Clinical Challenges

What is your diagnosis?

A 68-year-old woman with a history of pulmonary sarcoidosis, chronic lymphocytic thyroiditis, hyperlipidemia, and osteopenia was evaluated for elevated liver enzymes. Liver enzymes were found to be elevated 7 months earlier. Routine laboratory tests showed aspartate aminotransferase of 57 U/L (upper limit, 39 U/L), alanine aminotransferase of 54 U/L (upper limit, 52 U/L), alkaline phosphatase of 175 U/L (upper limit, 117 U/L), and total bilirubin of 0.5 mg/dL (upper limit, 1.3 mg/dL). She was on prednisone 5 mg/d, methotrexate 17.5 mg/wk, and atorvastatin 40 mg/d. Methotrexate and atorvastatin were stopped and prednisone increased to 10 mg/d.

Two months later, repeat laboratory tests showed aspartate aminotransferase of 213 U/L, alanine aminotransferase of 93 U/L, alkaline phosphatase of 1,472 U/L, and total bilirubin of 6.0 mg/dL. The initial ultrasound scan was normal. On further assessment, she complained of malaise, weight loss, shortness of breath, dry eyes, dry mouth, and insomnia. She denied any significant alcohol use. No new medications or supplements were started recently. Vital signs were normal. Physical examination was unremarkable. Viral hepatitis serologies were negative. Antinuclear antibody, anti-smooth muscle antibody, and antimitochondrial antibody were negative. She had a magnetic resonance cholangiopancreatography, which showed splenomegaly but was otherwise unremarkable. She had a liver biopsy (Figure A), which showed non-necrotizing granulomas (yellow arrows) with a chronic inflammatory lymphocytic infiltrate.

Given these findings, prednisone was increased to 20 mg. In the interim, the patient was admitted with acute acalculous cholecystitis. She had a laparoscopic cholecystectomy and an intraoperative liver biopsy. She developed respiratory failure postoperatively and was transferred to intensive care. Stress dose steroids and antibiotics were initiated. Laboratory tests showed a white blood cell count of 13.8 × 109/L, hemoglobin of 9.4 g/dL, platelets at 223 × 109/L, aspartate aminotransferase of 97 U/L, alanine aminotransferase of 63 U/L, alkaline phosphatase of 1,607 U/L, total bilirubin of 5.8 mg/dL (direct 3.3), and albumin of 2.4 g/dL. Pathology from the gallbladder (Figure B) and the intraoperative liver biopsy (Figure C) showed cells pathognomonic for the condition (green arrows).

On the basis of these findings, what is the final diagnosis?


 

Hodgkins lymphoma of the liver

The gallbladder (Figure B) as well as the intraoperative liver biopsy (Figure C; insert showing cells under higher power) showed non-necrotizing granulomas along with scattered infiltration by atypical large cells morphologically consistent with Hodgkin-Reed-Sternberg cells in a lymphoid background (Figures B, C, green arrows). Immunohistochemistry showed these were positive for CD30 (Figure D, liver biopsy), weakly positive for PAX5, and negative for CD15, CD20, CD79a, and ALK-1. Given the pathologic findings, the patient was diagnosed with Hodgkins lymphoma.

The patient had a history of mediastinoscopy and lymph node biopsy in the past at an outside hospital with reported noncaseating granulomas and no other abnormalities; those slides could not be obtained for independent review. Primary lymphomas of the liver are exceedingly rare, but advanced lymphoma can have liver involvement.1 Hodgkins lymphoma of the liver is extremely uncommon.2 It can present with fever, hepatomegaly, and jaundice.1 The diagnostic yield of a liver biopsy ranges from 5% to 10% depending on core versus wedge biopsy.1 Pathologically, there is portal inflammation and atypical histiocytic aggregates but Hodgkin-Reed-Sternberg cells are required for diagnosis. These cells stain positive for CD15 and CD30 in around 80% of cases.3 Lymphoma should remain in the differential when granulomas are seen in the liver biopsy. Our patient clinically decompensated by the time the diagnosis was confirmed. The family decided not to pursue aggressive treatment in hospital and the patient was discharged home where she expired.

References

1. in: R.N.M. MacSween (Ed.) Pathology of the liver. Edinburgh: Churchill Livingstone. ; 1979

2. Levitan R, Diamond H, Lloyd C. The liver in Hodgkin’s disease. Gut. 1961;2:60.

3. Kanel GC, Korula J. Atlas of liver pathology. Elsevier/Saunders, Philadelphia; 2005.

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