vessels within nodule.

Case 5 - Figure 5 - Vessels within nodule

Case 5 - Figure 6 - Reticulin stain of nodule



Case 5 - Figure 7 - Cytoplasmic inclusions within hepatocytes

Case 5 - Figure 8 - Inflammatory infiltrate in adjacent liver

Case 5 - Figure 9 - Additional section of nodule