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Epstein Barr Virus-positive large T-cell lymphoma presenting as acute appendicitis 17 years after cadaveric renal transplant: a case report
© Ratuapli et al; licensee BioMed Central Ltd. 2011
Received: 20 February 2010
Accepted: 12 January 2011
Published: 12 January 2011
The majority of post-transplant lymphoproliferative disorders in renal transplant patients are of the B-cell phenotype, while the T-cell phenotype is rare. We report a case of Epstein Barr Virus-positive, T-cell lymphoma in a renal transplant patient, presenting unusually as acute appendicitis.
A 45-year-old Hispanic male renal transplant patient presented with right-side abdominal pain 17 years after transplant. The laboratory studies were unremarkable. Laparoscopic exploration showed an inflamed appendix so a laparoscopic appendectomy was performed. Pathology of the appendix showed large cells positive for CD3, CD56 and Epstein Barr Virus-encoded RNA staining, and negative for CD20 and CD30. The tissue tested positive for T-cell receptor gene rearrangement by polymerase chain reaction analysis. Treatment management involved reduction of immunosuppression and initiation of chemotherapy with cisplatin, etoposide, gemcitabine, and solumedrol followed by cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone). He recovered and the allo-grafted kidney is fully functional.
We report a rare case of post-renal transplant large T-cell lymphoma, with an unusual presentation of acute appendicitis and Epstein Barr Virus-positivity, which responded well to chemotherapy.
Solid organ transplantation has been increasingly performed in recent years with the use of highly potent immunosuppressive agents to avoid rejection by the host. Post-transplant lymphoproliferative disorders (PTLD) are well known malignancies found in transplant patients, with an incidence reportedly 28 to 49 times greater than in the general population . PTLD in renal transplant patients is reported to be higher in the paediatric population (10.1%) than the adult population (1.2%) . PTLD in renal transplant patients was first described as a complication with azathioprine-based therapy , but was later described after therapy with multiple more novel immunosuppressive agents.
While the majority of PTLD in renal transplant patients are of the B-cell phenotype, a few exhibit the T-cell phenotype . We report a case of Epstein Barr Virus (EBV)-positive T-cell lymphoma in a patient, who underwent cadaveric renal transplant 17 years ago and was on chronic multi-drug immunosuppression. Our patient presented unusually with abdominal pain and acute appendicitis.
A 45-year-old Hispanic male who underwent cadaveric renal transplant in the right lower quadrant 17 years earlier, presented to the hospital with a three-month history of generalized abdominal pain with localization to the right side for two weeks. He was on chronic immunosuppression with tacrolimus, azathioprine, sirolimus and prednisone. The pain was more pronounced in the right upper quadrant, and the ultrasound imaging of the abdomen was suggestive of cholecystitis. Laboratory studies did not reveal any abnormalities. He could not confirm if he had had any problems or surgeries on his gall bladder. Hence, he underwent laparoscopic exploration of the gall bladder fossa. During surgery, adhesions of the omentum were found in the gall bladder fossa in the absence of the gall bladder, and an inflamed appendix was found elevated due to the transplanted kidney in the right lower quadrant. Laparoscopic appendectomy was performed and the tissue underwent pathological examination. He was discharged after an uneventful post-operative course.
Initial treatment management involved reducing the dose of the patient's immunosuppressive agents and starting chemotherapy. Administration of azathioprine, prednisone and tacrolimus was stopped and low dose sirolimus at 1 mg was given daily. The first cycle of chemotherapy (PEGS) included cisplatin 25 mg/m2, etoposide 40 mg/m2 and solumedrol 250 mg administered on days one, two and three, and gemcitabine (Gemzar) 1000 mg/m2 on day one (ongoing Phase II trial SWOG 0350). Our patient had a positive and rapid clinical response to this regimen. Thus, the chemotherapy was changed to a standard CHOP regimen (cyclophosphamide, doxorubicin [Adriamycin], vincristine, prednisone). His gastric outlet obstruction was supported with total parenteral nutrition (TPN) for a few weeks, after which the patient was able to eat well. A repeat PET scan after the second cycle of CHOP showed a significant response.
The main complications during the therapy were pancytopenia, febrile neutropenia and pneumonia. These were managed successfully. He recovered well and is presently receiving treatment as an outpatient. His allo-grafted kidney is also fully functional. Restaging is planned after a total of six cycles of CHOP with a PET scan and EGD.
Our case is interesting due to the latency of PTLD development, the lack of hematological abnormalities and the EBV-positivity, even though the lymphoma was of T-cell origin. The diagnosis became apparent when an appendectomy was performed for abdominal pain. The cytopathology of our patient shows all the typical features of a peripheral T-cell variant of PTLD, where the T-cell lineage of the lymphoma was confirmed by TCR gene rearrangement studies.
While presenting symptoms in the majority of patients are non-specific such as fever and weight loss, approximately 15% of cases present as an emergency with intestinal perforation . Similar to other reports on T-cell type PTLD, which generally occurred more than five years after transplant, this case occurred 17 years after the renal transplant. The high levels of immunosuppression were due to two episodes of graft rejection in the preceding four years.
The World Health Organization classification of PTLD.
Reactive Plasmacytic Hyperplasia
• Diffuse large B cell lymphoma
• Burkitt/Burkitt-like lymphoma
• Plasma cell myeloma
• Peripheral T cell lymphoma
• Large CellAnaplastic
• Raretypes (gammadelta, Hepatosplenic, T/NKcell)
1. Hodgkin's disease-like
The etiopathogenesis of T-cell PTLD is not entirely known, although it may be similar to non-Hodgkins lymphoma (NHL) seen in the general population. While a putative role of EBV has been suggested in 89% of cases of B-cell PTLD , no direct role for this lymphotropic virus has been confirmed in T-cell PTLD. EBV infects and immortalizes B cells causing unchecked proliferation of EBV-infected cells, as the critical T-cell control of B-cells is lacking in immunosuppressed patients . Human T-cell Lymphotropic Virus 1 (HTLV1) has been reported to cause post renal transplant T-cell lymphomas in Japan , due to a higher prevalence of the virus among hemodialysis patients. Our case was unusual in that the lymphoma tested positive for EBV, even though it was of T-cell origin, which is only seen in a small minority of patients .
The initial step in treating PTLD is reduction in immunosuppression, and the response is usually seen in three to four weeks, resulting in long term remission in 25% to 63%  of adults. Early polyclonal PTLD responds well to a reduction in immunosuppression, whereas monoclonal PTLD generally does not respond to the reduction and has a high mortality rate of 50% to 90% . Early use of anthracycline-based chemotherapy results in long term disease free survival rates of 50% to 60% in monoclonal B-cell lymphomas , whereas T-cell PTLD responds very poorly. There are no standardized chemotherapy regimens for PTLD in general and for the T-cell phenotype in particular. Multiple treatment regimens such as CHOP, VAPEC-B (Adriamycin, etoposide, cyclophosphamide, methotrexate, bleomycin and vincristine), anti-IL-6 mAb, bexarotene and antiviral agents have been used with varied results. Other salvage regimens for high-grade lymphomas have also been suggested in the literature [14, 15].
In summary we report the case of a patient with post-renal transplant large T-cell lymphoma, with an unusual presentation of acute appendicitis and EBV positivity. We report successful treatment with chemotherapy and stress the need for heightened awareness of this malignancy in patients with prolonged immunosuppression. Monoclonal T-cell PTLD remains a high mortality disease, and further large multi-centre studies are required to understand the pathogenesis and develop better treatment regimens.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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