bubble_chart Overview

Primary lymphoma of bone is a lymphoma originating in the bone. If left untreated, the lesion may remain confined or appear confined to one or more bones for several years; if treated, the likelihood of cure is high. Primary lymphoma of bone is a round cell fleshy tumor originating from lymphocytes in the bone marrow. Its histological features, clinical characteristics, disease course, and prognosis are distinctly different from Ewing's fleshy tumor, although the distinction between the two is not always clear. The difference between primary lymphoma of bone and systemic lymphoma is even less obvious. Primary lymphoma of bone lacks a morphological and immunological classification system like that of systemic lymphoma.

bubble_chart Pathogenesis

1. Gross examination: The tumor tissue appears grayish-white in color, soft in texture, and rich in fluid, presenting a medullary appearance. It is difficult to differentiate from cervical malignancy with cachexia, Ewing's fleshy tumor, and any other cellular fleshy tumor.

Similar to Ewing's fleshy tumor, primary lymphoma of the bone may invade beyond the cortical bone or spread within the bone, leading to the discovery of multiple tumor nodules and/or extensive tumor infiltration in bones located far from the primary lesion.

Like Ewing's fleshy tumor, primary lymphoma of the bone often exhibits areas of hemorrhage, necrosis, and liquefaction within the tumor tissue. During surgical exploration, these liquefied areas can be mistaken for osteomyelitis.

Occasionally, regional lymph nodes may become enlarged, firm, and elastic, sometimes fusing into sheets. On sectioning, the medulla of the lymph nodes may be partially or entirely replaced by white, swollen medullary tumor tissue.

2. Microscopic examination: The tumor tissue is highly cellular, with cells displaying pale and scant cytoplasm. Some cells have abundant, well-defined cytoplasm, and their cytoplasmic processes may interconnect, forming a delicate intercellular network.

The nuclei are generally larger than those of Ewing's fleshy tumor, varying in size and exhibiting significant polymorphism. They may be round, oval, pear-shaped, or feature notches or lobulation. Some cells may have large nuclei or binucleation, but no giant nuclei are observed. Chromatin may appear as fine granules or larger clumps. The nuclei often contain vacuoles and may have one or more prominent nucleoli. Mitotic figures are frequently seen. Among these reticular cells, lymphoblasts and lymphocytes are often present.

The tumor tissue may contain collagen bands of varying thickness, dividing it into irregular lobules. Silver staining often, though not always, reveals a thick layer of reticular fibers surrounding small cell clusters or even individual cells. P.A.S. staining is negative, with no intracellular glycogen detected. Immunohistochemistry (on non-decalcified specimens) may show positive staining for lymphocyte markers.

In well-differentiated primary lymphoma of the bone, the cells are smaller and exhibit a lymphocytic appearance. Compared to Ewing's fleshy tumor, their nuclei are smaller, darker, and have more clearly defined cytoplasmic boundaries.

bubble_chart Clinical Manifestations

Cervical malignancy with cachexia refers to a group of systemic lymphoid tissue tumors, among which two types often involve bone lesions, namely Hodgkin's disease and non-Hodgkin's disease.

Systemic cervical malignancy with cachexia may produce bone lesions through three pathways: ① adjacent lymph nodes invading the bone, which explains why such lesions are commonly seen in the spine, pelvis, ribs, and sternum; ② hematogenous and lymphogenous metastasis; ③ primary occurrence in the bone marrow tissue itself.

Hodgkin's disease: The initial symptoms may manifest as bone lesions, while lymph node involvement may be insignificant or even concealed, but it will eventually develop into noticeable lesions. Bone lesions are part of systemic Hodgkin's disease.

Non-Hodgkin's disease: It can form bone lesions, and systemic lymph node and visceral organ involvement may occur sooner or later, but it can also remain confined to the skeletal system indefinitely. Therefore, lymphoma can be divided into two types: one involves lymph nodes and visceral organs and often affects the skeletal system, with bone lesions being part of systemic cervical malignancy with cachexia; the other type is limited to the skeletal system, where bone lesions are not part of systemic lymphoma but are primary bone tumors. Histological examination cannot distinguish between these two types of lymphoma, and their clinical manifestations may represent different stages or intermediate states of the two types. Thus, the possibility of systemic cervical malignancy with cachexia must be considered in cases of primary lymphoma. It should be noted that a diagnosis of primary and non-systemic lymphoma of the bone can only be confirmed after several years of follow-up. In cases presenting as primary lymphoma of the bone, a thorough examination of systemic lymph nodes, non-lesional bones, visceral organs, bone marrow, and peripheral blood is required.

Primary lymphoma of the bone is much less common than Ewing's fleshy tumor. It predominantly affects males. Compared to Ewing's fleshy tumor, primary lymphoma of the bone occurs in adults or the elderly, with the majority of cases appearing after the age of 25–30. It is rare before the age of 20 and exceedingly rare before 15.

Compared to Ewing's fleshy tumor, primary lymphoma of the bone more frequently involves the trunk bones and craniofacial bones, accounting for about 50% of all cases. The remaining 50% occur in long bones, typically the femur, tibia, and humerus.

In long bones, lesions are equally distributed between the metaphysis and diaphysis. Since lymphoma often occurs after the disappearance of growth cartilage, its incidence of epiphyseal involvement is higher than that of Ewing's fleshy tumor.

Primary lymphoma of the bone can involve two or more adjacent or distant bones, and this is not uncommon.

If the lymphoma is located in the epidural space of the spine, it is difficult or impossible to confirm its origin in the bone through imaging or findings during laminectomy.

Compared to Ewing's fleshy tumor, the most notable characteristic of primary lymphoma of the bone is the patient's generally good condition, at least for an extended period, with no fever, anemia, weight loss, elevated ESR, or leukocytosis.

The main symptom is pain, which may present as intermittent mild pain over a long period. Other possible symptoms include localized swelling and pathological fractures. If spinal nerve roots are compressed, there may be radiating pain and neurological dysfunction. Compared to Ewing's fleshy tumor, the incidence of regional lymphadenopathy is lower.

When primary lymphoma of the bone is suspected or confirmed, a comprehensive examination of all bones (bone scan), lymph nodes, liver, spleen, bone marrow smears, and peripheral blood should be conducted.

bubble_chart Auxiliary Examination

X-ray findings The imaging manifestations of primary lymphoma of bone are not significantly different from those of Ewing's fleshy tumor, with no typical imaging features. The difference from Ewing's fleshy tumor is its slow growth, usually occurring in adulthood, with less reactive osteogenesis of the bone membrane.

The imaging manifestations of primary lymphoma of bone are predominantly osteolytic lesions, usually punctate osteolysis with blurred boundaries, and bone destruction often appears moth-eaten. In rare cases, osteolysis may fuse into a uniform osteolytic image.

Adjacent to the osteolytic areas, there may be regions of increased bone density, representing reactive osteogenesis, which is diffusely infiltrated by tumor tissue and not resorbed. In a few cases, the imaging may mainly show dense osteosclerosis.

The cortical bone is generally interrupted, but sometimes it can remain relatively intact. In advanced stages, the tumor may spread into soft tissues, forming a radiolucent mass with blurred boundaries and some reactive ossification streaks. The periosteum shows little or no reactive osteogenesis. If the patient is an adolescent and the tumor is located in the diaphysis, periosteal osteogenesis may be more active, but it rarely produces an onion-skin-like image. Pathological fractures are common.

The anatomical extent of primary lymphoma of bone is usually much larger than what is seen on imaging, similar to Ewing's fleshy tumor. In this sense, bone scans and MRI are more accurate. Due to the slow progression and lack of symptoms in primary lymphoma of bone, some cases have long-standing lesions at the time of diagnosis, and the imaging may show very large lesions. Sometimes, the tumor may involve half or even the entire diaphysis on imaging.

Lymphangiography can check for regional lymph node involvement, bone scans can exclude lesions in other bones, and isotope scans of the liver and spleen can also be performed.

bubble_chart Treatment Measures

Primary lymphoma of bone is sensitive to radiotherapy, which is suitable for primary {|###|} sexually transmitted disease {|###|} lesions, metastatic lesions, and multicentric bone lesions. The radiation dose ranges from 50 to 80 Gy (5000–8000 rad), and the irradiation field must be more extensive than the imaging findings, often including the entire affected bone.

Radiotherapy must be combined with chemotherapy, using a multi-drug chemotherapy regimen, administered long-term and cyclically.

If the primary lymphoma {|###|} tumor diseases {|###|} lesion compresses the spinal nerve roots, laminectomy decompression can be performed along with biopsy, followed by radiotherapy. Alternatively, needle biopsy can be performed, followed immediately by radiotherapy. If a long bone is severely destroyed and accompanied by pathological {|###|} fracture {|###|} or impending pathological {|###|} fracture {|###|}, tumor resection can be performed. Functional reconstruction may involve prosthetic implants or artificial joints, or osteosynthesis combined with bone cement, followed by radiotherapy and chemotherapy. For lesions in the scapula, ribs, or anterior pelvic arch, tumor resection can be performed, combined with radiotherapy and chemotherapy.

Amputation should be strictly limited to a few cases, applicable when the lesion is too extensive for limb-sparing surgery or radiotherapy, when radiotherapy fails to control tumor progression, or when there is extensive local recurrence after radiotherapy.

bubble_chart Prognosis

The course of primary lymphoma of bone is variable, slow, and insidious, making it difficult to predict the prognosis even 10 years after treatment. The 5-year survival rate holds little significance for primary lymphoma of bone, as it could reach 40–50% even before the application of chemotherapy, while the 10-year survival rate was only about 30%. With the combination of chemotherapy, the 10-year survival rate has now improved to 60–80%, and its prognosis is better than that of Ewing's fleshy tumor.

Factors suggesting a poor prognosis include a large extent of intraosseous lesions or lesions located in the trunk bones or pelvis. Occasionally, primary lymphoma of bone may recur within the irradiated area. In rare cases, a radioactive fleshy tumor may develop at the same site several years after radiotherapy.

bubble_chart Differentiation

The clinical and imaging manifestations of primary lymphoma of bone can resemble certain non-neoplastic diseases, such as osteomyelitis or eosinophilic granuloma. However, in most cases, the imaging findings are neoplastic in nature. Yet, in individual cases, it may be confused with fibrous fleshy tumor, malignant fibrous histiocytoma, Ewing's fleshy tumor, or osteosarcoma.

During surgery, a few cases may show significant liquefaction within the tumor tissue, which is encapsulated and could be misdiagnosed as osteomyelitis.

Definitive diagnosis relies on pathological examination, but even with seasonal disease pathology, the diagnosis may remain uncertain. If tumor tissue exhibiting the aforementioned histological features is obtained from a lymph node, the diagnosis can be confirmed, though it may still be confused with Hodgkin's fleshy tumor at most. However, when the examined tissue originates from bone, it becomes difficult to differentiate from Ewing's fleshy tumor.

Finally, in rare cases, primary lymphoma of bone must be distinguished from bone metastases of undifferentiated epithelial carcinoma or bone lesions of histiocytosis X, due to the prominent inflammatory reaction at the margins of primary lymph tumor diseases of bone.