AJR 2000; 175:183-188
© American Roentgen Ray Society
CT Findings in Posttransplantation Lymphoproliferative Disorder of Renal Transplants
Thomas G. Vrachliotis1,2,
Kuldeep K. Vaswani1,
Elizabeth A. Davies3,
Elmahdi A. Elkhammas3,
William F. Bennett1 and
James G. Bova1
1
Department of Radiology, Ohio State University Medical Center, Rhodes Hall,
450 West 10th Ave., Columbus, OH 43210.
2
Present address: Department of Radiology, Beth Israel Deaconess Medical Center
and Harvard Medical School, 330 Brookline Ave., Boston, MA 02215.
3
Department of Surgery, Ohio State University Medical Center, Columbus, OH
43210.
Received September 17, 1999;
accepted after revision December 17, 1999.
Poster Exhibit at the annual meeting of the American Roentgen Ray Society,
New Orleans, May 1999.
Address correspondence to T. G. Vrachliotis.
Introduction
Posttransplantation lymphoproliferative disorder (PTLD) occurs as a direct
sequela of chronic immunosuppression. The Epstein-Barr virus is believed to
induce PTLD in most patients
[1]. Approximately 1% of kidney
transplants are affected, and, if untreated, PTLD is almost always fatal
[2]. The clinical
manifestations of PTLD are nonspecific or silent. Many cases are incidentally
detected while imaging the patient for other reasons. Therefore, the
radiologist should be familiar with the imaging manifestations of PTLD so that
early diagnosis can be made and appropriate treatment started. In this
pictorial essay, we show PTLD manifestations on CT with emphasis on transplant
kidney involvement with or without extension of the mass beyond the confines
of the transplanted kidney or to other organs.
Posttransplantation Lymphoproliferative Disorder
Malignant neoplasms are increased in the chronically immunocompromised
patient with the most common being skin, cervical, and rectal neoplasms;
Kaposi sarcoma; and lymphoma
[3]. Lymphoma in transplant
patients shows aggressive atypical features unlike the lymphomas that occur in
the general population. Furthermore, if detected early and treated by
reduction of the immunosuppressive agents, most cases will resolve. Because
these lymphomas are almost always fatal if untreated
[2], awareness of their imaging
appearance will prompt early diagnosis and intervention. The dose threshold
for an immunosuppressive drug above which PTLD increases has not been
established [4].
Most of the transplant patients who develop lymphoma are actively infected
with Epstein-Barr virus, the causative agent for infectious mononucleosis. The
virus is also believed to be a cofactor in the development of Burkitt's
lymphoma [1]. The Epstein-Barr
virus directly infects B lymphocytes in infectious mononucleosis and
immunocompromised patients and induces a diffuse polyclonal B-lymphocyte
proliferation. In infectious mononucleosis, this proliferation is ultimately
reversed mainly by an intact cytotoxic T-cell function. In immunocompromised
patients, however, weak or suppressed T-cell function leads to an excessive
B-cell proliferation which results in a disease spectrum ranging from mild
diffuse polyclonal adenopathy to malignant monoclonal lymphoma. This disease
spectrum, referred to as posttransplant or posttransplantation
lymphoproliferative disorder (PTLD), mostly occurs in transplant patients.
Most lymphomas in immunocompromised patients are of the B-cell non-Hodgkin's
type, although Hodgkin's, Burkitt's, and T-cell lymphomas have been reported
[1].
The incidence of malignancies in organ transplant patients is approximately
6% and PTLD accounts for 20% of the tumors
[3]. The frequency of PTLD
varies depending on the type of transplant: 2.2% of liver, 1% of kidney, 1.8%
of heart, and 4.6% of heart-lung transplants
[1]. Higher rates in heart,
liver, and heart-lung transplant patients occur at least partially because of
the more aggressive immunosuppression required
[1].
PTLD occurs as early as 1 month after transplantation
[4]. If azathioprine is the
immunosuppressant medication taken, the average length of time to develop PTLD
is 48 months, whereas with cyclosporine, it is 15 months
[4].
Reduction of immunosuppression is the major form of therapy for PTLD. This
treatment may be combined with the administration of acyclovir, an antiviral
agent that is given to combat the Epstein-Barr virus infection
[1,
4].
Imaging Manifestations
Extranodal disease (81%) is more common than lymphadenopathy (22%) in
patients with PTLD [5]. Single
(Figs.
1A,1B
and
2A,2B,2C)
or multiple (Figs.
3A,3B,3C,3D
and
4A,4B,4C)
organ masses are the characteristic radiographic presentations of PTLD
[6]. Any of the solid organs,
hollow viscera, abdominal, retroperitoneal and iliac lymph nodes (Fig.
5A,5B),
retroperitoneal musculature, or peritoneum of the abdomen can be involved in
PTLD [4,
5]. In a review by Miller et
al. [6] the transplanted kidney
was the most common site of involvement (47% of renal transplant patients with
PTLD).
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Fig. 1A. —76-year-old man with transplanted right kidney who presented with
signs of renal outflow obstruction necessitating nephrostomy tube placement.
Contrast-enhanced CT scan at level of renal pelvis shows nephrostomy tube in
renal pelvis and heterogeneous enhancement of tumor (arrows). A
CT-guided biopsy (not shown) found posttransplantation lymphoproliferative
disorder (PTLD). Patient underwent transplant nephrectomy because obstruction
failed to resolve.
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Fig. 1B. —76-year-old man with transplanted right kidney who presented with
signs of renal outflow obstruction necessitating nephrostomy tube placement.
Planar gallium-67 scan in anterior projection performed 1 week after A
at 48 hr after radionuclide administration shows focal area of increased
uptake in mid pelvis (arrow) consistent with PTLD and corresponding
to mass in renal pelvis. Scintigraphy was performed before transplant
nephrectomy to assess gallium avidity of tumor for future follow-up.
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Fig. 2A. —50-year-old man with kidney and pancreas transplant presented with
right-sided abdominal pain and significant drop in hemoglobin. Unenhanced CT
scan was obtained to determine retroperitoneal bleeding. No bleeding was seen.
Unenhanced axial CT scan shows transplanted kidney (K) was within normal
limits. Pancreatic transplant (P) was heterogeneous and enlarged.
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Fig. 2B. —50-year-old man with kidney and pancreas transplant presented with
right-sided abdominal pain and significant drop in hemoglobin. Unenhanced CT
scan was obtained to determine retroperitoneal bleeding. No bleeding was seen.
Transverse sonogram through right iliac fossa shows well-circumscribed
hypoechoic mass arising from transplanted pancreas (arrows).
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Fig. 2C. —50-year-old man with kidney and pancreas transplant presented with
right-sided abdominal pain and significant drop in hemoglobin. Unenhanced CT
scan was obtained to determine retroperitoneal bleeding. No bleeding was seen.
On longitudinal sonogram through pancreatic transplant, organ is seen replaced
by mixed echogenicity mass (arrows). No normal pancreatic tissue is
sonographically identified. Patient underwent CT-guided biopsy (not shown);
pathology disclosed posttransplantation lymphoproliferative disorder.
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Fig. 3A. —43-year-old woman with kidney and pancreas transplant who underwent
CT as part of her diagnostic evaluation for malfunctioning renal transplant.
Contrast-enhanced axial CT scan through transplanted kidney shows small
low-attenuation nonenhancing area that was interpreted as simple cyst
(arrow). Renal transplant was otherwise normal on CT. P = pancreatic
transplant.
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Fig. 3B. —43-year-old woman with kidney and pancreas transplant who underwent
CT as part of her diagnostic evaluation for malfunctioning renal transplant.
Contrast-enhanced axial CT scans through native kidneys show several
low-attenuation areas in native kidneys and spleen (arrows) that
proved to be posttransplantation lymphoproliferative disorder (PTLD).
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Fig. 3C. —43-year-old woman with kidney and pancreas transplant who underwent
CT as part of her diagnostic evaluation for malfunctioning renal transplant.
Contrast-enhanced axial CT scans through native kidneys show several
low-attenuation areas in native kidneys and spleen (arrows) that
proved to be posttransplantation lymphoproliferative disorder (PTLD).
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Fig. 3D. —43-year-old woman with kidney and pancreas transplant who underwent
CT as part of her diagnostic evaluation for malfunctioning renal transplant.
Contrast-enhanced axial CT scan through liver and spleen shows several
low-attenuation areas in hepatic parenchyma (arrows) that also proved
to be PTLD.
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Fig. 4A. —51-year-old man with history of right renal transplant who presented
with right-sided flank pain, chills, and fever. CT was performed in search of
abscess. Contrast-enhanced CT scan shows heterogeneously enhancing mass in
region of renal pelvis (arrows). CT-guided biopsy (not shown) showed
necrotic tissue. Patient underwent removal of transplant, and pathology
disclosed posttransplantation lymphoproliferative disorder (PTLD).
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Fig. 4B. —51-year-old man with history of right renal transplant who presented
with right-sided flank pain, chills, and fever. CT was performed in search of
abscess. Contrast-enhanced CT scans show several areas of low-attenuation in
liver and spleen (arrows) that are new since prior CT and presumed to
be PTLD.
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Fig. 4C. —51-year-old man with history of right renal transplant who presented
with right-sided flank pain, chills, and fever. CT was performed in search of
abscess. Contrast-enhanced CT scans show several areas of low-attenuation in
liver and spleen (arrows) that are new since prior CT and presumed to
be PTLD.
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Fig. 5A. —36-year-old man with right renal transplant. Unenhanced CT scan
shows soft tissue-density mass in left common iliac bifurcation
(arrow) consistent with posttransplantation lymphoproliferative
disorder.
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Fig. 5B. —36-year-old man with right renal transplant. Unenhanced CT scan at
same level as A obtained 1 year later shows mass (arrow) has
decreased in size after withdrawal of immunosuppression and administration of
acyclovir.
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Sonography is the primary technique for evaluating the complications of
renal transplantation. With inconclusive sonographic findings, however, CT or
MR imaging should be performed to confirm the presence of a mass
[7]. Sonographic findings of
PTLD include a hypo- or mixed-echogenicity mass. However, small ill-defined
PTLD masses cannot be initially identified on sonography, and the diagnosis is
made on later sonography when the mass is larger. The diameter usually ranges
from 3 to 6 cm at the time of discovery
[7].
CT findings of PTLD are also nonspecific and may include a nonenhancing
(Fig.
6A,6B,6C,6D,6E,6F)
or peripherally enhancing low-attenuation mass arising from the transplanted
kidney (Fig.
7A,7B,7C,7D).
Calcifications in the lymphoproliferative mass may represent tumor necrosis or
sequelae after treatment (Figs.
6A,6B,6C,6D,6E,6F
and
7A,7B,7C,7D).
Tumor growth in the renal pelvis can cause renal pelvic outflow obstruction,
necessitating the placement of a drainage catheter. Occurrence of PTLD in the
renal hilum with hilar vessel encasement was observed in four of five renal
transplant patients as reported by Ali et al.
[8]. This predilection for the
renal pelvis (Figs.
1A,1B
and
4A,4B,4C)
may indicate predisposition of the anastomotic site for PTLD development
[8].
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Fig. 6A. —26-year-old man who underwent right renal transplantation.
Contrast-enhanced CT scan shows heterogeneous nonenhancing mass
(arrow) originating from transplanted organ. Remainder of renal
parenchyma shows normal CT characteristics.
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Fig. 6B. —26-year-old man who underwent right renal transplantation.
Contrast-enhanced CT scan obtained 1 month after A reveals slight
increase (arrows) in size of tumor. After patient developed acute
rejection, transplanted kidney was removed and hemodialysis instituted.
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Fig. 6C. —26-year-old man who underwent right renal transplantation. CT scan
obtained after initiation of hemodialysis shows heterogeneous mass in surgical
bed. Mass was attributable to hematoma (arrows) after surgery.
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Fig. 6F. —26-year-old man who underwent right renal transplantation. Follow-up
CT scan obtained 2 months after biopsy shows significantly smaller mass
(arrow) caused by administration of acyclovir and reduction of
immunosuppressive medication.
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Fig. 7A. —48-year-old man with normally functioning left renal transplant.
Patient had prior right renal transplant in right iliac fossa that had failed
12 years earlier. Unenhanced (A) and contrast-enhanced (B and
C) CT scans show radiographically normal left iliac fossa transplanted
kidney. In right iliac fossa, however, large soft tissue-density mass (m)
originates from rejected transplant with rim of peripheral enhancement
(arrows) and dystrophic calcifications. CT-guided biopsy (not shown)
disclosed posttransplantation lymphoproliferative disorder.
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Fig. 7B. —48-year-old man with normally functioning left renal transplant.
Patient had prior right renal transplant in right iliac fossa that had failed
12 years earlier. Unenhanced (A) and contrast-enhanced (B and
C) CT scans show radiographically normal left iliac fossa transplanted
kidney. In right iliac fossa, however, large soft tissue-density mass (m)
originates from rejected transplant with rim of peripheral enhancement
(arrows) and dystrophic calcifications. CT-guided biopsy (not shown)
disclosed posttransplantation lymphoproliferative disorder.
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Fig. 7C. —48-year-old man with normally functioning left renal transplant.
Patient had prior right renal transplant in right iliac fossa that had failed
12 years earlier. Unenhanced (A) and contrast-enhanced (B and
C) CT scans show radiographically normal left iliac fossa transplanted
kidney. In right iliac fossa, however, large soft tissue-density mass (m)
originates from rejected transplant with rim of peripheral enhancement
(arrows) and dystrophic calcifications. CT-guided biopsy (not shown)
disclosed posttransplantation lymphoproliferative disorder.
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Fig. 7D. —48-year-old man with normally functioning left renal transplant.
Patient had prior right renal transplant in right iliac fossa that had failed
12 years earlier. In follow-up contrast-enhanced CT scan 2 months later, after
administration of acyclovir and reduction in immunosuppressant medication,
mass (m) had decreased in size. B = urinary bladder.
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Scintigraphy may be used in the evaluation of patients with residual or
recurrent disease in whom the tumor was initially gallium-avid
[5] (Figs.
1A,1B
and
6A,6B,6C,6D,6E,6F).
MR findings include a hypointense lesion on T1- and T2-weighted images in
the renal hilum that is traversed by renal hilar vessels and shows minimal
enhancement [8]. MR imaging is
a promising technique in the study of renal transplants because of its
multiplanar capabilities, lack of ionizing radiation, and lack of
contrast-induced nephrotoxicity. However, its role has not yet been
established.
Conclusion
PTLD affecting the transplanted kidney is a common manifestation of the
disease in renal transplant patients. Gray-scale sonography and CT are the
primary imaging techniques, with MR imaging showing promise because of its
multiplanar capabilities, superior soft-tissue contrast resolution, and lack
of ionizing radiation and nephrotoxic effects. Findings of PTLD are overall
nonspecific; however, a predilection for tumor growth exists in the region of
the renal pelvis. A combination of imaging techniques, including scintigraphy,
may be necessary for the diagnostic examination of such patients. Percutaneous
biopsy may be performed to confirm the diagnosis. The role of imaging is
crucial because early diagnosis of morphologic abnormalities of the renal
transplant will increase the chances for tumor regression through a reduction
in the immunosuppressive agents.
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Introduction
Posttransplantation...
