Spectrum of histopathologic diagnosis of lymph node biopsies after liver and kidney transplant.

OBJECTIVES: Our aim was to review our single center experience regarding histopathologic features arising from enlarged lymph nodes following solidorgan transplant. MATERIALS AND METHODS: In 2148 people who had solid-organ transplant from 1985 to 2013, there were 34 patients (1.58%) who developed lymphadenopathy. A retrospective review was performed to evaluate demographic, clinical, and histopathologic features of medical and pathologic records. RESULTS: Nonneoplastic lesions were more common, comprising 70.5% (n = 24) all cases which included nonspecific reactive lymphoid hyperplasia in 8 patients (33.3%), tuberculous lymphadenitis in 6 patients (25%), amyloid lymphadenopathy in 4 patients (16.6%), dermatopathic lymphadenopathy in 2 patients (8.3%), Kikuchi-Fujimoto disease in 1 patient (4.16%), hemangioma in 1 patient (4.16%), plasmacytic form of Castleman disease and amyloid lymphadenopathy in 1 patient (4.16%), and sea blue histiocytosis in 1 patient (4.16%). Neoplastic lesions comprised 29.41% (n = 10) cases which included posttransplant lymphoproliferative disorder in 6 patients (60%), Kaposi sarcoma in 2 patients (20%), posttransplant lymphoproliferative disorder and Kaposi sarcoma in 1 patient (10%), and metastatic carcinoma in 1 patient (10%). CONCLUSIONS: Detecting enlarged lymph nodes in solid-organ transplant recipients is an infrequent occurrence. Infectious diseases, posttransplant lymphoproliferative disorder, and malignancies related to transplant should be considered in the differential diagnosis when enlarged lymph nodes in solid-organ transplant recipients are encountered.

Bone marrow involvement by lymphoproliferative disorders after solid-organ transplant.

OBJECTIVES: Posttransplant lymphoproliferative disorders are classified as monomorphic, polymorphic, early lesions, or Hodgkin lymphoma. Bone marrow staging examination is recommended in posttransplant lymphoproliferative disorder patients. However, information about bone marrow involvement in these disorders is scarce. We evaluated 19 transplant patients with posttransplant lymphoproliferative disorder to investigate incidence of bone marrow involvement, associated morphologic changes, and prognosis. MATERIALS AND METHODS: We retrospectively assessed bone marrow findings of 19 transplant patients with posttransplant lymphoproliferative disorder who underwent bone marrow staging at Baskent University from 1985 to 2013. Clinical and pathologic data were reviewed from the medical records. Follow-up information was obtained from medical records or communication with patients or families. Data collected including age, sex, Epstein-Barr virus status, immunosuppressive therapy, elapsed time from transplant to diagnosis of posttransplant lymphoproliferative disorder, B symptoms, number of extranodal sites, involvement of different organs, Ann Arbor clinical staging, hematologic parameters, and serum lactate dehydrogenase levels. RESULTS: There were 5 of 19 patients (26.3%) who had bone marrow involvement with posttransplant lymphoproliferative disorder, including 2 patients diagnosed with posttransplant lymphoproliferative disorder by lymph node biopsy and 1 patient each diagnosed by native liver biopsy, nasopharyngeal biopsy, or allograft liver biopsy. In 4 patients, there was monomorphic posttransplant lymphoproliferative disorder subtype and 1 patient had early lesion posttransplant lymphoproliferative disorder subtype. In 10 of 19 patients (52.6%), Epstein-Barr virus was detected with in situ hybridization, including 3 patients with bone marrow involvement who were diagnosed with Burkitt lymphoma (n = 1), diffuse large B-cell lymphoma (n = 1), or early lesion (n = 1). CONCLUSIONS: Patients with posttransplant lymphoproliferative disorder have high incidence of bone marrow involvement and high mortality rates. Therefore, bone marrow examination may be important in the diagnosis and staging evaluation of posttransplant lymphoproliferative disorder.

Bone marrow biopsy in patients with renal transplant: spectrum of findings and diagnostic use.

OBJECTIVES: Renal transplant may be complicated by cytopenia, fever of unknown etiology, or hematolymphoid malignancies. Bone marrow biopsy may be indicated to evaluate these complications. However, to the best of our knowledge, no previous study has systematically documented the characteristics of bone marrow biopsy in these patients. The present study reports the range of bone marrow findings in renal transplant recipients. MATERIALS AND METHODS: We selected 85 patients who underwent bone marrow biopsy among 1745 renal transplant recipients who had transplant at Ba skent University from January 1990 to December 2013. The files of these patients were reviewed for age, sex, age at renal transplant, underlying renal disease, donor type, immunosuppressive therapy, presence or absence of acute humoral or cellular rejection, duration between transplant and bone marrow biopsy, indication for bone marrow biopsy, and histopathologic diagnoses of bone marrow biopsies. RESULTS: The most common cause of renal insufficiency leading to transplant in this patient group was unknown etiology, observed in 24 patients (28.2%). The most common indication for bone marrow biopsy was blood cytopenia, detected in 56 patients (65.9%). Neoplastic involvement of the bone marrow was detected in 6 patients (7.1%), all of which were hematolymphoid malignancies. Corticosteroids were the most commonly used immunosuppressive agents, administered to all patients. CONCLUSIONS: Bone marrow biopsy provides important information in renal transplant recipients, especially in cases of neoplastic bone marrow involvement, specific inflammation, and amyloidosis, which are uncommon in this patient group. The overall diagnostic use is related to the individual situation of each patient.

Invasive fungal infections in liver transplant recipients.

OBJECTIVES: We sought to assess the incidence of invasive fungal infections and identify the risk factors and outcome of invasive fungal infections in liver transplant recipient. MATERIALS AND METHODS: A retrospective analysis was made of 408 patients who received a liver transplant between January 1990 to December 2012 at Baskent University in Ankara, Turkey. Only 305 of 408 patients were included. Demographic and clinical findings were reviewed, and these findings were compared between patients with or without invasive fungal infections. RESULTS: Ten of 408 liver transplant patients (2.5%) developed invasive fungal infections. Aspergillus was the most common cause of invasive fungal infections (n=8), followed by Candida (n=1), and Cryptococcus neoformans (n=1). Pulmonary involvement was dominant in all patients (n=10), and only 1 patient had disseminated fungal infection (cryptococcosis). The mean time from transplant to invasive fungal infection diagnosis was 32 ± 19.2 days. Most patients with invasive fungal infection (9/10) died. Mean survival time between diagnosis of fungal infection and death was 24.2 ± 27.3 days in all 10 patients. Fungal infections occurred significantly more frequently in patients with older transplant age, diabetes mellitus, cytomegalovirus infection, renal insufficiency. In addition, other risk factors included long stays in the surgical intensive care unit, the overall length of stay in hospital, and having preoperative high creatinine level. CONCLUSIONS: Invasive fungal infections were associated with increased morbidity and mortality among liver transplant recipients, with Aspergillus spp. being the most common pathogen in our series. Because of its high mortality rate, it is important to follow up transplant patients for the development of invasive fungal infections.

Burkitt lymphoma after transplant: an aggressive lymphoproliferative disease.

Posttransplant lymphoproliferative disorder (Burkitt lymphoma) may occur after liver transplant. A 3.5-year-old boy who was 17 months after liver transplant developed multiple millimeter-sized nodular lesions in the liver. Before transplant, the patient tested seronegative for Epstein-Barr virus; within 1 month after transplant, he tested seropositive for Epstein-Barr virus (1000 copies). Biopsy of the liver nodules showed posttransplant lymphoproliferative disorder (Burkitt lymphoma). Tacrolimus was stopped, sirolimus was started, and the patient was treated with chemotherapy (etoposide, doxorubicin, cyclophosphamide, corticosteroids and intrathecal methotrexate). Remission was achieved, and follow-up at 76 months after transplant showed no recurrence of the posttransplant lymphoproliferative disorder. In conclusion, posttransplant lymphoproliferative disorder (Burkitt lymphoma) may occur after liver transplant, and monitoring Epstein-Barr virus level may helpful after transplant because of the association between Epstein-Barr virus and Burkitt lymphoma.

T-cell acute lymphoblastic leukemia after liver transplant.

T-cell posttransplant lymphoproliferative disorders after solid-organ transplant are rare and may be clinically aggressive. A 3-year-old boy had liver transplant from his grandfather because of hepatoblastoma. The immunosuppressive regimen was based on tacrolimus and prednisolone. At 22 months after transplant (age, 5 years), the patient presented to the hospital because of severe cough. Computed tomography scan of the chest showed a large left mediastinal mass (9 × 7.2 × 7 cm) and left pleural effusion. A Tru-Cut biopsy of the mediastinal mass showed diffuse infiltration with blast cells, and the diagnosis of T-cell acute lymphoblastic leukemia was made. Immunohistochemical examination of blasts showed strong and diffuse terminal deoxynucleotidyl transferase and CD3 antibody expression; Ki-67 proliferation index was > 95%, and tumor cells were negative for Epstein-Barr virus. Tacrolimus was stopped, sirolimus was started, and chemotherapy was given, but he died 2 months after diagnosis because of chemotherapy-induced sepsis. Monomorphic T-cell posttransplant lymphoproliferative disorder with features of acute lymphoblastic leukemia and lymphoblastic lymphoma is rare after liver transplant.

Posttransplant lymphoproliferative disorder after liver and kidney transplant.

OBJECTIVES: We evaluated posttransplant lymphoproliferative disorder after solid-organ transplant. MATERIALS AND METHODS: All 2224 solid-organ transplant recipients who underwent transplant between 1985 and 2013 were included. Clinicopathological findings were examined, and all patients with posttransplant lymphoproliferative disorder were reclassified to World Health Organization 2008 lymphoma classification. RESULTS: Only 27 of 2224 patients developed posttransplant lymphoproliferative disorder. The incidence of posttransplant lymphoproliferative disorder was 3.3-fold higher in children than in adults. The mean interval between transplant and diagnosis of posttransplant lymphoproliferative disorder was 65 months. Patients with tacrolimus were associated with a shorter posttransplant lymphoproliferative disorder development time compared with cyclosporine patients. Epstein-Barr virus-encoded small RNA positive showed shorter time for development of posttransplant lymphoproliferative disorder compared with Epstein-Barr virus-encoded small RNA negative patients. The risk of developing posttransplant lymphoproliferative disorder within the first year of transplant was higher in patients under tacrolimus protocol compared with patients under cyclosporine. Of 27 patients, 4 showed early lesion and 23 patients showed monomorphic posttransplant lymphoproliferative disorder. The development of T-cell monomorphic posttransplant lymphoproliferative disorder was significantly late compared with patients with B-cell monomorphic posttransplant lymphoproliferative disorder. Eight patients died at 38 ± 50 months after posttransplant lymphoproliferative disorder diagnosis. Four patients with early type posttransplant lymphoproliferative disorder were alive, and 3 of 4 patients with T-cell monomorphic posttransplant lymphoproliferative disorder died shortly after diagnosis. Five of 19 patients with B-cell monomorphic posttransplant lymphoproliferative disorder died at a mean 29 ± 18 months. A significant difference was found between the histologic types regarding patient survival. A significant difference was found between the Epstein-Barr virus-encoded small RNA positive and Epstein-Barr virus-encoded small RNA negative patients regarding mean survival time. CONCLUSIONS: To decrease the incidence of posttransplant lymphoproliferative disorder, risk factors should be evaluated and new approaches must be derived for prophylaxis, diagnosis, and treatment.