Courtesy: Prof James Wittig
Orthopaedic Oncologist
Sarcoma Surgeon
www.tumorsurgery.org
James Wittig books

 

Small Round Blue Cell Tumors of Bone

Overview

• Group of tumors composed of:
  • Small, round, blue-staining cells
  • No matrix production (key feature)
• Resemble hematopoietic cells
• Include both benign and malignant entities

Common Entities

• Benign
  • Eosinophilic granuloma (Langerhans cell histiocytosis)
• Malignant
  • Ewing sarcoma
  • Lymphoma
  • Multiple myeloma / Plasmacytoma
  • Metastatic neuroblastoma
  • Metastatic small cell carcinoma
  • Rhabdomyosarcoma (rare in bone)

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1. Eosinophilic Granuloma (Langerhans Cell Histiocytosis)

Nature

• Benign proliferation of Langerhans cells
• Often associated with:
  • Eosinophils
  • Lymphocytes
  • Plasma cells
• Considered immune dysregulation, not true neoplasm

Epidemiology

• Age: 5–15 years (most common)
• Male predominance (2:1)

Types

1. Solitary lesion (70%)
2. Multifocal disease
3. Disseminated forms:
   • Hand-Schüller-Christian disease
     • Triad:
       • Lytic bone lesions
       • Exophthalmos
       • Diabetes insipidus
   • Letterer-Siwe disease
     • <1 year
     • Highly fatal

Common Sites

• Flat bones (70%)
  • Skull
  • Pelvis
• Long bones (less common)

Clinical Features

• Pain + swelling
• Mild fever
• Peripheral eosinophilia (5–10%)

Radiology

• Variable:
  • Geographic (benign)
  • Moth-eaten / permeative (aggressive)
• Features:
  • Onion-skin periosteal reaction
  • Possible sequestrum (“button sequestrum”)
• Spine: Vertebra plana (classic)

MRI

• Marrow replacement
• T2 hyperintensity
• May show soft tissue mass

Pathology

• Langerhans cells – coffee-bean nuclei
• Birbeck granules (tennis racket appearance)
• Immunostains:
  • CD1a+
  • S100+
  • Vimentin+

Treatment

• Observation (many resolve)
• Curettage + bone graft (if fracture risk)
• Intralesional steroids
• Rare: radiation

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2. Ewing Sarcoma

Key Concept

• Most important malignant small round blue cell tumor
• Always considered micrometastatic at presentation

Epidemiology

• Age: 10–25 years
• Slight male predominance
• Rare in African ancestry

Genetics

• t(11;22) – EWS-FLI1 fusion protein

Common Sites

1. Femur
2. Humerus
3. Pelvis
4. Ribs

Diaphyseal origin (key exam point)

Clinical Features

• Pain + swelling
• Fever, anemia, elevated ESR (may mimic infection)
• Pathological fracture (~10%)

Radiology

• Permeative / moth-eaten lesion
• Onion-skin periosteal reaction
• Large soft tissue mass (90%)
• No matrix production

MRI

• Extensive marrow involvement
• Large soft tissue component
• Extends beyond what X-ray shows

Bone Scan

• Intense uptake

Pathology

• Uniform monotonous small round blue cells
• Minimal cytoplasm
• Glycogen-rich – PAS positive
• Immunostains:
  • CD99+
  • Vimentin+
  • HBA71+

Treatment

• Multi-agent chemotherapy (essential)
• Limb-sparing surgery (preferred)
• Radiation (selected cases)

Prognosis

• Localized disease:
  • ~65% 5-year survival
• Metastatic disease:
  • 15–30% survival
• Worse:
  • Pelvic tumors

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3. Primary Lymphoma of Bone

Definition

• Lymphoma arising in bone without systemic disease for 6 months

Epidemiology

• Usually >40 years
• Rare in children

Common Sites

• Femur
• Pelvis
• Humerus

Clinical Features

• Dull pain
• Palpable mass
• Pathological fracture (25%)

Radiology

• Permeative / moth-eaten
• Sometimes normal X-ray
• Soft tissue mass common

MRI

• Marrow replacement
• Soft tissue extension without cortical destruction

Pathology

• Mixed cell population:
  • Small lymphocytes
  • Large malignant B cells
• Variable size cells (unlike Ewing)

Markers

• CD20+
• CD45+
• Reticulin+
• Leukocyte antigen+

Treatment

• Chemotherapy ± radiotherapy
• Surgery only for stabilization

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4. Multiple Myeloma / Plasmacytoma

Nature

• Malignant proliferation of plasma cells

Types

1. Multiple myeloma (systemic)
2. Solitary plasmacytoma

Epidemiology

• Age: >50 years
• Most common primary bone malignancy

Common Sites

• Spine
• Pelvis
• Skull
• Ribs
• Proximal femur

Clinical Features

• Bone pain
• Anemia
• Hypercalcemia
• Renal failure
• Pathological fractures

Investigations

• SPEP: M protein spike
• Urine: Bence Jones protein
• ESR

Radiology

• Punched-out lytic lesions
• No sclerosis
• Diffuse osteopenia

Bone Scan

• May be negative

Pathology

• Plasma cells:
  • Clock-face nucleus
  • Perinuclear halo

Special Syndrome

• POEMS syndrome
  • Polyneuropathy
  • Organomegaly
  • Endocrinopathy
  • Monoclonal gammopathy
  • Skin changes

Treatment

• Chemotherapy
• Stem cell transplant
• Radiotherapy (localized disease)
• Surgery (fracture fixation)

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