Case Presentation:

A 45 year old female with history of psoriatic arthritis and renal transplant from a living unrelated donor (performed in the Philippines in 2014) presented with symptoms of fever, fatigue, weakness, tremors, epigastric pain, and loose stools. At the time of presentation, she had recently completed three cycles of plasmapharesis/IVIG and one cycle of rituximab due to biopsy-proven stage 1b rejection.  She denied chest pain, cough, dyspnea, vomiting, skin rashes, joint pain, or dysuria. On exam, she was febrile to 100.9° F and tachycardic (122 beats per minute). She was ill-appearing and tremulous. Her lung fields were clear to auscultation bilaterally, cardiac exam was negative for murmurs, there was no lymphadenopathy, and her abdomen was soft with right lower quadrant tenderness. Initial laboratory values were significant for WBC 11.4 x103/uL, hemoglobin 7.2 g/dL, creatinine 3.7 mg/dL, and Tacrolimus level 15.7 mcg/L. She was treated with empiric Vancomycin and Cefepime, blood and urine cultures were obtained, and Tacrolimus dose was decreased. Due to persistent abdominal pain, a CT abdomen/pelvis was obtained which was significant for multiple mesenteric soft tissue masses mainly in the pelvis with the largest lesion measuring 4.9 x 3.5 cm and a lesion encasing the ileum (see figure).  A CT chest was also completed which showed multiple ground glass opacities. Further investigation revealed elevated LDH (440 U/L), elevated uric acid (9.5 mg/dL) and a negative EBV viral load. Hematology/Oncology was consulted due to concern for Post-Transplantation Lymphoproliferative Disorder (PTLD).  During hospitalization, she also developed pancytopenia (nadir WBC 0.57 x103/uL, Hgb 6.4 g/dL, platelet 44 x103/uL, , ANC 340). Lymph node biopsy was performed and was positive for Mycobacterium tuberculosis with negative flow cytometry. Bone marrow biopsy and bronchoscopy with bronchoalveolar lavage were also positive for Mycobacterium tuberculosis. Treatment was then initiated with Rifampin, Isoniazid, Pyrazinamide, and Ethambutol (RIPE) for disseminated Mycobacterium tuberculosis. Three months later she remains on RIPE therapy. Repeat imaging shows decrease in size of lymphadenopathy and her symptoms are continuing to improve. 

Discussion:

Post-Transplantation Lymphoproliferative Disorder (PTLD), a major complication of hematopoietic stem cell and solid organ transplant, is challenging to recognize given its highly variable presentation. In addition to constitutional symptoms and pancytopenia, the majority of patients present with extranodal masses. Diagnosis of PTLD is confirmed via histopathologic evaluation of the involved tissue. It is important to consider disseminated mycobacterial and other opportunistic infections in the setting of immunosuppression despite initial concern for PTLD.  In this case, the diagnosis of disseminated TB was favorable from a prognostic and management perspective. The diagnosis of PTLD can be devastating and it is imperative to complete a thorough diagnostic work-up prior to causing undue emotional distress. 

Conclusions:

Constitutional symptoms, extranodal masses, and transplant dysfunction may be suggestive of Post-Transplant Lymphoproliferative Disorder. Given the highly variable presentation, impact on prognosis, and need to exclude other malignant or infectious etiologies tissue, biopsy is required for diagnosis.