• Malignant

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.

Incidence

• 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.

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

Imaging

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).

Hodgkin’s Lymphoma of the spine

Case courtesy of Dr Ian Bickle, <a href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/47856">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

Pathology

• 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.

Treatment

• 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.

Prognosis

• 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.

Features

• 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.

Presentation

• 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.

Pathology

• 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.

Imaging

• 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.

Histology

• 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.

Hypercellular marrow.Sheets of plasma cells 

Diagnosis

• 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.

Treatment

• 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.

Prognosis

• 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.

Acknowledgements