What are the causes of bony lytic lesions?

Causes of Bony Lytic Lesions

Bony lytic lesions result from five primary categories: metastatic malignancies (most commonly breast, lung, kidney, and thyroid cancers), hematologic malignancies (multiple myeloma, Waldenström's macroglobulinemia, leukemia), infectious processes (particularly tuberculosis), primary bone tumors, and benign conditions (bone cysts, angiomas). 1

Malignant Causes

Metastatic Disease

• Breast cancer causes lytic bone metastases in approximately 70% of patients with metastatic disease, representing the highest incidence of skeletal-related events across all tumor types 1
• Lung cancer produces lytic bone metastases in 40% of patients with metastatic disease 1
• Renal cell carcinoma causes lytic bone metastases in 40% of patients, with bone metastasis being the most significant independent variable associated with poor survival 1
• Thyroid cancer characteristically produces purely osteolytic lesions that are relatively insensitive to detection by radionuclide bone scans 1

Hematologic Malignancies

• Multiple myeloma is the classic presentation of lytic bone disease, affecting 95% of patients with extensive lytic lesions that typically do not heal despite successful anti-neoplastic treatment 1

  • Bone pain (particularly back pain from vertebral fractures) presents in three-quarters of MM patients 1
  • Lytic lesions require 30-50% loss in bone density to be visible on plain radiographs 1
  • The presence of lytic bone lesions distinguishes symptomatic myeloma requiring treatment from smoldering myeloma 1

• Waldenström's macroglobulinemia rarely presents with widespread osteolytic lesions and recurrent pathologic fractures, though this is an uncommon manifestation 2

• Leukemia produces numerous small lesions with "fronts of resorption" that differ from the "space-occupied" appearance of myeloma lesions 3

Infectious Causes

Tuberculosis

• Mycobacterium tuberculosis can cause isolated lytic bone lesions that closely mimic bone tumors (bone cysts, osteoblastoma, osteosarcoma) and metastatic disease radiologically 4, 5
• TB bone lesions can occur even in immunocompetent patients without pulmonary symptoms or known exposure 4, 5
• Definitive diagnosis requires histopathology showing granulomatous osteomyelitis and culture confirmation 4, 5

Distinguishing Features by Pathology

Multiple Myeloma Characteristics

• Sharply defined, spheroid lesions with smooth borders and completely effaced/erased trabeculae creating the classic "punched out" appearance 3
• Total absence of remodeling distinguishes myeloma from metastatic cancer 3
• Uniform effacement of both cortical and trabecular bone, contrasting with some cortical preservation in metastatic cancer 3

Metastatic Carcinoma Characteristics

• Irregular preservation of trabeculae with buttressing and isolated "fronts of cortical bone resorption" coalescing to confluence 3
• "Golf-ball surface" phenomenon observed in metastatic cancer but not in myeloma 3
• Variable lesion appearance with some cortical preservation 3

Diagnostic Approach

Imaging Modalities

• Plain radiographs are insensitive, requiring 30-50% bone density loss to detect lytic lesions 1
• CT scanning has improved sensitivity over plain films with better target-to-background ratio, useful for characterizing lesion size and cortical reaction 1
• MRI demonstrates high sensitivity (82-100%) and specificity (73-100%) for bone marrow metastases, detecting infiltration before osseous bone response occurs 1
• Radionuclide bone scans are relatively insensitive for purely osteolytic lesions (sensitivity 62-100%, lowest in predominantly lytic disease) but effective for mixed osteolytic-osteoblastic lesions 1
• FDG-PET directly assesses metabolic activity of metastatic tissue, helpful for detecting purely osteolytic lesions and marrow infiltration 1
• Whole-body low-dose CT (WBLD-CT) is optimal for detecting lytic lesions 6

Tissue Diagnosis

• Histological confirmation is strongly recommended for bone-only disease, especially with few lesions or equivocal imaging, given the major clinical and emotional consequences of a metastatic bone disease diagnosis 1
• CT-guided biopsy should be performed when feasible, with pathological assessment by a specialist familiar with bone tissue 1
• Mycobacterial cultures should be included when analyzing biopsies of lytic bone lesions to exclude tuberculosis 5

Critical Pitfalls

• Paraproteinemia does not confirm multiple myeloma: A patient with lytic bone lesions and paraproteinemia may have metastatic cancer with concurrent monoclonal gammopathy of undetermined significance (MGUS) 7
• Bone scan limitations: Purely lytic lesions from kidney, thyroid cancer, and multiple myeloma are poorly detected by technetium bone scans 1
• Benign mimics: Bone cysts and angiomas can present as solitary asymptomatic lytic lesions, requiring CT or MRI for differentiation 1
• Uniform size is unreliable: While traditionally attributed to myeloma, isolated uniform-sized lesions occur in metastatic cancer and variable-sized lesions occur in some myeloma cases 3