Team Member Role(s) Profile
Paul Banaszkiewicz Paul Banaszkiewicz Section Editor
Rebecca Rebecca Mazel Segment Author
Nicole Nicole Abdul Segment Author

Lymphoma of Bone

  • Known in the past as reticulum cell sarcoma.
  • Occurs as:
    • A solitary focus (primary lymphoma of bone) OR
    • In association with other bony sites and soft tissue lesions (nodal disease and soft tissue masses) OR
    • Multiple metastatic foci in bones.


  • Less than 5% of primary malignant bone tumours.
  • Over 20% of patients with lymphoma have secondary bone involvement.
  • Predilection to male individuals.
  • Patients usually middle aged but it can occur at any age.
  • Most intraosseous lesions are non-Hodgkin's B-cell lymphoma.

Clinical presentation

  • Commonly found in the femur and pelvis in patients 20 years of age and older.
  • 40–50% occur around the knee.
  • Presents with pain and swelling plus or minus soft tissue mass.
  • There is no history of trauma preceding symptoms.
  • Patients are at risk of pathological fractures.
  • It is relatively common in the spine and so may present with neurological symptoms.
  • Classic B-cell symptoms such as: night sweats, weight loss and fever may occur.

Haematopoietic tumours 1.png

Lytic lesion left intertrochanteric region, and pathological fracture left lesser trochanter


X-rays (Figure 2):

  • Early features are of mottled lucent areas.
  • Diffuse destructive lytic lesion with little periosteal reaction.
  • Usually combination of patchy sclerosis and mottled destruction.
  • Plain radiographs often underestimate the extent of the lesion.
  • Hodgkin’s disease has a typical appearance of “ivory vertebrae” on X-ray.
  • CT chest/abdo/pelvis (when diagnosis known for staging).
  • MRI will show the soft tissue masses in detail.
  • Bone scan will show areas of lymphoma as hot spots.
  • CXR (included in work-up of patient).

Haematopoietic tumours 2.pngHaematopoietic tumours 3.pngHaematopoietic tumours 4.png

Hodgkin’s Lymphoma of the spine

Case courtesy of Dr Ian Bickle, <a href=""></a>. From the case <a href="">rID: 47856</a>

Other investigations

  • Blood tests: FBC, blood smears (to rule out leukaemia), U&Es, LFTs, bone biochemistry, lactate dehydrogenase, ESR.
  • Bone marrow aspirate.
  • Bone biopsy
  • Abdominal exploration ® splenectomy ® staging.

Differential diagnoses

  1. Osteosarcoma
  2. Ewing's sarcoma
  3. Osteomyelitis
  4. Metastatic cancer
  5. Multiple myeloma
  6. Eosinophilic granuloma
  7. Neuroblastoma
  8. Rhabdomyosarcoma
  9. Leukaemia


  • Intraosseous components contain bone and fat, extraosseous components contain lymph node tissue giving it a yellow-beige colour.
  • Common features of tumours such as haemorrhage and necrosis may be seen.
  • Histology reveals sheets of poorly differentiated cells with irregular nuclei.
  • Malignant lymphoma tissue is composed of a mixture of tissues and cell types: reticulin, lymphocytes, and fibroblasts.
  • Most commonly of the B-cell lymphoma type.
  • In Hodgkin’s lymphoma “Reed–Sternberg” cells are present, visible histologically (large, sharply delineated cells with abundant cytoplasm and a double nucleus).
  • Immunohistochemistry can aid diagnosis as lymphoma tissues often express antigens such as CD3 and CD45.


  • Surgery:
    • Limb-sparing techniques
    • Excision of tumour
    • Prophylactic stabilisation in bones at risk of pathological fracture
    • Amputation
  • Radiotherapy for localised lesions.
  • Chemotherapy for systemic involvement.
  • Often surgery and radiotherapy used in conjunction.


  • Lymphoma of bone has the best prognosis of all primary malignant bone tumours.
  • 44% 5-year survival
  • Pure Hodgkin’s disease or lymphocytic disease ® worse prognosis.


  • MM is a malignant proliferation of abnormal plasma cells that causes widespread osteolytic bone damage.
  • The malignant plasma cells produce paraproteins (monoclonal immunoglobulins).
  • It is the most common primary malignant tumour of bone (~40%).
  • It may affect any bone with haematopoietic red marrow (spine, skull, ribs, sternum and pelvis).
  • Most commonly affects adults aged 50–80 years old.
  • Has a predilection to men.


  • Bone pain related to the deposits.
  • Pathological fractures
  • Constitutional symptoms related to anaemia, thrombocytopenia, hypercalcaemia, and renal failure.
  • Other symptoms may include cachexia and spinal cord compression.
  • Amyloidosis in 20%
  • Bacterial infections are common because of a lack of normal immunoglobulin production.


  • Osteoclastic activity is increased via pathways involving RANK-L, MIP-1alpha and IL6 (cytokines released by plasma cells).
  • Osteoblastic activity is inhibited.
  • Angiogenesis is stimulated.

Investigation results

  • FBC showing a normochromic, normocytic anaemia.
  • ESR raised ++ (often >100 mm/hour).
  • U&Es showing renal failure.
  • Hypercalcaemia (20–40%)
  • Monoclonal immunoglobulins (mostly IgG and IgA) found on serum protein electrophoresis (90%).
  • Bence Jones proteins (light chain subunits of immunoglobulin) present in urine (50%) shown on urine protein electrophoresis.


  • The radiological appearance of multiple myeloma is characterised by irregular lytic defects of different sizes, often described as “punched out” with no periosteal reaction.
  • Skeletal survey is the most sensitive investigation as a bone scan can fail to have increased uptake in 25%.
  • MRI is useful for delineating spinal and pelvic lesions.
Haematopoietic tumours 5.png


  • Biopsy reveals sheets of densely packed plasma cells.
  • The degree of cytological atypia of these cells has no prognostic value.
  • Different maturities of plasma cells will be present but characteristic features of MM include: perinuclear halo, basophilic cytoplasm, eccentric nuclei, and “clock-face” chromatin.

Haematopoietic tumours 6.png

Hypercellular marrow.Sheets of plasma cells 


  • Set criteria for diagnosing MM.
  • The criteria is explained in full, along with treatment regimens in the following paper:

Anderson KC, Alsina M, Atanackovic D, Biermann JS, Chandler JC, Costello C, et al. NCNN Guidelines Insights: Multiple Myeloma, Version 3.2016. J Natl Compr Canc Netw 2016; 14(4): 389–400.


  • No “cure” but some treatments such as stem cell transplantation can increase survival by a couple of years.
  • Radiotherapy:
    • MM is sensitive to radiotherapy, and reossification of tumour defects may occur within several months.
    • Radiotherapy is recommended for intractable bone pain as it can be dramatically effective in relieving symptoms.
  • Chemotherapy:
    • Palliative only.
    • May be used in conjunction with steroids.
  • Bisphosphonates are useful in the treatment of hypercalcaemia.
  • Surgery:
    • Prophylactic IM nails for femoral, humeral deposits.
    • ORIF of other pathological fractures.
    • 15% may need spinal decompression due to deposits or fracture.
  • Stem cell transplantation.


  • Untreated, a patient with bony lesions will only survive an average of 6–12 months with the cause of death usually infection or haemorrhage.
  • Patients have improved survival following chemotherapy.
  • With treatment, a survival time of 3–5 years is not uncommon.
  • Solitary lesions – 60% 5-year survival.
  • Multiple lesions – 5% 5-year survival.

Related conditions

  • Solitary plasmacytoma: atypical plasma cells only present in one bony location and patient does not meet criteria for diagnosis of MM.
  • Osteosclerotic myeloma: very rare.
  • Monoclonal gammopathy of undetermined significance (MGUS): this may progress to MM. Atypical plasma cells and monoclonal paraproteins are present but the number is lower than that required for diagnosis of MM. Annual surveillance is required in patients with MGUS.
  • Plasma cell dyscrasia.


Some text and images courtesy of Henry DeGroot III, MD found on


Case based Discussion

A 75 year old woman with a productive cough falls in a nursing home. Whilst being treated in the Care of the Elderly ward she reports pain in her left elbow

Haematopoietic Tumours 7 .png

Examiner: Please describe this X-ray

Candidate:AP plain radiograph of the left elbow with no fracture seen. There are multiple irregular lytic lesions with a “punched out” appearance and no periosteal reaction

Examiner: What is your diagnosis and differentials?

Candiate:Multiple myeloma. Differentials include osteomyelitis and metastatic disease. The productive cough could be due to a lack of normal immunoglobulin production (due to myeloma) making her more susceptible to bacterial infection.

Examiner: You review her recent blood tests. There is a FBC and U&E on the system. What derangements could be caused by myeloma? What further blood tests would you like?

Candidate:FBC: normocytic, normochromic anaemia

U&E: renal failure

Also useful would be Bone Profile for hypercalcaemia. ESR is commonly raised.

Examiner: What are the treatment options and prognosis for multiple myeloma?

Candidate:There is no cure for multiple myeloma, but treatment can improve survival. Radiotherapy can trigger re-ossification of lesions and significantly improve bone pain. Chemotherapy affects normal bone marrow stem cells, and therefore can cause further reduction in normal blood constituents. It is sometimes used on its own palliatively. Chemotherapy can also be given in conjunction with stem cell therapy. High dose chemotherapy agents are given, killing both the myeloma cells, and the healthy stem cells. The stem cells are then replaced with either donated or the patient’s own previously harvested stem cells.Bisphosphinates can be used to reduce hypercalcaemia. Surgery is indicated prophylactically or to stabilise pathological fractures. Spinal deposits/fracture may warrant decompression and/or stabilisation..With treatment survival can improve significantly, from 6-12 months to 3-5 years. Prognosis of solitary lesions is better than multiple lesions.



A 35 year old keen runner presents with a painful left hip. X-rays show a destructive bony lesion which is subsequently biopsied. This returns a diagnosis of Non Hodgkins Lymphoma
Which of the following statements about Non Hodgkins lymphoma is false


1. Approximately 10% occur around the knee
2. It is more common in males than females
3. Lesions are usually asymptomatic incidental findings
4. Night sweats, weight loss, and fever may occur in addition to localised pain
5. Patients are usually middle aged, but it can occur at any age


The histological appearance of Non Hodgkins lymphoma can be described as


1. Containing Reed-Sternberg cells
2. Densely calcified with fibroblasts
3. Large uniform clear cells
4. Owl eye appearance
5. Sheets of poorly differentiated cells with irregular nuclei, haemorrhage and necrosis


Choose the best answer that describes multiple myeloma


1. Is a rare primary malignant tumour of bone
2. Is due to a proliferation of abnormal plasma cells
3. Is more common in women than men
4. Usually affects young adults, but can be present at any age
5. Without treatment typical survival is usually 4-5 years