PET/CT guide

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 Mean SUV values
• Brain 6.0-8.0
• Pituitary if max >5.0, look for bilat adr hyperplasia or breast uptake
• Tonsils 3.5 (palatine), 3.1 (lingual)
• Soft palate 3.1
• Salivary glands variable (sublingual>submand>parotid)
• Vocal cords variable (post cricoarytenoid>cords)
• Thyroid 1.3 (focal uptake 30%CA; focal uptake>4.2 w/ hypodense
nodule on CT90%CA)
• Lung 0.7 (>1.8 is abnl)
• Mediastinum 1.5-2.5 (>2.5 is abnl)
• Malignant effusion 2.2-2.6
• Thymus 1.8 (max≤3.8; CA>5.0)
• Eso (distal) ≤4.0
• Liver 2.5-3.0 (SUV<1.6 insulin effect)
• Spleen 1.9
• Adrenal Adenoma=HU<10 or SUV≤3.1 or SUV ratio ≤2.5 (compared to liver)
High adr to liver ratio >2 consider: mets/ACC/pheo/primary lymphoma
• BM 1.0 (activity > than liver is considered abnl)
• Spinal cord 2.1 (physio c-spine, T11/12, L1 level esp in winter; focal
increased uptake=spondylotic vs XRTmyelopathy)
• Spinal compression fx 3.9+/-1.5 for malig and 1.9+/-1.0 for b9
• Breast 0.5-1.5 (max<2.5); axillary mets ≥2.3
• Testes 2.2 (max<5.7; normally decreases w/ age)
• Septic thrombosis >3.8max
• Bladder 30-60
Normal values
• Minimum SUV change ≥20%
• Baseline scan
– More important for solid tumor
– Also, important for low-FDG-avid lymphoma
• Quantitative assessment important to assess interval change
– Interim PET during therapy: SUV decrease ≥30-50% assoc w/ good prognosis
– End-of-therapy PET: SUV change at least 30% (visual assessment is sufficient)
• Careful with false positives on interim or end-of-therapy PET (consider biopsy
confirmation)
• Mixed response usually not seen with Lymphoma (can be seen with solid tumors)
• MRU (minimal residual dz): consider short term f/u in 3mos
• Tumor response can lag for extra-nodal dz in lymphoma
 Bottomline
• SUV values btwn institutions and between PET vs PET/CT may be poorly reproducible hence
for serial f/u patient should be scanned in same institution on same equipment with
standardized imaging protocols (avoid variation in uptake time and wide variation in patient
factors like BG level)
• Baseline PET is important esp if low-FDG avid primary tumor
• Mean SUVs to remember (these may be higher or overestimated in obese pts)
– Mediastinum 2.5 (ROI over asc vs desc aorta at level of carina, avoiding vessel wall)
– Liver 3.0 (3cm ROI over right hepatic lobe avoiding porta hepatis)
– Lung <1.0, Muscle <1.5, Brain 10, Bladder 50
• Pathology usually has max SUV >1.5-2 times mean SUV of liver (which means that max SUVs
≥5 are generally concerning)
• Tumor >2cm is not affected by volume averaging
• Calculate % change in max SUV
– Change of SUV ~10% is considered minimum significant change
– Change of ~30% maxSUV is significant for lymphoma
– For solid tumor, decrease of maxSUV by 35% is “minor” response and decrease by 60%
is “major” response
• Midtreatment (aka interim) PET provides info on “rate of tumor cell killing”
• Post-tx PET (performed after completion of tx) provided info on “log units of tumor
cell killing”
 Major vs Minor response for solid tumor

• Using SUV criteria, it has been established

– SUV reduction of 35% is reasonable to call it a minor
response
– SUV reduction of 60% is considered a major response
 MTV and TLG
• Metabolic Tumor Volume (MTV) is a total volume within a boundary
determined with a particular threshold (e.g., SUV > 3, SUV > reference
tissue, or SUV > 40% of SUVmax)
• Total lesion glycolysis (TLG) = MTV x SUVmean within the boundary
– This takes into account both ANATOMIC (size) + METABOLIC (SUV)
parameters
• SUVmax is a single max pixel value within ROI
• SUVpeak is max value within a small fixed round ROI 1cm3 (more pixels
included) within hottest region of the lesion so it is more reproducible
than SUVmax
– Don’t use for lesion <1cm in size
% change in SUVmax

SUVfu – SUVinitial x 100%

SUVinitial
 False Negatives
• Low-grade, slow-growing
• Well-differentiated tumor
• Highly necrotic, low-cellularity tumor
• Post-chemo tumor stunning
• <1cm in size (partial volume effect)
• High dose steroid therapy
• Tumor obscured by physiologic uptake
• Phosphatase related FDG dephosphorylation
• Specific tumors
– BRAIN
• Small mets at gray-white jct (upto 40% of brain mets not detected on PET)
• Low-grade glioma
False negatives
– H/N
• Salivary gland tumors (mucoepidermoid, adenoid cystic, spindle-cell=false neg; warthins and pleomorphic adnenomas=positive)
– THYROID
• Diff thyroid CA (medullary, anaplastic, and de-differentiated papillary/follicular= positive)
– LUNG
• BAC (adenoCA in-situ s/s 10/20%)
• Carcinoid (typical)
– BREAST
• DCIS/LCIS
• Lobular CA
• Tubular CA
– GI SOLID ORGAN
• HCC (50% b/c G-6-phosphatase; esp well-differentiated)
• Infiltrative cholangioCA (including klastin’s)
• AdenoCA of pancreas if BG>120
– GI BOWEL
• Mucinous CA (breast, GI like stomach/colon, pancreas, ovary)
• Signet-cell CA
• Neuroendocrine/APUD tumors like Carcinoid (false neg in 25%; except atypical carcinoid), islet cell tumor, pheo, and other
neuroendocrine tumors
• Cystic pancreatic CA
• Small peritoneal met (low sensitivity)—from GI like stomach/colon, pancreas, ovary, appendix (mucocele)
– GU
• RCC (has G-6-phosphatase like liver)
• Clear-cell renal CA
• Bladder (or transitional cell due to urinary excretion of radiotracer)
– PELVIC
• Clear cell CA of ovary
• Well-differentiated teratomas
• Prostate
– BONE/BM
• Low grade NHL (eg peripheral T-cell lymphoma, anaplastic large T-cell, small lymphocytic lymphoma, extranodal marginal zone lymphoma
including MALT and splenic marginal zone lymphoma) except follicular
• Plasmacytoma
• Low grade chondrosarcoma
– ST
• Low grade sarcoma; myxoid tumors
 Wait before PET
Post biopsy 1wk
Post surgery 4-6wks
Post chemo 2-4wks (~1mo)—atleast 10d to avoid stunning/flare
1-2cycles lymphoma
2-3cycles solid tumors
Post XRT 6-8wks (1.5-2mos)—Dr Bridwell 3mos
Post GCSF >5d (upto 30d for longer acting )

--Any activity 6mos after XRT is recurrence (unless if radiosurgery)

--Wait 6-8 wks after RF ablation (ring-shaped inflammatory uptake should
decrease on F/U)
 Wait before PET
WAIT
Biopsy 1wk
Surgery 4-6wks
Chemo 2wks to 1mo
Chemo-embo 6-8wks
XRT 3 mos
 PET vs CT

Metabolic changes can precede anatomic

changes by about 6-9mos
 FDA-approved PET tracers
• F-18 NaF (1972): Bone imaging
• Rb-82 (1989): Myocardial perfusion
• F-18 FDG (2004): Oncology, Viability, Seizure
• N-13 NH3 (2007): Myocardial perfusion
• I-123 MIBG (2008): Pheo and Neuroblastoma
• I-123 Ioflupane or DatScan (2011): Parkinson’s
• F-18 NaF (2011): Bone imaging
• F-18 Florbetapir or Amyvid (2012): Alzheimers
• C-11 Choline (2012 Mayo clinic only): Prostate
• F-18 Flutemetamol or Vizamyl (2013): Alzheimers (color images)
• Tc-Tilmanocept or Lymphoseek (2013): Lymphoscintigraphy (binds to LN)
• I-123 MIBG or Adre View (2013): Heart failure
• Ra-223 or Xofigo (2013): Prostate CA treatment
• F-18 Florbetaben or NeuraCeq (2014): Alzheimers
• F-18 Fluciclovine or Axumin (2016): Prostate CA relapse (AA transport)
• Ga-68 DOTATATE or Netspot (2016): NET (SST)
 NDA (new drug approval) process
• Target discovery  lead identity/eval  preclinical discover
(in-vitro/in-vivo)  clinical development (phase 0-3 trials) 
FDA approval
• Need CMS approval for reimbursement
• Usual cost for radiotracer is $100-150 Million and ~9year
process
• Hurdles
– Findings sponsor for clinical trials
– Market size (for return on investments)
– Safety
– Efficacy
 Future tracers in horizon
• Cardiology
– F-18 Fluripidaz
• Neurology
– C-11 PIB (univ of Pittsburgh)
– F-18 NAV-4694 (phase III)
– F-18 T807 (Tau protein, phase II)
• Oncology
– F-18 DOPA (neuroendocrine tumors, brain tumor)
– F-18 FACB (amino acid transport for tumor imaging)
– I-124 MIBG
– Ga-68 DOTA-TOC/NOC/TATE (imaging)
– Y-90 DOTATOC/Lu-177 DOTATATE (therapy)
– Zr-89 J591 (prostate CA)
– Tc/F-18/Ga-68 small mol PSMA inhibitor
 Targeted therapies for CA
• Adenocarcinoma of the stomach or gastroesophageal junction: Trastuzumab (Herceptin®)
• Basal cell carcinoma: Vismodegib (Erivedge™)
• Brain cancer: Bevacizumab (Avastin®), everolimus (Afinitor®)
• Breast cancer: Everolimus (Afinitor®), tamoxifen, toremifene (Fareston®), Trastuzumab
(Herceptin®), fulvestrant (Faslodex®), anastrozole (Arimidex®), exemestane (Aromasin®),lapatinib
(Tykerb®), letrozole (Femara®), pertuzumab (Perjeta™), ado-trastuzumab emtansine (Kadcyla™)
• Cervical cancer: Bevacizumab (Avastin®)
• Colorectal cancer: Cetuximab (Erbitux®), panitumumab (Vectibix®), bevacizumab (Avastin®),ziv-
aflibercept (Zaltrap®), regorafenib (Stivarga®)
• Dermatofibrosarcoma protuberans: Imatinib mesylate (Gleevec®)
• Head and neck cancer: Cetuximab (Erbitux®)
• Gastrointestinal stromal tumor: Imatinib mesylate (Gleevec®), sunitinib (Sutent®), regorafenib
(Stivarga®)
• Giant cell tumor of the bone: Denosumab (Xgeva®)
• Kaposi sarcoma: Alitretinoin (Panretin®)
• Kidney cancer: Bevacizumab (Avastin®), sorafenib (Nexavar®), sunitinib (Sutent®), pazopanib
(Votrient®), temsirolimus (Torisel®), everolimus (Afinitor®), axitinib (Inlyta®)
 Targeted therapies for CA
• Leukemia: Tretinoin (Vesanoid®), imatinib mesylate (Gleevec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib
(Bosulif®), rituximab (Rituxan®), alemtuzumab (Campath®), ofatumumab (Arzerra®), obinutuzumab
(Gazyva™), ibrutinib (Imbruvica™), idelalisib (Zydelig®)
• Liver cancer: Sorafenib (Nexavar®)
• Lung cancer: Bevacizumab (Avastin®), crizotinib (Xalkori®), erlotinib (Tarceva®), gefitinib (Iressa®), afatinib dimaleate
(Gilotrif®), ceritinib (LDK378/Zykadia)
• Lymphoma: Tositumomab and 131I-tositumomab (Bexxar®), ibritumomab tiuxetan (Zevalin®),denileukin diftitox
(Ontak®), brentuximab vedotin (Adcetris®), rituximab (Rituxan®), vorinostat (Zolinza®), romidepsin
(Istodax®), bexarotene (Targretin®), bortezomib (Velcade®), pralatrexate (Folotyn®), lenaliomide (Revlimid®), ibrutinib
(Imbruvica™), siltuximab (Sylvant™), idelalisib (Zydelig®), belinostat (Beleodaq™)
• Melanoma: Ipilimumab (Yervoy®), vemurafenib (Zelboraf®), trametinib (Mekinist®), dabrafenib
(Tafinlar®), pembrolizumab (Keytruda®)
• Multiple myeloma: Bortezomib (Velcade®), carfilzomib (Kyprolis®), lenaliomide (Revlimid®),pomalidomide (Pomalyst®)
• Myelodysplastic/myeloproliferative disorders: Imatinib mesylate (Gleevec®)
• Pancreatic cancer: Erlotinib (Tarceva®), everolimus (Afinitor®), sunitinib (Sutent®)
• Prostate cancer: Cabazitaxel (Jevtana®), enzalutamide (Xtandi®), abiraterone acetate (Zytiga®),radium 223 chloride
(Xofigo®)
• Soft tissue sarcoma: Pazopanib (Votrient®)
• Stomach cancer: Ramucirumab (Cyramza™)
• Systemic mastocytosis: Imatinib mesylate (Gleevec®)
• Thyroid cancer: Cabozantinib (Cometriq™), vandetanib (Caprelsa®), sorafenib (Nexavar®)
 Chest LN stations
• Supraclavicular zone
• Lower cervical
• Supraclavicular
• Sternal notch
• Sup mediastinal zone
• Pre-vascular
• Para-aortic
• AP window/ sub-aortic
• Upper paratracheal (above
arch)
• Retro-tracheal
• Lower paratracheal (below
arch)—includes precarinal
• Inferior mediastinal zone
• Subcarinal
• Paraesophageal (below
carina)
• Pulmonary ligament
• Others (pericardial,
cardiophrenic,
subdiaphragmatic)
• N1 nodes (aka hilar nodes)
• Hilar/interlobar zone
– Hilar
– Interlobar
• Peripheral zone
– Lobar
– Segmental
– Subsegmental
 Chest LN stations
• N1
– Intrapulmonary
– Peribronchial
– Hilar
• N2
– Ipsi/midline mediastinal
– Subcarinal
• N3
– Contralat med or hilar
– Supraclavicular
 Abdominal LN stations
• Pericardial, cardiophrenic • Celiac, SMA
• Subdiaphragmatic • Aortocaval, precaval, pre-aortic,
• Retrocrural para-aortic, retroaortic
• Paraeso • Perispinal
• Gastrohepatic lig • CIA, EIA, IIA (hypogastric),
• Perigastric obturator
• Perisplenic • Pre-sacral
• Peri-pancreatic, • Mesenteric, omental
pancreaticodudenal (head) • Pericolic, perirectal
• Portahepatis (hepatoduodenal) • Parametrial
• Portocaval • Pelvic sidewall
• Inguinal
• Popliteal
 Axillary LN stations
• Level I
– Intra-mammary
– Low axillary
• Level II
– Interpectoral (Rotter’s)
• Level III
– High axillary
– Internal mammary
2013
 CMS 6feb2014
• Will only pay for initial and 3 subsequent PET
for treatment strategy
– PI= PET initial
– PS= PET subsequent x3
• KX modifier if need additional PET (non-
surveillance)
– Obtain signed ABN (advanced beneficiary notice
of non-coverage) as claims may be denied
CMS=center for Medicare and Medicaid services
NOPR=national oncologic PET registry
CED=coverage with evidence development (need PET registry)
 NCCN
National Comprehensive Cancer Network guidelines
NCCN guidelines
General staging flowchart
General chemo flowchart
General neoadjuvant flowchart
 Relapse vs Refractory
• Relapse= disease comes back after treatment
ends
• Refractory= new or relapsed disease that does
not respond to treatment
 Cancer terminology
• Neoadjuvant=pre-surgery chemo
• Induction=pre-XRT chemo
• Definitive treatment=surgery/XRT
• Adjuvant=primary chemo after surgery
• Salvage=rescue therapy after standard therapy is ineffective
• Palliative=treat symptoms rather than expect cure
 Radiotherapy vs Radiosurgery
• Radiotherapy: IMRT
• Radiosurgery: SBRT, IGRT, tomotherapy,
cyberknife
– Radiosurgery delivers high radiation dose to small
volume in short time such that chronic
inflammation results in long term low-level focal
persistent SUV range of 2-4 is considered normal
Oncologic guidelines
 PET in oncology
• Increased glycolysis and glucose-utilization by cancer aka “Warburg effect”
• Over-expression of Glucose transporters (GLUT1) aka high levels of
hexokinase (HK2)
• Anaerobic glycolysis (hence less ATP per glucose molecule so more glucose
needed for ATP production)
• General increase in metabolism from high growth rates
• T staging = based on surgery or CT
• N and M staging = PET/CT
 Cancer Imaging: The Questions

• Is cancer present (detection)?

• Is a mass cancer or not?
• Is the cancer localized or spread?
• How should the cancer be treated?
• Is a treatment working?
• Is more treatment needed?
• Has cancer recurred, if so where?
• What is the prognosis?
 Limitations of anatomical imaging

• Detect lesions (anatomy) but does not characterize

them (physiology)
• Often difficult to detect small tumor foci, especially if
surrounded by normal tissues
• Performance limited in post-operative state due to
distortion of normal anatomy
• Displays limited information regarding tumor biology
(e.g. invasion)
• Does not predict response to a given therapy
• Slow to display response to treatment
• Difficult to measure cytostatic responses
 Molecular and Functional Alterations in CA

• Increased glucose metabolism

• Increased Amino acid transport
• Increased Protein and membrane synthesis
• Increased DNA synthesis
• Overexpression of receptors/antigens
• Increased blood flow or vessel density
• Decreased oxygen tension in lesions
• Increased apoptotic rates with effective Rx
 General indications in oncology
• B9 vs malignant
• Staging and restaging (after tx)
• Metastatic workup (rising tumor markers)
• Monitoring tx response
• Scar/necrosis/fibrosis vs recurrence
• Grading and prognosis
• Detection of unknown primary
 PET in oncology
• Diagnosis
• Staging (initial)
• Monitoring response during therapy
– Interim
– Neoadjuvant
• XRT planning
• Restaging (completion of therapy)
• Suspect recurrence
• Surveillance
• Specific tumors
– BRAIN
• Small mets at gray-white jct (upto 40% of brain mets not detected on PET)
• Low-grade glioma
False negatives
– H/N
• Salivary gland tumors (mucoepidermoid, adenoid cystic, spindle-cell=false neg; warthins and pleomorphic adnenomas=positive)
– THYROID
• Diff thyroid CA (medullary, anaplastic, and de-differentiated papillary/follicular= positive)
– LUNG
• BAC (adenoCA in-situ s/s 10/20%)
• Carcinoid (typical)
– BREAST
• DCIS/LCIS
• Lobular CA
• Tubular CA
– GI SOLID ORGAN
• HCC (50% b/c G-6-phosphatase; esp well-differentiated)
• Infiltrative cholangioCA (including klastin’s)
• AdenoCA of pancreas if BG>120
– GI BOWEL
• Mucinous CA (breast, GI like stomach/colon, pancreas, ovary)
• Signet-cell CA
• Neuroendocrine/APUD tumors like Carcinoid (false neg in 25%; except atypical carcinoid), islet cell tumor, pheo, and other
neuroendocrine tumors
• Cystic pancreatic CA
• Small peritoneal met (low sensitivity)—from GI like stomach/colon, pancreas, ovary, appendix (mucocele)
– GU
• RCC (has G-6-phosphatase like liver)
• Clear-cell renal CA
• Bladder (or transitional cell due to urinary excretion of radiotracer)
– PELVIC
• Clear cell CA of ovary
• Well-differentiated teratomas
• Prostate
– BONE/BM
• Low grade NHL (eg peripheral T-cell lymphoma, anaplastic large T-cell, small lymphocytic lymphoma, extranodal marginal zone lymphoma
including MALT and splenic marginal zone lymphoma) except follicular
• Plasmacytoma
• Low grade chondrosarcoma
– ST
• Low grade sarcoma; myxoid tumors
 False negatives
• Low-grade, slow-growing
• Well-differentiated tumor
• Highly necrotic, low-cellularity tumor
• Post-chemo tumor stunning
• <1cm in size (partial volume effect)
• High dose steroid therapy
• Tumor obscured by physiologic uptake
• SPECIFIC TUMORS
– Mucinous CA, signet-cell CA
– Mucoepidermoid and Adenoid cystic tumor of head/neck (salivary tumor and spindle cell neoplasms)
– DCIS, LCIS, lobular CA, tubular CA
– BAC (Thallium may be positive) S/S of 10%/20%
– APUD tumors like Carcinoid (false neg in 25%; except atypical carcinoid), islet cell tumor, pheo, and other
well-differentiated neuroendocrine tumors
– Cystic pancreatic CA
– Clear cell CA of ovary or kidney
– Well-differentiated teratomas
– RCC
– HCC (50%)—esp well-differentiated
– Infiltrative cholangioCA
– Prostate
– Bladder
– Low grade NHL (eg peripheral T-cell lymphoma, anaplastic large T-cell, small lymphocytic lymphoma,
extranodal marginal zone lymphoma including MALT and splenic marginal zone lymphoma) except
follicular
– Plasmacytoma
– Low grade sarcomas (eg low grade chondrosarcoma), myxoid tumors
– Mature (well-differentiated) teratoma
– Small peritoneal met (low sensitivity)
– Some brain mets have decreased uptake compared to normal brain (due to edema)—upto 40% of brain
mets not detected on PET
– AdenoCA of pancreas if BG>120
 False negatives with PET
• Common tumor types where FDG PET may fail include:
– Pure bronchoaveolar cell cancers of the lung
– Clear cell carcinoma of the ovary or kidney
– Mucinous carcinoma (of the colon etc)
– Adenoid cystic tumors of the head and neck
– Prostate tumors
– APUD tumors (carcinoids, gastrinomas, and pheochromocytoma)-well differentiated NET
– Well-differentiated teratomas
– Low grade lymphomas (except follicular) to include marginal zone B cell lymphomas etc
• The most common reasons that FDG PET fails include:
– The tumor type does not grow very fast, so its glucose consumption is not significantly higher
than the surrounding tissue (e.g. prostate)
– The tumor type is diffuse, so the signal gets blurred in with surrounding tissue (e.g.
bronchoaveolar cell cancer)
– The tumor type occurs near a place where FDG normally accumulates (e.g. bladder cancer)
– Poor contrast resolution - tumor uptake is not significantly higher than surrounding tissue
uptake (e.g. brain)
– Limited spatial resolution - tumors smaller than the spatial resolution of the scanner can blur
into the background
 False positives
• Infx and acute inflammation (activate macrophages w/ increased
glycolysis)
– eg sinusitis, PNA, abscess
– Fungal or granulomatous processes (TB/fungal, sarcoid)
– Progressive massive fibrosis (silicosis) and Talc pleurodesis
• Exercise related muscle activity
– r/o muscle strain or ST sarcoma
• Post-surgical inflammation
• Post XRT inflammation
• Growth factor (G-CSF) related diffuse BM uptake
• Vascular graft (diffuse uptake may persist from years)
• Catheter site, ostomies
• Brown fat mimicking pathologic nodes
• Dose infiltration with nodal uptake
• Fractures
• Thymic hyperplasia
• Cholangitis (activity along intrahepatic ducts can mimic liver lesions)
 NAC images
• High skin activity
• High lung activity (“black lungs”)
• Decreased central activity (esp abdomen)
• Lesion seen on AC and not on NAC is likely
attenuation correction artifact (this works for
peripheral lesions only, like subcm lung nodules)
• Better for superficial (skin) lesions--debatable
• Good for detecting artifact due to metal
 When to use NAC images
• Small peripheral pulmonary nodule
• Skin lesion
• Metallic artifact
• Liver heterogeneity
SUV window setting

Usually use 0-4.5, but if noisy scan adjust to 0-5

 General
• PET is non-specific (tumor vs infection vs inflammation)
• No magic SUV cutoff
• PET not good for T staging (cannot accurate discern locoregional dz aka local invasion or regional nodes)
• PET ok for N staging (can miss local nodal involvement esp microscopic diseasecannot replace surgical LN
sampling; PET is not sensitive but is usually specific; can detect nodal met within LN with anatomically normal
size/appearance)
• PET great for M staging (PET can upstage disease esp by findings occult/unsuspected regional or distant
metastasis)
• PET changes management in ~30% of patients by upstaging
• No PET surveillance (interim PET before completion of chemo may be controversial)
• Baseline PET before neoadj therapy  decrease in SUV >30-50% after neoadjuvant therapy is considered good
response
• NPV of interim PET higher than post-treatment PET
• Any residual metabolic activity 6mos after XRT is concerning for residual/recurrence
• Complete pathologic response is defined as <10% viable cells (pathology)
• Mixed response may suggest resistance to treatment
• PET may not be able to tell CR from MRU (minimal residual dz)—hence need to complete tx
• PET can detect synchronous CA (aka second primary) in up to ~8%
• PET is not sensitive for low grade, acellular tumor
• PET resolution is ~5mm (practically ≥1cm)
• False neg can be seen with lesions <1cm, primary tumor with low FDG avidity, and lesions with
necrosis/hemorrhage
• PET can miss disease in organs with physiologic uptake or organs with phosphatase related dephosporylation of
FDG (HCC, RCC)
• PET can miss mets at gray-white matter junction (sensitivity <60%)
 General
• Brain included in PET for patient with non-CNS malignancy only changed management in <1% of patient
• Mild uptake within anterior cervical and bilateral hilar nodes is common (esp if calcified or hyperdense on
non-contrast CT)
• PET is sensitive for liver mets >1cm but only 50% sensitivity for HCC (b9 lesions other than abscess don’t
have uptake)
• PET can miss small peritoneal or omental implants (sensitivity ~60%; some say CT is lower ~45%)—PET
cannot replace second look laparotomy
• Sensitivity of PET for bone mets depends upon primary tumor
• PET is better than BS for lytic lesion
• BS is more sensitive for sclerotic mets than PET esp for prostate cancer
• PET detects some mets that BS does not and vice versa for breast CA (so need both PET and BS)
• PET better than BS for bone mets from nasopharyngeal CA
• PPV for bone mets is 98% when PET and CT are concordant; PPV is 61% if PET is positive and CT is neg; PPV
is 43% for solitary PET positive bone lesion (need MRI eval)
• Treated bone mets tend to be blastic on CT and negative on PET
• Focal adrenal uptake can be adenoma (lipid rich or poor) vs metsfocal adrenal uptake twice that of liver
can help differentiate adenoma from mets (combining CT data (HU) and PET data (SUV) improves
specificity to 98%); ~5% of adrenal adenomas have substantial uptake
• MR is better than PET for liver (<1cm) and brain mets (including calvarial or leptomeningeal)
• CT chest with breath-hold important for detecting small pulmonary mets which are likely to be FDG-neg
• Potential flare phenomenon with breast CA treated with tamoxifen; colon CA s/p XRT/chemo; glioblastoma
after chemo (within 24hrs after 1st dose); liver mets s/p chemo (during 1st 2wks)
 BRAIN
• Keep eyes open (don’t fall asleep) otherwise physiologic occipital hypometabolism
• Total brain uptake is ~6% of injected dose
• Gray:white ratio upto 4:1
• BG sl more uptake than cortex
• Cerebellar uptake variable (less than seen w/ SPECT)
• Frontal lobe metabolism decreased w/ age
• Crossed cerebellar diaschisis similar to SPECT
• Quantitatively difference of >10-15% is significant
• Low metabolism during luxury perfusion unlike SPECT (subacute infarct “flow-metabolism
disconnect”)
• Low sensitivity for mets at gray-white jct ~60%
• Decreased brain metabolism w/ steroids, sedation, anticonvulsants
• FDG uptake is generally reduced in gray matter adjacent to WM edema which can increase
conspicuity btwn tumor and adjacent structures
• False pos=b9 tumors (meningioma, pituitary adenoma), recent ictal activity,
inflammatory/infectious
• CNS Lymphoma is generally very FDG-avid (as opposed to Toxo)
• Normal mildly hypermetabolic regions
– posterior cingulate cortex (located ant and sup to occipital cortex)
– wernicke’s (posterior superior temporal)
– frontal eye fields* (ant to primary motor cortex; may be asymm)
– posterior parietal cortex
– interestingly, the primary sensory and motor cortices don’t make this list
 BRAIN
• Indications
– Grading and prognosis (90% accuracy)
– Tumor recurrence
– XRT necrosis vs viable tumor (PET has similar accuracy as Thallium but better
resolution)
• Post-surg changes do not interfere with detection of recurrence
• Uptake greater than contralat WM (S/S 86%/22%)—preferred
• Uptake greater than contralat cortex (73%/56%) Ricci et al. AJNR 1998;19:407-413
• Specificity can be as low as 40%
• High-dose XRT (esp gamma-knife, radiosurgery, radioactive seed implants, or
radioimmunotherapy) can result in false positives
• Generalized reduction in glucose metabolism if treated with
steroids/sedatives/anticonvulsants (increased blood glucose levels)
• Suspicious area of uptake should correlate with abnormal enhancement on MR
(otherwise could be seizure focus)
– For toxo vs lymphomado Tl-201 (can use FDG PET as well; SUV much lower with Toxo
than Lymphoma)
– For tumor vs abscessdo In-111 WBC
– Not sensitive for intracranial mets (esp at gray-white jct) ~60% sens
– Note: flare phenomenon w/ GBM within 24hrs of 1st dose chemo (actually a good sign)
 Glioma
• Consider dual time point imaging (wait 2-3 hrs for delayed imaging)
• PET works best when fused with MRI
• Can help guide bx
• Amino acid PET great for tumor visualization but not for grading
• Glioma uptake depends upon cellular atypia, mitoses, endothelial
proliferation, necrosis
• Glioma grade correlates w/ degree of uptake on PET (uptake proportional
to grade)
– Tumor:WM ratio <1.5 is low grade
– Tumor:WM ratio >1.5 is hi grade
– Tumor:Cortex ratio <0.6 is low grade
– Tumor:Cortex ratio >0.6 is high grade
– Sens 94% and Spec 77% (Delbeke et al. Radiology 1995;195:47-52)
– 0: no uptake and 1: ≤normal WM (86% grade I or II)
– 2: normal WM<lesion<normal cortex and 3:≥normal cortex (94% grade
III and IV)
 BRAIN
• With malig tumors, there can be a wide rim of surrounding reduced
glucose metabolism
• This may be due to edema and/or due to functional inactivation by
infiltrating tissue
• Also, there can be decreased metabolism in contralateral cerebral cortex
and cerebellum (degree of decrease correlates with tumor size)—this may
partly be due to steroid therapy (but functional inactivation by tumor
cannot be excluded)
FDG uptake in CNS malignancy

Increased Variable Decreased

GBM Mets (melanoma Low-grade glioma
mets are quite
avid)
Medulloblastoma Oligodendroglioma s/p XRT
Primary CNS Meningioma Steroid therapy
lymphoma
Pituitary adenoma
PNET
 MRS in brain tumor
• Energy spectra based on chemical molecular structure
• Area under the curve of a certain peak rep concentration of metabolite within
sampled tissue; amount of shift is counted in parts per million
• Multivoxel imaging better than single voxel
• Relative (rather than absolute) quantification is generally used
• Always compared to normal contralateral tissue
• Help differentiate low grade from high grade tumor
• Can help guide stereotactic brain bx
• Can assess infiltrating brain tumors (since choline elevation can extend to areas
that anatomically appear normal and have no contrast enhancement)
• Increase in myoinositol indicates zone of glial activation towards infiltrating tumor
cells
• Can help diagnose certains tumore
– Meningioma has characteristic alanine resonance at 1.5ppm
– Mets tend to have low NAA resonance while showing high lipid and choline
 Choline= Creatine= NAA Lipid= Lactate= Myoinositol
Membrane Neuronal necrosis anerobic =glial
turnover destruction glycolysis activation
Peak 3.2 3.02-3.8 2.01-2.6 0-2 1.33 3.56, 4.06
position
(ppm)
Seen in Yes Yes Yes Only as No Yes
normal contamina
tissue tion
Tumor ↑ ↓ ↓ possible↑ possible↑ Suggest
(indicate (indicate infiltrating
higher higher tumor
grade) grade)

Elevated choline is not specific for high-grade tumor (yet cutoff of 1.6 for
astrocytoma and cutoff of 2.0 for oligodenroglioma).
 DWI in brain tumor
• Microscopic brownian motion of water molecules within tissue
• Decreased brownian motion (restricted diffusion) with increased cellular
density, reduction in extracellular space, and increase in viscosity
• Decreased brownian motion  decreased apparent diffusion coeff (ADC
in mm2/s) restricted diffusion bright on DWI
• Low values on ADC maps suggest high grade for solid gliomas
• In kids, medulloblastoma have lower ADC values than PCA
• Perfusion Weighted Imaging (PWI): high grade gliomas have vascularity
and hence increased relative cerebral blood volume (rCBV)—some use
threshold of 1.75 (cutoff for oligodendroglioma is 2.14)
• Diffusion tensor imaging: can visualize WM tracts disruption or
displacement by tumor
 H&N
• Waldeyer’s ring (lymphoid tissue uptake including palatine/lingual/adenoids)
• Soft palate (posterior) uptake more prominent in males
• Palatine (uptake decreases w/ age) > lingual tonsil uptake (2 vertical linear bands on coronal)
• Mylohyoid muscle (more inf and linear) and sublingual gland (more focal; ddx= genioglossus) uptake at
FOM (adenoid tissue at base of tongue in kids)
• Salivary uptake (sublingual>submand>parotid) usually less than tonsillar uptake
• Horseshoe cricoarytenoid muscle>vocal cords uptake (anterior uptake more concerning)
• Nasopharyngeal uptake concerning if asymmetric
• Longus colli muscle uptake can be asymmetric (extends from T1-3 thru C3-7)
• Pharyngeal constrictor muscle and larynx uptake if coughing
• Oral cavity or orpharyngeal CA have hi incidence of nodal mets (lower for laryngeal CA)
• Supraglottic CA spreads to bilateral cervical LNs
• Nasopharyngeal CA spreads to bilateral anterior cervical LNs and can involve posterior triangle LNs
• May see increased uptake with parathyroid adenoma or hyperplasia
• Not sensitive for malig salivary gland tumors like mucoepidermoid and adenoid cystic
• False positive for b9 salivary gland tumors like warthins (can be bilat) and pleomorphic adenoma
• PET not useful for assessment of cystic neck masses
• Dental extraction prior to XRT is common
• Osteonecrosis of jaw with bisphophonates
• 50% of Basal Cell CA (esp nodular subtype) is FDG avid
• HNSCC is FDG avid
• Delayed, hi-res PET with arms down can improve specificity
• PET better than BS for bone mets from nasopharyngeal CA
 H&N
• Detection of occult primary in pts with mets
– Useful for unknown/occult primary detection (in 25-70%) after neg clinical exam, CT/MR, and pan-
endoscopy with blind bx and tonsillectomies
– May miss superficial primary with <4mm depth
• Initial staging (detect cervical LN mets in clinically LN negative and detect distant mets in locally advanced
disease)
– PET more accurate for staging than CT/MR
– SUV>10 of primary tumor assoc with poor prognosis
– Cystic (necrotic) nodes may be falsely negative
– Some argue PET has limited role in N0 or clinical N0 dz (false positives)
• Detect residual or recurrent dz
– Post-radiation local recurrence detection can be challenging (recc wait 4-6mos)
• XRT planning (co-register PET with treatment planning CT)
– GTV assessment better with PET than CT/MR
• Decrease in SUV by <40% after neoadj therapy is suggestive of residual dz (>80-90% decrease is associated
with complete remission)
• DWI in H&N CA:
– ADC values normally decrease when b values are increased beyond 1000 (from 1000 to 2000) unless
tumor cellularity (cancer relapse)
– ADC ratio (ADC2000/ADC1000) and SUV mean correlate with tumor recurrence/relapse
 H&N pearls
• Know the predictable pattern of CA spread based on primary site
• Necrotic nodes in SCC can be PET negative (contrast enhanced CT or MRI
useful)—cystic nodes may only have thin-rim of uptake
• Look for second primary (upto 20% of patients with H&N malignancy)
• CN XI (accessory) paralysis leads to atrophy of SCM and trapezius muscles
which can have physiologic compensatory uptake within contralateral
scalene muscles
• With vocal cord paralysis, get compensatory uptake within contralateral
cord and also arytenoids
• Vocal cord uptake without arytenoid uptake can be suspicious
• Look for any uptake posterior to arytenoid which can be malignant
CANCER TYPE NODAL DRAINAGE COMMENTS

Nasopharynx Common: II (bilat) and V (bilat) Retropharyngeal node may be the

Uncommon: I first node involved
Oral cavity (FOM) Common: ipsilateral I > II > III
Uncommon: contralateral involvement
Oral cavity Common: II > I > III Occasionally skip mets directly to
(tongue) Uncommon: V and supraclavicular IV
Oropharynx (BOT) Common: II (ipsi>contra) > III (ipsi)
Uncommon: contralateral involvement other
than II
Oropharynx Common: mostly ipsi II > I/III/IV/V Can also involve retropharyngeal
(palatine tonsils) Uncommon: supraclavicular node
Oropharynx (soft Common: II (ipsi>contra) > ipsi III
palate)
Larynx Common: ipsi>contra II and III ipsi IV Level I and V
(supraglottic) Uncommon: I and V
Larynx (glottis) Common: ipsi II and III > ipsi paratracheal
Uncommon: I and V; contralateral

Larynx (subglottic) Common: III and IV

Uncommon: I and V
Pyriform sinus Common: ipsi II/III > ipsi IV/V Can also involve paratracheal >
supraclavicular nodes
 Nodal drainage pattern
• Upper lips drains to level I (also buccal or parotid)
• Lower lips rarely metastasize to nodes
• Anterior oral cavity to level I (+/- lingual node of FOM) while posterior to level I and II
• Oral cavity CA don’t drain into retropharyngeal nodes (while oropharyngeal CA do)
• Tongue cancer can sometimes have skip mets to level IV
• Oropharyngeal CA drain into II, III, and retropharyngeal node (RP node involvement has poor
prognosis with higher locoregional recurrence)
• Nasopharyngeal CA have high incidence of mets; retropharyngeal node (medial or lateral=node of
rouviere) are usually first nodes to be involved along with level II nodes
• Supraglottic and glottic CA drains into II and III
• Subglottic CA drains into III and IV
• Laryngeal CA don’t drain into I and V
• Pre-laryngeal node (Delphian) involvement in laryngeal CA is a poor prognosis (higher rate of
locoregional recurrence)
• Parotid gland is first site of involvement of skin SCCA
• Hypopharynx drains into II and III (less commonly IV); can also involve RP node
• Thyroid CA drains into central compartment (VI=pre/paratracheal), lateral compartment (in this
order IV, III, II), and superior mediastinal (VII)
 Separate dedicated neck
acquisition
• Smaller FOV
• Higher matrix and resolution
• Arms down
• SUV are higher than with standard protocol
 HPV-positive oropharyngeal SCCA
• HPV type 16
• Younger pts
• Usually oropharyngeal (palatine or lingual tonsil)--primary
tumor is smaller than nodes and mets
• Presents early with bulky cystic cervical level II-IV LAD
• Responds better to treatment and has better prognosis than
HPV-neg pts
• But does tend to have distant metastasis and mets to unusual
sites
 Thyroid
• Mean thyroid uptake 1.3
• Focal thyroid uptake 30% CA (recc U/S)
• Focal thyroid uptake SUV>4.2 with hypodense nodule on CT  90% CA
• Diffuse thyroid uptake may be seen w/ Graves or chronic>subacute
thyroiditis (Hashimotos)
• Not sensitive for well-differentiated thyroid CA (papillary/follicular)
• Useful to detect de-differentiated (90% accuracy) thyroid CA when RAI
scan neg and rising TG antigens (>10ng/ml)give thyrogen prior to scan
to improve sensitivity (not req if TG>100)
• Useful for Hurthle cell, Anaplastic CA, and Medullary thyroid CA (with
elevated calcitonin >1000ng/ml; of limited use if <500ng/ml)
• Hurthle cell (92%) > Medullary CA (78%)
• Parathyroid adenoma can have uptake
 MTC
• Medullary thyroid CA
– Primary treatment is surgery
– Consider PET if elevated postop calcitonin
– Calcitonin <150ng/ml  do u/s neck
– Calcitonin >150-500ng/ml  do PET for distant mets (esp
if >1000)
– Even with very high calcitonin, PET scan may be neg
– F18-DOPA has better sensitivity (100% if calcitonin >150)
than FDG (also F-DOPA is good for NET)
 SPN
• Nodule size ≥8-10mm
• Partial volume effect for lesion <1cm (not true for ≥2cm) due to small size and at lung base
due to breathing motion (resp motion under-estimates SUV)
• Visual analysis (rather than max SUV) may be more sensitive for nodule <1.5cm
• Use NAC for subcm peripheral nodules
• >1cm SPN with SUV ≥2.5  PPV for CA is 80%
• >1cm SPN with SUV ≥4.0  PPV for CA is 90%
• High sens 97% but low specificity 78% for characterizing malig SPN >1cm in dia
– S/S=97%/78% (Gould et al. JAMA 2001)
– Accuracy 86% (Coleman et al. JNM 1999)
– Negative PET more accurate than positive PET (FN less common than FP)
• PET is more cost-effective than F/U CT, transthoracic bx or surgery if pre-test risk for CA is
btwn 0.1-0.8 (Dietlein et al. Eur JNM 2000)
• Low to mod pretest prob of CA (btwn 5-60%)—not for very low prob (<5%) or high prob
(>60%)
• Also, useful when there is discordance btwn imaging findings and pretest prob
 SPN
• False neg: well-diff adenoCA (BAC), carcinoid, mucinous CA (low cellular
density)
• False neg rate of 25% for carcinoid (avg SUV in carcinoid is 3.0)—better for
atypical carcinoid (based on necrosis and mitotic activity)
• Low sens for BAC (btwn 10-30%); sensitivity for multifocal BAC is higher
than solitary BAC
• Hamartomas and round atelectasis are generally not FDG avid
• Dual time point imaging (remember progressive tumor FDG uptake up to
2-3hr)
– JNM 2002 Jul;43(7):871-5) : 10% increase over baseline (>2.5max SUV
is 80/94% and increases to 100%/89% w/ dual time)not needed if
baseline SUV<1.0
– Image btwn 90-120min (some same image at 1 and 3hrs)
– 10% SUV increase is significant
 SPN
• PET Sens 91.7% and Spec 82.3%
• CT Sens 95.6% and Spec 40%
• PET greater accuracy than CT for nodule >1cm (JNM vol49 Feb2008)
• Recovery coefficient at 1cm is 50% of true counts in lesion
• <1cm multiple/solitary nodule with perceptible or imperceptible uptake
on PET is not statistically sig (JNM vol48 Jan2007)
• Prevalence of Nodules: atleast 1 nodule seen on 28% of all CT chest; Risk
of CA is ~8% of all nodules
 What if nodule has uptake less than mediastinum??

SIZE VISUAL SUV

<1cm > than mediastinum <2.5 Suspicious

1-2cm < than mediastinum <2.5 Equivocal

(consider close f/u if SUV>1.6)
>2cm < than mediastinum <2.5 Prob b9

CAVEAT:
-SUV can be artifactually low in nodules at lung base due to breathing artifact
-nodules <1cm cannot be diagnosed as b9 by PET even if no FDG uptake
 Bottomline for SPN eval
• If positive  get tissue
• If negative  may continue imaging f/u
 Lung CA
• NSCLC more common than SCLC (10-15%; rare in non-smokers)
• SCLC staging
– Limited stage (treated with chemo+XRT): limited to one hemithorax with or without
contralateral med/supraclav LAD that can all fit in single radiation port
– Extensive stage (treated with chemo only)more common
• NSCLC types
– Squamous (epidermoid) 25-30%central
– AdenoCA 40% (more common in females and non-smokers; also seen in younger pts;
may have EGFR mutation)peripheral
• BAC (adenoCA-in situ better prognosis)
– Large cell 10-15% (grows fast and harder to treat)
• Others
– Carcinoid (better prognosis than both SCLC and NSCLC)
• PET sensitive for both NSCLC and SCLC
• Wedge resection (recurrence 30%; so do more frequent f/u) vs Lobectomy (recurrence
<10%)but 5yr survival is the same for both
 Lung CA
• Routine PET staging in SCLC not warranted (high SUV of >10-20 has poor
prognosis); but useful if contemplating doing XRT for “limited stage” disease
• PET is useful for staging (all stages I-IV), treatment planning (delineate gross tumor
volume GTV), and restaging of NSCLC
• Patients with NSCLC and EGFR (epidermal growth factor receptor) mutation are
treated with TKIs (Tarceva)
• Decrease futile thoracotomy rate by 50%
– Multiple lesions in same lobe=T3b and different lobe=T4
– Any T + any N + M (incld malig eff)=unresectable
– Any T + N3=unresectable
– T4 + any N=unresectable
• PET can reliably distinguish btwn malig (SUV >2.2-2.6) vs b9 pleural effusion
• Can assess tumor vs post-obstructive atelectasis for treatment planning
• PET better than CT in identifying involvement in non-pathologically enlarged nodes
• If PET performed after neoadjuvant therapy (before planned surgery), resolution
of med nodal activity is prognostically good
 Lung CA
• NPV for mediastinal nodal dz is 95% can avoid mediastinoscopy prior to thoracotomy
(Med staging CT S/S=59%/78% and PET S/S=8%/92% Birim et al. 2005)however,
pathologically-enlarged LN w/o FDG-uptake may still need to be bx and positive nodes
on PET should be confirmed with bx prior to excluding surgery as an optioncentral or
upper lobe (esp RUL) tumors, adenoCA, tumors w/ hilar involvement, and tumors with
SUV>10 are likely to have med mets
• PPV for med nodal dz is only 65% due to false pos from inflammatory nodesbx
confirmation needed
• Isolated bilateral hilar uptake can be commonly seen and should be interpreted with
caution (less false positives for upper mediastinal nodes)
• LUL malignancy first drains to AP window node (so if no uptake here, be cautious with
other nodes)
• PET is better than CT for staging mesothelioma (but can miss subtle transdia extension)
• Low uptake in fibrous tumor of pleura
• False positive PET s/p talc-pleurodesis
• XRT pneumonitis may be seen prior to anatomic abnl (linear geographic pattern)
• 4D resp –gated PET
 Bronchogenic CA
• Incidence: AdenoCA>SCC>BAC>Small cell (AFIP)
• Prognosis: SCC>Large cell>BAC>AdenoCA>Small cell
• ≥Stage 3B is unresectable
• Small Cell
– Smokers
– Unresectable
– Paraneoplastic syndromes (hypercalcemia, cushing, SIADH) with oat cell subtypes
– Centrally located (extensive LAD may result in SVC syndrome)
– Staging: “limited dz” (confined to tolerable radiation port incld supraclavicular node, regional
mediastinal, or effusion) vs “extensive dz”
• Non-small cell
– AdenoCA
• Non-smoker women
• Peripherally located
• Subtype=BAC, scar carcinoma
– SCC (epidermoid)
• Smokers
• Centrally located (around airways but not within it unlike small cell)
• May cavitate
• Dysplasiain-situSCC
• Good prognosis (b/c slow growing)
• Subtype=pancoast (superios sulcus tumor) w/ SVC syndrome, horner’s, brachial plexopathy, dysphagia
– Large cell
• Rapid growth
• Peripherally located
 Bronchogenic CA
• AdenoCA 40%
• Sq cell CA 30%
• Small cell CA 15%
• Large cell CA 10%
• BAC 4%
• Carcinoid 1%
 Resectability (old)
• Chest wall invasion
– Rib destruction (not just pleural thickening)
– Chest wall mass
– Vertebral body destruction (<50% may still be resectable)
– Less specific signs: loss of extrapleural fat plane; mass does not move independent of chest wall on dynamic
fluoroscopy; length of contact of mass with chest wall >3cm
• Mediastinal/Pericardial invasion
– May still be resectable as long as there is <90deg encasement of vessels; <3cm contact w/ mediastinal
pleura; no direct invasion of mediastinal structures; no extensive replacement of mediastinal fat
– Less specific signs: loss of fat plane; mediastinal shift; mediastinal pleural thickening
• Tracheal or central bronchial invasion
– Tracheal or carinal involvement is unresectable
– Involvement of central bronchi, however, may not preclude surgery
– CT not sensitive for airway involvement unless see definite airway mass
• Malignant effusion
– Only 66% of actual malig effusion is detectable as such on pleurocentesis
– Nodular thickening of pleura in setting of effusion is suspicious
– Non-malignant effusion has no bearing on staging
• Other things to note
– Location in relationship to pulmonary artery
– Does mass cross any incomplete fissure (i.e. fissure that does not extend to the hila)
– Distance of mass from carina (<2cm)
– Hilar involvement may still be resectable but need to do pneumonectomy instead of lobectomy
Stage IIIB is unresectable
ZONE STATIO
IASLC 2009
DESCRIPTION
(International Association for Study of Lung CA)
BOUNDARIES
N
SUPRACLAVICULAR 1 Low cervical, supraclavicular, Midline of trachea serves as border btwn 1L and 1R.
sternal notch Below lower margin of cricoid; above upper margin of manubrium and clavicles.
UPPER (SUPERIOR 2 R/L Upper paratracheal (adjacent Left lateral border of trachea serves as border btwn 2L and 2R.
MEDIASTINAL) to great vessels) 2L=btwn upper border of manubrium to upper margin of aortic arch.
2R=btwn upper border of manubrium to lower margin where left brachiocephalic vein
intersect
trachea.
3 A/P 3A=Prevascular (anterior From sternal notch to carina.
mediastinal) Prevascular=located anterior to left brachiocephalic vein and within anterior mediastinum
3P=Prevertebral (not left
(retrotracheal) lateral of asc aorta/arch; ant to ant border of SVC).
Prevertebral=located behind eso adj to vertebral body (not adj to trachea).
4 R/L Lower paratracheal Left lateral border of trachea serves as border btwn 4L and 4R.
4L=above upper margin of left main PA (medial to lig arteriosum)—includes precarinal node.
4R=above lower margin of azygos (carina).
AORTOPULMONARY 5 Subaortic (AP window) AP window nodes lateral to lig arteriosum (below inferior margin of aortic arch).
6 Para-aortic (phrenic) Anterior and left lateral to ascending aorta or aortic arch (btwn inf margin of aortic arch and
sup margin of LPA).
SUBCARINAL 7 Subcarinal Underneath carina (above superior margin of left lower lobe bronchus on the left; above
inferior margin of bronchus intermedius on the right).
LOWER (INFERIOR 8 Paraesophageal (below Below carina and adjacent to wall of esophagus (excluding subcarinal nodes).
MEDIASTINAL) carina)
9 Pulmonary ligament Between inferior pulm vein to diaphragm.
HILAR/INTERLOBAR 10 R/L Hilar Adjacent to mainstem bronchi and hilar vessels until interlobar region.
11 R/L Interlobar Between origin of lobar bronchi.
PERIPHERAL 12 R/L Lobar (peribronchial) Adjacent to lobar bronchi.
13 &14 Segmental/sub-segmental Adjacent to subsegmental bronchi.
R/L (peribronchial)
OTHERS Internal mammary; Paravertebral; Paracardiac (epicardiac nodes)
• Size (2cm, 2.1-3cm, 3.1-5cm, 5.1-7cm)
Lung CA staging
•
– Size>7cm (T3)
Location
(NSCLC, SCLC,
• Multicentric tumor (synchronous) of same histology Carcinoids)
– Satellite nodule in same lobe (T3)
– Nodule(s) in different ipsilateral lobe (T4)
– Contralateral lung nodule(s) i.e. intrathoracic met (M1a)
• Aggressive features
– Direct visceral pleural invasion (T2)
– Direct parietal pleural invasion aka chest wall (including superior sulcus tumors), diaphragm, phrenic nerve,
mediastinal pleura, and/or parietal pericardium (T3)
– Invasion of mediastinum, heart, great vessels, carina, trachea, eso, vertebral body, recurrent laryngeal nerve (T4)
• Endobronchial lesion
– Endobronchial lesion not proximal to lobar bronchus (T1)
– Endobronchial lesion ≥2cm from carina or complete atelectasis/post-obstr pneumonitis extending to hilum but
not involving entire lung (T2)
– Endobronchial lesion <2cm from carina or partial atelectasis/post-obstr pneumonitis involving entire lung (T3)
– Endobronchial lesion with involvement of carina (T4)
• Nodal involvement
– N1=ipsilateral hilar or peribronchial
– N2=ipsilateral mediastinal and subcarinal
– N3=contralateral hilar/mediastinal; supraclavicular; scalene
• Malignant effusion i.e. pleural dissemination or pleural nodules (not direct pleural invasion) and/or Malignant
pericardial effusion (M1a)
• Distant (extrathoracic) met (M1b)
EGFR mutation (Tarceva)
Lung lymphoma (BALT etc)
 Talc pleurodesis
• Treatment for recurrent PTX or pleural effusion to obliterate
pleural cavity
• Chemical vs mechanical (surgical)
• Chemical may be done with bleomycin (chemo) or talc
• Talc pleurodesis simulates dense pleural masses which have
intense uptake on PET
 Mediastinum
• Dia crus uptake (R is larger and extends more inferiorly)
• Hyperventilation or hiccups induced dia uptake
• Normal thymic uptake in kids (upto age 30)
• Thymic hyperplasia (as high as 3.8) in adults w/ photopenic clefts (inverted V
shape)
– Thymic hyperplasia is Gallium-positive but Thallium-negative
– So Thallium scan may be useful to differentiate btwn thymic hyperplasia vs thymic tumor
• Thymic uptake lowest right after chemo then increases and peaks at ~10mos and
then decreases over next 1-2yrs
• Thymoma
– SUV>5.0 concerning for thymic CA (not thymoma)
– 15% of pts w/ MG have thymoma
– 50% of pts w/ thymoma have MG
– 27% of pts w/ thymoma will have another malignancy
– Don’t bx thymoma (will get tract seeding or pleural drop mets)
 Heart
• Variable heart uptake (decreased septal uptake also normal variant and
can be due to LBBB)
• >12hr fast, heart switches from glucose to fatty acid metabolism
(generally, fatty acids are primary substrate)
• Elevated glucose levelincreased endogenous insulin increases
myocardial uptake (along with sk muscle and liver)decreased tumor
uptake
• Decreased lateral wall uptake (compared to septum) is a normal variant
for N-13 perfusion PET
• R ventricular uptake minimal unless hypertrophy
• Atrial uptake can be focal and irregular (R atrial uptake seen w/ A.Fib)
• 4 chamber activity w/ dilated heartcardiomyopathy (may be due to
chemo in CA pts)
• Inter-atrial lipomatous hypertrophy uptake w/ brown fat
 Breast
• Dose to breastfeeding infant <1mSv (~0.085mSv)—no need to stop breastfeeding
but close contact w/ infant (breast parenchymal uptake) should be avoided
• Prom peri-implant uptake is normal if recently placed (focal intense uptake
worrisome for implant rupture or adj tumor)
• Glandular uptake normal if mild and diffuse in premenopausal, postmenopausal
on HRT, and lactation
• Uptake is glandular (little if any in the milk), yet, it is best to interrupt
breastfeeding for ~8hr post-injection b/c of proximity issues
• False neg=lesion <2cm (NPV for lesion <2cm is only 50% unless PEM; sensitivity of
93% for lesion <4cm), DCIS, LCIS, lobular CA, tubular CA, ER+ cancer
• False pos= 10% of fibroadenoma; gynecomastia; fat necrosis; mastitis, silicone
injection granuloma; lactation; XRT; post-op
• Breast CA has lower metabolic activity on PET than other malignancies
• Incidental focal breast uptake can represent CA in up to 37% of cases (get
Mammo)
 Breast CA indications for PET
• Inner quadrant dz (risk of IM or supraclavicular node involvement)—esp
upper inner quadrant
• Triple negative (ER-, PR-, Her2/neu-)
• Her2 positive dz
• Large primary tumor
• Young premenopausal
• Suspect mets aka advanced dz T3 or T4 (including evaluate for systemic
involvement in inflammatory breast CA)recurrence likely if CA15-3
>60U/ml
• Equivocal MRI

Prefer to do PET prior to surgery/chemo

 Breast
• No role for screening or eval axillary LN (better for recurrence and mets) Neg PET does
not preclude sentinel node detection or ALN
• Flare-phenomenon after initiating (within 7-10d) Tamoxifen therapy for ER+ (breast
primary and mets respond differently to chemo)
• PET can predict responders to neoadjuvant therapy after only first chemo cycle (using
SUV decrease of ≥50%)need to do baseline before neoadjuvant therapy
• Can get false neg sentinel LNB after neoadjuvant therapy (so if PET has pos nodes ALND
should be done)
• High risk patients: BRCA1/2 mutation, hx of XRT to chest, sig family history
– CA prognosis depends upon primary tumor size, nodal location, metastatic burden, and hormone receptor
status
– High risk for mets =T3 tumor >5cm, triple neg, Ki-67 positive, N2 or N3 dz, inflammatory breast CA
– IM and supraclavicular LN involvement decreases survival
– Mets to liver has worse prognosis
– Triple neg (ER/PR and Her2 negative) have worst prognosis
• CEA and CA 15-3 are used for recurrence detection
• Ki67 is associated with aggressive tumor
• Most common distant mets to bone (can be lytic or sclerotic)
– Sens for PET is 96% (PET is gold standard)
– Sens for BS is 76% (BS may be more sensitive for sclerotic lesions)
 Breast
• Hormone receptor positive ER/PR (estrogen or progesterone receptor)
– 75% of all breast CA are ER+
– 65% of these are also PR+
– ER/PR+ CA are 65% likely to response to hormonal therapies like Tamoxifen (unlike ER/PR- CA
are only 5-10%)
– Tamoxifen has anti-estrogen (prevents recurrence by blocking estrogen receptors) affect on
breast but pro-estrogen effect on endometrium
– Hormonal therapy is generally not done until surgery, chemo/XRT are finished
– Aromatase inhibitors stops estrogen production (but only used in postmenopausal women)
• Her-2 positive
– 20-25% of breast CA over-express Her2/neu protein
– Tends to be much more aggressive and fast-growing
– Herceptin helps reduce risk of recurrence (can try Tykerb if Herceptin fails)
– Herceptin is given along with chemo (but does have risk of heart and lung damage)
• Triple negative
– About 10-15% are triple negative
– Usually these cancers are assoc w/ BRCA1 gene
– Respond well to chemo but overall have poorer prognosis than other types of breast CA
– No targeted therapies
 PEM and BSGI for detection of breast CA

• PEM (higher resolution with 3mCi and 10min imaging time;

immobilized breast; spatial res 1.6mm; CC and MLO; can do
PEM-guided bx) which has sensitivity similar to MR ~90% so
that PEM is an alternative to those pts who cant get MR
• Advantages of PEM: higher spatial resolution, shorter imaging
time, reduced ST attenuation
• Sensitivity of PET and BSGI are comparable
 Breast CA surgery
• Mastectomy has a local recurrence rate of 1% at 10 years
whereas lumpectomy and radiation has a local recurrence
rate of 5-6% at 10 years in node-negative women and 9-10%
in node-positive patients (long-term overall survival is the
same for both procedures)
• Approximately 2% chance of severe lymphedema with SLNB
and there can be injury to the long thoracic, thoracodorsal,
and intercostobrachial nerves causing winged scapula,
inability to raise/lower the arm, and pain/numbness along the
inner upper arm, respectively
 Esophagus
• Upper 2/3rd=SCC (smoking/alcohol) vs Distal eso=AdenoCA (reflux/HH/barett’s)
• Both SCC and adenoCA are FDG avid (but adenoCA at or near GEJ may be infiltrative or mucinous and have
lower FDG uptake)
• Esophageal leiomyomas can be falsely positive
• SUV >4 at GE jct is concerning for pathology (<4 if no reflux; >4 if reflux)
• Not good for diagnosis or locoregional disease (can miss local invasion or regional nodes)PET has poor
sensitivity but high specificity
• Endoscopic ultrasound (EUS) for staging
• Need to differentiate gastrohepatic (resectable; located cephlad and anterior to celiac artery) vs celiac
(unresectable) nodes
– M1a=mets to celiac or cervical LN
– M1b=mets to non-regional LN or organ mets
• PET better than CT for mets or distant recurrence
• False positive with reflux or XRT-related esophagitis (not present until 2wks but lasts for 4-6wks)
• Mets to adrenal, liver, lung, and bone can be seen
• PET sensitive but not specific for local recurrence at anastamotic site
• 2/3rd of recurrence occur within 1st year
 Esophagus
• Baseline PET  Neoadjuvant (chemo/XRT)  do PET after 2wks of
therapy (within 2 wks of XRT to avoid esophagitis) SUV decrease of
atleast 35% identifies responders  if no response, stop neoadj therapy
and proceed to surgical esophagetomy instead (MUNICON trial)
• PET after completion of therapy SUV decrease of 52% is good prognosis
while post-therapy SUV ≥4 is poor prognosis
• Delineation of GTV prior to XRT
• XRT induced esophagitis or ulcer can be falsely positive
 Gastric
• Proximal>distal gastric uptake; pyloric uptake; ring-like uptake
• Unlike eso, detection rate of gastric CA depends upon cell type
– 95% adenoca vs 5% others (carcinoid, lymphoma, leimyosarcoma, SCC)
– 2 subtypes of adenoCA (both assoc with H.pylori)
• intestinal-type (gland-forming; usually distal stomach,elderly pts)
• non-intestinal/diffuse (like mucinous and signet-cell) younger pts with
genetic predisposition
– Non-intestinal-subtypes (Mucinous, signet-cell, etc), MALT (lymphoma), any
early gastric CA have low FDG uptake
• EUS is gold standard and PET can miss locoregional disease, esp perigastric nodes
PET is best for detecting mets when conventional imaging fails; PET optional for
detection of recurrence b/c can miss peritoneal seeding (NCCN)
• Physiologic gastric uptake is diffuse or regional physiologic uptake decreased
with gastric distension with water or oral contrast
• Decrease in SUV by 45% predict responders to neoadjuvant therapy
 GIST
• GIST
– Stomach>SB>>LB
– Origin is intestinal cell of Cajal
– Middle age or older pts who are generally asymptomatic until tumor size >5cm
– High sensitivity and PPV (untreated GIST usually have high peripheral uptake
with central cold areas)
– 95% express c-kit (tyrosine kinase receptor CD117)
– Tyrosine kinase inhibitors like Imatinib (Gleevac) and Sunitinib (Sutent)
– TKI switch quickly off metabolic activity in tumor and these changes can be
seen as early as 24hrs on PET
• Lesions and hepatic mets usually get cystic and hypodense (decrease in HU by
25%) and may even enlarge on CT/MR (confusing)
• Decrease in SUV by at least 65-70% for responders (16% or less for non-
responders) and decrease in absolute SUV <2.5
• Lesions with partial response appear as focal areas of FDG uptake (corresponding
to enhancing nodule on CT) within larger mass
 Colorectal
• Physiologic uptake within LB>SB; cecum/asc colon>sigmoid colon; circumferential anal sphincter
• Diffuse (laxative/scope) vs segmental (colitis/IBD) vs focal (polyp/CA) uptake
• PET can miss pericolic LN involvement (so limited role in assessment of locoregional dz)
• Better than CT for nodal (internal iliac and retroperitoneal) and extra-nodal (liver, lung, bone) mets (but not for
peritoneal implants)
• PET can be helpful to determine feasibility of solitary hepatic met resection (curative surgery) by excluding co-existing
extrahepatic mets
• Also useful for clinically symptomatic patient w/ normal CEA or rising CEA (>10) with negative anatomic workup
• Better than CT/MR for assessing response to local ablative therapy (chemoembo/cryo/RF)
– Focal uptake (rather than peripheral rim uptake) is concerning for residual tumor
– Do PET early (within 2d of ablation) or late (wait 3-4wks after ablation therapy)
• Local recurrence after resection of rectal CA ~1/3rd
• Local recurrence after resection of colon CA ~1/5th
• PET better than CT/MR to distinguish btwn presacral XRT fibrosis vs recurrence/residual
• Flare phenomenon (like breast CA) may be seen after XRT/chemo—so don’t do scan during therapy and wait 2months
after end of therapy
• Hemorrhoids can have increased uptake due to inflammation
• Low rectal cancer are worse; specific value of PET in N-staging of low rectal CA (detects inguinal LN involvement)
• Rectal cancer more commonly bypasses liver for distant mets than colon CA
• For rectal CA, pay attention to mesorectal fascia (any node>5mm in MSF is abnl)
• LAR (low anterior resection) vs APR (abdominoperineal resection=more extensive; ostomy)
• Anal SCC rare but 4th most common malignancy in HIV pts
 HCC
• Physiologic liver uptake can be “homogenously heterogeneous” (adjust SUV range from 0-to-4.5 to
0-to-5 to decreased noise that can simulate lesions)
• FDG uptake in well-differentiated HCC variable due to phosphatase (like RCC) ~50% (but can detect
extra-hepatic disease >1cm)
• HCC have lower uptake than hepatic mets
• PET less sensitive than MRI for detection of liver mets (<1cm)
• Mets, fibrolamellar HCC, and cholangioCA are FDG-avid
• Most b9 hepatic tumors (like hemangioma, FNH, adenoma) are not-FDG avid
• False positives like abscess, nodular lymphoid hyperplasia (pseudolymphoma), sarcoidosis
• Decreased diffuse hepatic uptake with hepatic steatosis (10% decreased)
• Increased diffuse hepatic uptake with cirrhosis and hepatitis (further limits HCC detection)
• PET useful for detecting recurrent HCC only when conventional imaging normal and rising AFP (but
C-11 acetate is better)
• C-11 acetate can image these tumors better than F-18 FDG
– Tumors that accumulate both FDG and C-11 acetate, HCC is favored as diagnosis
• Recurrence after liver transplantation is higher in pts whose HCC was pos on FDG PET
• Biliary tract uptake may be normal if stent in place
• B9 GB polyps can have uptake
• PET can detect GB cancer; cant differentiate from cholecystitis
 CholangioCA
• Risk factors: cholangitis, PSC, choledochocyst, clonorchis
• 95% are adenoCA
• 3 locations:
– Intrahepatic 5-10% PET sensitivity>90%
– Perihilar (Klatskin) 60-70% PET sensitivity <60%
– Extrahepatic 10-20% PET sensitivity <60%
• 4 growth patterns:
– Mass forming (exophytic)85% of these are detected on PET
– Infiltrative (periductal)PET less sensitive for these
– Intraductal (polypoid)
– Mixed
• Partial hepatectomy may be curative
• Important to look for vascular and peri-ductal invasion (better on CT/MR)
• Malignant biliary strictures have higher SUV ~6.8 (as opposed to b9 ~3.3)
• PET is useful for detecting cholangioCA in pts with PSC
 Splenic
lesion eval
Splenic mets
Pancreas mets
 Pancreatic CA
• Elevated serum glucose can result in false neg (BG<120)—sens only 42%controversial
• PET s/s for adeno CA is 94%/90% (less sensitive for periampullary CA 70-80% due to adj physiologic duo
activity)
• 70% of locoregional LN mets can be missed on PET
• Dual phase CECT (arterial phase abdomen only CT before venous phase WB CT) as part of PET/CT can
improve detection of vascular invasion
• EUS is gold standard; PET useful in assessment of indeterminate solid or cystic pancreatic lesion who
cant undergo EUS or have non-diagnostic bx (PET useful for differentiating btwn b9 and malig cystic panc
neoplasm)
• Recurrence is common within 6-12mos after surgery
• Surveillance with CA19-9
• T3 N0 M0 can be resectable while T4 anyN M0 are unresectable
• PET useful for assessment of response to neoadj therapy (~50% decrease in SUV)
• PET ?likely useful for detection of recurrence if elevated CA19-9 but CT neg
• Well-differentiated neuroendocrine tumors are not FDG avid (but all neuroendocrine tumors that are
neg on octreoscan/MIBG are positive on FDG and have poor prognosis)
• False positive=acute pancreatitis (87% of chronic panc is neg on PET), biliary stent, recent ERCP, serous
cystadenoma, retroperitoneal fibrosis
• Focal uptake within suspected IPMN can be indicative of malignant IPMN requiring radical resection (as
opposed to premalignant IPMN requiring limited resection)
• SPEN is also FDG-avid
 Other GI
• Physiologic uptake along biliary stents
• Activity along intrahepatic ducts in cholangitis
• Bowel activity w/in mucosa (not intraluminal b/c no GI excretion)—due to
lymphoid tissue, metabolically active mucosa, smooth muscle peristalsis,
bacterial uptake
• Usually no GB wall or lumen uptake (think acute vs chronic cholecystitis)
• Diffuse spleen uptake equal to or less than liver (splenic uptake increased
w/ G-CSF tx)
• Abnormal splenic patterns: solitary vs multifocal vs diffuse (higher uptake
than liver)
• PET ~75% sensitive for carcinoid (size>1.6cm)—better for atypical
carcinoid (based on necrosis and mitotic activity)
Pelvic LN involvement by various CA
 Neuroendocrine tumors
• FDG PET was most helpful in patients with
negative Octreotide scintigraphy or in tumors with
high proliferation index (Ki-67)
• NETs with positive Octreotide uptake and
negative FDG uptake have the best prognosis, and
vice versa
• PET ~75% sensitive for carcinoid (size>1.6cm)—
better for atypical carcinoid (based on necrosis and
mitotic activity)
 Adrenal
• Focal adrenal uptake=adenoma (lipid rich or poor), mets, ACC,
myelolipoma, pheochromocytoma, oncocytoma, hemorrhage
• Diffuse adrenal uptake=hyperplasia, infection like histo/TB
• Adrenal uptake concerning if corresponding to focal mass or bilateral
nodularity (mets)
• Low avidity of adrenal mets if
– <1cm
– Low-FDG-avid primary tumor like carcinoid
– Lesion with hemorrhage or necrosis
Adrenal evaluation
 RCC and Bladder CA
• Physiologic urinary excretion limits evaluation
• FDG is filtered (GFR) thru kidneys
• RCC uptake is variable (only 50-70% have sig uptake)—b/c of phosphatases
(similar to liver)
• 50% sensitive for primary and ~100% for mets (others say that primary and metastatic
renal tumors have similar degree of FDG uptake)
• False pos=oncocytomas, AML, peri-renal fat, segmented ureteral uptake
with peristalsis
• PET uptake in indeterminate renal cyst is very specific for malignancy
• PET not useful for detecting bladder CA
 Ovary
• FDG uptake in ovaries=physiologic uptake during ovulation and early luteal phase of
menses (schedule PET a few day after onset on menses); corpus luteal cyst;
endometrioma; serous cystadenoma; thecoma
• Any FDG uptake in post-menopausal ovary should be considered suspicious for
malignancy
• Not sensitive for mature teratoma, mucinous CA, and clear cell adenoCA of ovaries
• Ovarian CA is staged surgically (laparotomy)
• PET does not add value to disease localized within pelvis but marginally useful for extra-
pelvic dz (peritoneum and LN)
• Useful for stage III or IV for detection of distant mets can avoid futile surgery by
upstaging
• PET useful for detection of recurrence for
– Symptomatic pts with normal CA-125 ≤35 (but CECT just as good as PET) Normal
CA-125 can fail to identify ~50% of pts with recurrence where foci are <2cm
– Also, when other modalities neg and CA-125 elevated (≥30) may rise 3-6mos prior
to clinical evidence for recurrence
 Peritoneal mets
• Peritoneal mets are seen with GI and ovarian malignancies
• PET can miss small peritoneal or omental implants
• Improved sensitivity if ascites is present
• PET cannot replace second-look laparotomy
• Pay special attention to:
– Serosal surface of liver/spleen
– Omentum
– Paracolic gutters (esp right)
– Medial to cecum
– Sigmoid mesocolon
– Btwn bladder and uterus or btwn uterus and colon
 Cervical CA
• Value of PET is yet to be fully defined (values of PET is diagnosing
extrapelvic dz)
• PET s/s for cervical CA is 70-90%/90% (adjacent bowel and bladder activity
limits detection of locoregional nodal mets); any gyn malignancy <1cm,
sensitivity is reduced to 30-50%
• 95% SCC and <5% adenoCA
• Cervical CA spreads by
– invasion of cervical stroma into adjacent parametrium/uterine body/vagina (upper 2/3
vs lower 1/3)
– then via lymphatics to pelvic/para-ortic/supraclavicular nodes
– hematogenous spread occurs in more advanced disease
• Status of para-aortic LN directs therapy
• Involvement of supraclavicular LN has poor prognosis
• SUV>10 of primary lesion or pelvic nodes has poor prognosis
 Endometrial CA
• Physiologic uptake during midcycle (ovulation) and menses (schedule PET a week before or a
few days after start of menses) and also post-partum
• Value of PET is yet to be fully defined
• PET s/s for endometrial CA is 90-95% (any gyn malignancy <1cm, sensitivity is reduced to 30-
50%)
• B9 fibroids may have mild FDG uptake (leiomyosarcoma should have moderate to intense on
PET)
• Postmenopausal endometrial mild uptake can be normal (1.7 +/- 0.5)
• 2 histological subtypes
– Type-I estrogen-assoc CA (75-80%; well-diff; endometroid adenoCA)
– Type II estrogen-independent CA (aggressive, un-diff; serous or clear-cell; typically
develop in atrophic endometrium; elderly pts or after XRT)
• Treatment is total hysterectomy with BSO and pelvic/para-aortic LND
• PET useful for detecting distant mets that obviate surgical staging
• SUV>12 of primary lesion assoc with poor prognosis
• Detection of tumor recurrence limited with clinical/lab markers (20% of pts have
asymptomatic metastatic disease)PET can be useful for local recurrence or distant mets
detection (but not included in NCCN guidelines)
 MEAN SUV
PREMENOPAUSAL Proliferative 2.6 +/- 1.1
Ovulatory 3.7 +/- 0.9
Secretory 2.5 +/- 1.1
Menses (1st 3days) 5.0 +/- 3.2
POST MENOPAUSAL On hormones 1.1 +/- 2.6
Not on hormones Shouldn’t have
uptake

Endometrial cancer has high uptake (SUV 11.2 +/-5.9).

Endometrial hyperplasia usually has mild uptake.
 Uterine lesions
LESION FDG UPTAKE
• Fibroid Variable (usually low but can be high; less
uptake in postmen than premen women)
• Leiomyosarcoma mod to hi (2.4 to 10.2)
• Adenomyosis mild
• Endometrial hyperplasia mild
• Endometrial CA hi (11.2 +/-5.9)
• Cervical cancer hi

BOTTOMLINE: cant tell btwn fibroid and leiomyosarcoma!

 Prostate
• Sensitivity ~50-65% (due to slow-growing well-differentiated cells)
• Even aggressive prostate CA can be negative on FDG PET
• False positive=BPH, prostatitis, post-op scarring
• BS more sensitive than FDG PET for sclerotic mets
• NaF PET more s/s than traditional BS for prostate mets to bone
• C-11 acetate/choline/methionine better than FDG PET
• Patient with flare phenomenon on BS can be better assessed with PET (no
flare on PET)
• FDG PET indicated in recurrent and metastatic disease when
– PSA>4 (or increasing 0.2 per mo)
– Advanced dz (hi grade/hi stage)
– neg BS
• FDG PET better than Prostascint in detecting distant mets in setting of
rising PSA
 Testis
• Physiologic testicular uptake ranging in SUV from 1.0 to 6.0
(mean 2.7)decreases with age
• Seminomas are FDG-avid but variable uptake for non-
seminomatous germ cell tumors
• Mature teratomas can be falsely negative
• PET is very sensitive in differentiating residual tumor from
fibrosis in lesions ≥3cm
 MM
• Monoclonal proliferation of plasma cells (BM)  excess IgG (paraproteins)  end organ
damage (MM)
• 50-70yo
• Lab tests: monoclonal gammopathy (M-spike), Bence Jones proteins in urine, anemia (Hgb),
hypercalcemia, renal failure (elevated Cr)
• Imaging: lytic lesion
• Treatment: thaliamides, bortezomib (protease inhib), chemo, steroids; for
advanced/aggressive disease stem cell transplantation
• MM is typically preceded by: SPB (solitary plasmacytoma of bone), MGUS (monoclonal
gammopathy of undetermined sig), SMM (smoldering/asymptomatic MM)
• SPB=lytic bone lesion with malig plasma cells usually seen within pelvis or vertebral body;
treated with XRT (if truly solitary); 80% subsequently develop MM within 5yrs of tx
• MGUS=detected incidentally on labs; progression to MM is slow but long term (~1% per year
for next 15yrs)
• SMM=very similar to MM but no evidence of end-organ damage (conversion rate of 10% per
year for the 1st 5years)
• POEMS=polyneuropathy, organomegaly, endocrinopathy, myeloma (sclerotic lesion not very
FDG avid), skin changes
 SPB MGUS SMM MM
Monoclonal proteins <3 <3 ≥3 Present
Marrow plasma cells <10% <10% ≥10 to <60% clonal Present
End-organ damage (see None None None Present from MM cells
below)
Annual MM progression 15-20% 1-2% 10%

END ORGAN DAMAGE

C Hypercalcemia (Ca>11.5)
R Renal insuff (Cr>2)
A Anemia (Hgb<10)
B Bony lytic lesions
DURIE-SALMON PLUS staging PET/CT or MRI
MGUS All negative

Stage IA (smoldering MM) Negative or single plasmacytoma

Stage 1B (MM) <5 focal lesions (mildly diffuse BM involvement)

Stage 2A/B (MM) 5-20 lesions (moderately diffuse BM involvement)

Stage 3A/B (MM) >20 lesions (severely diffuse BM involvement)

A= Cr<2 + no extra-medullary disease

B= Cr>2 or extramedullary disease
 MM
• Image MM from vertex of skull thru atleast knees
• MM can have variable (usually moderate) uptake on PET
• Many patients demonstrate sig heterogeneity in FDG uptake in their own MM lytic
lesion
• PET more sensitive than skeletal survey and as sensitive as MRI
• PET better than MRI for determining active vs inactive disease
• For all pts with MGUS and most pts with SMM, there is no role of PET until clinical
evidence for progression (PET useful for evaluating progression of MGUS or SMM
which may progress to MM)
• In SPB, PET is used to detect additional bone lesions (which would preclude
localized XRT for therapy and use chemo instead)
• In MM, PET is useful for treatment response and detect recurrence
• Look for extra-medullary lesions (uncommon; seen in LN, spleen, liver; almost any
organ can be involved)—marker for aggressive disease and generally don’t
respond well to traditional treatment
• PET not sensitive for sclerotic lesions of POEMS
 MM
• Limitations:
– LN mets if volume<80mm3, <50% involvement, and size
5mm
– Uveal melanoma
– Small cerebral mets
– Small pulm nodules
 Treatment planning in MM
• No BM transplant planned
– 6 cycles of chemo  PET for response assessment
• BM transplant planned
– 3-4mos of combo chemo in prep for transplant  PET for response
assessment
– If decrease in SUV by 50%  transplant
– If SUV not decreased by 50%  additional/alternative chemo followed
by transplant vs experimental tx protocol
MILD MOD SEVERE
 PET report in MM
• Number and extent of lytic lesions
– <5
– 5-20
– >20
• SUVmax and extent of FDG uptake
• Overall assessment of marrow replacement by MM
– Mild diffuse
– Mod diffuse
– Severe diffuse
• Any pathologic fx, epidural extension, or cord compromise
 Melanoma
• 5 important factors for staging
– Primary tumor thickness/depth (>4mm)
– +/- ulceration
– Number of regional/satellite/in-transit LN mets vs distant LN mets
– Mets
• M1a=mets to skin/subcut or distant LN
• M1b=mets to lungs
• M1c=all other visceral mets (MR better than PET for liver and brain lesions)
– Elevated serum LDH level (poor prognosis)also useful for monitoring tx response
• High pre-test likelihood of distant mets if
– Trunk or upper arm lesion
– Breslow thickness >4mm
– Ulceration
– High mitotic rate
• Reasons to include skull and LE on WB PET
– Primary melanoma in H/N or LE or known mets to these regions
– Clinical suspicion for widespread or aggressive disease
 Melanoma
• PET sensitivity for detecting melanoma lesion >1cm is ~95%
(80% for lesions 6-10mm and 20% for lesions <5mm)
• PET not useful for stage I or II disease
• PET useful for palpable regional LAD (clinical stage III),
macroscopic LN mets (stage IIIb), and suspected distant mets
(stage IV)
• Treatment is wide surgical excision of primary lesion with
SLNB
• PET cannot replace sentinel node mapping or LND
• PET limited for detection of small brain, liver, lung lesion
• Check NAC PET to improve sensitivity of detecting skin and
subcutaneous lesions
 Melanoma
• Melanoma mets to brain are T1 hyperintense on MRI
• Primary uveal (intra-ocular) melanoma is usually detected late and is commonly
assoc with liver mets 50% (solitary hepatic met with ocular melanoma may be
surgical candidate)
• Rarely melanoma can arise in iris, choroid, sinonasal mucosa, or eso
• Cervical melanoma lymphatic drainage is notoriously unpredictable (id of true
sentinel node difficult)
• On rare occasion, can get mets to thyroid
• Interferon-α (IFN- α) commonly used as systemic chemo can cause
hyperstimulation marrow pattern along with false positive hypermetabolic LAD
(pseudolymphoma); cessation of this therapy can also cause rebound marrow
stimulation with diffuse splenic uptake
• Beware of FDG extravasation related LN activity
• Poor prognosis if lung mets
• Cardiac mets not uncommon but usually detected postmortem
• Melanoma is one of the most common mets to bowel
• Vagina is a known site of primary melanoma
 Sarcoma
• Sarcoma and rhabdomyosarcoma have variable uptake (sensitivity 80-90%); 98% of
ST sarcomas are FDG-avid
• SUV cutoff ≥2.0 for int/hi grade ST sarcoma (cant reliably tell btwn low grade ST
sarcoma vs b9 lesion; Use SUV cutoff of 5.2 for ST sarcoma vs b9 fluid collection
like hematoma/abscess)
• Useful for guiding bx, assess prognosis, tx planning, response to chemo, recurrence
(may be useful for staging is large primary tumor aka AJCC T2 or high grade aka
FNLCC grade2-3)
• Lung is predominant site of mets followed by bone and other ST (myxoid or round
cell liposarcoma like retroperitoneal and bone mets)
• Can help detect response (>35%) to neoadj therapy since tumor size generally
does not change (pt with large int and hi grade sarcomas generally get neoadj
chemo and sometimes XRT)
• Poor prognostic factors: deep tumor location; size>5cm; locally recurrent disease;
proximal location in extremity; involved surgical margins
• Describe: maxSUV (corresponds to histologic grade), FDG heterogeneity (poor
prognosis), necrosis (guide biopsy; assess response to therapy), ST extension, skip
lesion, distant mets (like lung and bones)
• Heterogeneous uptake (with necrotic areas) infer high grade tumor
 Sarcoma
• ST and Bone sarcomas
• Examples
– Fibrosarcoma
– Liposarcoma
– MFH
– Leiomyosarcoma
– Rhabdomyosarcoma
– Angiosarcoma
– Kaposi’s sarcoma
– Hemangioendothelioma
– Chondrosarcoma
– Osteosarcoma
– Ewing’s sarcoma
– Malig gaint cell tumor
– Chordoma
 MSK
• Most fractures do not have substantial uptake >2-3mo
• Normal bone marrow uptake is low (unless red marrow due to anemia, post-chemo recovery,
BM stimulation by G-CSF/cytokines, myeloprolif d/o)
• Increased BM uptake 5d-1mo after GCSF (confirm w/ increased splenic uptake) but some say
ok to scan >1mo
• Chronic B9 vert compression fx SUV<2; pathologic compression fx>2 (usually~4)
• Decreased osseous uptake (but increased regional ST uptake) w/ XRT
– 1d after XRT increased uptakedecreased uptake by day 9normalized uptake by 30d
• Vertebral hemangiomas are cold
• Mild to moderate uptake can be seen in degenerative geodes, schmorl’s node, exostosis
• Decreased BM uptake s/p XRT (similar to BS)
• Flip-flop phenomenon of treated BM disease
– Cold mets and hot (post-chemo) normal marrow reactivation
• Osteosarcoma
MSK
– Osteosarcoma freq metastasizes to secondary bone sites in 10-20% of patients
– 50% reduction in metabolic tumor volume (size and SUV) is significant
– PET useful in patient with prosthesis or s/p XRT to look for recurrence
– Diffuse uptake in stump up to 18mos post-amputation
– PET less sensitive than BS for detecting bone mets from osteosarcoma
– CT better than PET for detecting lung mets from osteosarcoma
• Ewings
– pts 5-25yo; pelvis, metadiaphysis of long bone, or ribs; large ST component; onion-skin periosteal rxn; 30%
mets to bone, lungs
– FDG-avid (sens 90%)
– PET better than BS for bone mets (and also shows LN involvement)
– PET not reliable for determining responders to neoadj therapy in Ewings
– Ewings has more profound response to chemo than osteosarcoma
– 80-90% reduction in metabolic tumor volume (size and SUV) is significant
• Chondrosarcoma
– Surgery is primary tx (refractory to XRT/chemo)
– Uptake can be low to moderate (mirror histologic grade)
– Some use cutoff of 2.0 for detecting chondrosarcoma arising from osteochondroma
• Use SUV cutoff of 0.81 for differentiating liposarcoma from lipoma
• MFH is PET avid
• B9 lesions like osteomyelitis, paget’s, and fibrous dysplasia are also avid on PET
• False neg=plasmacytoma, low-grade chondrosarcoma, myxoid tumor
 Bone mets
• Sensitivity of PET for bone mets depends upon primary tumor
• PPV for bone mets is 98% when PET and CT are concordant; PPV is 61% if
PET is positive and CT is neg; PPV is 43% for solitary PET positive bone
lesion (need MRI eval)
• Bone lesion in pts >40yo can be secondary to mets or MM
• Any skeletal lesions with SUV >2.0 potentially may be malignant
• PET good for lytic mets and BS good for sclerotic mets (esp prostate)
• Need both PET and BS for bone mets from breast CA
• PET better than BS for bone mets from nasopharyngeal CA
• Bone lesions <3mm have limited detectability on PET
 ST uptake
• Brown fat uptake (USA-fat=uptake in supraclavicular area)
– generate heat in response to cold esp in young thin females
– supraclavicular, mediastinum around vessels, inter-atrial septum, azygoeso recess,
paraspinal, intercostal, perinephric
– Infradiaphragmatic uptake usually seen in conjunction w/ supradiaphragmatic uptake w/
brown fat
• Diaphragmatic crus uptake with increased resp efforts (right crus larger than left; exclude
retrocrural node) or hiccups
• Intercostal muscle uptake with smokers/COPD (coughing)
• Teres minor horizontal uptake may be asymmetric
• Extraocular muscle uptake due to eye movement
• Skeletal muscle uptake
– Anxiety related neck uptake
– Focal in muscle strain or exercise
– Diffuse: recent insulin (also diffuse heart uptake) or recent meal
• Catheter insertion site, ostomies, surgical wound, stents/grafts, stump (upto 18mos post-
amputation), pressure sore (decub ulcer)
• Mild uptake in subcutaneous injection granulomas, fat necrosis panniculitis, sebaceous cyst
• Moderate surgical site uptake upto 2mos
• Truncation artifact due to larger PET FOV (60cm) compared to CT (50cm)
 Skin and ST mets
• Women with skin metastases (have the following distribution
in decreasing order of frequency of primary malignancies)
– breast, ovary, oral cavity, lung, and colorectal
• Men with skin metastases (the distribution is as follows)
– lung, colorectal, oral cavity, kidney, breast, esophagus,
pancreas, stomach, and liver
• Mets to ST tissues
– lung, kidney, colorectal (unlikely for breast, prostate,
thyroid which love bone mets)
 Skin CA
• Cutaneous T cell and B cell lymphoma (CTCL,
CBCL)
• Merkel cell carcinoma (MCC)
• Basal cell carcinoma (BCC)
• Squamous cell carcinoma (SCC)
• Melanoma
• Rare adnexal neoplasms: eccrine, apocrine,
sebaceous, and hair follicle tumors
B9 vs malig spine compression fx
HIGH MODERATE LOW

Osteosarcoma MM (variable) Chondrosarcoma

Ewings Fracture Osteochondroma

Mets CMF Enchondroma

Giant cell tumor Fibrous dysplasia Osteoid osteoma

OM Plasmacytoma
 Others
• WM (Waldenstrom’s Macroglobinemia)
– Indolent NHL with elevated IgM
– >60% with WM demonstrate FDG-avid dz
– Sig PET positivity may demonstrate poor prognosis
• EG
– PET better than CT/MRI/BS for detection and response to therapy of EG in
bones and ST
• Neuroblastoma
– Neuroblastoma is FDG-avid but MIBG is still superior than PET for BM
involvement and for detection of residual dz
• Pheo/Paragangliomas
– FDG PET only 70% detection rate for pheo (useful for MIBG negative pheo)
– F-DOPA PET is better
– For neuroendocrine tumors, FDG PET works well when SRS (somatostatin
receptor scintigraphy with In-octreoscan is neg)PET with Ga-68
DOTATOC/NOC is best
 Myeloid disorders
• Myeloid disorders
– Myeloproliferative disorders (MPD) =excessive clonal proliferation (get
organomegaly)
• Polycythemia Vera (PV)
• Essential Thrombocytopenia (ET)
• Myelofibrosis (MF)=can be primary or part of other MPD
• CML
– Myelodysplastic disorders (MDS) =ineffective cell production (basically
preleukemia; usually in pts >70yo; can be primary or secondary to chemo/XRT;
usually don’t get organomegaly) NOT IMP IN RADIOLOGY
• Refractory Anemia and subtypes
• Refractory Cytopenia and subtypes
– AML (MPD or MDS can lead to AML)
• Lymphoproliferative disorders
– HD
– NHD
– Plasma cell dyscrasias
– CLL
MPD
MPD
MPD
 MPD
• PV
– Excessive RBC
– Splenomegaly
– P32 treatment
– Increased BM uptake
• ET
– Low platelets
– Splenomegaly
• MF
– Can be primary or assoc with other MPD
– Massive HSM + extramedullary hematopoiesis (intense FDG uptake)
– Osteosclerosis (low BM uptake)
• CML (increased BM uptake)

Note: all can transform into AML (increased BM uptake)

 PET/CT in MPD/MDS
• Increased BM uptake in MPD (except MF) and
MDS
• Also increased BM uptake in Leukemia (CML,
AML)
• MF
– Increased uptake within massive HSM and
extramed hematopoiesis
– Low uptake in BM with osteosclerosis
 Mastocytosis
• More common in kids (2-15yo) than adults (~55yo)
• Excessive mast cells
• 2 forms
– Cutaneous
– Systemic (+/- cutaneous)=organ failure some characterize this as
myeloproliferative dz
• Systemic Mastocytosis
– Skin
– BM fibrosis (diffuse osteosclerosis like MF; can have lytic lesions)
– GI (ascites, LAD, omental thickening, peptic ulcers, SB thickening)
– Liver/spleen (HSM)
– Pulm nodules (rare)
• Mast cell Leukemia
• PET/CT may have uptake within cortical bone and BM
 Leukemia
• Acute • Chronic
– All ages – Usually adults
– Sudden onset – Insidious onset
– Immature >30% blasts – Mature cells
– Prominent anemia, – Mild anemia, thrombocytopenia
thrombocytopenia – WBC count increased
– WBC count variable – Prominent LAD and
– Mild LAD and splenomegaly splenomegaly
 Leukemia
• Imaging findings
– Acute Leukemia
• Organomegaly due to leukemic infiltration
– HSM (splenomegaly milder than chronic leukemia; ALL>AML)
– Nephromegaly
– Testicular infiltration (may also involve epididymis)
– Thymic infiltration (esp T-cell ALL)
– Bones: lucent metaphyseal bands (leukemic lines); permeative or moth eaten bone lesions; osteopenia;
periostitis; vertebral compression fx
– CNS involvement (leptomeningeal involvement with ALL and AML)
– Skin rash
• LAD (milder than chronic leukemia; ALL>AML)
– Chronic Leukemia
• Splenomegaly (more so than acute leukemia; CML causes massive splenomegaly)
• LAD (more so than acute leukemia)
• BM involvement
• Skin rash
 Leukemia
• Acute (rapid, progressive with blast cells)
– ALL
– AML
• Chronic (insidious, less aggressive with mature
cells)
– CLL
– CML
 Acute Leukemia
• Nearly all childhood leukemia are acute
• ALL
– Most common peds malignancy (2-5yo)
– Also seen in adults (all ages esp >45yo)
– CNS involvement common (so consider intrathecal chemo and/or
brain XRT)
– Organ infiltration can occur (see previous slides)
• AML
– Most common acute leukemia in adults (~50yo)
– Can be caused secondary to chemo/XRT for other malignancy
– Extramedullary infiltration much less common than ALL
 Chronic Leukemia
• Seen in adults
• Can involve blood, BM, spleen, and LN
• CLL
– Most common chronic leukemia
– Similar to low grade SLL lymphoma (not very FDG-avid)
– >60yo adults
– Tx not curative and is delayed until sx develop
– Prolymphobastic leukemia, Lymphoma leukemia (aka leukemia develops after
lymphoma), Hairy cell, Sezary syndrome are also characterized under CLL
– PET/CT only useful to detect richter transformation to higher grade lymphoma like
DLBCL
• CML
– Less common than CLL
– 45-55yo adults
– Significant splenomegaly
– Philadelphia chromosome
– Tx with Imatimib
– Has indolent phase followed by either accelerated phase or blast phase
 Infx/Inflammation
• It is not uncommon for persistence of metabolic activity while anatomic findings related to inflammation have already
resolved
• Vasculitis (see next slide)
• Fibrosing mediastinitis and Retroperitoneal fibrosis
– Variable uptake (higher during active fibrosis)
• TB/Sarcoidosis
– PET better than Ga-67 for sarcoidosis
– Can differentiate btwn active vs inactive dz
• OM
– Useful for peripheral OM in non-postop and non-DM; also useful for vertebral OM
– Uptake in simple fracture should sig decrease or resolve by 8weeks
– In chronic b9 vertebral fx, SUV <2 (pathologic fx SUV>2)
– For spodylodiskitis use SUV cutoff of >3
– Better than 3phase BS or Ga-67 for chronic OM esp in axial skeleton (negative PET excludes chronic OM)
– In-111-WBC better for prosthesis eval (PET uptake common at head-neck of hip prosthesis and does not imply
infx)
• FUO (defined by criteria by Durack and Street)
– Better than In-111-WBC or Ga-67
– Can detect CA and infection/inflammation
– Good for IBD (esp in ped who have less physiologic bowel activity), large vessel vasculitis, granulomatous disease,
vertebral OM, chronic OM in axial skeleton, infective endocarditis
THA loosening vs infx PET criteria
 Systemic sarcoidosis
• CNS: neurosarcoidosis involves basilar leptomeningeal enhancement (aseptic meningitis);
intramedullary spinal cord lesion; diabetes insipidus due to hypothalamic involvement (loss of post
pit bright spot); Cranial neuropathy (esp bilateral facial nerve palsy); optic nerve and chiasm can also
be involved
• EYES: bilateral parotiditis + bilateral lacrimal enlargement (panda sign); acute uveitis
• NECK: posterior triangle LAD (more common than anterior)
• MED: 1-2-3 Right paratracheal and bilat hilar; egg-shell calcifications
• CARDIAC: infiltrative CM
• LUNGS: perilympahtic micronodules; upper lobe predominant fibrosis; PMF; cavitation
• ABD: splenic granulomas larger and more common than liver; simultaneous involvement of spleen +
liver favor sarcoidosis over lymphoma; minimal hepatomegalt if any; LAD in retrocural station favors
lymphoma over sarcoidosis; gastric antrum involvement
• GU: hypercalcemia and nephrocalcinosis; interstitial nephritis; epididy
• TESTIS: bilateral epididymal involvement (+/- testicular involvement; isolated testicular involvement
is unlikely)
• BONES: lace-like lesions in phalanges; in long bone can be permeative; arthralgias; may have bone
marrow involvement
• MUSCLES: intramuscular soft tissue nodules (low signal centrally on all MR sequences with
peripheral high T2 and enhancement)
• SKIN: erythema nodosum legs (acute); lupus pernio face (chronic; assoc. w/ lung fibrosis)
 PET not useful for…
• Diabetic foot infx
• Prothesis eval
• Vascular graft infection
• IBD
• Endocarditis
 Vascular
• Active atherosclerosis, vasculitis, and thrombosis (acute or chronic)
• Thrombophlebitis also has uptake
• Uptake related to activated macrophages
• Mural thrombus within aneurysm may actually be photopenic
• Vascular access devices like collagen plug may have focal uptake
• Graft infection
– S/S=91%/64%
– Normal mild diffuse uptake w/in vascular graft (may persist for years)look
for focal or heterogenous uptake instead
– Look for focal uptake w/ focal CT abnormality like dirty fat (diffuse uptake
may persist for years)
– Vein graft vs Synthetic graft (Dacron for large vessels vs Gore-Tex for
medium vessels)
• Physiologic FDG uptake within vein graft declines over time
• Physiologic diffuse FDG uptake within synthetic graft
(Dacron=inhomogenous; Gore-Tex=homogenous) persists for years and
remains unchanged
 Vasculitis
• Sensitivity 77% and Specificity 89-100%
• Accumulation of FDG w/in arterial wall reflects vasculitis
• Better at detection of vasculitis affecting large or medium sized arteries (like Gaint cell arteritis and
Takayasu’s)
• Decreased sensitivity for diagnosis if on steroid therapy and no baseline comparison
• With CRP<12 or ESR<12, sensitivity of <50%
• Visual score:
– Grade 0=Arterial wall not visible
– Grade 1=wall<liver
– Grade 2=wall=liver
– Grade 3=wall>liver
• Quantification:
– SUV of the arterial wall and ratios to liver or blood pool (right atrium)
– SUV cutoff 1.3 (sensitivity of 90.9% and specificity of 88.8%)
– Some say 1.0 (thoracic aorta to liver ratio) S/S of 89 and 95% for GCA
– Ratio to liver better than max SUV of arterial wall
• IV contrast may artificially increase arterial wall SUV and ratios
• Not reliable for diagnosis of temporal artery inflammation
• Can be used to f/u therapy
HIV
 HIV
• HIV-related lymphadenopathy (b9)
– HIV infection related FDG uptake in lymphoid tissue follows
predictable anatomic sequence from upper to lower torso
– 3 phases
• Acute phase=increased FDG in H&N nodes
• Mid phase=generalized LN with increased FDG (including cervical/axillary/inguinal)
• Late phase=increased FDG uptake in abdominal LN (esp mesenteric/ileocecal nodes)
and colon
– Also, diffuse spleen uptake greater than liver
– High overlap in mean SUV btwn HIV-related LAD and malig LN
– Degree of FDG uptake in LN correlates with viral load (plasma viremia)
and inversely with CD4 (see next slide)so if image pt with viral load
of 0, chance of false positive is low
• Lipodystrophy
– HAART (highly active antiretroviral therapy) results in peripheral fat
loss, abdominal obesity, HLD, hyperinsulinemia, increased C-peptide,
insulin resistance and impaired glucose tolerance
– This is seen in 60-80% of pts on HAART
– PET shows increased FDG uptake in subcutaneous adipose tissues (see
image)
 HIV
• Infection
– Different pathogens affect HIV+ pts at different stages of disease
– TB can occur at any stage!
– CD4 200-500 (TB, salmonella, shigella, corynebacterium)
– CD4<200 (TB, cyptosporidia, PCP)
– CD4<60 (TB, CMV, atypical mycobacterial)
• Malignancy
– 3 common CA
– Kaposi (mucocutaneous ie nose/mouth/genitalia/skin and extra-cutaneous sites like GI and later
lungs)
– Lymphoma (B-cell NHL, Burkitts)B-cell lymphoma involves unexpected sites like BM, CSF (less
involvement of GI)
– Anogenital CA (invasive cervical CA)
• Multi-centric Castleman Disease (MCD)
• Issues:
– Lymphoma presents in similar ways to TB (can be difficult on PET if you just focus on LAD or
pulmonary findings)—consider serial scans
– Biopsy is the only reliable way to distinguish btwn infection vs malignancy (PET may help guide
biopsy)
– PET is useful to distinguish btwn CNS lymphoma (avid) vs less-avid infection (like Toxo and TB)
 PET in peds
• Prep
– Arrange for sedation
– Consider bladder cath to avoid rad contamination and reconstruction artifacts from spontaneous
voiding
– Fast 4-6hrs
– Use lidocaine cream to decrease pain with starting IV (peds nurse)
– FBG<7mmol/L
– Time inj close to feeding time  feed 30min post-inj
– Warm blankets to minimize brown fat
• Protocol
– Weight-based dosing (dose range 0.10-0.14mCi/kg, min 1.0mCi)
– Prefer PET only (without CT) with radionuclide attenuation correction if available
– Low dose CT (80kVp and 30mAs)
– Wrap patient in sheets to avoid motion
– WB imaging for neuroblastoma and sarcoma
• PET findings to be aware of in children
– More extensive distribution of hematopoietic marrow than in adults (abnl if > than liver)
– High FDG uptake in the thymus, in the adenoids, and tonsils (uptake in waldeyer ring peaks at 6-8 yo)
– High FDG uptake in the skeletal growth centers
– More issues with brown fat
 PET in peds
• Indications
– Lymphoma
– Sarcoma
– Neuroblastoma
– Osteosarcoma
– Ewings sarcoma
– Germ cell tumor
– Hepatoblastoma
– Wilms
– NF type I (malig transformation of plexiform neurofibroma)
• Others
– Alveolar rhabdomyosarcoma (has propensity to mets to unusual ST sites)
– EG
 PET in pregnancy
• Informed consent (consider PET after 1st trimester)
• Reduced dose 5-9mCi
• Prefer PET only (without CT) with radionuclide attenuation correction if
available
• Hydrate (500cc water oral + 500cc IV NS) during uptake period
• 10mg Lasix diuresis 15min after injection
• Void at least 4 times during uptake
• Consider foley placement
• F-18 FDG crosses placenta and accumulates in fetus (myocardium)
• Fetal dose exposure 1.1-2.4mGy for various trimesters in pregnancy
Response Criteria for Solid Tumor
Baseline

1cycle

4cycles
Baseline

1cycle

4cycles
 RESPONSE CRITERIA
• ANATOMIC eval
– WHO: Cancer 1981
– RECIST 1.1 (CT): EJ of Cancer 2009

• METABOLIC eval
– Solid Tumor
• EORTC: EJ of Cancer 1999
• PERCIST (PET/CT): JNM 2009 (based of SULean)
– Lymphoma
• Revised (IWG=international working gp) Response Criteria (Cheson
criteria): JCO 2007
• International Harmonization Criteria (IHC): JCO 2007
• Deauville criteria (interim PET in HD)
 RECIST 1.1 for CT (use this)
• Target lesions are selected at baseline (selection based on size and reproducibility
of measurements)
• Measurable lesion
– Lesions with longest dia ≥1cm
– LN with short dia ≥1.5cm (LN <1cm are considered normal)
– 2 lesions per organ
– 5 total lesions
• Non-measurable lesion
– Skeletal lesion (unless there is a ST component)
– Ascites, pleural effusion
– Lymphangitic spread
– Leptomeningeal dz
– Inflammatory breast dz
– Cystic/necrotic lesion
– Lesion within irradiated area
– Mass not confirmed by imaging
 Eval of target lesion
• EVAL OF TARGET LESION
– CR=disappearance of all target lesions & decrease in size of all
pathologic LN to be <1cm
– PR= ≥30% decrease in sum of all target lesions
– PD= ≥20% increase in sum of all target lesions + 5mm absolute
increase in sum of all target lesions
– SD=neither PR or PD
• EVAL OF NONTARGET LESION
– CR=disappearance of all non-target lesions and normalization of all
tumor markers
– SD=persistent of all non-target lesions and/or maintenance of tumor
marker above normal limits
– PD=appearance of one or more new lesions and/or unequivocal
progression of existing lesions
 Pitfall of RECIST 1.1
• Tumor response in GIST (Choi criteria)
– Choi criteria=10% decrease in unidimensional size or 15%
decrease in CT attenuation
• Paradoxical increase in lesion size s/p therapy with
antiangiogenesis agents or tyrosine kinase inhibitors
due to hemorrhage or necrosis (often seen in liver
tumors like HCC or mets from GIST or melanoma)
• Cavitation of lung lesion
RECIST 1.1
PERCIST
• Minimum SUV change ≥20%
• Baseline scan
– More important for solid tumor
– Also, important for low-FDG-avid lymphoma
• Quantitative assessment important to assess interval change
– Interim PET during therapy: SUV decrease ≥30-50% assoc w/ good prognosis
– End-of-therapy PET: SUV change at least 30% (visual assessment is sufficient)
• Careful with false positives on interim or end-of-therapy PET (consider biopsy
confirmation)
• Mixed response usually not seen with Lymphoma (can be seen with solid tumors)
• MRU (minimal residual dz): consider short term f/u in 3mos
• Tumor response can lag for extra-nodal dz in lymphoma
Lymphoma response

Response criteria (*use this)

 Lymphoma
• PET is great for HD (regardless of histologic subtypes like MC>NS>LP)
• PET is great for certain NHL (variable sensitivity depending upon
histological subtypes)
– high grade NHL like DLBCL/Burkitt’s are high avidity (exception is
peripheral T-cell lymphoma where PET has high sensitivity for nodal
and non-cutaneous nodal sites but low sensitivity for BM and
cutaneous sites)
– Low grade NHL like SLL/CLL are generally low avidity (exception is
follicular lymphoma which is very FDG avid)
– Good sensitivity for nodal MZL (rare) while poor sensitivity for extra-
nodal MZL or MALT (most common)
• Of extra-nodal MZL, Gastric MALT may have no uptake while pulmonary MALT and
MALT with plasmacytic features have uptake
• Not so good for low grade NHL
– Exception is low-grade Follicular lymphoma is very FDG-avid
– Good for detecting transformation of any low-grade to higher grade
(richter transformation)
 Lymphoma
• PET useful for pre-tx staging and restaging after completion of chemo/XRT
• Interim PET ok in HD (research trials for certain NHL)
• Organ response lags behind LN in lymphoma after treatment
• S/S=90-96%/94-99% (CT=80%/80%)
• PET accuracy >15% higher than CT
• CNS lymphoma: FDG 100%, Tl-201 44% accuracy (Erez et al JNM 2006)
• Suspect splenic involvement (if uptake > liver; unless G-CSF)
• PET is superior to Ga-67 for lymphoma eval
• Focal uptake posterior ilium make be secondary to BM biopsy
• High NPV for PET during or after tx in HD
• Relapse usually recurs at regions of previous disease seen on baseline scan
(abnormalities on f/u PET outside these area should be interpreted with
caution)
• Minimal Residual Uptake (MRU)
– In HD, count this as negative for residual disease
– In early stage (I or II) NHL, count this is as negative for residual disease
– In later stage (III or IV) NHL, count this as positive for residual disease and continue f/u
• Neg PET after salvage chemo in patients with relapsed/refractory disease
predicts response to autologous stem cell transplantation (ASCT)
 Sensitivity of PET
Hodgkin’s
Excellent

NHL

High to int grade Excellent (variable for low)

DLBCL, Follicular(int-hi), MC Excellent
SLL, Peripheral TC Fair
MZ Poor for extranodal (but good for nodal)
 Lymphoma (HD and NHL)
Sens Spec
Nodal CT 88% 86%

PET/CT 94% 100%

Extra- CT 50% 90%

nodal
PET/CT 88% 100%

Schaefer NG. Radiology. 2004; 232:823-829.

 Lymphoma

PET/CT PET/CT CT CT
SENSITIVITY SPECIFICITY SENSITIVITY SPECIFICITY

NODAL 94% 100% 88% 86%

EXTRANODAL 88% 100% 50% 90%
(BM and organ)
 Lymphoma
• Low FDG avid lymphoma require baseline scan prior to therapy (to assess
feasibility of PET for response assessment)
• HL and aggressive NHL (like DLBCL, angioimmunoblastic T-cell, NK/T-cell,
anaplastic large cell, Burkitt’s) are FDG avid (exception is low grade
Follicular lymphoma which is also avid)
• 35% of Marginal zone lymphoma (better detection of nodal than extra-
nodal MZ) including gastric MALT lymphoma may have no FDG uptake
(whereas Lung MALT lymphoma is usually FDG avid)
• Low avidity for SLL/CLL
• T-cell lymphoma are frequently primarily extra-nodal or involve extra-
nodal sites for which PET is useful for eval
• PET useful for detection of transformation (Richter transformation) of low
grade lymphoma to higher grade (SUV>13)
 Lymphoma
• Staging (Ann Arbor classification)
– Number and location of nodal sites (above/below diaphragm)
– Extranodal involvement
– BM involvement
– Presence or absence of B (systemic/constitutional) symptoms
• B-cell stain with CD-20 and T-cells stain with CD-3 (pathology staining)
• Specificity of PET for BM involvement is high; but sensitivity not high enough
to replace BM bx (those with heterogenous involvement, PET can detect BM
involvement when bx is negative)
• Interim treatment response assessment after 1-4 cycles of chemo for HL (not
recommended for NHL)  use Deauville criteria
– PET can detect tx failure with HL
– In sig subsets of pts with NHL, interim positive PET is false positive
– Ongoing trials (PETAL and IVS) for interim PET in DLBCL (SUV cutoff of 66% after 2 cycles)
• Restaging after completion of therapy  use IHC criteria
– Good prognosis if PET negative (complete remission is more reliable in DLBCL and HL than
follicular lymphomas and other low-grade NHLs)
• Surveillance PET not recommended b/c high rate of false positives
 Tip for reporting (SNM annual meeting)

• Oncologist from Houston

– No routine surveillance PET/CT (do CT instead)—unless symptoms or
+ve markers
– Rituximab results in false positive PET early on and becomes true
negative after completion of chemo/rituximab
• R-CHOP (R=rituximab or rituxan) is standard of care for NHL q3wks (+/-
Neupogen/Neulasta)
– PET/CT not useful for f/u or treatment response for DLBCL NHL (false
positives)
 Tip for reporting (SNM annual meeting)
• Ask for baseline PET/CT (avid or not ?)
• Cant use SUV cutoff to discriminate btwn indolent and aggressive subtypes
• LN involvement
– Single gp vs multiple gp
– Same side of dia vs both above/below dia
– Retrocrural nodes are considered above dia
• Extranodal involvement
• Treated indolent lymphoma may recur even after >1.5-2y
• Treated aggressive lymphoma usually does not recur after >1.5-2y
• Transformation
– Bx hottest node
– Low SUV are unlikely to be transformed
– Mix of warm and hot nodes (2-3x higher)
 Tips for reporting continued…

-PET Complete response

END OF THERAPY Consider Bx

+PET

Interim –PET Good prognosis

DURING THERAPY Bx before sending for intensified therapy

Interim +PET
vs salvage therapy vs stem cell transplant
 Dr Robert Bridwell
• Solid tumor (cannot assess PET w/o pre-therapy baseline scan) vs Lymphoma (not true for
lymphoma)
• STAGING: initial prior to start of therapy
• EARLY RESPONSE TO THERAPY: prefer after 1-3cycles of chemo (before traditional 4cycles) for
both HD and NHL
– CMR (complete metabolic response)better prognosis and 88.8% long-term clinical
remission
– PR (partial response including MRU minimal residual uptake) or PD
(progression/worsening dz)entails poor prognosis and shorter PFS (progression free
survival) DO SERIAL OR STACKED PET/CT (some oncologist may consider early ASCT
autologous stem-cell BM transplant to improve EFS or event free survival)unlike
lymphoma, for solid tumor need to wait longer for post-chemo eval
– Extranodal dz (like solid organ or BM dz) can lag in response
• LATE RESPONSE TO THERAPY (RESTAGING): wait 6-8wks after completion of chemo
• MRU (minimal residual dz): post-tx inflammation vs residual dzrecommend surveillance
• ASYMPTOMATIC SURVEILLANCE: generally not recommended and not reimbursable
– May be useful for anyone who has anything but CMR on early response PET/CT
– Anyone who was initially a PR partial response but was CR complete response only after
end of chemo
– Anyone who has morphological residual mass on CT after successful treatment
 Dr Robert Bridwell
• Advantage of PET over CT
– Extranodal dz (BM or organ involvement)
– S/S of 96%/94% and PPV of 90%
• Splenic involvement patterns
– Diffuse (non-focal)
– Solitary
– Multi-focal
• Clinical impact rate of PET/CT is ~20-40%
• Any equivocal PET may be repeated in 3mos
• “Mixed response” usually not seen with lymphoma (rather
seen with solid tumors)
 Lymphoma s/p RIT
• s/p Zevalin or Bexxar
• Pre-therapy 12wk post-therapy24wk post-therapy
• Metabolic response may be gradual with continued decline in max SUV
btwn 12 to 24wks
• Use IWC-PET criteria (international workshop criteria including PET)
• Those who respond at 12wks have longer “overall survival”
• If progression, tend to see new sites rather than recurrence at old sites
 IHC
• International Harmonization Project/Criteria
• FDG PET is strongly recc before treatment in pts with routinely FDG avid
lymphomas (such as DLBCL and HL)
• Treatment response should be assessed 6-8wks after completion of
chemo
• Quantification of SUV not necessary (visual assessment is sufficient)
Harmonization criteria
Cheson criteria 2007
Revised Response Criteria for Malig Lymphoma (Cheson criteria 2007)
 HOW PET AFFECTS THE CT FINDINGS
CR (complete res) -if PET +ve pre-tx, a residual mass of any size is permitted if PET –ve
-if PET –ve pre-tx, all LN and masses must be normal size
PR (partial res) -if PET +ve pre-tx, scan should be +ve in at least one previously
involved site
-if PET –ve pre-tx, standard CT criteria should be used
SD (stable) -if PET +ve pre-tx, PET should be +ve at prior sites with no new areas
involved
-if PET –ve pre-tx, no change in size of previous lesions by CT
PD (progression) -if PET +ve pre-tx, should be PET +ve at PD
London/Deauville score for HD for
interim PET evaluation
 Deauville score for HD
• Interim PET (after 2 cycles) evaluation only
• Visual scoring using Deauville score
– Scores 4 and 5 are considered positive for metabolically active dz
– Scores 1, 2, and 3 are metabolically negative (for score 3 get concurrence of a second
observer)
– New lesion (compared to baseline PET) = score 5 (if there is also progression of dz on
existing lesions)
• If baseline PET available, then calculate % max SUV change (comparison
with baseline PET) for most intense lesion with decreased >66% is
considered favorable response (despite D-score)
– Find lesion with most intense uptake on both PETs and remember that lesion may not be
the same of both PETs
– Now use these lesions to calculate % change in max SUV
– Decrease >66% is considered favorable response (even if Deauville score is bad)
• Tips
– New lesion in setting of improved existing lesion is probably not lymphoma
– Focal marrow uptake in setting of improved existing lesions is also probably not
lymphoma
– Diffuse liver or spleen uptake is probably not lymphoma
 Deauville score
On the baseline study, the most FDG-avid lesion was [describe type/location
of lesion] at slice position [___], measuring [A x B] cm and with maximum
standardized uptake value (SUV) of [x].

On the current study, the most FDG-avid lesion is [describe type/location of

lesion] at slice position [___], measuring [A x B] cm and with maximum SUV
of [y].

The percentage decrease in maximum SUV from baseline is [z] % .

Impression
The PET findings indicate [no/persistent] metabolically active disease based
on the qualitative London/Deauville criteria.
 Deauville criteria
• Complete response (CR) was defined as disappearance or
reduction of FDG uptake to levels equal to liver uptake at
documented sites of disease as seen on baseline scans
(Deauville score 1-3)
• Partial response (PR) was taken as persistent FDG activity
greater than that of liver (Deauville score of 4-5)
• Stable disease (SD) was persistence of FDG activity at all initial
sites
• Progressive disease (PD) was taken as uptake at a new site
with score 4-5
Lymphoma

comprehensive
 HD and NHL
• Lymphoma (lymphoid) differs from leukemia (lymphoid or myeloid)
– Tumor cells not in peripheral blood
– Disease not usually centered in bone marrow
– “Lymphoma” is a general term for hematopoietic solid malignancies of the lymphoid
series
– “Leukemia” is a general term for liquid malignancies of either the lymphoid or the
myeloid series
• Malignancies of the lymphoid series are considered to be different from those of the myeloid
series
– Therefore, a lymphoid malignancy arising after diagnosis of a myeloid malignancy (or
myelodysplastic or myeloproliferative disorder) would be considered a subsequent
primary
– However, a myeloid (aka BM dz) malignancy diagnosed after a previous lymphoid
malignancy would not count as a subsequent primary
• 60% NHL and 40% HD
– B-cell malignancy arising later in the course of a patient previously diagnosed with a T-
cell malignancy would be considered a subsequent primary
– However, a T-cell malignancy diagnosed later in the same patient would not
be considered a subsequent primary (think transformation?)
 Hodgkins Disease
• Seen in young pts (20-30s) and small peak around age 60
• Usually involves cervical and mediastina nodes and spreads “contiguously” (does not skip)
nodal stations
• HISTOLOGIC SUBTYPES “RYE classification” (not as important as staging)
– 95% Classical HL (has reed-sternberg cells)
• 4 subtypes: Nodular Sclerosis (most common), Mixed cellularity, Lymphocyte-
depleted, Lymphocyte-rich
– 5% Lymphocyte-predominant HL (no reed-sternberg cells)
• Ann Arbor staging (applies to both Hodgkins and ND lymphoma)
– Stage I-IV
– Each stage subdivided into A vs B categories (B has constitutional/systemic symptoms
like fever/unexplained wt loss/drenching night sweats)
• Prognosis
– Early-stage favorable (stage I-II with no unfav factors) vs Early-stage unfavorable (stage I-
II with unfav factors)
• Unfavorable factors= mediastinal bulky disease (≥10cm), B symptoms, >2-3 nodal
sites, ESR≥50
• Treated with XRT to affected areas
– Advanced disease (stage III-IV)
 Ann Arbor Staging (for HD)
STAGE I 1 LN region on same side of O Localized involvement of 1
dia R extralymphatic organ/site
STAGE II ≥2 LN regions on same side O ≥1 LN region + 1 extralymphatic
of dia R organ/site on same side of dia
STAGE III LN involvement on both sides of dia
+/- localized involvement of 1 extralymphatic organ/site
+/- spleen involvement
STAGE IV Disseminate/mutifocal O Isolated extralymphatic organ
involvement of ≥1 R involvement with distant
extralymphatic organ/site (nonregional) LN involvement
+/- LN involvement

BASICALLY BONE MARROW

INVOLVEMENT!!

A No systemic/constitutional symptoms present

B Unexplained fever >38C; drenching night sweats; or wt loss >10% of body
wt (within 6mos prior to diagnosis)
London/Deauville score for HD for
interim PET evaluation
 Deauville score for HD
• Interim PET (after 2 cycles) evaluation only
• Visual scoring using Deauville score
– Scores 4 and 5 are considered positive for metabolically active dz
– Scores 1, 2, and 3 are metabolically negative (for score 3 get concurrence of a second
observer)
– New lesion (compared to baseline PET) = score 5 (if there is also progression of dz on
existing lesions)
• If baseline PET available, then calculate % max SUV change (comparison
with baseline PET) for most intense lesion with decreased >66% is
considered favorable response (despite D-score)
– Find lesion with most intense uptake on both PETs and remember that lesion may not be
the same of both PETs
– Now use these lesions to calculate % change in max SUV
– Decrease >66% is considered favorable response (even if Deauville score is bad)
• Tips
– New lesion in setting of improved existing lesion is probably not lymphoma
– Focal marrow uptake in setting of improved existing lesions is also probably not
lymphoma
– Diffuse liver or spleen uptake is probably not lymphoma
 Deauville score
On the baseline study, the most FDG-avid lesion was [describe type/location
of lesion] at slice position [___], measuring [A x B] cm and with maximum
standardized uptake value (SUV) of [x].

On the current study, the most FDG-avid lesion is [describe type/location of

lesion] at slice position [___], measuring [A x B] cm and with maximum SUV
of [y].

The percentage decrease in maximum SUV from baseline is [z] % .

Impression
The PET findings indicate [no/persistent] metabolically active disease based
on the qualitative London/Deauville criteria.
WHO CLASSIFICATION
WHO CLASSIFICATION continued…
AGGRESSIVE INDOLENT
 Non-Hodgkins Lymphoma
• Specific histologic subtype more important than staging (as apposed to HD)
• Unlike HD, more likely to involve extralymphatic organs (other than LN) like stomach, lung, salivary glands, etc
• Histologic subtypes (90% B-cell and rest T-cell/NK)
– B-cell (90%)
• DLBCL (diffuse large B-cell lymphoma)—most common (30% of all NHL)
• Follicular Lymphoma—2nd most common (20% of all NHL)
• SLL/CLL* (SLLymphoma is similar to CLLeukemia)
• MZL* (Marginal zone lymphoma)
– Splenic MZL
– Extranodal MZL of mucosa-associated lymphoid tissue (MALT lymphoma)
» Gastric MALT (1/3)
» Non-gastric MALT
– Nodal MZL (rare)
• MCL* (Mantle-cell lymphoma)
• Bukitt’s lympoma
• AIDS-related B-cell lymphoma
• Primary cutaneous B-cell lymphoma
• Hairy-cell leukemia
• Lymphoplasmocytic lymphoma (Waldenstorm’s macroglobulinemia)
 Non-Hodgkin’s Lymphoma
• Histologic subtypes
– T-cell/NK (10%)—poorer prognosis than B-cell lymphoma and have
frequent extranodal involvement
• Peripheral T-cell lymphoma (PTCL)*
• Adult T-cell leukemia/lymphoma (ATLL)
• Lymphoblastic lymphoma (similar to ALL acute lymphoblastic
leukemia)
• Cutaneous T-cell lymphoma (Mycosis Fungoides and Sezary
syndrome)
• Extra-nodal NK/T-cell lymphoma (nasal-type)
• T-cell prolymphocytic leukemia (T-PLL)
– Post-Transplant Lymphoproliferative Disorder (PTLD)

*=Not very FDG avid

 Cotswolds modification of Ann
Arbor Staging of NHL
STAGE
I Single LN gp

II Multiple LN gps on same side of dia

III Multiple LN gps on both sides of dia

IV LN + extranodal organ/site OR multiple extranodal sites

X Bulky >10cm

E Extranodal extension or single isolated site of extranodal dz

A/B B symptoms: fever>38C or drenching night sweats or wt loss >10% of body wt

 NHL grading
• Aggressive or high-grade (60% of NHL)—more aggressive but often curable
– “Lymphoma Brings Death Period”
• Lymphoblastic lymphoma
• Burkitt’s
• DLBCL
• Peripheral T-cell
• Indolent or low-grade—slow growing but present later and often recur
– Follicular lymphoma
– All the M’s (mantle-cell, marginal zone, MALT)
– SLL
 DLBCL
• Most common subtype of NHL (40%)
• Aggressive (usually involves organs other than
LN)
• R-CHOP = Rituxan (Rituximab) + chemo
• Chemo + XRT if disease is localized
• FDG-avid
 Follicular lymphoma
• 2nd most common subtype (20%)
• Indolent but no cure
• May transform into more aggressive subtype
(like DLBCL)
• Chemo, monoclonal ab (Zevalin), and/or XRT
• FDG-avid even though it is low-grade
 Mantle cell lymphoma
• >60yo
• LN, BM, spleen, and GI
(eso/stomach/intestine)
• Chemo may not be effective
 Marginal zone (MZL)
• Indolent
• Nodal vs Extranodal vs Splenic
– 70% Extra-nodal MZ (mucosa-associated)=aka
MALT (usually involves stomach; treated for
H.Pylori; can also be seen with Sjoren’s dz)
– 20% Splenic MZ= involves spleen and LN;
splenectomy performed
– 10% Nodal MZ=rare; involves LN
 MALT
• Extranodal Marginal Zone lymphoma of
mucosa-associated lymphoid tissue (MALT)
• Most commonly involves stomach (1/3) but
may also occur in lung, thyroid, breast, skin,
salivary gland, or eye
• Lung MALT (see next slide)
• Gastric MALT pts are treated for H.Pylori
• Seen in pts with autoimmune d/o likely Lupus,
RA, Sjorgrens
Lung MALT (BALT)
 SLL
• Small-cell lymphocytic lymphoma (SLL)
• Closely related to CLL (chronic lymphocytic leukemia)
– CLL and SLL are different manifestations of same disease
• CLL=abnormal lymphocytes in BM and blood
• SLL=abnormal lymphocytes predominantly in LN
• Indolent
• Most common adult leukemia in western countries (rare in east asia)
• PET/CT not useful in CLL unless using it to guide bx if richter
transformation to DLBCL (NPV 97%)
• For PET/CT assess for LAD and HSM
– Partial response: decrease in LAD, hepatomegaly, or splenomegaly
≥50%
– Progression: increase in LAD, hepatomegaly, or splenomegaly ≥50%
 Burkitt’s
• Very rare
• Aggressive (but often curable)
• 2 forms
– Endemic (EBV in African children’s jawbones)
– Sporadic
– Immunodeficiency-related (HIV)
• In US, most commonly presents as mass in abdomen
Waldenstrom’s Macroglobulinemia
• Lymphoplasmacytic lymphoma (if secrete protein in blood,
referred to as WM)
• Indolent
• elevated IgM
• Involves LN, BM, and spleen
• >60% with WM demonstrate FDG-avid dz
• Sig PET positivity may demonstrate poor prognosis
 Peripheral T-cell lymphoma
• Aggressive
• >60yo
• Tx similar to DLBCL
• Not FDG-avid
 Adult T-cell lymphoma/leukemia
• ATLL (rare)
• Associated with retrovirus infx with HTLV-1 (human T-cell
lymphotropin virus) similar to HIV (endemic in Japan and
Caribbean)
• Only 2-5% of pts w/ HTLV-I may develop ATLL (some may have
Leukemia or Lymphoma, or both)
• Involves bone and skin
• Poor prognosis
• Treated with chemo (does not work well) +
acyclovir/interferon-alpha
 Lymphoblastic lymphoma
• Aggressive but curable
• Young adults
• Similar to ALL (acute lymphoblastic leukemia)
• When located mainly in LN  LL
• When located mainly in blood or BM  ALL
 Extranodal NK/T-cell lymphoma,
nasal-type
• Rare in US/Europe (more common in asia and
Hispanic communities)
• Children and adults
• Involves nasal and sinuses (may also involve
trachea, GI, testicles, or skin)
• Chemo does not work well
 Mycosis Fungoides
• Rare
• MF (mycosis fungiodes) is primary cutaneous T-cell
lymphoma which involves skin and nodes and in
advanced disease can have visceral involvement
• SS (sezary syndrome) is a leukemic variant of MF with
skin lesions, LAD, and circulatory peripheral blood
sezary cells
• Higher SUV suggest Large Cell transformation
 NHL treatment
• Most common initial tx= CHOP
– Cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine, and
prednisone
– May add Rituximab (monoclonal ab that targets CD20 on B-cells)—for DLBCL
• XRT for localized disease
• Immunotherapy
– Unlabeled Monoclonal ab (like Rituximab)
– Radioimmunotherapy (RIT) like Zevalin and Bexxar
– Vaccines (for low-grade lymphoma; prevents recurrence after tx)
• Stem-cell/BM transplantation
– Stem-cell transplantation is better term than BM transplant since we replace
stem cells in blood not actual BM
– Pretreated with high dose chemo and/or total body irradiation (TBI)
– 2 types: allogenic (ALLO) vs autologous (AUTO)
– Used for aggressive or recurrent NHL
– High risk for myelodysplastic syndrome which can also lead to acute myeloid
leukemia (AML)
Cheson 2007
Revised Response Criteria for Malig Lymphoma (Cheson criteria 2007)
Response assessment w/ PET
Concerns about assessing 18FDG uptake in
malignant tissue:

Visual: subjective

Standardized Uptake Value (SUV): semi-

quantitative

Kinetic analysis: quantitative

 RECIST CT criteria

• CR = disappearance of all target lesions

• PR = 30% decrease in the sum of the longest diameter

of target lesions

• PD = 20% increase in the sum of the longest diameter of

target lesions

• SD = small changes that don’t meet above criteria

 RECIST CT criteria
‘Target’ lesions
• All measurable lesions up to a maximum of five
lesions per organ, and 10 lesions in total
• Unidimensional measurement of largest dia
• Measurable lesion >2cm (>1cm by CT)
• Sum of the longest diameter (SLD) of all of the target
lesions
 RECIST
(Response Eval Criteria in Solid Tumors by NCI)
CR Complete disappearance (@ ≥4wks)

PR ≥30% decrease in SUV from baseline (@ ≥4wks)

SD (stable dz) Neither PR nor PD

PD (dz progression) ≥20% increase in SUV or new lesions

Criteria does not take into account change in HU of the lesion

NOTES
-Remember any change in SUV ≥20% is significant
-A negative PET implies a certain amount of tumor cell death (btwn 2-10 log units of tumor cell)
IWC+PET 2005
 Revised IWC+PET 2007
Revised response criteria for malignant lymphoma
Cheson et al. Journal of Clinical Oncology, Vol 25, No 5 (Feb 10), 2007: pp. 579-586
 Revised IWC (IWC PET) 2007
(international workshop criteria for lymphoma)

CRu=Complete Response unconfirmed; OS=overall survival; PFS=progression free survival

 Richter’s Transformation
• Development of aggressive non-Hodgkin's lymphoma (most
commonly DLBCL) or Hodgkin's lymphoma in patients with
chronic lymphocytic leukemia (CLL)
• Occurs in approximately 3% to 11% of patients with CLL
• Rapid clinical deterioration with fever in the absence of
infection, progressive lymph node enlargement, and increase
in serum lactate dehydrogenase
• Confirmed with bx
• Sites of abnormal FDG uptake with an SUVmax of greater than
5 are considered to be highly suggestive of Richter
transformation (?some use max SUV >13 as RT likely and <6 as RT unlikely)
Cases
Brown fat Cervical lymphoma
Brown Fat (anerobic glycolysis) Cervical nodal lymphoma
 USA fat
CT PET FUSED
 FLIP FLOP SIGN

Pre-treatment Post-GCSF
GCSF stimulation (diffuse BM and spleen)
Diffuse lymphoma or leukemia can mimic BM stimulation by chemo or GCSF

Smooth homogenous spleen (>liver) and BM uptake favors BM stimulation assoc w/ chemo/GCSF.

HSM with heterogenous uptake (liver=spleen) and heterogenous “salt and pepper” BM favors leukemia/lymphoma.

Heterogenous “salt and pepper” BM (look at prox femur and shoulder) favors diffuse marrow mets.
Variable normal cardiac uptake

FBG=97 FBG=169
FDG layers on top of IV contrast
within bladder

Flip patient over and do both supine and prone imaging to find bladder CA
Arterial injection
Bladder CA
Bilateral adrenal hyperplasia
Lung CA (non-avid)
Lung CA (avid)
Lung CA
Lung CA and scarring
Lung CA and LN met
CA Granuloma?
Low-grade NHL
FLIP FLOP
SIGN
Spine met
NHL met
High Grade

Low Grade
Tumor recurrence in XRT bed
Internal mammary node
Ovarian CA met
Brain mets
Hodgkin’s Lymphoma (spleen)
Warthin’s tumor
Left vocal cord paralysis
R mandibulectomy with recurrence
posterior to muscle flap
Lymphoma after 2cycles of chemo
Before 1 month after XRT

Lymphoma
 Hodgkin’s

Pre-chemo

Post-chemo
(2cycles)
Diffuse large B-cell after 1cycle of chemo
Peripheral T-cell lymphoma s/p 3cycles of chemo
NHL
 T1 Gad

F/U
Follow up
Atherosclerotic uptake AAA
Infected AAA graft
Mycotic pseudoanuerysm
Tumor thrombus
Prosthesis infx
Solitary node, no breast CA
Lymph node classification
Midline prevasc or retrotracheal
are considered ipsilateral
 3P=posterior

3A=anterior
LEVEL KNOWN AS DESCRIPTION
1 Highest mediastinal Nodes above left brachiocephalic vein as it
crosses trachea
3A Prevascular
3B Retrotrach/Prevertebral
2 Upper paratracheal Btwn left brachiocephalic vein and upper margin
of aortic arch
4 Lower paratracheal Below upper margin of aortic arch

5 AP window or subaortic

6 Para-aortic Pre-aortic (asc aorta)

7 Subcarinal

8 Paraesophageal Below carina

9 Pulm ligament nodes Along lung bases

10 Hilar
 Important info to include
• Size <3cm or >3cm
• >2cm or <2cm from carina or involves carina
• Pleural effusion
• Invasion of lobar bronchus
• Invasion of chest wall, pericardium

• Lobectomy vs pneumonectomy
– Transfissural growth
– Invasion of main or upper/lower lobe bronchus
– Pulm vascular invasion
 Location
Level1 Submandibular, submental

Level2 IJ from skull base to carotid bifur

Level3 IJ below carotid bifur to omohyoid

Level4 IJ below omohyoid

Level5 Posterior triangle

Level6 Adjacent to thyroid

Level7 Tracheo-eso groove and sup mediastinum

 Probable source
Level1 Oral cavity, submandibular gland

Level2 Nasopharynx, Oropharynx, parotid, supraglottic

larynx
Level3 Oropharynx, Hypopharynx, supraglottic larynx

Level4 Hypopharynx, subglottic larynx, eso, thyroid

Level5 Nasopharynx, oropharynx

Level6/7 Thyroid, larynx, lung

Bilateral Soft pallet, tongue, epiglottis, nasopharynx

 Cervical nodal staging (TNM)
• Number of nodes:
– 0, 1, >1
• Size:
– <3cm, 3-6cm, >6cm (largest dimension)
– Level I and II (jugulo-digastric) <15mm
– Retropharyngeal <8mm (located medial to medial margin of carotids at skull
base)
– All other <10mm
• Side of neck involved:
– Ipsilateral, contralateral, bilateral
• Necrotic (hypodense on CT w/ foci of T2 bright on MRI)
• Extranodal spread
– Irreg margin
– thick enhancing rim
– Spiculated
– Fat stranding
– Encasement of vessels
– Will require XRT
 AJR nodal classification
• Level I
– Submental and submandibular nodes bounded by posterior margin of submandibular
gland and inferiorly by hyoid bone
• Level II
– Upper jugular nodes (lateral to medial margin of carotid, anterior to posterior margin of
SCM, superior to inferior margin of hyoid)
• Level III
– Middle jugular nodes from hyoid bone to inferior margin of cricoid cartilage
• Level IV
– Lower jugular nodes from inferior margin of cricoid cartilage to superior margin of
manubrium
• Level V
– Posterior triangle nodes (posterior margin of SCM and anterior border of Trapezius)
– A=above inferior margin of hyoid
– B=below inferior margin of hyoid (above level of clavicle)
• Level VI (aka visceral nodes)
– Anterior compartment nodes from hyoid to superior margin of manubrium (btwn
carotid sheaths on each side)
• Level VII
– Upper mediastinal node (below suprasternal notch)
 Cervical LN
• Zone 1
– Below the jaw
– 1A=submental (btwn bellies
of digastric muscles w/in
submental triangle)
– 1B=submandibular (anterior
and lateral to submandibular
gland; between anterior and 1A 1B

posterior bellies of digastric

muscles)
 Cervical LN
• Zone 2
– From skull base inferiorly along IJ and
spinal accessory chains
– Above the level of hyoid bone
– Posterior edge of submandibular gland
to posterior edge of SCM
– 2A=IJ chain (adj and anterior to IJ vein)
– 2B=upper spinal accessory chain
(posterior to IJ vein and separated from
it by fat plane)
 Cervical LN
• Zone 3
– IJ chain btwn hyoid and cricoid
• inferior to level of hyoid
• Superior to inferior border of
cricoid cartilage
– In other words, lateral to larynx
– Anterior to posterior edge of SCM
– Drains glottis, subglottic,
hypopharyngeal spaces
 Cervical LN
• Zone 4
– IJ chain btwn cricoid to thoracic
inlet
• inferior to inferior border of
cricoid cartilage
• Above thoracic inlet (first rib
and manubrium)
– Posterior margin of SCM
– Supraclavicular nodes involve
zones 4 and 5
– Easily missed on CT or MRI (PET
very useful)
– Rarely involved alone
Cervical LN
• Zone 5
– Posterior cervical chain (posterior triangle)
– Posterior to posterior edge of SCM
– Draw line across posterior edges of bilateral
SCM
– Supraclavicular nodes involve zones 4 and 5
– Rarely involved in non-advanced H&N CA
 Cervical LN
• Zone 6
– Midline and anterior to the
viscera in the midline neck
below hyoid bone
– Medial to carotid arteries
– Drains thyroid
 Cervical LN
• Outside the zones
– Retropharyngeal
• anterior to vert bodies, above hyoid
• medial to carotid
• usually mets from nasopharyngeal CA
• most superior is node of Rouviere (cant tell
from other retropharyngeal nodes)
• Up to 5mm
– Occipital
• superficial to occipital bone
• receive mets from scalp lesions
– Facial
• lateral to body of mandible
• unlike zone 1, are superficial to jaw
 Cervical LN
• Named nodes
– Virchow’s
• Lies w/in zone 4
• Recieves mets from distant
sources (w/o intervening LAD)
• Proximal to distal thoracic duct
– Jugulo-digastric
• Lies w/in IJ chain at or just
above the level of hyoid (border
btwn zones 2 and 3)
• Frequent site of lymphatic mets
• Normally larger than other
cervical nodes (up to 15mm)
 Cervical LN
• Size (short axis)
– Retropharyngeal nodes <5mm
– Jugulodiagastric nodes <15mm
– Others <10mm
• Appearance
– Central necrosis
– Extracapsular spread
– Spherical vs reniform shape
 Abd/Pelv LN
• Retrocrural nodes <6mm
• Portahepatis nodes <5mm
• All others <10mm