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Liver Pathology
Sunday, February 27, 2005 - 7:30 PM
Rivercenter Salon M,G
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Moderator:
Mary Kay Washington
Vanderbilt University Medical Center
Nashville, TN
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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
Submitted by:
Milton J. Finegold
Texas Children's Hospital
Houston, TX
Three weeks prior to admission a 13 year old boy with cystic acne presented to his dermatologist to
begin Accutane and had blood drawn per protocol. The acne was originally treated two months earlier
with oral minocycline for one month. His liver functions at that time included total bilirubin 0.8
mg/dl, AST 22 U/L, ALT 17 U/L, and alkaline phosphatase 202 U/L. A complete blood count revealed an
"increased white blood cell count". He proceeded to take two one-half doses of Accutane as
prescribed. Five days prior to admission he had four days of nausea and vomiting. He was
hospitalized, rehydrated, given vitamin K and his nausea and vomiting improved. He was transferred to
Texas Children's Hospital due to the findings of lymphoblasts on a peripheral smear as well as
abnormal liver chemistries. At the time of admission, he complained of increased fatigue, easy
bruising, intermittent chills and fevers for over the past one and one-half weeks, and jaundice for
the prior three days. There was a 10 pound weight loss in 2 weeks.
About two years ago, he had iron deficiency anemia, which was treated briefly with oral iron sulfate.
His immunizations were up to date and he had completed his Hepatitis B series. His food allergies
included strawberries but he did not have any known allergies to medications. Nutritional
supplementation consisted of Brewer's yeast pills from GNC and Wal-Mart brand Vitamin E 400 IU daily.
At TCH he had hemoglobin 9.8 g/dl, hematocrit 28.8%, platelets 22 x
103/UL and white blood cells 3.41 x 103/UL. The
differential showed 10% neutrophils, 8% bands, and 77% lymphocytes. Peripheral smear revealed
"relative lymphocytosis with atypical blast like cells". Liver tests revealed elevated AST 3095 U/L,
ALT 3872 U/L and GGT 124 U/L with alkaline phosphatase 192 U/L. Conjugated bilirubin was 9 mg/dl and
uric acid was 6.6 mg/dl. Viral serology for Hepatitis A, B, and C were negative except for the
hepatitis B surface antibody. Pro-time was 25.4 seconds with an INR of 2.3. His PTT was within
normal limits at 32.6 seconds and D-dimer was negative.
Negative serological viral studies included cytomegalovirus IgM and IgG, Human Immunodeficiency Virus,
Herpes virus IgM and IgG, Parvovirus B19 IgM and IgG. Epstein Barr virus IgG was elevated at 640. A
rapid toxicology screen was negative except for benzodiazepines. Serology for antinuclear antibody
and smooth muscle IgG were negative. Alpha-1 antitrypsin and factor V Leiden were normal. Blood
copper level within normal limits. Ammonia was slightly elevated at 50 μmol/L.
The marrow biopsy contained 98% blasts, which marked as early B-lineage ALL (CD10, 19, 20, 22 and
HLA-DR+). Karyotyping and FISH revealed t (5q; 9p) (12;22) and t (9p;16q) (22;24). There were no
chromosome 4 or 10 abnormalities and probes specific for BCR/ABL and TEL/AML1 were negative. The next
day Allopurinol and prednisone (40mg/m2 /day) were initiated in preparation for
chemotherapy. Other medications included Ceptaz, Zofran and Zantac. The Ceptaz was initiated as a
precaution due to low grade fevers, even though blood cultures remained negative. The next day he
underwent a liver needle biopsy at the same time that a left subclavian catheter was placed.
Question:
The pathologic findings in this biopsy are most consistent with:
- Viral hepatitis.
- Autoimmune hepatitis.
- Lymphoblastic leukemia.
- Accutane-induced hepatic necrosis.
- Minocycline toxicity.
Submitted by:
Dale C. Snover
Fairview Southdale Hospital
Minneapolis, MN
 | 55 year old female with mild transaminase elevations (2-3X nl), and mild elevation of alkaline phosphatase |
| Hepatitis studies negative |
| No history of diabetes or obesity |
| Numerous medications including nitrofurantoin, amitriptyline, ciprofloxicin |
| Liver biopsy performed (history as provided at the time of biopsy) |
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Submitted by:
Romil Saxena
Indiana University School of Medicine
Indianapolis, IN
A 21 year old Hispanic female underwent liver transplantation for massive hepatomegaly, intractable
abdominal pain and multiple enhancing liver lesions consistent with hepatic adenomas. The patient has
had a long-standing medical history since childhood that includes multiple episodes of hypoglycemia,
epistaxis, bleeding gums, hepatomegaly and chronic abdominal pain. An abdominal CT scan in November
1999 showed diffuse increased echogenicity of the liver without any focal lesions. In March, 2004 she
was admitted for increasing abdominal pain – mainly over the right hypochondrium and epigastrium,
nausea, vomiting and episodes of hypogylcemia. Her mother had also noticed an increase in the
abdominal girth since January 2004. A CT scan of her abdomen showed multiple enhancing lesions
consistent with hepatic adenomas. Her liver function tests were as follows: bilirubin 1.0, alkaline
phosphatase 77, AST 72 and ALT 63, ammonia 28 and INR 1.03. She continued to have abdominal pain and
nausea despite medication and during a repeat admission, her lipase was over 1000 and triglycerides
were 1105, suggestive of chemical pancreatitis. A CT scan of the abdomen did not show any changes in
the liver lesions; alpha-feto protein was 1.6. The pancreatitis responded to discontinuation of oral
intake, TPN and Lopid to lower her triglycerides. She was worked up for liver transplantation during
which time a lytic lesion was found in her left shoulder and a mass was present in her mediastinum.
She underwent surgical resection of the 2 lesions.
In September 2004, she underwent orthotopic liver transplantation. The liver weighed 3080 grams, and
was soft and pale in appearance. Eight nodules measuring between 0.3 to 3.5 cm in diameter were
present, 6 in the right and 2 in the left lobe. A representative section is submitted.
Case 3 - Figure 1 - The liver showed extensive macro and microvesicular steatosis.
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Case 3 - Figure 2 - High power view illustrating macrovesicular steatosis.
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Case 3 - Figure 3 - High power view illustrating microvesicular steatosis in which numerous small fat droplets have accumulated around a central nucleus.
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Case 3 - Figure 4 - An adenoma consisting of crowded small basophilic hepatocytes arranged in one to 2 cell thick plates. Focal sinusoidal dilatation is present.
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Case 3 - Figure 5 - Hepatocellular carcinoma consisting of sheets of cells with abundant eosinophilic cytoplasm and centrally placed nuclei with prominent eosinophilic nucleolus.
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Submitted by:
Sanjay Kakar
VA and University of California San Francisco Medical Center
San Francisco, CA
This 40 year old woman presented with fatigue and abdominal pain. Physical exam revealed low grade
ascites, mild jaundice, mildly enlarged liver and splenomegaly. There was a history of bloody
diarrhea lasting for a few months two years back, but it was not clear if the diagnosis of
inflammatory bowel disease was clearly established at that time. There were no gastrointestinal
symptoms at this presentation. Alkaline phosphatase was five times normal and transaminaseswere
barely out of the normal range.A liver biopsy was performed (since the needle biopsy has limited
material, an open biopsy obtained at a later date is being provided. The needle biopsy and open
biopsy show similar features).
Case 4 - Figure 1 - Sinusoidal dilatation and congestion predominantly affecting zone 3 of the liver.
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Case 4 - Figure 2 - Pericentral fibrosis accompanied by sinusoidal dilatation and congestion.
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Case 4 - Figure 3 - Many portal tracts are expanded and show bile ductular proliferation.
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Case 4 - Figure 4 - Bile ductular proliferation is accompanied by a mild lymphoplasmacytic infiltrate.
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Case 4 - Figure 5 - In addition to pericentral fibrosis, there is portal-based fibrosis with irregular septa.
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Submitted by:
Neil D. Theise
Beth Israel Medical Center
New York, NY
The patient is a 56 year old man with hepatitis B cirrhosis who underwent liver transplantation. A
2.2 cm distinctive nodule was found upon sectioning the explanted liver. Sections are from the
nodule.
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