What is the differential diagnosis for an 80-year-old woman with recurrent falls, presenting with pelvic pain, a CT scan showing bone lucency (lytic lesion), and elevated Alkaline Phosphatase (ALP) levels?

Differential Diagnosis for Pelvic Lytic Lesion with Elevated ALP in an 80-Year-Old Woman with Recurrent Falls

In an 80-year-old woman presenting with pelvic pain, recurrent falls, bone lucency on CT, and elevated alkaline phosphatase, metastatic carcinoma to bone is the most likely diagnosis and must be excluded first, followed by consideration of Paget's disease, primary bone malignancies, pathological fracture, and metabolic bone disease. 1

Primary Differential Considerations

Metastatic Carcinoma (Most Likely)

• In patients over 40 years, metastatic carcinoma in bone is the most common cause of lytic bone lesions and should be investigated promptly before considering other diagnoses. 1
• Immediate workup should include:
  • CT chest, abdomen, and pelvis to identify primary malignancy 1
  • Whole skeletal imaging (isotope bone scan or whole-body MRI) 1
  • Myeloma screen (serum protein electrophoresis, immunofixation, free light chains, urine protein electrophoresis) 1
• Common primary sources in elderly women include breast, lung, thyroid, kidney, and gastrointestinal malignancies 1
• Multiple myeloma must be specifically excluded given the age and presentation 1

Paget's Disease of Bone

• Paget's disease presents with characteristic features: family history, pelvic or skull localization, markedly elevated ALP (often 2-4 times upper limit of normal), bone deformities, and mixed osteolytic/sclerotic lesions on imaging. 2, 3
• Affects 1-2% of the population over 55 years, making it common in this age group 3
• Typically shows mixed osteoblastic and lytic changes rather than purely lytic lesions 4, 5
• Plasma total alkaline phosphatase is elevated in most untreated patients but may be normal in monostotic or limited disease 6
• In Asian populations, Paget's disease is rare and can be mistaken for metastatic disease, leading to unnecessary investigations 5
• Diagnosis confirmed by typical radiological features on plain films; nuclear bone scan assesses disease extent 3, 7

Primary Bone Malignancies

Spindle Cell Sarcomas (MFH/Fibrosarcoma):

• Spindle cell sarcomas typically present in older patients with a lytic lesion in bone, and the differential diagnosis often includes metastasis. 1
• High incidence of pathological fracture at presentation 1
• Full staging and biopsy required before any surgical intervention 1
• Patients with proven solitary bone lesions should be referred to a bone sarcoma center to exclude primary malignant bone tumor (PMBT). 1

Chondrosarcoma:

• Most present with a painless mass; pain at the site suggests malignancy 1
• In long bones and pelvis, central cartilaginous lesions should be considered low-grade chondrosarcoma until proven otherwise 1

Pathological Fracture

• Recurrent falls in an elderly patient with bone lucency raises high suspicion for pathological fracture, which may be the presenting feature of underlying malignancy or metabolic bone disease. 1
• If pathological fracture exists in a possible primary malignant bone tumor, adequate imaging including MRI should be performed before any intervention, followed by biopsy. 1
• Internal fixation is contraindicated before diagnosis as it disseminates tumor cells and increases local recurrence risk 1
• External splintage is recommended with appropriate pain control 1

Metabolic Bone Disease

Osteomalacia:

• Presents with generalized bone pain, muscle weakness, low serum phosphate, elevated ALP, low vitamin D, increased PTH, and bone demineralization 2
• More likely to show diffuse demineralization rather than focal lytic lesions 2

Hyperparathyroidism:

• Can cause elevated ALP and lytic bone lesions 2
• Check serum calcium, phosphate, and parathyroid hormone levels 2

Critical Diagnostic Pitfalls

Common Errors to Avoid:

• Do not perform internal fixation before establishing diagnosis, as this can disseminate malignant cells if present 1
• Do not assume insufficiency fracture without excluding malignancy in this age group 1
• In Asian populations or areas where Paget's disease is rare, do not overlook this diagnosis and pursue unnecessary cancer investigations 5
• Elevated ALP must be confirmed as bone-specific, as only ~50% of circulating ALP originates from bone tissue 2

Age-Specific Considerations:

• The 2025 UK guidelines emphasize that in patients over 40 years with bone lesions, metastatic carcinoma is most likely, warranting prompt investigation before referral to specialized centers 1
• Bone-specific ALP (B-ALP) is preferred over total ALP in adults 2

Recommended Diagnostic Algorithm

Immediate workup (before any biopsy or surgical intervention):

1. CT chest, abdomen, pelvis to identify primary malignancy 1
2. Whole skeletal imaging (bone scan or whole-body MRI) 1
3. Myeloma screen (SPEP, immunofixation, free light chains, UPEP) 1
4. MRI of pelvis including whole bone and adjacent joints 1
5. Laboratory: CBC, ESR, bone-specific ALP, calcium, phosphate, PTH, vitamin D, renal function 1, 2

If solitary lesion confirmed after staging:

• Urgent referral to bone sarcoma center before biopsy 1
• All biopsies must be performed by specialists, as poorly performed biopsies compromise treatment 1

If multiple lesions or primary malignancy identified:

• Proceed with oncology referral and management of metastatic disease 1

If imaging suggests Paget's disease (mixed lytic/sclerotic, bone expansion):

• Plain radiographs of affected areas 3, 6
• Nuclear bone scan to assess extent 3, 7
• Consider bone biopsy if diagnosis uncertain 4, 5