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Gastrointestinal Imaging |
1 From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110. Received December 9, 1998; revision requested January 14, 1999; revision received January 28; accepted April 30. Address reprint requests to M.J.S. (e-mail: siegelm@mirlink.wustl.edu).
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Abstract |
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 TOP Abstract IntroductionMATERIALS and METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: The authors retrospectively analyzed pretreatment abdominal CT scans in 51 patients (mean age, 36 years) with PTLD after solid organ transplantation. All diagnoses were proved at either abdominal (n = 26) or extraabdominal (n = 25) pathologic examination. Presence or absence of abdominal involvement, appearance and distribution of disease, and association with abdominal symptoms were all analyzed.
RESULTS: CT scans were abnormal in 36 of the 51 patients (71%). Fifteen patients (29%) had no CT, clinical, or pathologic evidence of abdominal involvement. Of the 36 patients with abdominal PTLD at CT, 22% had lymph node enlargement, 28% splenic involvement, and 81% extranodal or extrasplenic involvement. Extranodal abdominal sites included liver (53%), small bowel (25%), kidney (17%), mesentery (14%), adrenal gland (8%), abdominal wall (8%), colon (6%), stomach (3%), and gallbladder (3%). Frequency of abdominal involvement was greater for heart and liver transplant recipients (94%) than for lung and kidney transplant recipients (58%) (P < .01). Seventeen of 36 patients (47%) with abdominal PTLD had no evidence of extraabdominal disease.
CONCLUSION: Extranodal involvement is more common than splenic or nodal involvement in patients with abdominal PTLD. The presence of such findings in a patient after transplantation strongly suggests the diagnosis of PTLD and warrants aggressive evaluation.
Index terms: Heart, transplantation, 51.459 • Kidney, transplantation, 81.455 • Liver, transplantation, 761.459 • Lung, transplantation, 60.459 • Lymphoma, 60.1211, 70.1211 • Transplantation
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Introduction |
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TOPAbstractIntroductionMATERIALS and METHODSRESULTSDISCUSSIONReferences |
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Computed tomography (CT) is a commonly performed study in symptomatic organ allograft recipients to evaluate complications related to transplantation. Recognition of the CT findings of PTLD is important because early diagnosis may result in an improved response to therapy, which often consists of only reducing the level of immunosuppression (4,7,8). CT manifestations of thoracic involvement by PTLD have been previously described in relatively large patient series (9,10). To our knowledge, the description of abdominal findings at CT has been limited to smaller patient series and review articles (11–17). We studied the pretreatment abdominal CT scans obtained in patients with pathologically proved PTLD after solid organ transplantation to better characterize the distribution and appearance of abdominal involvement.
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MATERIALS and METHODS |
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TOPAbstractIntroductionMATERIALS and METHODSRESULTSDISCUSSIONReferences |
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Abdominal CT is not performed routinely after organ transplantation at our institution but rather is reserved for suspected or known complications. The abdominal CT examinations were performed with different scanners (Somatom Plus, Somatom Plus S, and Somatom Plus 4; Siemens Medical Systems, Iselin, NJ). CT technique varied somewhat due to the retrospective nature of the study. In general, adult examinations were performed with spiral technique with 5–10-mm collimation and 5–10-mm reconstruction intervals, and pediatric studies were performed with 4–8-mm collimation and 4–8-mm reconstruction intervals. Our standard protocol for adults consists of a total volume of 100 mL nonionic intravenous contrast material administered by means of power injection at a rate of 3 mL/sec and with a scanning delay of 55 seconds. Total contrast material volume and scanning delay are incrementally increased for patients weighing more than 200 lb (91 kg). For children, intravenous contrast material volume was 2 mL per kilogram of body weight, not to exceed 150 mL, administered by means of bolus hand injection or power injection, depending on the type of venous access. Overall, iodinated intravenous contrast material was administered to 40 of the 51 patients (78%). The majority of nonenhanced studies involved renal transplant recipients with elevated serum creatinine levels. Contrast material was given to 49 of the 51 patients (96%) prior to scanning.
The CT studies of the 51 patients with PTLD were reviewed to determine the presence or absence of intraabdominal involvement. All abdominal CT examinations were performed prior to immunomodulation or chemotherapy. The studies were evaluated for lymph node enlargement, splenic disease (splenomegaly, focal lesions, or both), and extranodal disease (abdominal involvement beyond splenic and nodal disease). In adolescent and adult patients, nodal and splenic size were considered abnormal if their diameter exceeded 15 and 14 mm, respectively. In preadolescent patients, any lymph node regardless of size was considered abnormal. The spleen was considered enlarged if the tip extended below the level of the lower pole of the left kidney. Individual lesions were further characterized on the basis of number, size, distribution, and attenuation characteristics. The diagnosis of disease was based on consensus reading by two radiologists (P.J.P., M.J.S.).
Diagnostic proof of abdominal involvement by PTLD was based on findings at pathologic examination or a combination of imaging and clinical features, including pathologically proved extraabdominal PTLD.
Statistical analysis was performed to compare the frequency of abdominal PTLD versus type of transplant, frequency of abdominal PTLD versus presence of symptoms, and frequency of allograft involvement versus type of transplant. The Fisher exact test was used for analysis of data.
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RESULTS |
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TOPAbstractIntroductionMATERIALS and METHODSRESULTSDISCUSSIONReferences |
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The most common indication for performing CT in these 51 patients was the presence of unexplained abdominal signs or symptoms, which accounted for 30 of the 51 cases (59%). Abdominal pain, varying widely in severity and location, was the most frequent symptom (n = 24); three of these patients also experienced gastrointestinal bleeding, one had gross hematuria, and 12 were febrile. In the six patients without pain or other symptoms, abnormal clinical findings that led to abdominal CT included splenomegaly with or without hepatomegaly (n = 3), painless jaundice (n = 2), and palpable abdominal wall masses (n = 1). Twenty-one of the 51 patients (41%) did not have clinically important abdominal symptoms or findings but underwent CT for the staging of suspected or newly diagnosed extraabdominal PTLD.
The diagnosis of abdominal PTLD was based on findings at pathologic examination in 26 of 36 patients (72%). Sites of abdominal tissue sampling included liver (n = 14), small bowel (n = 6), lymph node (n = 4), abdominal wall (n = 3), colon (n = 2), kidney (n = 2), stomach (n = 1), adrenal gland (n = 1), spleen (n = 1), gallbladder (n = 1), and mesentery (n = 1). In 10 patients with abdominal PTLD, the diagnosis was based on CT findings and pathologic evidence of extraabdominal disease, including the thorax (n = 7), cervical lymph node (n = 2), or bone marrow (n = 1). In the 15 patients without abdominal disease, the diagnosis of PTLD was based on results at tissue sampling from the thorax (n = 5), brain (n = 5), cervical node (n = 3), bone marrow (n = 1), or skin (n = 1). Seventeen of 36 patients (47%) with abdominal PTLD had no clinical or pathologic evidence of extraabdominal disease. Allograft involvement by PTLD was more frequent in lung (11 patients [61%]) and liver (four patients [50%]) transplant recipients than in kidney (one patient [7%]) and heart (no patients) transplant recipients (P < .001).
CT Findings
CT findings of abdominal involvement by PTLD were present in 36 of 51 patients (71%). Of these 36 patients, eight (22%) had abdominal lymph node enlargement, 10 (28%) had splenic involvement, and 29 (81%) had extranodal involvement. Evidence of PTLD was seen at CT in all 30 patients (100%) with clinical symptoms related to the abdomen but in only six of the 21 patients (29%) without clinically important abdominal symptoms (P < .001). None of the 15 patients without findings of abdominal PTLD at CT had clinical or pathologic evidence of abdominal involvement.
In the eight patients with nodal disease, abdominal lymph nodes were 2–3 cm in diameter in six and 4–6 cm in diameter in two. Three patients had enlarged retroperitoneal lymph nodes, one had enlarged peritoneal nodes, and four had both retroperitoneal and peritoneal nodal enlargement (Fig 1). Involved lymph nodes were homogeneously enlarged; no nodes demonstrated necrosis.
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Extranodal PTLD was seen at CT in 29 of 36 transplant recipients (81%) with abdominal involvement. Most commonly affected were the liver (n = 19), small bowel (n = 9), and kidney (n = 6). Other sites of extranodal disease included the mesentery (n = 5), adrenal gland (n = 3), abdominal wall (n = 3), colon (n = 2), stomach (n = 1), gallbladder (n = 1), and adnexa (n = 1). The pancreas, ureters, bladder, and rectum were not involved at CT.
The liver was the most common site of PTLD involvement at CT, present in 19 of 36 patients (53%). Three patterns of hepatic disease were seen (Fig 2). Discrete, low-attenuating nodular lesions, ranging from 1 to 4 cm in diameter and from one to more than 20 in number, was the most common pattern, present in 13 patients. An infiltrative pattern, consisting of a geographic or ill-defined region of low attenuation, with or without hepatomegaly, was seen in three patients. A third pattern, characterized by a porta hepatis mass with direct extension into the biliary tree, was seen in three patients. This third pattern, along with periportal lymphadenopathy (Fig 1a), was unique to liver transplant recipients. Diffuse gallbladder wall thickening in one patient corresponded to PTLD infiltration at pathologic examination.
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS and METHODSRESULTSDISCUSSIONReferences |
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Chest radiography and CT are useful in evaluating thoracic involvement and predicting outcome (9,10). For the abdomen, there is no simple surveillance examination analogous to chest radiography for detecting early disease. Recognition of intraabdominal involvement is particularly important since as many as one-half of these patients have disease confined to the abdomen. Abdominal PTLD was seen in more than 70% of patients in our series who underwent CT for evaluation of abdominal symptoms or for staging purposes. Although splenic and lymph node disease were not uncommon, extranodal involvement occurred three to four times more frequently. Although PTLD can arise in virtually any organ or space within the abdomen and pelvis, the liver and gastrointestinal tract are the most common sites of disease. A high index of suspicion is necessary when examining transplant recipients since PTLD can mimic other disease processes both clinically and radiographically and can occur as early as 1 month after transplantation or many years later.
The imaging features of PTLD have much in common with those of lymphoproliferative disorders associated with other immune-compromising diseases, most notably lymphoma related to acquired immunodeficiency syndrome (AIDS). Extranodal involvement was seen at CT in more than 80% of cases of AIDS-related lymphoma in one large series, similar to the frequency of extranodal disease among transplant recipients in our series (19). There are, however, certain differences in the distribution of disease between these two entities. In AIDS-related lymphoma, gastrointestinal involvement is more frequent than hepatic involvement, whereas in PTLD, hepatic disease predominates. Additionally, abdominal lymph node enlargement is seen in more than half of patients with AIDS-related lymphoma; in our series of patients with PTLD, fewer than 25% had nodal disease at CT.
The CT manifestations of non-Hodgkin lymphoma occurring in the general population and PTLD in transplant recipients demonstrate important differences. The most striking distinction is the relatively high frequency of extranodal disease (81%) and lower frequency of nodal disease (22%) in patients with PTLD. In comparison, extranodal disease occurs in approximately 25% of nonimmunosuppressed patients with non-Hodgkin lymphoma (20). In addition, several patterns of extranodal involvement appear somewhat unique to transplant recipients. Periportal lymphomatous infiltration of the liver, seen only in liver transplant recipients in our series, was also recently reported in a pediatric transplantation series (21). To our knowledge, this pattern of periportal infiltration at CT has not been described in nonimmunosuppressed patients. Regarding gastrointestinal disease, although PTLD may occur in the duodenum, stomach, and colon, the small bowel appears to be the predominant site of involvement. Among immunocompetent patients, lymphoma affects the stomach most frequently, accounting for about 80% of cases with gastrointestinal involvement (22). Last, renal PTLD in our series manifested as unilateral disease, whereas renal lymphomas in the general population are bilateral in distribution in 75% of cases (23).
Overall, abdominal involvement was significantly more frequent among heart and liver transplant recipients than among lung and kidney recipients in our series. This difference is probably underestimated since the vast majority of patients with PTLD who were not examined with abdominal CT in our series were lung transplant recipients without abdominal symptoms. Some authors have emphasized a propensity for PTLD to occur in the same anatomic region as the solid organ transplant, including involvement of the allograft itself (21). This statement appears to be valid for lung transplant recipients, in whom both thoracic and allograft involvement are present in the majority of cases, and for liver transplant recipients, in whom abdominal involvement is seen in the vast majority and allograft involvement is seen in half of the cases (10). Among heart transplant recipients with PTLD in our series, however, thoracic disease was seen in fewer than half of the patients, and there were no patients with allograft involvement. Likewise, only one case of allograft involvement by PTLD was seen among kidney transplant recipients, and abdominal disease was present in only about half of all cases.
There are several limitations to our study. A subset of transplant recipients in whom PTLD was diagnosed at our institution were not examined with abdominal CT. The majority of these patients did not have abdominal symptoms but, as we have shown, abdominal involvement by PTLD cannot be excluded on this basis alone since 29% of asymptomatic patients who underwent CT were found to have abdominal disease. Therefore, the true frequency of abdominal involvement in our population is not precisely known. In addition, the diagnosis in some patients with evidence of abdominal disease at CT was established only at extraabdominal tissue biopsy. As with staging of lymphoma in the general population, however, tissue sampling of every nodal and extranodal mass is not necessary when concurrent disease is proved elsewhere in the body. In fact, when findings suspicious for PTLD are found at body imaging, a thorough examination of the patient is indicated to ascertain the safest approach to a tissue diagnosis, such as cervical lymph node disease. Conversely, patients with negative CT scans did not undergo laparotomy, so small tumors or organ infiltration without enlargement could be missed. A final limitation to this study was that some of the CT examinations were performed without administration of intravenous contrast material, usually because of elevated serum creatinine levels. Therefore, solid organ involvement by PTLD, especially the liver and spleen, could have been underestimated.
In conclusion, our results show that abdominal PTLD has a pattern of distribution different from that of lymphoma in the general population but more similar to that of AIDS-related lymphoma, with extranodal sites of disease predominating. Such CT findings in a transplant recipient should be regarded as highly suspicious for PTLD until proved otherwise, especially in symptomatic patients.
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Footnotes |
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Author contributions: Guarantor of integrity of entire study, P.J.P.; study concepts and design, P.J.P.; definition of intellectual content, P.J.P.; literature research, P.J.P.; clinical studies, P.J.P., M.J.S.; data acquisition and analysis, P.J.P., M.J.S.; statistical analysis, P.J.P., M.J.S.; manuscript preparation, P.J.P.; manuscript editing, M.J.S.; manuscript review, P.J.P., M.J.S.
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TOPAbstractIntroductionMATERIALS and METHODSRESULTSDISCUSSIONReferences |
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