Malignant lymphomas that originate in lymph nodes are most common, but can occur in extra-lymph node lymphoreticular tissue with any organ. The biology of extra-lymph node malignant lymphomas is essentially similar to that of intra-lymph nodes, but non-Hodgkin’s lymphomas predominate and Hodgkin’s disease is rare. The digestive tract is the common site of extranodal lymphoma, but lymphoma originating in bone is rare. According to the statistics of the United States from 1973 to 1975, primary bone malignant lymphoma accounts for only 4.8% of extranodal lymphoma. In 1901, Wieland first described the manifestation of this tumor; in 1932, Oberling et al. named this tumor as reticulocytic sarcoma to distinguish it from Ewing sarcoma; in 1939, Parker et al. first reported 17 cases of reticulocytic sarcoma of bone, which established the diagnosis of this tumor from the clinicopathological point of view. in 1993, the WHO histologic classification of bone tumors was malignant lymphoma of bone. Malignant lymphoma of bone accounts for 4.4% of malignant bone tumors and is more common in men than in women. Diagnostic criteria When malignant lymphoma occurs in bone tissue, every effort should be made to determine whether it is primary or secondary. The criteria for diagnosing primary bone malignant lymphoma are: (a) The first (or even the only) site or symptom of the tumor must be in the bone, and the diagnosis of malignant lymphoma is made by pathological histological examination (including immunohistochemistry), even in the middle or late stage, when the tumor spreads or metastasizes, the development pattern is generally In order, the tumor progresses from the primary bone to the adjacent tissues or nearby lymph nodes, then to the liver, spleen, bone marrow, and finally to the peripheral blood. Immunohistochemical examination, positive for leukocyte common antigen (CD45), B-cell antibody (CD20), T-cell antibody (CD45RO) and negative for monocyte antibody (MAC387), can exclude easily confused tumors such as Ewing tumor, small cell osteosarcoma, metastatic neuroblastoma and small cell undifferentiated carcinoma, and the pathological diagnosis of malignant lymphoma of bone is undoubted. (b) No primary tumor was found in other tissue systems by clinical and other various auxiliary examinations. (iii) Signs and symptoms of malignant lymphoma in other sites are present only 6 months after the discovery of bone destruction. If bone, lymph node or/and soft tissue lesions coexist, or if lymph node and soft tissue lesions appear within 6 months after the discovery of bone lesions; if bone lesions appear only after the diagnosis of lymphoma with primary lymph nodes or/and soft tissues, all should be clinically diagnosed as secondary bone malignant lymphoma for malignant lymphoma with bone invasion. Treatment principles Lymphoma is very sensitive to radiotherapy and chemotherapy, and most current experiences agree that the treatment principles should be mainly radiotherapy and chemotherapy, supplemented by surgery, but the specific treatment plan should depend on each specific case after making a clear diagnosis, depending on the high, medium or low malignancy, and whether it is solitary or multiple. Local radiotherapy is mostly used for early and limited lesions and adjuvant treatment after surgery, mostly advocated in 4-5 weeks, with high dose (40-55 Gy) for the former and medium dose (30-35 Gy) for the latter. Chemotherapy is commonly used for multiple lesions, and for tumors with large soft tissue masses and unclear borders, preoperative chemotherapy can make the surgical borders of the tumor clearer and greatly reduce the risk of recurrence. Adjuvant chemotherapy after surgery plays an equally crucial role in improving prognosis. Surgery is indicated for pathologic fractures requiring reconstruction of stability and spinal cord compression paralysis requiring resection and decompression. The chemotherapy regimen for primary lymphoma of bone can be COPP, CHOP, COMP and CHOA depending on the immunophenotype and clinical stage, etc. A regimen based on MTX is recommended for T-cell disease, which is prone to relapse and should be treated for a long period of 15-32 months. 1. Inert NHL stages I,II: expanded field radiotherapy (40~45GY); stages III,IV: CHOP chemotherapy + local radiotherapy + interferon therapy. 2. Aggressive NHL stages I, IIA: CHOP regimen 4-6 cycles plus local radiotherapy (30-40GY); IIA, IIB: chemotherapy CHOP regimen 2-3 cycles, local radiotherapy (30-40GY), followed by CHOP regimen 2-3 cycles; stages III, IV: CHOP chemotherapy 6-8 cycles, plus local radiotherapy (30-40GY). 3. Highly aggressive NHL: systemic chemotherapy plus local radiotherapy, or BMT/PBSCT supported by mega-dose chemotherapy. In terms of treatment, new chemotherapy regimens are emerging. Take aggressive non-Hodgkin’s lymphoma as an example: the first generation chemotherapy regimens include COP, CHOP, MOPP, HOP, CHOP-Bleo/BACOP and COMLA; the second generation chemotherapy regimens include COP-BLAM, ProMACE-MOPP, M-BACOD and m-BACOD; the third generation chemotherapy regimens include COP-BLAM III Although second- and third-generation chemotherapy regimens are more intense than first-generation regimens, a prospective randomized study of 1,138 patients by Fisher et al. showed that m-BACOD, ProMACE-CytaBOM The CHOP regimen has become the “gold standard” for the treatment of aggressive non-Hodgkin’s lymphoma. However, this also suggests that there may be limited scope for traditional cytotoxic chemotherapeutic agents to further improve the clinical efficacy of malignant lymphoma. Molecular targeted therapy 1. Anti-CD20 antibody Meroval (IDEC-C2B8, Rituximab, Rituxan) CD20 is expressed in almost all normal B cells and malignant B cells, but not in stem cells. Meroval is a human-mouse chimeric anti-CD20 monoclonal antibody that does not trigger human anti-mouse antibodies (HAMA) in humans. Its anti-tumor mechanisms: antibody-dependent cell killing (ADCC), complement-dependent cell killing (CDC), induction of apoptosis and chemosensitization of tumor cells. A multicenter phase II clinical study looked at the clinical efficacy of melphalan in 166 patients with relapsed, refractory follicular or transformed non-Hodgkin’s lymphoma. The result was an overall remission (OR) rate of 48%, with a complete remission rate of 6% and a median time to tumor progression of 12 months. For patients who progressed after effective initial treatment, remission rates remained up to 40% with a median time to tumor progression of 17 months with re-treatment with melphalan. This clinical study prompted the U.S. Food and Drug Administration (FDA) to approve Meroval for CD20-positive relapsed or refractory low-grade malignant or follicular B-cell non-Hodgkin’s lymphoma on November 26, 1997, making it the first monoclonal antibody approved for tumor treatment. 2.Nucleotide labeled CD20 antibodies Nucleotide labeled CD20 antibodies can be used without having to rely entirely on CDC and ADCC, but mainly on radiation to kill tumor cells. It can work by direct contact with the corresponding antigen on the surface of tumor cells in vivo, and is still effective for tumor tissues with large tumor size and poor internal blood supply. Compared to the single use of melphalan, the emitted beta-particles can penetrate multiple cell diameters, thus allowing the eradication of surface antigen-modulated tumor cells by “crossfire”. This feature also allows it to kill cells with antigen-negative mutations that are located deep in the tumor where antibody penetration is difficult. The success of radioimmunotherapy in non-Hodgkin’s lymphoma is partly due to the fact that non-Hodgkin’s lymphoma is a radiosensitive tumor and partly because it overcomes the disadvantage that not all tumor cells are loaded with specific antigens and not all tumor cells can be reached by specific antibodies. On February 19, 2002, Zevalin (ibritumomab tiuxetan) became the first radioimmunotherapy drug approved by the FDA for patients with relapsed or refractory low-grade malignant non-Hodgkin’s lymphoma. chemically bound to the linker chelator tiuxetan to form an immunoconjugate. It forms stable complexes with 111In or 90Y in a tight conformation. In a phase III clinical randomized controlled study, 143 chemotherapy-resistant follicular or transformed non-Hodgkin’s lymphomas were randomized into two groups, one receiving 90Y-Zevalin 0.4 mCi/kg after intravenous administration of Meroval 250 mg/m2, and the other receiving Meroval 375 mg/m2 intravenously only, administered in four weekly cycles. Kaplan-Meier survival analysis showed that the median duration of remission was 14.2 months in the Zevalin group and 12.1 months in the Meroval group. The median duration of remission was 14.2 months for the Zevalin group and 12.1 months for the Meroval group (P = 0.6), 11.2 months for disease progression and 10.1 months for disease progression (P = 0.173), and the incidence of remission of less than 6 months was 64% and 47% (P = 0.030), respectively. In 2003, the FDA approved Bexxar (tositumomab and iodine-131-labeled tositumomab) for the treatment of follicular non-Hodgkin’s lymphoma (NHL) refractory to Rituximab monotherapy and relapsed after chemotherapy, CD20-positive, with or without transformation. bexxar was developed by GlaxoSmithKline and Corixa, Inc. and Corixa. A multicenter phase III clinical study evaluated one course of Bexxar in 60 patients with low-grade malignant or transformed low-grade malignant non-Hodgkin’s lymphoma who were chemotherapy-resistant to prior intermediate chemotherapy. All patients had received more than two regimens of chemotherapy. Bexxar had an overall efficacy rate of 65% (including a complete remission rate of 17%) in these patients compared to an overall remission rate of 28% (including a complete remission rate of 3%) in patients treated with the previous rational chemotherapy regimen (LQC)