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PA32.2-3 | Bone & Soft Tissue Tumors — SDL Guide (Part 3)

Metastatic Bone Disease

Metastatic bone disease is the most common malignancy involving bone — far more frequent than all primary bone tumors combined. This is a critical epidemiologic fact.

Sources (the 'BBC KT' mnemonic)
The five primary tumors that most commonly metastasize to bone are:
1. Breast cancer (most common in women — osteolytic and mixed lesions)
2. Bladder / Bronchus (lung cancer — usually osteolytic)
3. Colon — rare bony mets in late disease
4. Kidney (renal cell carcinoma — highly vascular, osteolytic, may bleed on biopsy)
5. Thyroid (follicular carcinoma — osteolytic, expansile, "pulsatile bone tumor")

Add prostate cancer — the classic source of osteoblastic (sclerotic) metastases. "Ivory vertebra" (uniformly dense vertebral body) on X-ray in an elderly man = prostatic metastasis until proved otherwise.

Side-by-side schematic X-ray comparison showing lytic vertebral metastases with punched-out radiolucencies from breast cancer (left) versus dense sclerotic ivory vertebrae from prostate cancer blastic metastases (right), with labeled lumbar vertebrae L1–L5. — **Panel A:** Lytic metastases in L2–L4 (punched-out radiolucent defects, cortical thinning, confluent destruction); breast cancer pattern; RANKL-driven osteoclast activation mechanism callout. **Panel B:** Blastic metastases in L1–L5 (ivory vertebra appearance, uniform hyperdensity, loss of trabecular pattern); prostate cancer pattern; osteoblast stimulation mechanism callout.

Lytic vs blastic metastases
- Osteolytic: tumor cells destroy bone by activating osteoclasts via RANKL and other cytokines. Appear as punched-out lucencies. Common in: breast, lung, kidney, thyroid, multiple myeloma.
- Osteoblastic: tumor cells stimulate osteoblasts. Appear as dense sclerotic foci. Classic in: prostate cancer.
- Mixed lytic-blastic: breast cancer (most common cause of mixed pattern in women).

Mechanism of spread to bone
- Hematogenous (arterial); Batson's vertebral venous plexus (valveless, low-pressure) explains the predilection for the axial skeleton — vertebrae (especially lumbar), pelvis, ribs, sternum, proximal femur, skull.

Clinical consequences
- Bone pain (the most common symptom of advanced cancer).
- Pathological fracture — especially through lytic lesions in weight-bearing bones (vertebral crush fractures → paraplegia; femoral neck fracture after trivial fall).
- Hypercalcemia — from extensive osteolysis → nausea, confusion, polyuria, constipation ("bones, groans, moans, stones").
- Spinal cord compression from epidural extension of vertebral metastasis — an oncological emergency.

Histology: metastatic deposits typically retain the morphology of the primary — acinar glands (breast or prostate carcinoma), clear cells (renal cell carcinoma), follicular thyroid tissue. Immunohistochemistry (CK7, CK20, PSA, TTF-1, PAX8, GATA3) helps identify the primary.

Three-panel H&E histology diagram showing bone marrow biopsy with metastatic adenocarcinoma: Panel A medium-power view with labeled glandular tumor clusters in acinar pattern, residual bone trabecula, and fibrotic stroma; Panel B high-power detail of a single acinar glandular cluster with atypical nuclei; Panel C schematic comparison of normal versus infiltrated bone marrow. — **Panel A:** Glandular tumor clusters (acinar pattern), Residual bone trabecula, Fibrotic desmoplastic stroma, Displaced hematopoietic marrow. **Panel B:** Malignant glandular epithelium, Central lumen (acinar pattern), Atypical hyperchromatic nuclei, Cytoplasmic mucin vacuoles. **Panel C:** Normal marrow — hematopoietic cells, adipocytes, intact trabecula; Infiltrated marrow — tumor clusters, reactive fibrosis, compressed trabecula.

Soft Tissue Tumors: Principles and Classification

Soft tissue tumors (PA32.3) arise from mesenchymal tissues outside the skeleton — fat, skeletal muscle, smooth muscle, fibrous tissue, synovium, blood vessels, and peripheral nerves.

General principles — apply these to every soft tissue sarcoma:

Benign soft tissue tumors are far more common than malignant ones — the ratio is approximately 100:1. Every lump is not a sarcoma.

2. Grading (FNCLCC system): sarcomas are graded 1–3 based on:
- Differentiation (how closely the tumor resembles normal tissue)
- Mitotic count (mitoses per 10 high-power fields)
- Necrosis (percentage of tumor showing necrosis)
Higher grade = more aggressive = worse prognosis.

Staging: TNM (tumor size, lymph node, metastasis) + grade. Size >5 cm and deep location (beneath deep fascia) = higher risk.

4. Routes of spread:
- Primary route: hematogenous to the lungs (most soft tissue sarcomas bypass lymph nodes and go directly to lung).
- Lymph node spread is unusual — exceptions: synovial sarcoma, rhabdomyosarcoma (embryonal), epithelioid sarcoma (these do spread to lymph nodes).
- Local recurrence after inadequate excision is common — margin status is critical.

Radiology: MRI is the modality of choice for soft tissue sarcomas — delineates tissue planes, extension, and compartment involvement.

Two-panel diagram: Panel A shows a schematic T2-weighted axial MRI cross-section of the thigh with a labeled heterogeneous high-signal soft tissue sarcoma deep to the deep fascia abutting the femur, surrounded by edema; Panel B is a classification chart of soft tissue tumors by cell of origin listing lipoma/liposarcoma, rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma with hallmark features. — **Panel A:** Soft tissue sarcoma (heterogeneous T2 high-signal mass), Tumor margin (dashed red boundary), Femur (central bone with cortical rim), Deep fascia (dark encircling line), Subcutaneous fat (outer bright ring), Surrounding/peritumoral edema (bright halo). **Panel B:** Cell of origin column (Adipose tissue, Skeletal muscle, Smooth muscle, Fibroblasts); Benign column (Lipoma, —, Leiomyoma, —); Malignant column (Liposarcoma, RMS embryonal/alveolar, LMS, Fibrosarcoma); Hallmark features (Lipoblasts, Cross-striations Desmin+, Cigar-shaped nuclei, Herringbone pattern).

Tumor	Origin	Benign	Malignant	Hallmark feature
Lipoma / Liposarcoma	Adipose tissue	Lipoma	Liposarcoma	Lipoblasts (malignant)
Rhabdomyosarcoma	Skeletal muscle	—	RMS (embryonal, alveolar)	Cross-striations, desmin+
Leiomyosarcoma	Smooth muscle	Leiomyoma	LMS	Cigar-shaped nuclei
Fibrosarcoma	Fibroblasts	—	Fibrosarcoma	Herringbone pattern
Synovial sarcoma	Synovioblasts	—	Synovial sarcoma	Biphasic pattern, t(X;18)

Lipoma and Liposarcoma

Lipoma — the most common benign soft tissue tumor of adults.
- Lobulated mass of mature adipocytes; well-encapsulated, soft, mobile, non-tender.
- Sites: subcutaneous tissue of trunk, neck, and proximal extremities.
- Radiologic: homogeneous fat-signal mass (similar to adjacent subcutaneous fat on MRI).
- Histology: mature lipocytes, uniform, no atypia, thin fibrous septa.
- Treatment: excision if symptomatic; no malignant potential for ordinary lipoma.

Liposarcoma — the most common soft tissue sarcoma in adults (along with leiomyosarcoma, competing for this position; liposarcoma is first in many classifications).
- Sites: retroperitoneum (most common site, often very large at presentation) and deep thigh.
- Identifying feature on histology: lipoblasts — cells with multiple lipid vacuoles that scallop the hyperchromatic nucleus ("spider-cell" or "signet-ring" with fat vacuoles). The lipoblast is the morphologic hallmark of liposarcoma at any grade.

Histologic subtypes and their prognosis:

Subtype	Histology	Molecular	Prognosis
Well-differentiated (WDLPS)	Resembles lipoma + scattered atypical stromal cells	MDM2/CDK4 amplification (12q13-15)	Good (locally aggressive, rarely mets)
Dedifferentiated	WDLPS + non-lipogenic high-grade sarcoma	MDM2/CDK4 amp	Intermediate
Myxoid / round cell	Lipoblasts in myxoid stroma	t(12;16) FUS-DDIT3	Intermediate to poor
Pleomorphic	Marked pleomorphism + lipoblasts	Complex	Poor