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• Definition & Introduction
• Classification / Types (where applicable)
• Mechanism / Radiobiology (physics + biology basis)
• Clinical details (indications, technique, dose, fractionation)
• Complications & Management
• Key exam points / mnemonics to remember

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• Ask me one topic at a time for deep coverage, or give me a list and I'll prioritize
• Tell me if you want short notes (5-10 marks) or long answers (15-20 marks)
• I'll flag "examiner favorites" - points that frequently appear in MD exams

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PERCENTAGE DEPTH DOSE (PDD)

Definition

• D_d = dose at depth d
• D_dmax = dose at the reference depth (depth of maximum dose)

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Reference Conditions for PDD Measurement

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Factors Affecting PDD

1. Beam Energy (Most Important Factor)

• Higher energy → Higher PDD (better depth dose)
• As energy increases, the depth of maximum dose (d_max) shifts deeper
• d_max values:
  • Cobalt-60: ~0.5 cm
  • 6 MV: ~1.5 cm
  • 10 MV: ~2.5 cm
  • 15 MV: ~3.0 cm
  • 18 MV: ~3.5 cm
• Higher energy beams are skin-sparing due to deeper d_max

2. Field Size

• Larger field size → Higher PDD
• Reason: More scatter radiation reaches the central axis from larger fields
• Relationship is significant at depth but less at d_max

3. Depth

• PDD decreases with increasing depth beyond d_max
• Caused by:
  • Inverse square law (beam divergence)
  • Attenuation and scatter in tissue

4. Source-to-Skin Distance (SSD)

• Larger SSD → Higher PDD
• At greater SSD, the beam geometry is more parallel (less divergence)
• Governed by the inverse square law
• PDD at extended SSD is calculated using the Mayneord F-factor:

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PDD Curve - Key Characteristics

100% |----peak (d_max)
     |   \
     |    \
PDD  |     \
     |      \
     |       \
  0% |________\______
        Depth in tissue →

• Build-up region: From surface to d_max - dose increases due to secondary electron buildup
• d_max: Point of maximum dose = 100% reference point
• Beyond d_max: Exponential fall-off of dose with depth

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Skin-Sparing Effect

• A unique property of megavoltage beams (>1 MV)
• At the skin surface, dose is lower than d_max because:
  • Secondary electrons (from Compton interactions) travel forward
  • They deposit maximum energy at a depth (d_max), not at the surface
• Clinical importance: Allows delivery of high tumor doses while sparing skin
• Lost when:
  • Bolus material is applied
  • Very large field sizes used
  • Beam obliquity increases
  • Beam modifiers (trays, blocks) are close to skin

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PDD vs. TAR vs. TMR - Comparison (Exam Favorite)

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Clinical Applications of PDD

1. Treatment planning - To calculate dose at tumor depth from surface dose
2. Choosing beam energy - Higher energy for deep tumors
3. Calculating MU (Monitor Units):

1. Comparing beam quality of different machines
2. Bolus prescription - To deliberately reduce PDD and increase surface dose

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PDD at Specific Depths - Approximate Values

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Extended SSD Technique and PDD Correction

• If SSD is increased (e.g., large patient, special techniques like TBI - Total Body Irradiation):
  • PDD increases slightly
  • Must recalculate using F-factor

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Relationship Between PDD and Other Dosimetric Quantities

• TAR = PDD × (SSD + d)² / (SSD + d_max)² × (1/BSF)
  • BSF = Backscatter Factor
• TMR = PDD × (SSD + d)² / (SSD + d_max)²

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Key Exam Points / Mnemonics

• Field size ↑
• Energy ↑
• Extended SSD ↑
• Depth... wait, depth decreases PDD (the exception!)

• PDD is an SSD-dependent quantity - this is why TAR/TMR (SSD-independent) are preferred in isocentric techniques
• 10 MV at 10 cm depth ≈ 74% - a commonly asked value
• Cobalt-60 d_max = 0.5 cm - shallowest d_max among megavoltage beams
• Skin sparing is a megavoltage phenomenon - not seen with orthovoltage (kV) beams

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Quick Recall Summary (For Last-Minute Revision)

PDD = (Dose at depth / Dose at d_max) × 100 Measured in water phantom, 10×10 field, 100 cm SSD Increases with: ↑ Energy, ↑ Field size, ↑ SSD Decreases with: ↑ Depth SSD-dependent (unlike TAR/TMR) Skin sparing = d_max shifts deeper with higher energy

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DOSE CONSTRAINTS IN CRANIOSPINAL IRRADIATION (CSI) FOR EPENDYMOMA - ORGANS AT RISK (Excluding Head & Neck)

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Context: CSI Dose in Ependymoma

• CSI dose: 23.4 - 36 Gy (standard risk) / 36 - 39.6 Gy (high risk/disseminated)
• Boost to primary site: total 54 - 59.4 Gy (1.8 Gy/fraction)
• The spinal field traverses thorax, abdomen, and pelvis - hence anterior visceral organs receive low-to-intermediate dose bath, and this is the primary concern

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WHY VISCERAL OARs MATTER IN CSI

• Lungs (posterior portions)
• Heart (especially with cervico-thoracic spine irradiation)
• Kidneys (posterior, close to spine)
• Liver (right lobe, adjacent to lower thoracic spine)
• Bowel / small intestine (lumbar spine level)
• Gonads / ovaries (lumbosacral irradiation)
• Vertebral bodies and growth plates (pediatric concern)

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OAR DOSE CONSTRAINTS IN CSI - COMPLETE TABLE

1. LUNGS

• Complication feared: Radiation pneumonitis, pulmonary fibrosis
• Note: In proton CSI, lung dose dramatically reduced vs. photon CSI - major advantage of protons

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2. HEART

• Complication feared: Radiation-induced pericarditis, cardiomyopathy, coronary artery disease
• Pediatric note: Children are far more susceptible to late cardiac effects - mean heart dose should be minimized as much as possible (ideally < 5 Gy with proton therapy)
• The upper thoracic spine field junction region is critical here

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3. KIDNEYS

• Complication feared: Radiation nephropathy, hypertension, renal failure (TD5/5 for whole kidney = 20 Gy)
• Kidneys lie posterior and are directly in the path of spinal fields at L1-L2 level
• This is one of the most critical OARs in CSI - especially in pediatric patients who have long life expectancy

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4. LIVER

• Complication feared: RILD (veno-occlusive disease), hepatic failure
• Right lobe of liver is adjacent to lower thoracic spine (T8-T12 level)
• TD5/5 for whole liver = 30 Gy; TD50/5 = 40 Gy

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5. SMALL BOWEL / LARGE BOWEL

• In CSI, lumbar spine fields are adjacent to small bowel and large bowel loops
• Bowel irradiation leads to: enteritis, malabsorption, adhesions, obstruction (late)
• In lumbosacral ependymoma with boost to cauda equina, this becomes even more critical

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6. SPINAL CORD (within CSI field - applies to boosted cord segments)

• The cord within the CSI field receives ~36 Gy from the whole-spine dose
• Boost to spinal ependymoma site can bring total cord dose to 50.4 - 54 Gy
• Below the conus medullaris (cauda equina level), tolerance is higher - doses up to 59.4 Gy considered acceptable

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7. GONADS / OVARIES / TESTES

• Lumbosacral field irradiation exposes gonads
• Oophoropexy (surgical ovarian transposition) may be done pre-radiotherapy in young female patients to move ovaries out of the field
• Proton CSI virtually eliminates gonadal dose vs. photon CSI

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8. ESOPHAGUS

• At risk during cervico-thoracic junction field in CSI

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9. THYROID GLAND

• Radiation-induced hypothyroidism common after CSI
• Thyroid lies at the cervico-thoracic junction - within the field junction overlap zone
• Screen TSH annually post-treatment (endocrine follow-up mandatory)

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10. VERTEBRAL BODIES / GROWTH PLATES (Pediatric - Special Concern)

• Uneven irradiation of vertebral epiphyses causes radiation-induced scoliosis and kyphosis
• CTV must include entire width of vertebral body to prevent asymmetric growth
• Hemi-vertebral irradiation is contraindicated

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SUMMARY TABLE - QUICK RECALL

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EXAM KEY POINTS

1. Kidneys are the most critical OAR in the spinal field - they lie directly posterior, within the treatment volume at L1-L2 level
2. Proton therapy advantage: Dramatically reduces dose to all anterior visceral OARs (heart, lungs, liver, bowel, gonads) compared to photon CSI - this is the prime clinical indication for proton CSI in pediatric ependymoma
3. Vertebral body rule: Always irradiate full vertebral width in pediatric CSI to prevent scoliosis - partial vertebral irradiation is a known cause of radiation-induced spinal deformity
4. QUANTEC source: These constraints are derived from the landmark QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) guidelines - published in Int J Radiat Oncol Biol Phys, 2010
5. Below conus medullaris (cauda equina): Spinal cord tolerance is higher, allowing doses up to 59.4 Gy for lumbosacral ependymoma
6. Gonadal protection: Oophoropexy before CSI in young females with lumbosacral involvement is a valid clinical decision to preserve fertility

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OAR DOSE CONSTRAINTS - CSI 36 Gy / 20 Fractions (1.8 Gy/fraction)

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Fractionation Context

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OAR CONSTRAINTS (Excluding Head & Neck) - For 36 Gy / 20 # CSI

LUNGS

• At 36 Gy CSI, posterior lung portions receive low-intermediate scatter dose
• Actual mean lung dose observed in photon VMAT CSI planning studies: ~6-10 Gy (well within limits)
• With proton CSI: mean lung dose drops to < 1 Gy - major advantage

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HEART

• In 36 Gy CSI VMAT planning studies, actual mean heart dose achieved: ~9-10 Gy
• Thoracic spine irradiation is the main source of cardiac dose
• Pediatric patients: aim for mean heart dose < 15 Gy (ideally < 5 Gy) due to lifetime cardiac risk

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KIDNEYS

• Kidneys lie directly posterior (L1-L2 level) - in the path of the lumbar spine field
• In 36 Gy CSI, actual mean kidney dose in photon planning: ~11-13 Gy (close to but within limit)
• This is the tightest constraint to meet in photon CSI at 36 Gy - requires careful planning
• Proton CSI reduces kidney dose to near zero

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LIVER

• Right lobe of liver adjacent to T8-T12 vertebral levels
• Actual mean liver dose in 36 Gy CSI photon planning: ~6-7 Gy - well within limits
• Constraint easily met at this dose level

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BOWEL (Small & Large Intestine)

• At CSI dose of only 36 Gy, the bowel Dmax will be well below 54 Gy from the spine field alone
• Constraint becomes critical only when lumbosacral boost is added (total dose approaching 54 Gy)
• Lumbar spine field overlap with bowel loops is the main concern

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GONADS

• Lumbosacral field at 36 Gy puts gonads at significant risk
• Even 4-6 Gy to ovaries can cause premature ovarian failure in young girls
• Oophoropexy prior to CSI is standard recommendation when lumbosacral field is used
• In male patients: testicular shielding and sperm banking discussed pre-treatment

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ESOPHAGUS

• At risk in cervico-thoracic junction - the field junction overlap zone in CSI
• At 36 Gy CSI, esophageal dose is well within tolerance unless junction overlap occurs

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THYROID

• Sits at cervical/upper thoracic junction
• Even at 36 Gy CSI, thyroid receives significant dose (~16 Gy mean in VMAT planning studies)
• Post-CSI hypothyroidism in 30-60% of patients - screen TSH every 6-12 months

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VERTEBRAL BODIES / GROWTH PLATES

• Asymmetric vertebral irradiation → radiation-induced scoliosis (most common long-term skeletal complication)
• All vertebral bodies within CSI field must receive homogeneous dose

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ACTUAL DOSES ACHIEVED IN 36 Gy / 20 # VMAT CSI PLANNING STUDIES

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QUICK RECALL - ONE-LINER CONSTRAINTS (Exam Viva Format)

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EXAM KEY POINT

At 36 Gy / 20 fractions, the kidneys are the most challenging OAR to protect in photon CSI because they lie directly posterior within the lumbar spine field. The mean kidney dose (~12-13 Gy) approaches but stays within the QUANTEC limit of 18 Gy. This is one of the strongest arguments for proton beam CSI in pediatric ependymoma - protons virtually eliminate kidney, gonadal, and cardiac dose.

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MANAGEMENT OF SQUAMOUS CELL CARCINOMA (SCC) LUNG - STAGE-WISE STANDARD OF CARE WITH EVIDENCE

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Preliminary Notes

• SCC of lung = NSCLC (Non-Small Cell Lung Cancer), ~25-30% of all lung cancers
• Predominantly central, hilar location - different from adenocarcinoma (peripheral)
• Key difference from adenocarcinoma: SCC has low rates of actionable driver mutations (EGFR ~2.7%, ALK ~1%) - so targeted therapy plays a smaller role; immunotherapy + chemotherapy is the backbone
• Staging: 8th Edition AJCC/UICC TNM (2017 onwards)

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STAGING OVERVIEW (8th Ed AJCC)

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STAGE I (T1-2a N0 M0) - EARLY STAGE

Standard of Care: SURGERY (Lobectomy)

Adjuvant Chemotherapy:

• Stage IA: No adjuvant chemotherapy
• Stage IB (T2a): Adjuvant chemo - controversial; consider if high-risk features (visceral pleural invasion, poor differentiation)
• Regimen: Cisplatin + Vinorelbine x 4 cycles (LACE meta-analysis evidence)

For Medically Inoperable Stage I:

• SABR/SBRT - Standard of care
• Dose: 54 Gy / 3 fractions (peripheral) or 60 Gy / 8 fractions (central)
• Evidence: TROG 09.02 (CHISEL trial) - SABR vs. conventional RT; SABR showed superior LC (89% vs. 65% at 2 years)
• SPACE trial and STARS/ROSEL (underpowered) suggest SABR comparable to surgery in operable Stage I
• NCCN 2024: SABR now appropriate even for patients with poor cardiac function (new update)

RT Dose (Conventional): 60-66 Gy / 30-33 fractions (if SABR not available)

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STAGE II (T2b-T3 N0 or T1-2 N1 M0) - EARLY-INTERMEDIATE

Standard of Care: Surgery + Adjuvant Chemotherapy

Key Evidence:

• LACE Meta-analysis (Pignon et al., JCO 2008): Adjuvant cisplatin-based chemo improves 5-yr OS by 5.4% in Stage II-III
• LungART Trial (NEJM 2022): PORT (54 Gy) did NOT improve disease-free survival in resected N2 NSCLC; increased cardiac toxicity - ended routine PORT use

Adjuvant Immunotherapy (SCC-specific):

• Atezolizumab (IMpower010): Approved as adjuvant therapy post-resection + chemo for PD-L1 ≥1%, Stage II-IIIA NSCLC
• Pembrolizumab (PEARLS/KEYNOTE-091): Adjuvant pembrolizumab after resection + chemo improved DFS regardless of PD-L1 status

Medically Inoperable Stage II:

• Concurrent Chemoradiation (CCRT): 60-66 Gy + weekly Carboplatin/Paclitaxel or Cisplatin/Etoposide

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STAGE III (N2/N3 disease) - LOCALLY ADVANCED

This is the most important and complex stage in Radiation Oncology exams

Subdivisions:

• Stage IIIA: Potentially resectable (T1-3 N2) - multidisciplinary decision
• Stage IIIB/IIIC: Unresectable (N3 or T4 with extensive N2)

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IIIA - POTENTIALLY RESECTABLE

Approach 1: Surgery-based

• Neoadjuvant chemo (Cisplatin + Gemcitabine/Docetaxel) x 3 cycles → Surgery
• OR Neoadjuvant CCRT → Surgery (if single-station N2)
• Evidence: INT 0139 trial: CRT → surgery vs. CRT → RT only; surgery arm improved PFS but not OS (excess pneumonectomy mortality)

Approach 2: Definitive CCRT (if unresectable after restaging)

• Same as Stage IIIB below

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IIIB/IIIC - UNRESECTABLE (DEFINITIVE CCRT)

GOLD STANDARD: Concurrent Chemoradiotherapy (CCRT) + Durvalumab consolidation

Radiation:

After CCRT - Durvalumab (Anti-PD-L1):

PACIFIC regimen is the single most important trial to know for Stage III NSCLC

SCC-specific note on PACIFIC:

• Durvalumab works in squamous cell carcinoma - unlike EGFR-targeted approaches which have minimal benefit in SCC
• For adenocarcinoma with EGFR mutation: LAURA trial (2024) showed osimertinib after CCRT is superior to durvalumab, but this is not applicable to SCC (SCC has very low EGFR mutation rate)

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Radiation Technique Considerations in Stage III SCC:

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STAGE IV (Metastatic SCC) - SYSTEMIC THERAPY

Key difference: SCC has low driver mutation rates - immunotherapy + chemo is the primary approach

First-Line Treatment Algorithm:

Step 1 - Biomarker Testing:

• PD-L1 IHC (mandatory)
• EGFR, ALK, ROS1, KRAS, BRAF, MET, RET, NTRK - consider even in SCC (NCCN 2024 recommends broad genomic testing for all advanced NSCLC including SCC, as cumulative actionable rate is 2-10%)

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Based on PD-L1 Expression:

PD-L1 ≥ 50% (High expression)

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PD-L1 1-49% (Intermediate)

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PD-L1 < 1% (Low/Negative expression)

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Stage IVA with Oligometastatic Disease (M1b - single site):

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Palliative Radiation in Stage IV SCC:

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MASTER SUMMARY TABLE - SCC LUNG STAGE-WISE

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LANDMARK TRIALS - ONE-LINE SUMMARY (Viva Essentials)

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EXAM KEY POINTS

1. PACIFIC trial = most important trial to know for Radiation Oncology exam regarding Stage III NSCLC - durvalumab after CCRT is now standard of care
2. RTOG 0617 = most important trial showing dose escalation (74 Gy) is HARMFUL - 60 Gy remains standard
3. KEYNOTE-407 is the landmark trial specifically for squamous cell carcinoma Stage IV - pembrolizumab + carboplatin + paclitaxel
4. For SCC: EGFR/ALK targeted therapy has minimal role due to low mutation rates - immunotherapy is the backbone
5. PORT (post-operative RT) is no longer standard after LungART trial (2022)
6. In Stage IIIB unresectable SCC: the sequence is CCRT → Durvalumab consolidation (not concurrent immunotherapy - PACIFIC used sequential)

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WORKUP FOR MULTIPLE MYELOMA

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Definition

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When to Suspect Multiple Myeloma - Clinical Clues

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DIAGNOSTIC CRITERIA - IMWG (2014, Updated)

Step 1: Clonal Plasma Cells

• Bone marrow clonal plasma cells ≥ 10% OR
• Biopsy-proven plasmacytoma (bone or extramedullary)

Step 2: At Least ONE Myeloma-Defining Event (MDE)

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CRAB Criteria (End-Organ Damage)

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SLiM Biomarkers (IMWG 2014 - allows treatment BEFORE end-organ damage)

Key exam point: The SLiM criteria allow diagnosis of active myeloma in patients who previously would be called "smoldering myeloma" - enabling earlier treatment before organ damage occurs

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COMPLETE STANDARD WORKUP

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SECTION 1: Investigations to Evaluate Clonal Plasma Cells

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SECTION 2: Investigations to Evaluate Clonal Paraprotein

Hierarchy of sensitivity: Immunofixation > SPEP > urine immunofixation > sFLC

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SECTION 3: Investigations to Evaluate End-Organ Damage (CRAB)

Blood Tests:

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Imaging:

IMWG Imaging Recommendation: For suspected smoldering MM or solitary plasmacytoma - perform one of: PET-CT / LDWBCT / whole-body MRI

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SECTION 4: Investigations for Risk Stratification and Staging

For ISS / R-ISS Staging:

ISS Staging (International Staging System):

R-ISS (Revised ISS - 2015):

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Cytogenetics / FISH (Fluorescence In Situ Hybridization):

High-risk cytogenetics = del17p, t(4;14), t(14;16) - memorize this triad

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Additional Tests:

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SPECTRUM OF PLASMA CELL DYSCRASIAS - Differential Diagnosis

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QUICK MNEMONIC SUMMARY

"C-P-D-R"

• Clonal plasma cells (BM biopsy)
• Paraprotein (SPEP, SIFE, sFLC, 24h urine)
• Damage (CRAB - CBC, creatinine, Ca, imaging)
• Risk stratification (β2M, albumin, LDH, FISH)

• S = Sixty percent BMPC
• Li = Light chain ratio ≥ 100
• M = MRI ≥ 2 focal lesions
• C = Calcium ↑
• R = Renal failure
• A = Anemia
• B = Bone lesions

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KEY EXAM POINTS

1. Serum alkaline phosphatase is NORMAL in myeloma - because osteoclasts are active but osteoblasts are suppressed - classic distinguishing point from bone metastases of carcinoma
2. Immunofixation is more sensitive than SPEP - can detect M-protein even when SPEP shows no spike (especially in light-chain-only disease)
3. Rouleaux formation on PBS = classic finding; caused by M-protein coating RBC surfaces
4. del(17p), t(4;14), t(14;16) = high-risk cytogenetics triad
5. IMWG 2014 update: Added SLiM criteria - patients with ≥60% BMPC or sFLC ratio ≥100 are now classified as ACTIVE myeloma even without CRAB
6. Whole-body low-dose CT or PET-CT is preferred over plain skeletal survey in current IMWG guidelines - more sensitive for detecting lytic lesions ≥5mm
7. t(11;14) = standard risk but important because it makes tumor sensitive to venetoclax (BCL-2 inhibitor)
8. IgG most common (52%) → IgA (21%) → light chain only (~16%) → IgD (~2%)

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URINE BENCE JONES PROTEINS (BJP)

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Definition

• Molecular weight: ~22 kDa (light chains are small enough to be freely filtered at the glomerulus)
• They represent free, unpaired κ or λ light chains - not bound to heavy chains

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Historical Significance

• Precipitated on heating to 40-60°C
• Redissolved at 100°C (boiling)
• Re-precipitated on cooling

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Source and Pathophysiology

Malignant Plasma Cells
        ↓
Produce excess monoclonal Ig 
        ↓
Free light chains (κ or λ) produced in excess 
(more than needed to pair with heavy chains)
        ↓
Freely filtered at glomerulus (MW ~22 kDa, below GFR threshold)
        ↓
Partially reabsorbed by proximal tubule cells
        ↓
Excess spills into urine → BJP
        ↓
Tubular reabsorption overloaded → tubular cell damage → cast nephropathy

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Conditions Associated with BJP

Key fact: BJP present in ~2/3 of myeloma patients who have a serum M component, and in 20% of myeloma cases BJP is the ONLY paraprotein (no serum M-spike detectable) - these are "light chain only" myelomas

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Chemical Properties of BJP

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Detection Methods - Comparison

1. Classical Heat Test (Bence Jones Test)

• Principle: BJP precipitates at 40-60°C, dissolves at 100°C
• Procedure: Urine acidified to pH 4.5-5.0 → heated gradually
• Sensitivity: POOR - falsely negative in ~50% of light chain myeloma patients (Harrison's 22e)
• Status: Largely obsolete - not recommended as sole test

2. Bradshaw Test

• Urine layered over concentrated HCl
• BJP forms a precipitate at the interface
• Also largely obsolete

3. Urine Protein Electrophoresis (UPEP) - Standard

• 24-hour urine collection is mandatory for quantitation
• BJP migrates as a discrete monoclonal band (usually in gamma or beta region)
• Can quantify amount in grams/24 hours
• Sensitivity better than heat test but still may miss low-level BJP

4. Urine Immunofixation Electrophoresis (UIFE) - Most Sensitive

• Gold standard for BJP detection
• Confirms the class (κ or λ) and clonality
• Can detect very low concentrations not visible on UPEP
• Should be performed in all suspected myeloma cases even if UPEP is negative

5. Serum Free Light Chain (sFLC) Assay - Modern Standard

• Measures serum κ and λ free light chains
• κ:λ ratio: Normal = 0.26-1.65
• Abnormal ratio indicates clonal light chain production
• Supersedes urine BJP in most clinical settings (serum sample, no need for 24h urine)
• Detects BJP even when urine levels too low to detect
• Especially useful in: Nonsecretory myeloma, oligosecretory myeloma, AL amyloidosis, LCDD
• Now incorporated into SLiM criteria: sFLC ratio ≥100 = myeloma-defining event

Sensitivity Hierarchy (Most → Least Sensitive):

sFLC assay > Urine Immunofixation > UPEP > Heat test > Dipstick

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BJP in Urine - Interpretation

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Renal Damage from BJP - Mechanisms

1. Cast Nephropathy (Most Common - "Myeloma Kidney")

• BJP filtered → binds to Tamm-Horsfall glycoprotein (uromodulin) in distal tubules
• Forms obstructive casts → tubular obstruction → AKI
• Worsened by: Dehydration, NSAIDs, contrast agents, loop diuretics (↑ Cl⁻ → ↑ Tamm-Horsfall secretion)
• Classic finding: "fractured cast" appearance on renal biopsy

2. Proximal Tubular Damage (Fanconi Syndrome)

• Excess BJP reabsorption by proximal tubular cells → direct cytotoxicity
• Leads to: Glucosuria, aminoaciduria, phosphaturia, bicarbonaturia
• → Acquired Fanconi syndrome in some myeloma patients

3. AL Amyloidosis

• λ light chains preferentially (more than κ) form amyloid fibrils
• Deposits in glomeruli → nephrotic syndrome
• Congo red stain → apple-green birefringence under polarised light

4. Light Chain Deposition Disease (LCDD)

• κ light chains preferentially
• Non-amyloid granular deposits → nodular glomerulosclerosis
• Similar to Kimmelstiel-Wilson nodules of diabetic nephropathy

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BJP vs Albumin - Key Distinguishing Points (Exam Favourite)

Key exam point: Dipstick proteinuria is NEGATIVE in light chain myeloma because dipstick only detects albumin, not light chains - this is why a normal dipstick does NOT rule out BJP/myeloma

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Clinical Approach to BJP Testing

Suspected Myeloma
       ↓
1. Serum: SPEP + SIFE + sFLC assay
2. Urine: 24h UPEP + UIFE
       ↓
BJP detected?
    ↓YES                    ↓NO
Quantify (g/24h)    → sFLC assay (catch
Monitor response         remaining cases)
to treatment

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Monitoring BJP in Treatment Response

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Quantitative Reference Values

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Quick Summary Mnemonics

• Bence Jones = Big protein overflow
• Just detected by immunofixation (not dipstick!)
• Precipitates at 40-60°C, re-dissolves at 100°C

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Key Exam Points

1. Dipstick is negative for BJP - classic exam trap; dipstick detects albumin, not light chains
2. Heat test is falsely negative in ~50% of light chain myeloma - unreliable; urine immunofixation is gold standard
3. 24-hour urine collection is mandatory for quantitation of BJP
4. 20% of myeloma cases: BJP is the ONLY paraprotein - no serum M-spike (light chain only myeloma)
5. sFLC assay has now largely replaced 24h urine BJP in monitoring - but urine immunofixation still required for complete response assessment
6. λ light chains → more likely to cause amyloidosis; κ light chains → more likely to cause LCDD
7. BJP causes cast nephropathy - worsened by dehydration, loop diuretics, contrast, NSAIDs - all should be avoided in myeloma
8. BJP was first described by Henry Bence Jones in 1847 - the very first tumour biomarker in history

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