AJR 2001; 177:1057-1059
© American Roentgen Ray Society
Posttransplantation Lymphoproliferative Disorder
Osseous and Hepatic Involvement
Shaifali Kaushik1,
Ann S. Fulcher1,
William J. Frable2 and
David A. May1
1
Department of Radiology, Medical College of Virginia, Virginia Commonwealth
University, 401 N. 12th St., Box 980615, Richmond, VA 23298-0615.
2
Department of Pathology, Medical College of Virginia, Virginia Commonwealth
University, Box 980115 Richmond, VA 23298-0615.
Received February 21, 2001;
accepted after revision April 17, 2001.
Address correspondence to S. Kaushik.
Introduction
Posttransplantation lymphoproliferative disorder is an abnormal
proliferation of B lymphocytes found in solid-organ transplant recipients
receiving immunosuppression treatment
[1]. A relationship with
primary or reactivated Epstein-Barr virus has been established
[2]. It has been postulated
that posttransplantation lymphoproliferative disorder occurs as a result of
the marked immunosuppression required to prevent graft rejection
[1,
3]. In most patients, the
disorder occurs within the first year after organ transplantation
[3]. A series by Nalesnik
[3] found that the rate of
posttransplantation lymphoproliferative disorder was lowest (1%) among renal
transplant recipients and highest (4.6%) among liver or heart—lung
transplant recipients. Central nervous system, tonsil, lymph node, thoracic,
and abdominal manifestations of posttransplantation lymphoproliferative
disorder have been well documented
[4,5,6].
To our knowledge, bone marrow involvement with posttransplantation
lymphoproliferative disorder has not been described. We present a case of
synchronous osseous and hepatic posttransplantation lymphoproliferative
disorder in a renal allograft recipient.
Case Report
A 25-year-old man who had end-stage renal disease associated with focal
segmental glomerulosclerosis had undergone living-related-donor renal
transplantation. Eighteen months after renal transplantation, liver MR imaging
was performed to determine the cause of abnormal results of liver function
tests; the MR images revealed two liver masses and bilateral iliac lesions.
The larger liver mass measured 3 cm and was located in the anterior segment of
the right hepatic lobe, and the smaller lesion measured 2 cm and was located
in the posterior segment of the right hepatic lobe.
Both masses appeared hyperintense relative to normal liver tissue on turbo
spin-echo T2-weighted and half-Fourier acquisition single-shot turbo spin-echo
sequences (Fig. 1A) and were
hypointense relative to normal liver tissue on gradient-echo T1-weighted
sequences. After the IV administration of gad-olinium dimeglumine, the masses
enhanced during the arterial and portal venous phases but became isointense to
liver parenchyma during the equilibrium phase. No lymphadenopathy was
noted.
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Fig. 1A. —25-year-old man with renal transplant who developed liver and
osseous lesions 18 months after solid-organ transplantation. Coronal
half-Fourier acquisition single-shot turbo spin-echo MR image (TR/TE,
infinite/6; flip angle, 150°) of liver shows 3-cm mass (arrow) in
right hepatic lobe that is hyperintense compared with hepatic parenchyma.
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The left ilium contained a well-circumscribed mass that had lower signal
intensity on T1-weighted images than the adjacent bone marrow. Enhanced
gradient-echo T1-weighted images revealed that the lesion enhanced to a
greater degree than the adjacent marrow
(Fig. 1B). A second bone marrow
lesion with similar signal intensity features was noted in the right ilium
(Fig. 1B). This lesion was not
associated with cortical destruction or soft-tissue extension. Both lesions
were of higher signal intensity on T2-weighted images than the adjacent bone
marrow (Fig. 1C). Unenhanced CT
was performed on the same day as MR imaging to localize the left iliac mass
for biopsy. The CT scan showed mixed sclerotic and lytic foci in the mass
(Fig. 1D). The right iliac
lesion was purely sclerotic.
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Fig. 1B. —25-year-old man with renal transplant who developed liver and
osseous lesions 18 months after solid-organ transplantation. Enhanced axial
T1-weighted fat-suppressed gradient-echo MR image (200/4.4; flip angle,
4.4°) shows enhancement of left iliac marrow lesion (straight
arrow) and soft-tissue components (open arrows). Note enhancing
right iliac lesion (curved solid arrow). Both lesions represented
osseous involvement by posttransplantation lymphoproliferative disorder. Renal
transplant (curved open arrow) is visible.
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Fig. 1C. —25-year-old man with renal transplant who developed liver and
osseous lesions 18 months after solid-organ transplantation. Axial T2-weighted
turbo spin-echo MR image (3500/138) of pelvis without fat suppression shows
minimally hyperintense marrow lesion (straight solid arrow) in left
ilium. Adjacent soft-tissue component (straight open arrows) is seen
as hyperintense signal in iliacus and gluteal muscles. A second lesion of
similar signal intensity is seen in right ilium (curved solid arrow).
Both lesions represented osseous involvement by posttransplantation
lymphoproliferative disorder.
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Fig. 1D. —25-year-old man with renal transplant who developed liver and
osseous lesions 18 months after solid-organ transplantation. Axial CT image of
pelvis shows mixed-attenuation lesion in left ilium with discrete sclerotic
and low-attenuation foci (small arrows). Irregular, sclerotic focus
is seen in right ilium (curved arrow). Renal transplant (open
arrow) is seen anterior to right psoas muscle.
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The left iliac mass was biopsied with CT guidance. The biopsy specimens
revealed monoclonal lymphoma. Results of the cell block
(Fig. 1E) and immunoperoxidase
test were indicative of large B-cell lymphoma. A diagnosis of
posttransplantation lymphoproliferative disorder was based on the biopsy
findings and the history of organ transplantation. The liver masses and the
right iliac lesion were also assumed to represent posttransplantation
lymphoproliferative disorder because of clinical and imaging findings and
synchronicity with the left iliac lesion. Intense immunosuppression treatment
was discontinued, and the patient was treated with oral acyclovir (800 mg
three times a day) and oral prednisone (10 mg daily). No chemotherapy was
administered.
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Fig. 1E. —25-year-old man with renal transplant who developed liver and
osseous lesions 18 months after solid-organ transplantation. Photomicrograph
of cell block from fine-needle aspiration. Note replacement of marrow with
degenerated large atypical cells (arrow) compatible with appearance
of large cell lymphoma. (H and E, x 200)
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Abdominal and pelvic MR imaging conducted 2 and 6 months after the biopsy
showed a 40% decrease in the size of the lesions in the left iliac marrow and
complete resolution of the enhancing soft-tissue components
(Fig. 1F). Complete resolution
of both liver lesions occurred at 6 months. Because the progressive renal
dysfunction had been caused by rejection of the renal allograft, the patient
underwent a transplant nephrectomy and was subsequently treated with
peritoneal dialysis.
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Fig. 1F. —25-year-old man with renal transplant who developed liver and
osseous lesions 18 months after solid-organ transplantation. Enhanced coronal
T1-weighted fat-suppressed gradient-echo MR image (200/4.4; flip angle,
4.4°) obtained 6 months after termination of immunosuppression shows
decrease in size of enhancing left iliac marrow lesion (arrow).
Soft-tissue components have resolved.
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Discussion
Posttransplantation lymphoproliferative disorder is abnormal proliferation
of lymphocytes seen in recipients of solid-organ transplants who have been
treated with immunosuppression
[1]. Diagnosis of
posttransplantation lymphoproliferative disorder requires biopsy confirmation.
The histopathologic types of posttransplantation lymphoproliferative disorder
include hyperplastic infiltration by plasma cells, polymorphic, and
monomorphic. Monomorphic posttransplantation lymphoproliferative disorder has
histologic features similar to primary lymphoma. Posttransplantation
lymphoproliferative disorder should be considered as a potential diagnosis in
a transplantation patient presenting with new lesions.
Unlike treatment required for other marrow infiltrative malignancies, the
only effective treatment of posttransplantation lymphoproliferative disorder
is often the reduction or elimination of intense immunosuppressive therapy.
Radiation therapy, chemotherapy, surgery, or antiviral therapy may also be
required in some patients. The treatment response and prognosis of the
disorder are related to the clonality of the tumor; monoclonal tumors
resembling lymphoma require more aggressive therapy than polyclonal
lesions.
Extranodal disease is the hallmark of posttransplantation
lymphoproliferative disorder. The liver is the most frequent site of abdominal
involvement, occurring in 69% of all posttransplantation lymphoproliferative
disorder patients [6]. Hepatic
involvement may be diffusely infiltrative or consist of discrete lesions. Our
patient developed two discrete liver masses, which subsequently resolved after
termination of immunosuppression.
Our patient also had biopsy-proven intraosseous involvement by
posttransplantation lymphoproliferative disorder, which, to our knowledge, has
not been described previously. The frequency of such intraosseous involvement
is not known but likely is rare, given the lack of previous reports. Of all
extranodal forms of non-Hodgkin's lymphoma, primary lymphoma of bone
represents 5% of reported cases
[7]. Histopathologic features
of osseous posttransplantation lymphoproliferative disorder in our patient are
similar to non-Hodgkins (B-cell) lymphoma of bone. However, the pattient's
history of organ transplantation and his clinical response to termination of
immunosuppression led to the diagnosis of posttransplantation
lymphoproliferative disorder.
The MR imaging and CT features of osseous posttransplantation
lymphoproliferative disorder in our patient were nonspecific and could be seen
in patients with metastatic disease, infection, or primary bone lymphoma
[8]. The diagnosis of
posttransplantation lymphoproliferative disorder rested on the combination of
the histologic, clinical, and imaging findings
[8].
A case of posttransplantation Epstein-Barr virus-associated myogenic tumor
involving bone was reported in the recent literature
[9]. The histopathology in our
patient is different—that of a B-cell lymphoma.
In conclusion, we presented a case of osseous involvement by
posttransplantation lymphoproliferative disorder after renal transplantation
that we believe is the first example of osseous involvement by this entity.
Posttransplantation lymphoproliferative disorder should be considered in the
differential diagnosis of new osseous lesions in patients receiving
immunosuppression therapy after solid-organ transplantation.
References
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Introduction
Case Report
