Primary lymphoma of the bone
Synonyms and keywords: PLB; Reticulum cell lymphoma

# Overview
Primary lymphoma of the bone (also known as  "PLB") is an uncommon malignancy that accounts for less than 5% of all primary bone tumors. The majority of cases are of the non-Hodgkin type; Hodgkin disease accounting for only 6% of the cases.  Primary lymphoma of the bone was first discovered by Parker and Jackson in 1939. The pathogenesis of primary lymphoma of the bone is characterized by excessive osteoclast activation. Primary lymphoma of the bone is commonly located in bone marrow, axial skeleton, or femur (most common). Primary lymphoma of the bone may be classified according to location into solitary, multifocal, distant, and visceral subtypes. Mutations in BCL2 and BCL6 genes have been associated with the development of primary lymphoma of the bone. Primary lymphoma of the bone is rare; the prevalence of primary lymphoma of the bone is approximately 0.01 per 100,000 individuals worldwide. Primary lymphoma of the bone is more commonly observed among middle aged adults and elderly patients. MRI is the imaging modality of choice for primary lymphoma of the bone. The mainstay of therapy for primary lymphoma of the bone is chemotherapy.

# Historical Perspective
Primary lymphoma of the bone was first discovered by Parker and Jackson in 1939.

# Classification
Primary lymphoma of the bone may be classified according to location into 4 groups:
- PBL 1: solitary bone lymphoma
- PBL 2: multifocal bony lesions
- PBL 3: cases with distant nodal disease
- PBL 4: cases with visceral disease

# Pathophysiology
- The pathogenesis of primary lymphoma of the bone is characterized by excessive osteoclast activation.
- Mutations in BCL2 and BCL6 have been associated with the development of primary lymphoma of the bone.
- Common locations of primary lymphoma of the bone are bone marrow, axial skeleton, or femur. The metaphysis of the femur is the most commonly affected site.
- On gross pathology, characteristic findings of primary lymphoma of the bone include:
- Fish flesh appearance of lymphoma
Extraosseous extension and indistinct margins
- Fish flesh appearance of lymphoma
- Extraosseous extension and indistinct margins
- On microscopic histopathological analysis, characteristic findings of primary lymphoma of the bone include:
- Diffuse growth pattern
Infiltrating between bone trabeculae
Large atypical cells
Abundant cytoplasm
Large bizarre cells, centroblasts, and immunoblasts
Positive CD20 and CD79a
- Diffuse growth pattern
- Infiltrating between bone trabeculae
- Large atypical cells
- Abundant cytoplasm
- Large bizarre cells, centroblasts, and immunoblasts
- Positive CD20 and CD79a

# Causes
There are no established causes for primary lymphoma of the bone.

# Differentiating Primary Lymphoma of the Bone from Other Diseases
Primary lymphoma of the bone must be differentiated from other diseases that cause bone pain, fever, and limited range of motion such as:
- Osteosarcoma
- Bone metastasis
- Spindle cell sarcoma
- Myeloid sarcoma

# Epidemiology and Demographics
- Primary lymphoma of the bone accounts for less than 5% of all primary bone tumors.
- The prevalence of primary lymphoma of the bone is approximately 0.01 per 100,000 individuals worldwide.
- Primary lymphoma of the bone is more commonly observed among patients aged 50 to 70 years old.
- Primary lymphoma of the bone affects men more frequently than women.
- There is no racial predilection for primary lymphoma of the bone.

# Risk Factors
The most common risk factor in the development of primary lymphoma of the bone is previous exposure to radiation.

# Screening
There is insufficient evidence to recommend routine screening for primary lymphoma of the bone.

# Natural History, Complications, and Prognosis
- The majority of patients with primary lymphoma of the bone are symptomatic at the time of diagnosis.
- Early clinical features include bone pain or a palpable mass.
- If left untreated, patients with primary lymphoma of the bone may progress to develop metastasis.
- The most common complication of primary lymphoma of the bone is a pathological fracture.
- The prognosis of primary lymphoma of the bone is generally good; the 5-year survival rate of patients with primary lymphoma of the bone is commonly >80%.

# Diagnosis

## Diagnostic Study of Choice
MRI is the imaging modality of choice for the diagnosis of primary lymphoma of the bone.

## History and Symptoms
Symptoms of primary lymphoma of the bone may include the following:
- Bone pain
- Limited range of motion
- Morning stiffness
- Low grade fever
- Night sweats

## Physical Examination
Patients with primary lymphoma of the bone usually appear pale or malnourished. Physical examination may be remarkable for:
- Swelling of the affected area
- Limited range of motion
- Gait disturbances
- Palpable mass

## Laboratory Findings
There are no specific laboratory findings associated with primary lymphoma of the bone. In some cases, non-specific findings may include:
- Elevated LDH
- Elevated 2 microglobulin

## Electrocardiogram
There are no ECG findings associated with primary lymphoma of the bone.

## X-ray
On conventional radiograph, the following non-specific findings of primary lymphoma of the bone may be found:
- Solitary metadiaphyseal lesion
- Layered periosteal reaction
- Affected bone may be normal or affected by lytic, sclerotic or mixed pattern
- A lytic pattern with permeative bone destruction and a wide zone of transition

## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with primary lymphoma of the bone.

## CT scan
There are no CT scan findings associated with primary lymphoma of the bone.

## MRI
On MRI, findings of primary lymphoma of the bone include:
- Abnormalities in bone marrow
- Soft tissue mass

## Other Imaging Findings
There are no other imaging findings associated with primary lymphoma of the bone.

## Other Diagnostic Studies
There are no other diagnostic studies associated with primary lymphoma of the bone.

# Treatment

## Medical Therapy
The mainstay of therapy for primary lymphoma of the bone is chemotherapy combined with radiotherapy. Response to chemotherapy or radiotherapy can be monitored with imaging studies.

## Surgery
Surgical intervention is not recommended among patients with primary lymphoma of the bone.

## Primary Prevention
There are no established measures for the primary prevention of primary lymphoma of the bone.

## Secondary Prevention
There are no established measures for the secondary prevention of primary lymphoma of the bone.