Vanishing Bile Duct Syndrome Associated with
Peripheral T Cell Lymphoma, Not Otherwise Specified,
Arising in a Posttransplant Setting
patient presented complaining of increasing abdominal
girth as well as bilateral upper quadrant pain and nau-
sea. Physical examination was significant for cachexia,
scleral icterus, and massive ascites. The posttransplant
23-year-old man with end-stage renal disease
of uncertain etiology underwent deceased do-
nor renal transplant. Seven years later, the
clinical course was reportedly free of cytomegalovirus
infection and rejection. Although scleral icterus and as-
cites were new findings, the patient had reportedly
experienced progressive cachexia with intermittent
fever of unknown origin (despite an extensive infec-
tious disease work-up) over the preceding two years.
Serum chemistries were remarkable for an alanine
aminotransferase level of 94 U/L, an aspartate amino-
transferase level of 110 U/L, alkaline phosphatase level
of 237 U/L, and a total bilirubin level of 5.1 mg/dL.
Typical viral hepatitides (A, B, C) were excluded by
serological and polymerase chain reaction-based test-
ing, although Epstein-Barr virus was detected by poly-
merase chain reaction (<1000 copies/mL serum).
Fig. 1. Hematoxylin and eosin stained sections of a liver core biopsy showing a portal based lymphohistiocytic infiltrate and severe steatosis
(A, 100? magnification); a medium size artery with infiltration by lymphoma cells, an arrow highlights the infiltrating atypical lymphocytes
(B, 400? magnification); a portal tract without an apparent interlobular bile duct, arrows highlight interlobular hepatic arterioles (C, 400? mag-
nification); and a CD3 immunohistochemical stain highlighting a T-cell predominant infiltrate (D, 100? magnification).
Address reprint requests to: Ryan M. Gill, M.D., Ph.D., Department of
Pathology, University of California, San Francisco, 505 Parnassus Avenue, Box
0134, San Francisco, CA 94143-0134. E-mail: Ryan.Gill@ucsfmedctr.org; fax:
Published online in Wiley InterScience (www.interscience.wiley.com).
Potential conflict of interest: Nothing to report.
C 2010 by the American Association for the Study of Liver Diseases.
Results from coagulation testing were abnormal (inter- Download full-text
national normalized ratio ¼ 2.0). The creatinine was
markedly elevated (4.68 mg/dL) and there was evi-
dence of metabolic acidosis. The complete blood count
was normal except for slight leukocytosis (14.9 ? 109
cells/L) and neutrophilia (12.7 ? 109cells/L). Com-
puted tomography imaging confirmed massive ascites
and identified mesenteric and retroperitoneal lymphad-
enopathy. Ultrasound did not detect hepatobiliary
abnormalities and specifically, there was no evidence of
portal hypertension (further supported by a serum-as-
cites albumin gradient of 0.7). To further assess the
etiology of acute liver dysfunction, a transjugular liver
biopsy was performed.
Histological sections of the liver core biopsy show
hepatic parenchyma with severe (grade 3) macrovesicu-
lar steatosis and a primarily portal-based lymphohistio-
cytic infiltrate (Fig. 1A). Relatively monomorphous
smudgy chromatin, infiltrate the endothelium and
focally extend into lobular parenchyma (Fig. 1B).
Cholestasis and ductopenia were appreciated (0 of 13
[0%] portal tracts with interlobular bile ducts) (Fig.
1C); the latter was confirmed by absence of cytokera-
tin-7 immunostaining. Steatosis in this biopsy may
reflect the patient’s nutritional state, particularly given
that the overall features do not appear characteristic of
steatohepatitis and that the patient did not have other
risk factors for fatty liver disease. The infiltrate was
composed predominantly of T cells (CD3/CD4-posi-
tive) with aberrant loss of CD7 (Fig. 1D), and without
coexpression of Epstein-Barr virus (as determined by
Epstein-Barr virus-encoded RNA in situ hybridiza-
tion), CD30, or CD20. This immunophenotype was
consistent with flow cytometric findings obtained con-
currently from a retroperitoneal lymph node fine-nee-
dle aspirate (and also from ascites fluid, thereby sup-
porting an etiologic role for malignancy in this
patient’s massive ascites) with the lack of CD20
expression arguing against a diagnosis of B cell lym-
phoma and the lack of CD30 expression arguing
against classification as an anaplastic large cell lym-
phoma. Aberrant loss of CD7 expression and identifi-
cation of clonal rearrangement of the T cell receptor
gamma chain gene, determined by polymerase chain
reaction amplification, further support consideration of
a neoplastic T cell population and, taken together with
the morphology, other immunophenotypic findings,
and clinical context, are consistent with a peripheral T
cell lymphoma, not otherwise specified, arising in a
posttransplant setting (i.e., a monomorphic T cell
posttransplant lymphoproliferative disorder). An etiolo-
gic role for immunosuppression is unclear in this
Vanishing bile duct syndrome (i.e., ‘‘idiopathic
adulthood ductopenia’’) has been histologically defined
as the absence of interlobular bile ducts in at least
50% of portal tracts1and has been well described in
association with classical Hodgkin lymphoma,2,3either
from direct damage by lymphoma cells or more likely
through paraneoplastic bile duct destruction by lym-
phoma-derived cytokines.4In at least one report, these
histologic findings are reversible with successful chem-
otherapy.5Other ductopenic entities in the differential
diagnosis in adults would primarily include primary
sclerosing cholangitis, primary biliary cirrhosis, auto-
immune cholangiopathy, sarcoidosis, and drug-induced
This case represents the first report of posttransplant
peripheral T cell lymphoma, not otherwise specified,
in association with bile duct paucity. Although a cyto-
kine-mediated paraneoplastic effect could represent the
underlying mechanism, direct damage may be likely
given the extent of portal-based involvement in this
case. Following treatment with a single dose of cyclo-
phosphamide, this patient experienced catastrophic
decline in all organ functions and died 5 weeks after
admission to the hospital.
RYAN M. GILL, M.D., PH.D.
LINDA D. FERRELL, M.D.
Department of Pathology
University of California San Francisco
San Francisco, CA
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Northup PG. A case of vanishing bile duct syndrome and IBD second-
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4. Hubscher SG, Lumley MA, Elias E. Vanishing bile duct syndrome: a
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HEPATOLOGY, Vol. 51, No. 5, 2010GILL AND FERRELL1857