Multiple myeloma is a primary systemic bone marrow tumor, also known as plasmacytoma, which is a malignant tumor arising from plasma cells. It can occur in any bone containing red bone marrow and often invades multiple sites and tissues. The most common sites are the vertebrae, the femur and the epiphysis of the radius, and the flat bones (pelvis, skull and ribs).
I. Etiology and pathology
The lesions originate from cells of the endothelial reticular system that produce B lymphocytes and are characterized by plasma cell differentiation. Although it may present as a single lesion at the time of presentation, it will eventually involve any or all of the organs containing plasma cell stem cells. Although the genetic factors are not well defined, the phenomenon of sibling aggregation in multiple myeloma is suggestive of inheritance in a recessive manner.
II. Clinical manifestations
The initial symptoms are mild, with pain being the predominant first symptom. The site of pain is usually located in the pelvis, spine and thorax, and is relieved by bed rest and worsened by weight bearing and activity. Spinal lesions are sometimes excruciatingly painful, and radiating lower extremity pain may occur. Extensive involvement of the vertebrae, ribs, and sternum can lead to thoracic deformity, kyphosis, and height shortening. As the disease continues to progress, multiple fractures, severe pain, weight loss, and anemia may occur. Patients with advanced disease may show weight loss, fever, bleeding tendency, large soft tissue masses and severe bone pain, etc.
Third, auxiliary examination
Laboratory tests: Early laboratory tests can be completely normal, but in the late stage, there are significant abnormalities, such as anemia, increased globulin in serum, inverted albumin/globulin ratio, abnormal alpha or gamma globulin in protein electrophoresis, B-J protein in urine, hypercalcemia, elevated serum alkaline phosphatase, and metabolite accumulation due to renal insufficiency.
2.X-ray examination: It shows round “chisel-like” bone destruction, scattered in the skull, vertebral body, iliac bone and other parts. Occasionally, osteogenic myeloma is seen, and the x-ray shows multiple extensive sclerosis.
Radionuclide scan: Since myeloma cells do not produce stroma and there is no osteogenic reaction in the lesion, the uptake of radionuclide is very low compared to the extent of the lesion, which appears as “cold nodules”. The presence of such manifestations suggests a high possibility of myeloma.
4.CT examination: It shows various forms of worm-like, cystic, chisel-like, and map-like osteolytic destruction, as well as soft tissue masses of different sizes, without ossification and calcification, and there may be scattered residual bone.
5.MRI examination: The lesion tissue is low signal in T1-weighted image and high signal in T2-weighted image due to its high degree of vascularization.
6.Pathological examination.
(1) Visual inspection: The tumor does not invade the adjacent soft tissues, but its envelope is incomplete, the tumor tissue is soft, fragile and has few solid components. The tumor is soft, fragile and has few solid components. It is bright red in appearance due to its more blood vessels.
(2) Microscopic view: The tumor tissue replaces normal bone marrow, and the morphology of tumor cells ranges from mostly undifferentiated round cells with only a few identifiable plasma cells to almost all cells in the lesion are identifiable plasma cells. The undifferentiated cells are tightly arranged, moderately anisotropic, tightly arranged basophils, while the better differentiated plasma cells are round, uniform in size, with eccentric nuclei and clear cytoplasm containing many blocks of basophilic chromatin.
IV. Diagnostic points
1. Minor bone pain, fatigue, debility, weight loss, or lower back pain, or pathological fractures of vertebrae and long tubular bones.
2. Laboratory tests show anemia, increased globulin in serum, inversion of albumin/globulin ratio, abnormal alpha or gamma globulin in protein electrophoresis, B-J protein in urine, hypercalcemia, elevated serum alkaline phosphatase, and metabolite accumulation due to renal insufficiency.
3. X-rays show areas of osteolytic destruction with unresponsive bone and poorly defined borders. The number of lesions is large, and the bone cortex in the lesion area may appear mildly distended, the bone cortex becomes thin but remains intact, and pathological fractures may occur.
4, Pathological examination shows large areas of basophilic garden cells with a high number of small capillaries between them. The cells are separated by abnormal globular proteins produced by amorphous, non-fibrillar eosinophilic myeloma cells. The morphology of the tumor cells ranges from mostly undifferentiated round cells with only a few identifiable plasma cells to almost all cells in the lesion being identifiable plasma cells.
V. Differential diagnosis
Bone metastatic cancer: Bone metastatic cancer is a secondary malignant tumor that metastasizes from the primary cancer outside the bone to the bone. The age of onset is more than 50 years old, and it usually occurs in bones containing red bone marrow, such as the skull, vertebrae, ribs, pelvis and epiphysis of long tubular bones. Most patients with metastatic bone cancer have a history of primary cancer and present with diffuse bone pain and occasional soft tissue masses with tenderness, and the radiographic appearance is mostly indistinct, patchy osteolytic destruction. The differentiation between myeloma and myeloma mainly relies on laboratory tests, especially serum immunoelectrophoresis, which mostly shows abnormalities of globulin in myeloma patients, but rarely in bone metastasis cancer patients, but pathological examination is required for final diagnosis.
VI. Treatment and rehabilitation
1.Non-surgical treatment
(1) Radiotherapy: For single-onset myeloma, radiotherapy is preferred if it has less impact on function than surgical treatment. For patients with multiple myeloma, if survival is not long, radiotherapy should be chosen to relieve pain, control the growth of local tumor and prolong life.
(2) Chemotherapy: The most effective ones are cyclophosphamide (cancer dextran) and levomepromazine nitrogen mustard (Milphalan) and combined with corticosteroids (prednisone), vincristine, adriamycin and other drugs. Systemic chemotherapy is only indicated for patients with multiple myeloma with systemic symptoms, and not for patients with only a single lesion without systemic symptoms.
(3) Stem cell transplantation: High-dose chemotherapy plus stem cell transplantation can greatly reduce the tumor load in the patient’s body. At present, peripheral blood stem cells are recommended as the source of transplantation, which is relatively efficient and effective.
2. Surgical treatment
The most common indication for surgery is the prevention and treatment of pathological fractures. It makes sense to perform prophylactic internal fixation at sites prone to pathological fractures prior to radiotherapy. Sometimes, surgical excision of a single lesion without systemic symptoms is better than radiotherapy alone. If the lesion is large enough to cause irrecoverable dysfunction, surgery is required, although radiotherapy alone can control the progression of the disease. When paraplegia first appears, surgery is feasible to reduce spinal cord compression.
Although chemotherapy and biotherapy for tumors have made significant progress in recent years, no matter what treatment regimen is used, only a very small number of patients can be cured. Even the high-dose chemotherapy combined with inbred donor-matched allogeneic bone marrow and/or peripheral blood stem cell transplantation used in recent years has resulted in cure or long-term tumor-free survival in less than 20% of patients under 55 years of age, although the treatment-related mortality rate for the latter can be as high as 50% or more.
For most patients, a realistic treatment goal is to maximize survival time and improve quality of life with long-term relief of pain and other symptoms. Based on this, treatment options should be chosen that are safe, easily tolerated by the patient, and result in long-term remission or stabilization of the tumor. It should be individualized, depending on the patient’s age, disease duration, physical condition, initial treatment/retreatment and response to treatment as important reference factors for choosing specific treatment regimens.
VII. Difficulties and countermeasures
In most cases, a definitive diagnosis can be reached without puncture biopsy, relying mainly on serum protein electrophoresis and laboratory biochemical tests. In some cases, when only a single lesion is present, bone marrow aspiration of the non-lesioned bone can clarify whether the disease has disseminated. When there is a high clinical suspicion and a biopsy is needed for a definitive diagnosis, a puncture biopsy is the preferred method. The diagnosis is confirmed by visualizing highly vascularized myeloma tissue, and puncture biopsy has fewer complications than excisional biopsy, while the consistency of histologic features greatly reduces sampling errors.
If the possibility of a myeloma is not considered clinically in parallel with an incisional biopsy, unexpected, frightening hemorrhage is common. In such cases, having local bone cement as a thermal hemostatic agent is often very effective.