post-transplant lymphoproliferative disease
Introduction
Introduction to lymphoproliferative diseases after transplantation Posttransplantly mphoproliferative disorder (PTLD), one of the most serious complications after organ and cell transplantation, has been recognized more than 30 years ago, but the relevant questions raised at that time are still not fully answered. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: non-infectious Complications: lymphoma
Cause
Causes of lymphoproliferative diseases after transplantation
(1) Causes of the disease
The main reason for the basic cause of PTL is immunosuppression and EBV infection.
Although the specific role of various immunosuppressive agents in the pathogenesis is still unclear, the overall degree of immunosuppression is the main factor determining the occurrence of this disease. EBV-specific T cell-mediated immune function damage plays an important role in the pathogenesis. Under normal circumstances, EBV-infected B cells are controlled by cytotoxic T cells, and B cell growth and death are in equilibrium. Once T cell function is impaired, this balance is broken, leading to the occurrence of PTL.
About 1 in 1 million B cells in the bone marrow donors infected with EBV are transformed B cells carrying viruses, which are in equilibrium in healthy donors as described above, but to reduce graft versus host When graft-versus-host disease (GVHD) is used for T-cell transplantation, the transformed B cells retained in the graft will rapidly proliferate by escaping the monitoring of cytotoxic T cells. It has been shown that the mature T in the graft is simultaneously removed. And B cells (such as soybean lectin removal) can significantly reduce the incidence of EBV-related PTLD after allogeneic bone marrow transplantation. On the other hand, the destruction of autoimmune function of bone marrow transplant recipients before transplantation also brings proliferation opportunities for transformed B cells. Early stage after bone marrow transplantation is a period of risk of developing PTLD.
The more common causes of PTLD in children are also associated with a higher proportion of EBV serological negatives in this population before transplantation.
(two) pathogenesis
The pathogenesis of NHL after most transplantation is that patients with long-term immunosuppressive state, infected EBV induces B cell proliferation, and the internal mechanism of EBV-induced B cell proliferation is now clear: an EBV-associated protein LMP-1 triggers host cells Some members of the tumor necrosis factor family, which leads to cell transformation and growth.
PTLD has a variety of histopathological manifestations, which are described below:
1. The common pathological feature of early pathologically reactive plasmacytosis and infectious mononucleosis-like lesions is that the affected tissue retains a certain degree of normal structures such as lymph node sinus, tonsil crypts and residual reactive follicles, The former is characterized by a large number of plasma cell proliferation, containing a very small number of immunoblasts, while the latter has the morphological characteristics of a typical infectious mononucleosis, manifested by the expansion of the paracortical region, in T cells and plasma cells. The background contains a large number of immunoblasts.
2. Polymorphic PTL, also known as pleomorphic B cell hyperplasia and pleomorphic B cell lymphoma, the pathological morphological feature is that the normal structure of the affected tissue is completely destroyed, and replaced by cell infiltration at various B cell differentiation stages. These include immunoblasts, plasma cells, small and medium-sized lymphocytes, and central cell-like cells with irregular nuclei. In addition, necrotic areas and scattered large atypical immune cell infiltration are observed, and mitosis is common.
3. Monomorphic PTL
(1) PTL of monomorphic B cells: the structure of lymph nodes or other affected tissues disappears, and a large number of transformed cells are formed into flaky tumor growth. The cell bodies of tumor cells are large, the nucleoli are obvious, and the cytoplasm is basophilic. Monomorphism is not absolute. It only means that most cells are homogenous, and may contain a certain number of strange and multinucleated cells as well as cells differentiated by plasmacytoid or plasma cells.
Most of the monomorphic B cell PTLs are DLBCL, and most of them are immunoblastic variants, followed by central parental cell type and anaplastic cell type, and a few cases are BL, plasma cell myeloma and plasmacytoma-like PTL. Rare.
(2) Monomorphic T cell PTL: less common, accounting for 4% to 14% of the total number of PTL cases. The reported histopathological types are diverse, covering almost the entire T cell tumor spectrum, including subcutaneous panniculitis-like T cells. Lymphoma, hepatosplenic T-cell lymphoma, NK/T-cell lymphoma, T-cell large granular lymphocytic leukemia and peripheral T-cell lymphoma (non-special).
4. HL and HL-like PTL Because RS-like cells can also be found in some cases of polymorphic PTL, EBV should always be positive for HL-like PTL based on typical morphological and immunophenotypic characteristics in the diagnosis of HL. Cellular immunology Immunophenotypic analysis of reactive plasmacytosis and infectious mononucleosis-like lesions revealed the presence of polyclonal B cells, T cells, plasma cells, immunoblasts typically EBV-LMP+, polymorphic PTL B and T cells exist in the lesion, sIg and cIg are polymorphic or monotype. In most cases, EBV-LMP1 and EBNA2 can be detected in immunoblasts, and tumor cells of monomorphic B cell PTL express CD19, CD20, CD79a. 50% of cases express monoclonal IgH, and most cases are positive for EBNA2 and LMP1. Some tumor cells also express T cell antigens, especially CD4 and CD45RO. These antigens are up-regulated in EBV-infected B cells, so they cannot be used alone. The expression of these antigens was considered to be the source of T cell lines. In addition, CD30 was expressed in many cases. Regardless of whether the tumor cells were anaplastic cells, the phenotype of monomorphic T cell PTL was positive for whole T antigen, and according to Types can express CD4 or CD8, CD56 or CD30, TCR or TCR, EBV positive in some cases, CD15 and CD30 in classical HL, phenotype of HL-like PTL is often atypical, often express B cell antigen, almost all cases are EBV positive.
Prevention
Post-transplant lymphoproliferative disease prevention
Because the occurrence of PTL is closely related to the degree of immunosuppression, the prevention measures are mainly to reduce the number of immunosuppressive agents used in patients. A group of 82 patients with renal transplants showed that 29 patients were used in FK506 from 1989 to 1992. After treatment with a basic anti-rejection regimen, 5 of them developed PTL with an incidence of 17%; 53 patients from 1993 to 1996 took a rapid reduction in FK506 and glucocorticoid use, while only 2 developed PTL. That is, the incidence rate is reduced to 4%.
Currently, anti-EBV-specific cytotoxic T cells have been used prophylactically in high-risk allogeneic bone marrow transplant recipients of EBV-induced lymphoma. In addition, since donor B cells appear to be the origin of EBV-associated lymphoma after bone marrow transplantation, Removing donor B cells may also be a simpler precaution.
Complication
Complications of lymphoproliferative disorders after transplantation Complications lymphoma
Generally no complications.
Symptom
Symptoms of lymphoproliferative disease after transplantation Common symptoms Lung infection Intestinal function is not good Liver dysfunction
More than 50% of PTL patients present with extranodal masses, involving organs including the gastrointestinal tract, lung, skin, liver, CNS and graft itself, especially CNS, seen in 20% to 25% of patients, which is rare in the general population, grafts The probability of being involved is also high. Similar to the CNS, graft involvement can lead to abnormal function of the transplanted organ.
Examine
Examination of lymphoproliferative diseases after transplantation
Check the items in accordance with the actual situation of the patient.
Diagnosis
Diagnosis and differentiation of lymphoproliferative diseases after transplantation
Tissue biopsy is the main basis for diagnosis. However, it has been recognized that, unlike most other lymphomas, histopathological examination is often difficult to diagnose. In the diagnosis of fashion, consider the following:
1 disease is defined as a polyclonal or monoclonal process;
2 non-histological features for diagnosis such as DNA rearrangement, standardization of mutation and clonality assays;
3 EBV positive application in tumor tissue;
4 Identification of tumor cell sources: donor or host, although these problems are often difficult to treat clinically, experts have recently suggested that the optimal diagnostic criteria for tumor-type EBV-positive PTL are as follows:
1 has internal structural damage caused by lymphoproliferative disorders;
2 the presence of a monoclonal or oligoclonal cell population as determined by a cell or viral marker;
3 There are many EBV-infected cells, which can be confirmed by any two of the above three conditions.
PTL is mainly characterized by extranodal lesions in the clinic, and most of them are non-specific, so it needs to be highly vigilant to be discovered. Moreover, the biological characteristics and histopathological characteristics of various types of PTL are different, so multiple examinations are needed. The method is diagnosed and identified.
