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Bone Tumor Imaging - Tough Viva Questions

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SECTION 1: RADIOLOGICAL ASSESSMENT PRINCIPLES

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• Type 1 (Geographic) - benign/low-grade: 1A has a sclerotic rim, 1B is well-defined lytic without sclerosis, 1C has a slightly less sharp non-sclerotic margin
• Type 2 (Moth-eaten) - intermediate aggression: multiple lucent areas 2-5 mm separated by intact trabecular bone
• Type 3 (Permeative) - most aggressive/malignant: multiple coalescing tiny ill-defined lesions ≤1 mm with a zone of transition of several centimetres

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• Chondral (ring-and-arc/nodular) - dense nodular calcification - chondrogenic tumors (enchondroma, chondrosarcoma)
• Osseous (cloud-like) - amorphous mineralisation in a soft-tissue mass - osteosarcoma
• Ground-glass - diffuse, hazy - fibrous dysplasia
• Non-specific/irregular - intra-osseous lipoma, other

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• Best delineates intramedullary extent (radiographs underestimate this)
• Identifies soft-tissue extension and neurovascular involvement
• Detects skip metastases (same bone, separate focus)
• Assesses response to neoadjuvant chemotherapy via dynamic contrast-enhanced sequences
• Evaluates epiphyseal and joint involvement

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SECTION 2: SPECIFIC TUMOR IMAGING - BENIGN

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• The classic triad is young patient, diaphyseal/metaphyseal location, night pain relieved by NSAIDs
• X-ray may miss it - the nidus (≤15 mm, may be lytic, sclerotic, or mixed) is often buried in dense cortical sclerosis
• CT is the investigation of choice - demonstrates the nidus even when radiographically occult; also used for CT-guided radiofrequency ablation
• MRI shows florid reactive marrow oedema that can mimic infection or malignancy - potential pitfall
• ~13% are intra-articular, presenting as monoarthropathy - another diagnostic trap
• Differential from osteoblastoma: nidus >1.5-2 cm = osteoblastoma; OO nidus ≤15 mm

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• Pedunculated (thin stalk) or sessile (broad base) bony outgrowth in the metaphysis, always pointing away from the adjacent joint
• The cortex and medullary cavity are continuous with the parent bone (key feature)
• Cartilage cap is normally thin (<1.5 cm post-puberty)

• Cartilage cap >2 cm after skeletal maturity on MRI
• New or increasing pain in an adult
• Rapid growth after skeletal maturity
• Soft-tissue mass around the lesion
• Irregular calcification developing within the cap

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• Location: Epiphyseal + metaphyseal in a skeletally mature patient (growth plate must be closed) - most commonly distal femur, proximal tibia, distal radius
• Radiograph: eccentric, subarticular lytic lesion with NO sclerotic margin, no matrix mineralisation (if present, consider secondary ABC change)
• MRI: heterogeneous signal; low-intermediate T1; low-intermediate T2 (hemosiderin from blood products - a key feature); may show fluid-fluid levels if secondary ABC change present
• Locally aggressive: cortical destruction and soft-tissue extension indicate aggressive behavior
• Benign pulmonary metastases can occur in up to 3% without implying malignancy
• Multifocal GCT + hypercalcemia = investigate for hyperparathyroidism (brown tumors mimic GCT)

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• Shepherd's crook deformity of proximal femur (varus from weight-bearing + pathological fracture)
• Ground-glass matrix on CT/radiograph (hallmark)
• Whole-body MRI or bone scintigraphy for polyostotic disease mapping
• Malignant transformation in ~0.5% - higher in polyostotic disease and post-radiotherapy

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• Eccentric, intracortical/endosteal, metaphyseal
• Lobular with its long axis parallel to the bone
• Well-defined sclerotic margins (type 1A)
• MRI: predominantly hypointense on T2 (~80%) - differentiates from ABC (which has FFLs)
• Incidental finding in children; regresses spontaneously with skeletal maturity
• Periosteal reaction only if complicated by fracture

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SECTION 3: SPECIFIC TUMOR IMAGING - MALIGNANT

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• Young patient, metaphysis of distal femur > proximal tibia > proximal humerus
• Plain X-ray: mixed lytic and sclerotic destruction, cloud-like osteoid matrix in soft-tissue mass
• Sunburst periosteal reaction + Codman triangle
• MRI: heterogeneous mass, low T1/variable T2; essential to image the entire bone (skip metastases in ~5%)
• Pulmonary metastases: peripheral, may be mineralised, rare chronic pneumothorax

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• Young patient (second decade), diaphysis of long bone (more commonly than originally taught) OR flat bones (pelvis, ribs - poor prognosis)
• Plain X-ray: permeative/moth-eaten destruction, onion-skin periosteal reaction, cortical saucerisation
• Hair-on-end and Codman triangle also occur
• Large soft-tissue mass often disproportionate to the degree of bone destruction (unlike osteomyelitis)
• MRI: large intramedullary and extra-osseous mass; intermediate T1, high T2

• Osteomyelitis (most important - can have identical periosteal reaction and marrow changes)
• Osteosarcoma
• Lymphoma of bone
• Langerhans cell histiocytosis (LCH/eosinophilic granuloma)

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SECTION 4: ADVANCED/SPECIALIST QUESTIONS

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• Plain X-ray is notoriously unreliable for sacral lesions (overlying bowel gas)
• MRI is the modality of choice - best soft-tissue delineation, marrow involvement, neural foraminal involvement
• CT for bone destruction and matrix detail

• Chordoma: midline, below S3, intermediate T1/high T2, lobulated hyperintense on T2, septal enhancement; soft-tissue mass anteriorly into pelvis; most common primary sacral malignancy (>50% of primary sacral tumors)
• Giant cell tumor: upper sacrum, eccentric, crosses midline
• Metastases: multifocal, usually posterior elements
• Ependymoma: myxopapillary type, intrasacral, remodels bone

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• Established role in response assessment after chemotherapy (osteosarcoma, Ewing sarcoma)
• FDG-PET preferred over bone scintigraphy for local recurrence in osteosarcoma due to lack of metallic artefact susceptibility
• PET-MRI is emerging as a hybrid combining metabolic and morphological data
• Initial staging: complementary but not primary modality
• Pulmonary osteosarcoma metastases can show increased uptake on bone scintigraphy if mineralised

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• Background pagetic changes: bone expansion, cortical thickening, coarsened trabeculae, "picture frame" vertebra, "cotton wool" skull
• Superimposed aggressive features: lytic destruction, cortical breakthrough, soft-tissue mass, Codman triangle
• Most commonly osteosarcoma, occasionally fibrosarcoma or chondrosarcoma
• MRI best delineates the soft-tissue component and extent of marrow involvement

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QUICK-FIRE VIVA FACTS

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Giant Cell Tumor (GCT) of Bone - Tough Imaging Viva Questions

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SECTION 1: FUNDAMENTALS

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1. Eccentric position within bone
2. Subarticular/subchondral - extends to the articular surface (95-99% of cases at presentation)
3. Lytic - no matrix mineralisation
4. Non-sclerotic margin (type 1B Lodwick) - no rim of reactive sclerosis (key differentiator from NOF, ABC)
5. No periosteal reaction - unless a pathological fracture has occurred

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• Fluid-fluid levels (FFLs) layering within the lesion (blood products of different ages separating by gravity)
• These represent blood-filled cavities that have developed within the primary GCT

• Primary ABC
• GCT with secondary ABC (15% of GCTs)
• Telangiectatic osteosarcoma (but has solid enhancing nodules)
• Chondroblastoma
• Fibrous dysplasia with cystic change
• Simple bone cyst (after fracture)

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SECTION 2: LOCATION-SPECIFIC PITFALLS

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1. Distal femur
2. Proximal tibia (knee = ~55% combined)
3. Distal radius (~10%)
4. Proximal humerus (~6%)
5. Proximal femur, pelvis, sacrum

• Distal radius GCT: Very aggressive behavior; cortical destruction with soft-tissue mass is common. Tends to recur more than GCT at other long bone sites.
• Sacral GCT: Radiograph unreliable (overlying bowel gas). MRI is mandatory. Sacral GCT typically involves the upper sacrum and frequently crosses the midline (contrasts with chordoma which is below S3 and is the most common primary sacral malignancy).
• Vertebral GCT: Almost always involves the vertebral body (unlike most benign tumors which favor posterior elements). May expand and balloon the body. MRI essential for cord compression assessment.
• Small bones (hands/feet): More aggressive behavior, higher recurrence rate. GCT of the hands more aggressive than feet.
• Flat bones (pelvis, ilium): Atypical radiological appearances - eccentric subarticular features less obvious; may appear as large lytic lesions. Higher risk of malignant transformation.

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SECTION 3: DIFFERENTIALS AND MIMICS

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1. GCT - no sclerotic rim, no matrix
2. Lytic osteosarcoma - more aggressive features, periosteal reaction, younger age, may have matrix
3. Undifferentiated pleomorphic sarcoma (UPS/MFH) - aggressive, older patients (>40 yrs), permeative, soft-tissue mass
4. Plasmacytoma - older patient, may appear identical; check serum protein electrophoresis
5. Subarticular lytic metastasis - especially from renal cell carcinoma (hypervascular, expansile, may look identical to GCT on radiograph)
6. Clear cell chondrosarcoma - rare malignant epiphyseal tumor; chondroid matrix may be present
7. Pigmented villonodular synovitis (PVNS) - intra-articular, periarticular erosions, juxta-articular rather than central bone lesion

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SECTION 4: ADVANCED MRI & CT QUESTIONS

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1. Cortical integrity - best modality for demonstrating cortical breakthrough and extent of cortical destruction
2. Cortical expansion and trabeculation - optimally visualised on CT
3. Occult matrix - confirms absence of chondroid or osteoid matrix (rules out other diagnoses)
4. Surgical planning - maps the exact size of cortical window needed
5. Lung staging - chest CT is mandatory for GCT (both at diagnosis and follow-up) because of the risk of benign pulmonary metastases

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• The soft-tissue mass is continuous with the intraosseous component
• Signal characteristics mirror the primary tumor (iso-T1, heterogeneous T2 with hemosiderin)
• Joint involvement must be actively sought - direct subchondral extension may breach the articular cartilage, requiring joint sacrifice or arthroplasty
• Neurovascular bundle proximity determines resectability

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• Primary malignant GCT: De novo malignancy at first presentation (rare, ~1%)
• Secondary malignant GCT: Develops at the site of a previously treated GCT; notably associated with prior radiation therapy (radiation-induced sarcoma reported in ~20% of GCTs treated with radiation - this is why radiation is not recommended as primary treatment)

• Rapid progression on serial imaging
• Development of periosteal reaction in a previously quiescent lesion
• Increasing soft-tissue mass
• Pulmonary metastases that enlarge (in contrast to the stable benign metastases of GCT)

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SECTION 5: PULMONARY METASTASES AND DENOSUMAB

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• Histologically identical to the primary tumor (benign giant cells and stroma)
• Usually slow-growing or stable
• Can spontaneously regress
• May respond to denosumab
• Rarely cause death, but can progress to malignant transformation

• Well-defined nodules, often peripheral
• No calcification (unlike osteosarcoma metastases)
• If mineralised or rapidly enlarging, consider malignant transformation

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• Progressive sclerosis and mineralisation of the previously lytic lesion
• New shell of reactive periosteal bone formation around the lesion
• Apparent "normalisation" of the lesion may make surgical margins harder to define

• Reduction in soft-tissue component
• Decrease in T2 hyperintensity as cellularity drops
• Marrow reconversion (fat signal returning)

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SECTION 6: SPECIAL SCENARIOS AND QUICK-FIRE

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1. Exclude hyperparathyroidism - Brown tumors are the most important mimic of multifocal GCT
2. Exclude metastatic disease - especially if patient is >45 years
3. Exclude Paget's disease with secondary change
4. Confirm all lesions have histological confirmation

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1. Plain radiograph - first line; look for new lysis at the cement-bone interface or beyond the cement margins (marginal recurrence appears as a lucent halo around cement)
2. CT - better than MRI for assessing the cement-bone interface and cortical integrity
3. MRI with metal suppression sequences (MARS/VAT) - can partially overcome artefact but interpretation is limited
4. FDG-PET - useful for detecting recurrence and pulmonary metastases when MRI is compromised

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QUICK-FIRE GCT IMAGING FACTS

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Chondroblastoma Imaging - Tough Viva Questions

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SECTION 1: FUNDAMENTALS

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• Represents ~1% of all primary bone tumors
• Age: 80-90% present between 5-25 years (mean ~20 years); flat bone lesions (talus, calcaneus) commonly present later
• Sex: M:F ratio of 2.7:1 (male predominance)
• Monostotic - multicentric disease is exceedingly rare
• Rare lung metastases reported (<5% of cases) - makes it one of a small number of benign tumors with metastatic potential

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• Patella - chondroblastoma is the most common primary bone tumor of the patella
• Calcaneus and talus - the foot is the next most common area; these flat bone lesions present in older patients
• Greater trochanter of femur (apophysis)
• Greater tuberosity of humerus (apophysis)
• ~2% are purely metaphyseal or diaphyseal (atypical)

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1. Epiphyseal location - centered in the epiphysis; with partial growth plate closure it extends into the metaphysis (~55% at presentation cross the physis into metaphysis)
2. Well-defined, round/lobular lytic lesion measuring 1-4 cm
3. Thin sclerotic rim (geographic type 1A Lodwick) - this is a key differentiator from GCT (which has no sclerotic rim)
4. Matrix mineralisation in 30-50% - stippled/punctate chondroid calcification (better seen on CT)
5. Linear metaphyseal periosteal reaction in ~60% of long bone cases - this is disproportionately prominent and can alarm the unwary

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• Fluid-fluid levels (FFLs) seen in ~15-20% due to secondary ABC change
• Low SI rim on all sequences (corresponding to sclerotic margin)
• Profound T2 hypointensity from hemosiderin (similar to GCT but in an immature skeleton)

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SECTION 2: DIFFERENTIALS AND TRAPS

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• Cortical destruction
• Extra-osseous soft-tissue extension (visible on both radiograph and MRI)
• Less well-defined margins

• Clear cell chondrosarcoma
• Low-grade chondrosarcoma
• GCT with cortical breakthrough

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SECTION 3: SPECIAL LOCATIONS

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• CB is the most common primary bone tumor of the patella - high-yield fact
• Patella is an epiphyseal equivalent (sesamoid)
• Appears as a well-defined lytic lesion with or without a thin sclerotic rim
• May cause joint effusion and perilesional edema on MRI
• Can be challenging to detect on plain radiograph due to superimposition; MRI/CT confirm
• Differential: patellar stress fracture, intraosseous ganglion, subchondral cyst (OA), rare cases of GCT

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• Presents in an older age group than long-bone CB (occasionally even adults)
• Calcaneus: lytic lesion in the posterior calcaneal body/apophysis; may have sclerotic rim
• Talus: lytic epiphyseal-equivalent lesion
• Matrix calcification may be less prominent
• Perilesional edema on MRI remains a characteristic feature
• Important differential: intraosseous lipoma of calcaneus (central fat signal on T1, may have calcified center), simple bone cyst of calcaneus, stress fracture
• A lytic calcaneal lesion with a sclerotic rim and edema in a teenager = chondroblastoma until proven otherwise

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SECTION 4: ADVANCED IMAGING CONCEPTS

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1. Hemosiderin - deposited from recurrent microhemorrhages within the tumor (same as GCT)
2. Chondroid matrix - mineralized cartilage matrix is intrinsically low signal on T2

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1. Detecting matrix calcification that is radiographically occult - CT is much more sensitive for punctate chondroid calcification (30-50% of CB show this; CT picks it up in a higher proportion)
2. Cortical integrity - assessing whether the thin cortex over an expanding lesion is intact
3. Flat bones (calcaneus, talus) - CT gives better anatomical delineation for surgical planning
4. Post-treatment - assessing recurrence at the bone-graft/cement interface

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• With partial growth plate closure (adolescent), the lesion commonly extends into the metaphysis (~55% at presentation)
• A well-circumscribed epiphyseal lesion that crosses an open physis in a child is highly suggestive of chondroblastoma - this is a discriminating point against most other lesions
• The only other entity that crosses an open physis reliably is infection (osteomyelitis/Brodie abscess)

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• Fluid-fluid levels (FFLs) - layering of blood products of different ages
• Rapid expansion of the lesion
• May obscure the underlying diagnosis

• Does NOT change the benign nature - curettage is still the treatment
• The underlying CB must not be misidentified as a primary ABC (which would lead to inadequate treatment)
• Histological sampling must include the solid areas, not just the cystic component, to confirm CB
• Secondary ABC change is a recognized feature of CB, GCT, osteoblastoma, fibrous dysplasia, and osteosarcoma - a secondary ABC diagnosis should always prompt a search for the underlying lesion

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SECTION 5: FOLLOW-UP AND RECURRENCE

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• Radiographs of the primary site + chest every 6 months for at least 3 years, then annually
• This is because:
  1. Local recurrence - 10-35% after curettage alone; higher in aggressive lesions and axial locations
  2. Pulmonary metastases - rare (<5%) but described even from histologically benign CB; lung mets can appear years after primary treatment
  3. Malignant transformation - exceedingly rare, reported after radiotherapy (which is now avoided)

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QUICK-FIRE FACTS

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Why Does Chondroblastoma Cause Perilesional Edema and Joint Effusion?

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The Short Answer

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The Mechanistic Breakdown

1. COX-2 Overexpression and Prostaglandin Production

Arachidonic acid  →  [COX-2]  →  Prostaglandin G2 → Prostaglandin H2
                                                         ↓
                              PGE2  /  PGI2  /  TXB2

2. What Prostaglandins Do to Local Tissue

3. Anatomical Amplifier - the Epiphyseal Location

• The epiphyseal bone marrow is only millimetres from the articular cartilage and synovium
• Prostaglandins diffuse freely through subchondral bone into the synovial space
• The thin overlying articular cartilage offers little barrier to chemical diffusion
• The result: a small 1-4 cm lesion produces an inflammatory response disproportionately involving the adjacent joint - this is why CB commonly presents as a monoarthropathy clinically

4. Why the Edema is So Extensive on MRI

• PGE2 and PGI2 are lipid-soluble and diffuse widely through the marrow fat
• They stimulate vasodilation in capillaries several centimetres from the lesion
• The result is reactive marrow edema (increased water content in marrow) - visible as T2/STIR hyperintensity covering a wide zone

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Clinical Correlates

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Why This Is Unique to Chondroblastoma

• GCT: Has some edema but far less prominent - GCT does not overexpress COX-2 to the same degree and produces far lower PG concentrations
• Brodie abscess: Has edema from bacterial toxins and cytokines (IL-1, TNF-α) - different mechanism (infectious, not prostaglandin-driven)
• Clear cell chondrosarcoma: Less peritumoral edema than CB on MRI - a useful differentiating feature
• Osteoid osteoma: Also COX-2/PG driven (explains NSAID response), but diaphyseal not epiphyseal, so no joint effusion

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One-Line Viva Answer

"Chondroblastoma tumor cells overexpress COX-2, producing high concentrations of prostaglandins - particularly PGE2 - which cause local vasodilation and vascular permeability, generating extensive marrow edema. The subchondral epiphyseal location allows direct prostaglandin diffusion into the joint, irritating the synovium and producing a reactive effusion."

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Ewing Sarcoma - Tough Viva Questions

Anchored to the Case: Large Expansile Proximal Humeral Metaphyseal Mass, Soft-Tissue Extension Laterally (under deltoid) and Medially (into axilla), T1 isointense/T2 heterogeneous high/avid enhancement

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SECTION 1: INTERPRETING THIS MRI

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• Large expansile lesion centered on the proximal humeral metaphysis
• Metaphyseal ± diaphyseal extension (typical - Ewing most often arises in the metadiaphyseal region, ~60%)
• T1 isointense to muscle = replaces fatty marrow with hypercellular small round blue cell tumor
• T2 heterogeneously high = viable hypercellular tumor + areas of necrosis/hemorrhage
• Avid contrast enhancement = hypercellular, highly vascular tumor

• Lateral component beneath the deltoid - within the deltoid musculature compartment
• Medial component into the axilla - involves the axillary space (neurovascular structures at risk)
• This is a large soft-tissue mass disproportionate to the degree of bone destruction - this is the radiological hallmark of Ewing sarcoma

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• Ewing sarcoma is an intramedullary central tumor arising from marrow elements
• It spreads through the Haversian canals and Volkmann's canals of the cortex without necessarily destroying the cortex first
• The periosteum is elevated as tumor tracks through these channels into the soft tissues
• Because the tumor can exit the cortex via the canal system before radiologically visible cortical destruction occurs, a massive soft-tissue mass can develop while the bone appears only mildly involved on plain film
• Additionally, the cortex undergoes "saucerisation" - the periosteum restrains the tumor temporarily, allowing it to erode back through the cortex from outside

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1. Does the mass encase or directly invade the brachial plexus (medial, posterior, lateral cords)?
2. Is the axillary artery/vein displaced or encased?
3. Is there a fat plane between the mass and neurovascular structures (preservable = limb-salvage possible; obliterated = forequarter amputation territory)?

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• The lesion has replaced normal bright fatty marrow with cellular tumor tissue
• The soft-tissue component also approximates muscle signal (no fat, no hemorrhage, no significant necrosis in those areas)
• It confirms the lesion is solid and highly cellular (consistent with small round blue cell tumor)

• Osteosarcoma: often heterogeneous T1 with areas of low signal (osteoid matrix) and areas of necrosis
• ABC: T1 variable with haemorrhagic hyperintense areas
• Lymphoma of bone: also T1 isointense (key mimic - discussed below)

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SECTION 2: DIFFERENTIALS

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SECTION 3: STAGING THIS CASE

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• MRI of the entire humerus (full bone - not just the lesion) with gadolinium
  • Skip metastases occur in 12% of Ewing sarcoma (unlike osteosarcoma - this is often incorrectly taught as unique to osteosarcoma)
  • Must include the elbow and shoulder joints
• MRI with neurovascular detail (already described above - axilla and brachial plexus)
• CT of the humerus - cortical integrity, periosteal reaction detail

• CT chest - lungs are the most common site of metastases
• Bone scintigraphy (Tc-99m) - bone is the second most common metastatic site; detects multifocal bone disease
• FDG-PET/CT - now the emerging new standard; higher sensitivity than conventional imaging for initial staging, detection of recurrence, and assessment of chemotherapy response; the initial SUV of the primary tumor correlates with tumor aggressiveness
• Whole-body MRI - alternative to PET for detecting marrow and soft-tissue metastases, avoids radiation
• Bone marrow biopsy (posterior iliac crest) - traditionally performed to exclude marrow involvement; FDG-PET/CT may replace blind biopsy (sensitivity equivalent in recent studies)

• FBC, ESR, CRP (elevated = systemic disease burden)
• LDH - elevated LDH is an independent adverse prognostic factor
• Urine catecholamines (to exclude neuroblastoma in younger children)

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1. Glenohumeral joint involvement - does the mass breach the articular surface? Joint contamination changes the surgical approach (glenohumeral resection vs. extra-articular resection)
2. Rotator cuff and deltoid involvement - lateral soft-tissue component; which muscles are involved determines the functional outcome of reconstruction
3. Axillary neurovascular bundle - medial component: fat plane between tumor and axillary artery/vein/brachial plexus - presence or absence determines limb-salvage feasibility
4. Subscapular space and chest wall - medial extension; is the serratus anterior, chest wall, or apex of lung involved?
5. Axillary lymph nodes - Ewing sarcoma can involve regional nodes (unusual for bone sarcomas generally)

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SECTION 4: IMAGING FEATURES IN DEPTH

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• More often metaphyseal or metadiaphyseal (~60%) than purely diaphyseal (~35%)
• Periosteal reactions (in decreasing frequency):
  • Hair-on-end/spiculated: 50% - also seen in osteosarcoma
  • Interrupted (Codman triangle): 27%
  • Onion-skin (multilamellar): classic but actually uncommon
• Soft-tissue extension evident in 80% on plain radiograph
• Mixed or mainly sclerotic appearance in flat bones and spine - due to reactive sclerosis and end-on spiculated periosteal reaction being visualised; NOT due to tumor osteoid (Ewing sarcoma does not produce osteoid - this is how you distinguish sclerosis in Ewing from osteosarcoma)
• May be radiographically occult in early/aggressive lesions
• Entire bone involved in some cases (especially in children - the whole fibula or whole humerus)

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• Reduced enhancement + reduced size of soft-tissue mass = good histological response
• Persistent or increasing enhancement = poor response, may need change of chemotherapy regimen
• MRI response (particularly reduction in soft-tissue mass size) correlates with histological necrosis at surgery
• FDG-PET: reduction in SUV correlates with percentage tumor necrosis

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SECTION 5: BIOLOGY AND HISTOLOGY FOR THE RADIOLOGIST

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• All share the same reciprocal chromosomal translocation t(11;22)(q24;q12) in >90% of cases
• This produces the EWS-FLI1 fusion protein, a transcription factor driving oncogenesis
• Other translocations: t(21;22) and t(7;22) in the remainder
• All are small round blue cell tumors - hence identical imaging appearances

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• Localized disease: ~60-75% with modern multiagent chemotherapy
• Metastatic disease: <30%
• Before multiagent chemotherapy: <10%

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QUICK-FIRE FACTS

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Multiple Myeloma with Proptosis - Tough Imaging Viva

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SECTION 1: THE VIVA OPENER - PROPTOSIS IN MYELOMA

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• Direct extramedullary plasmacytoma involving the orbital wall or retrobulbar soft tissue
• Arises from skull base/sphenoid wing lytic lesion extending into the orbit
• Or primary soft-tissue extramedullary plasmacytoma within the orbit
• Imaging: MRI orbit with gadolinium - shows T1 iso to muscle, T2 intermediate, uniformly enhancing soft-tissue mass; CT shows associated lytic bone destruction of orbital walls

• Myeloma lytic lesion in the orbital roof (frontal bone), lateral wall (sphenoid/zygoma), or medial wall (ethmoid/lacrimal)
• Subperiosteal expansion of the lesion pushes the globe forward
• Imaging: CT skull base best for bone destruction; MRI for soft-tissue component

• Skull vault plasmacytoma with intracranial extension through the inner table compressing frontal lobe
• Less likely to cause proptosis unless very anterior

• High IgG/IgA/IgM paraprotein → hyperviscosity → orbital venous engorgement → bilateral proptosis
• Associated with dilated tortuous retinal veins, retinal haemorrhages
• Imaging: Orbital MRI shows engorged orbital veins; no mass

• Complicates ~10-15% of myeloma
• Amyloid deposits in orbital fat, extraocular muscles, lacrimal glands
• Imaging: MRI - amyloid in muscles is T2 hypointense (fibrillar nature); diffuse orbital infiltration

• Waldenström's macroglobulinemia (IgM): hyperviscosity with bilateral proptosis, retinal "sausage" vein formation

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SECTION 2: MYELOMA IMAGING - MODALITIES AND CURRENT GUIDELINES

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• Skeletal survey cannot detect a lytic lesion unless 50-75% of cancellous bone is destroyed (very insensitive)
• LDWBCT detects lesions ≥5 mm with much higher sensitivity
• CT can guide percutaneous biopsy and radiotherapy planning
• A lesion visible on CT (≥5 mm) fulfills the IMWG CRAB bone criteria even if not visible on plain radiograph

1. LDWBCT - first line for bone lesion detection
2. Whole-body MRI (WBMRI) - best for diffuse marrow infiltration, focal lesions, and spinal cord compression; NICE UK recommends as first-line
3. FDG-PET/CT - best for extramedullary disease, metabolically active lesions, staging, and treatment response

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• ≥10% clonal plasma cells in bone marrow, OR
• Biopsy-proven bony or soft-tissue plasmacytoma

• C - hyperCalcaemia (>2.75 mmol/L or >1 mg/dL above ULN)
• R - Renal insufficiency (creatinine >177 µmol/L or CrCl <40 mL/min)
• A - Anaemia (Hb <100 g/L or >20 g/L below LLN)
• B - Bone lesions: ≥1 osteolytic lesion on skeletal radiograph, CT, or PET-CT

• S - Sixty percent clonal marrow plasma cells
• Li - Light chain ratio ≥100 (involved:uninvolved free light chain)
• M - MRI: ≥1 focal lesion ≥5 mm (on WB-MRI)

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• T1: Hypointense (replaces normal bright fatty marrow - this is the key sequence)
• T2/STIR: Hyperintense (cellular tumor with high free water)
• DWI: Restricted diffusion (high b-value bright, low ADC) - reflects high cellularity
• Post-gadolinium: Enhancement (variable - moderate in focal lesions, diffuse in infiltrative)

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• Pure lysis occurs with no compensatory osteoblastic repair
• Bone scan is cold or photopenic in myeloma lesions
• A "normal" bone scan in a patient with widespread myeloma is not reassuring - it reflects the absence of osteoblastic activity, not absence of disease

• Pathological fracture (healing response activates osteoblasts temporarily)
• Amyloid deposition (Tc-99m MDP can bind amyloid)
• Concurrent Paget's disease

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SECTION 3: SPECIFIC IMAGING PATTERNS - VIVA TRAPS

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• "Pepper-pot" or "rain-drop" skull - multiple well-defined, rounded lytic lesions without a sclerotic rim, of varying sizes scattered throughout the vault
• No sclerotic rim - differentiates from other lytic conditions (healing/benign lesions have sclerotic rims)
• No periosteal reaction - pure lytic, no bone forming response
• General osteoporosis of the skull vault (diffuse marrow infiltration)

• Myeloma (most common, >40 years)
• Metastases (breast, kidney, thyroid, lung)
• Langerhans cell histiocytosis (in children/young adults - "beveled edge" lesion)
• Hyperparathyroidism (Brown tumors - but associated changes)
• Paget's sarcoma (lytic phase)

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1. Biopsy-proven single bone lesion of clonal plasma cells
2. PET-CT (or LDWBCT) AND MRI of spine and pelvis must show NO other lesions
3. Bone marrow aspirate: no clonal plasma cells (or <10% = "with minimal marrow involvement")
4. M-protein may be present but should disappear after treatment

• CT: detects cortical lytic lesions anywhere in the skeleton
• MRI: detects diffuse bone marrow infiltration that may be invisible on CT; identifies focal lesions in the spine and pelvis (high marrow red cell content zones)
• If MRI shows diffuse marrow infiltration = not truly solitary = reclassify as myeloma
• FDG-PET/CT is actually superior to MRI of spine/pelvis alone because it detects plasmacytomas in skull, ribs, extremities, and soft tissues outside the MRI field of view

• Solitary plasmacytoma → myeloma within 3 years: ~10%
• Solitary plasmacytoma with minimal marrow involvement → myeloma within 3 years: ~60%

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• 80% involve the upper respiratory tract: nasal cavity and sinuses (most common), nasopharynx, larynx
• Other sites: GI tract, CNS, urinary bladder, thyroid, breast, testes, parotid gland, lymph nodes
• Orbit - via direct extension from adjacent skull/sinus plasmacytoma or as primary orbital EMP

• CT/MRI: homogeneous soft-tissue mass, T1 iso to muscle, T2 intermediate
• Avid enhancement (highly cellular)
• Adjacent bone: may show erosion/remodeling but less aggressive destruction than osseous plasmacytoma
• FDG-PET: avid uptake - FDG-PET/CT is the preferred modality for EMP because it detects lesions outside the field of view of spinal MRI

• Development of EMP during treatment = sign of disease transformation to a more aggressive phenotype
• Associated with resistance to standard chemotherapy
• Poor prognosis - median survival ~6 months after EMP development in relapsed myeloma

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• Diffuse marrow assessment: prefer MRI
• Extramedullary disease, staging, treatment response: prefer PET/CT
• Emerging: FDG-PET/MRI hybrid - combines both advantages but not yet guideline-recommended

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SECTION 4: COMPLICATIONS AND SPECIFIC SCENARIOS

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1. Pathological vertebral fracture (most common)
2. Epidural plasmacytoma with cord compression
3. New lytic lesion expanding into the spinal canal
4. Hypercalcemia causing bone pain (no fracture)

• MRI spine STAT - modality of choice for:
  • Cord/conus compression assessment
  • Differentiating acute benign osteoporotic fracture from malignant infiltration
  • Identifying epidural tumor extension
  • Mapping extent of vertebral involvement

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• Amyloid deposits in orbital fat, extraocular muscles (especially superior rectus and levator palpebrae), lacrimal gland
• Causes restrictive ophthalmopathy and proptosis
• MRI: T2 hypointense deposits in extraocular muscles and orbital fat (amyloid fibrils are fibrillar/dense = low water = T2 dark) - distinguishes from inflammatory myositis (T2 bright)
• Fat-suppressed sequences: deposits persist as dark areas in orbital fat
• CT: may show faint calcification within amyloid deposits (rare but specific)

• Cardiac: concentric hypertrophy, "sparkling" appearance on echo; MRI shows LV hypertrophy with late gadolinium enhancement in a diffuse subendocardial pattern
• Renal: enlarged echogenic kidneys (ultrasound)
• Hepatosplenic: enlarged, homogeneous signal reduction

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QUICK-FIRE FACTS