Primary bone lymphoma (PBL) is an uncommon malignant neoplasm,
usually manifesting as a solitary bone lesion.
PBL mainly involves extranodal non-Hodgkin's lymphoma (NHL),
with B-cell subtype being the most common.
On the contrary,
Hodgkin's PBL is strikingly rare and patients may have concurrent nodal disease detected at staging.
Multifocal subtype of the disease is infrequent.
Primary muscular lymphoma (PML) is also uncustomary.
PBL/PML manifest with non-specific symptoms,
usually subtle intermittent pain.
Other symptoms include soft-tissue edema,
and rarely “B-symptoms” (almost exclusively seen in stage IV).
Patients may also present with a pathological fracture or hypercalcemic crisis.
Neurological disorders (radical symptoms,
spinal cord compression) may be the presenting symptoms in case of vertebral involvement.
Etiology remains unidentified,
although relation to immunological and DNA disorders,
Paget’s disease and traumas,
has been reported.
The majority of patients are >45 years old,
with a peak prevalence in the sixth and seventh decades.
The disease rarely presents under the age of 10 years.
The male population demonstrates a slightly higher predilection.
While any part of the skeleton may be involved in the disease,
PBL usually affects the appendicular skeleton,
customarily the femur (involving approximately 50% of the cases) and the pelvis (affected in a percentage of about 20%).
Multifocal subtype may incorporate both axial and appendicular lesions,
usually in the distal femur,
proximal tibia and spine.
secondary osseous lymphoma shows a preference for the axial skeleton (spine,
ribs and facial bones).
PML is more common in the thigh and upper arm,
presenting as a focal mass or diffuse muscular infiltration.
It should be mentioned that PBL is one of few entities where lesions may involve adjacent bones by invading joint or vertebral spaces.
chondrosarcoma and metastases are also included in the differential diagnosis list.
On suspicion of PBL/PML,
imaging investigation includes X-rays,
scintigraphy and MRI.
Plain radiograph remains the initial study for osseous lesions whereas MRI provides excellent depiction of bone-marrow replacement,
soft-tissue mass and cortical erosion.
PET-CT is currently used for staging and follow-up.
- The results of plain radiographs are usually normal at the time of presentation.
Krishnan et al.
 presented the following classification of radiographic patterns: i) The lytic-destructive (permeative or moth-eaten) pattern,
ii) The blastic-sclerotic pattern (rare) with/without areas of mixed sclerotic-lytic appearance,
iii) Subtle or "near-normal" findings.
In case of locally aggressive disease,
x-rays might demonstrate a localized lytic lesion near the end of a long bone,
with a permeative appearance and associated periosteal reaction.
These findings are similar to that of Ewing's sarcoma,
osteosarcoma and metastatic bone lesions,
which should be considered in the diagnostic process.
- CT is excellent in delineating cortical erosion,
although imaging features are usually non‑specific.
It is also useful for post-treatment follow-up,
demonstrating bone remodeling with an appearance similar to Paget's disease of the bone.
- PBL shows a hypermetabolic behavior on FDG-PET.
PET-CT is sensitive for evaluating response to therapy,
particularly in determining a complete response.
- MRI depicts PBL marrow involvement as low intensity on T1-WI and high intensity on T2-WI,
while low intensity areas within the tumor on T2-WI correspond to fibrosis.
Peritumoral edema and reactive marrow changes are also depicted as bright on T2-WI.
STIR images further help delineate the normal from abnormal marrow.
Contrast-enhanced MRI demonstrates areas with variable patterns of enhancement (homogeneous,
MRI allows earlier detection of cortical destruction,
compared to CT and it is also useful for the assessment of extra-osseous soft tissue.
- Bone scintigraphy with 99mTc-methylene diphosphonate is a valuable study in PBL staging,
detecting multifocal involvement,
which may alter the therapeutic plan and disease prognosis.
The presence of a solitary bone lesion with a permeative/moth-eaten appearance and associated layered periosteal reaction on x-rays,
and an extra-osseous soft-tissue mass on MRI,
particularly in a patient older than 30 years,
is highly indicative of PBL lesion.
- Ultrasonography shows non-specific findings,
usually a heterogeneously hypoechoic solid mass with irregular or ill-defined borders.
- CT reveals a lesion isodense or slightly hypodense comparing to normal muscle and varying contrast enhancement.
- FDG-PET is used for assessment of post-treatment response,
due to its ability to distinguish between viable tumour and necrosis/fibrosis in residual masses.
- On MRI,
the tumour appears as a discrete mass or abnormal signal intensity within the muscle.
It is depicted as isointense or slightly hyperintense to normal muscle on T1-WI,
while on T2-WI it demonstrates intermediate signal intensity between muscle and fat.
On contrast MRI the lesions show diffuse homogeneous,
predominately peripheral (ring-like),
enhancement or marginal septal enhancement,
with/without irregular enhancement of deep and/or superficial muscular fascia.
Imaging characteristics highly suggestive of lymphoma,
include: orientation of the tumour along muscle fascicles,
involvement of more than one muscle compartment with traversing vessels within involved muscles,
extension along the neurovascular bundle and adjacent subcutaneous stranding with/without skin thickening.
Decrease in size,
T2 signal intensity and contrast enhancement are indicative findings of response on post-treatment MRI.
According to the Ann Arbor system ,
PBL is divided into the following four stages,
determined by histology:
- Stage I: Single bone lesion with or without soft‑tissue infiltration.
- Stage II: More than two lesions beside one side of the diaphragm,
or a single bone lesion with soft-tissue infiltration.
- Stage III: Lesions beside two sides of the diaphragm.
- Stage IV: Infiltration of the central or peripheral nervous system,
or bone marrow.
- Lytic-destructive pattern: Differential diagnosis is varied,
metastasis and Ewing’s sarcoma.
In case of well-defined lytic lesions,
the appearance may mimic multiple myeloma.
Presence of bone sequestrum should incorporate osteomyelitis,
radiation necrosis and eosinophilic granuloma in the differential diagnosis list.
- Blastic-sclerotic pattern: Purely sclerotic lesions are mostly described with Hodgkin disease,
although it may also demonstrate a lytic radiological appearance.
Differential diagnosis includes post-therapeutic sclerosis of lytic lesions,
Paget’s disease of the bone,
osteosarcoma and osseous lymphoma.
Ewing’s sarcoma and osteomyelitis should be considered in the differential diagnosis list of the younger population,
whereas the main differential diagnosis in older patients is bone metastasis of solid-organ tumors.
Treatment - Prognosis
Therapy is multifaceted,
chemotherapy and rituximab.
the role of surgery is usually limited to the diagnostic biopsies and the management of pathological fractures.
PBL/PML have an improved prognosis compared with other bone malignancies,
such as osteosarcoma or secondary involvement of the bone with lymphoma.
A younger age has been identified as an independent survival predictor.
Disease stage has a significant effect on five‑year survival.
Multifocal PBL has a poorer prognosis than localized PBL tumor.
presenting either diffuse or as lamellated onion peel,
is an indicator of poor prognosis.