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 lymphomas originating in bone are rare. The prevalence is high. Malignant lymphoma of bone accounts for 4.4% of malignant bone tumors and is more common in men than women.
Diagnostic criteria
When malignant lymphoma occurs in bone tissue, every effort should be made to determine whether it is primary or secondary, and 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 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 in order. 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 beyond doubt.
(2) No primary tumor was found in other tissues and systems by clinical and other 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 of the discovery of bone lesions; if bone lesions appear only after the primary lymphoma in lymph nodes or/and soft tissues is diagnosed, all should be clinically diagnosed as secondary bone malignant lymphoma for bone invasion of malignant lymphoma.
Principles of treatment
Lymphoma is very sensitive to radiotherapy and chemotherapy, and most experiences nowadays agree that the treatment principle 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 degree, 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 pathological fractures requiring reconstruction of stability and spinal cord compression paralysis requiring excision and decompression.
The chemotherapy regimen for primary lymphoma of bone can be COPP, CHOP, COMP and CHOA depending on the immunophenotype and clinical stage. t-cellularity is preferable to MTX-based regimen, which is easy to relapse and should be treated for a long period of 15 to 32 months. b-cellularity is preferable to high-dose CTX-based regimen, which should be treated for an intense and short period of 6 to 12 months.
1.Inert NHL
Stage I, II: expanded field radiotherapy (40 to 45 GY).
Stage III, IV: CHOP chemotherapy + local radiotherapy + interferon therapy.
2.Invasive NHL
Stage I, IIA: 4-6 cycles of CHOP regimen plus radiotherapy in the involved field (30-40GY).
IIA, IIB: 2 to 3 cycles of chemotherapy CHOP regimen and local radiotherapy (30 to 40 GY) followed by 2 to 3 cycles of CHOP regimen.
Stage III, IV: 6 to 8 cycles of CHOP chemotherapy plus local radiotherapy (30 to 40 GY).
3.Highly aggressive NHL
Systemic chemotherapy mainly plus local radiotherapy, or mega-dose chemotherapy supported by BMT/PBSCT.
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-BLAMIII 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 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 antitumor 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 at 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 antibody
Nuclide-labeled CD20 antibodies may not have 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.