Vanishing bile duct syndrome associated with peripheral T cell lymphoma, not otherwise specified, arising in a posttransplant setting.
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ABSTRACT: Vanishing bile duct syndrome has been associated with different pathologic conditions (adverse drug reactions, autoimmune diseases, graft versus host disease, and cancer). Though its causes are unknown, an immune-related pathogenesis is the most likely one. Vanishing bile duct syndrome can evolve to hepatic failure and, eventually, to death. The treatment is uncertain, but it needs the resolution of the underlying pathologic condition.BMC Research Notes 08/2014; 7(1):529.
- Canadian journal of gastroenterology = Journal canadien de gastroenterologie 07/2011; 25(7):356-7. · 1.97 Impact Factor
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ABSTRACT: BACKGROUND: Posttransplantation lymphoproliferative diseases (PTLD) are mainly Epstein-Barr virus (EBV)-associated disorders of B-cell origin. Due to the rarity of monomorphic T-cell PTLD (T-PTLD), knowledge about pathogenesis, risk factors, therapy, and prognosis relies predominantly on case reports and small series. Therefore, we aimed to provide an overview and a retrospective analysis of this rare PTLD subtype. METHODS: We analyzed all available articles on T-PTLD in the PubMed database as well as in our own databases (Institute of Pathology/Department of Paediatric Haematology and Oncology, Hannover Medical School) from 1988 to 2010. Reevaluated parameters were gender, age, transplanted organ, immunosuppressant regimen, time between transplantation and T-PTLD manifestation, T-PTLD subtype, virus positivity, localization, therapy, and follow-up. RESULTS: A total of 163 cases were evaluated. We found that hematopoietic stem cell transplantation was associated with early-onset T-PTLD, whereas late onset occurred after immunosuppression with steroids and azathioprine without administration of calcineurin inhibitors. The major independent favorable prognostic factors were T-PTLD of the large granular lymphocytic leukemia subtype, young age, and a combination of radiotherapy/radiochemotherapy and reduced immunosuppression, whereas the hepatosplenic T-cell lymphoma subtype and cases with involvement of bone marrow, the central nervous system, or graft had an adverse prognosis. CONCLUSION: T-PTLD is a heterogeneous group of different aberrant T-cell proliferations and represents a significant complication following transplantation, showing a uniformly poor prognosis.Transplantation 01/2013; · 3.78 Impact Factor
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-
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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A cause of chronic cholestatic liver disease and biliary cirrhosis. J Hepa-
2. DeBenedet AT, Berg CL, Enfield KB, Woodford RL, Bennett AK,
Northup PG. A case of vanishing bile duct syndrome and IBD second-
ary to Hodgkin’s lymphoma. Nat Clin Pract Gastroenterol Hepatol
3. Lefkowitch JH, Falkow S, Whitlock RT. Hepatic Hodgkin’s disease sim-
ulating cholestatic hepatitis with liver failure. Arch Pathol Lab Med
4. Hubscher SG, Lumley MA, Elias E. Vanishing bile duct syndrome: a
possible mechanism for intrahepatic cholestasis in Hodgkin’s lymphoma.
5. Crosbie OM, Crown JP, Nolan NP, Murray R, Hegarty JE. Resolution
of paraneoplastic bile duct paucity following successful treatment of
Hodgkin’s disease. HEPATOLOGY 1997;26:5-8.
HEPATOLOGY, Vol. 51, No. 5, 2010GILL AND FERRELL1857