Imaging NonImaging Non--Hodgkin’s Hodgkin’s LymphomaLymphoma
GuibensonGuibenson HyppoliteHyppoliteHarvard Medical School Year IIIHarvard Medical School Year III
Gillian Lieberman, MDGillian Lieberman, MD
Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
22
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Our Patient: Ms. MOur Patient: Ms. M
Ms. M: 24 year old femaleMs. M: 24 year old femaleChief Complaint: Chief Complaint: stabbing chest pain, SOBstabbing chest pain, SOBReview of Systems: no fevers, sweats, chills, or Review of Systems: no fevers, sweats, chills, or weight lossweight lossPast Medical History: status post appendectomy Past Medical History: status post appendectomy one year prior; EBV infection two years priorone year prior; EBV infection two years priorSocial History: past cocaine useSocial History: past cocaine useFamily History: diabetes, heart diseaseFamily History: diabetes, heart diseasePhysical Examination: unremarkablePhysical Examination: unremarkable
33
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Chest XChest X--ray Findingsray FindingsLateralPA Trachea
Silhouetting out of right heart border Soft-tissue density inretrosternal areaPACS, BIDMC
44
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Ms. M’s Thoracic CT with ContrastMs. M’s Thoracic CT with Contrast
PACS, BIDMC
Lobular soft tissue mass inanterior mediastinum withmass effect on heart
RV
LVRV, right ventricle
LV, left ventricle
Aorta
55
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Anterior Anterior MediastinalMediastinal AnatomyAnatomy
Clemente CD. Anatomy: A Regional Atlas of the Human Body. Fig. 152.
Thymus
Thyroid
66
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
MediastinalMediastinal Lymph NodesLymph Nodes
Clemente CD. Anatomy: A Regional Atlas of the Human Body. Fig. 187.
Superior AnteriorMediastinal Lymph Nodes: 34% involvement in NHL
77
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Differential DiagnosisDifferential Diagnosis
ThymomaThymoma
Thyroid MassThyroid Mass
TeratomaTeratoma
LymphomaLymphoma
88
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Patient 2: Patient 2: ThymomaThymomaMost common anterior Most common anterior mediastinalmediastinal mass in adultsmass in adults
40% present with 40% present with parathymicparathymicsyndromes: myasthenia syndromes: myasthenia gravis, gravis, aplasticaplastic anemia, red anemia, red cell cell aplasiaaplasia
FeaturesFeatures–– Asymmetric location on Asymmetric location on
one sideone side–– Homogenous densityHomogenous density–– Some have cystic Some have cystic
componentscomponents–– 20% have calcifications20% have calcifications
Courtesy of Fabio Komlos, MD, BIDMC
Thoracic CT
99
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Thyroid MassThyroid Mass
Well defined mass contiguous with cervical Well defined mass contiguous with cervical thyroidthyroid
Tracheal displacement common on CXRTracheal displacement common on CXR
HeterogenousHeterogenous density on CT with marked density on CT with marked contrast enhancementcontrast enhancement
1010
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Patient 3: Thyroid MassPatient 3: Thyroid Mass
www.medscape.com/.../ 91/449156/449156_fig.html
Hypodense center
Soft tissue densityperipherally
Tracheal deviation
Thoracic CT
••Well defined massWell defined masscontiguous with cervicalcontiguous with cervicalthyroidthyroid
••Tracheal displacementTracheal displacementcommon on CXRcommon on CXR
••HeterogenousHeterogenous densitydensityon CT with markedon CT with markedcontrast enhancementcontrast enhancement
1111
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
TeratomaTeratoma
20% malignant; all are surgically removed20% malignant; all are surgically removed
Typically present as large mass lesionsTypically present as large mass lesions
Variable tissue content: calcification in Variable tissue content: calcification in 30%, fat or fat30%, fat or fat--fluid levels, cystic areas, fluid levels, cystic areas, soft tissuesoft tissue
1212
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Patient 4: Patient 4: TeratomaTeratoma
Courtesy of Fabio Komlos, MD, BIDMC
Thoracic CT
Calcific density
Fat & soft-tissuedensities
Notice the size!
1313
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
LymphomaLymphoma
Hodgkin’sHodgkin’sReedReed--Sternberg cellsSternberg cells90% originate in lymph 90% originate in lymph nodenode95% superior 95% superior mediastinalmediastinalnodalnodalContiguous progressionContiguous progressionIncidence: 1:50,000Incidence: 1:50,000Bimodal age distribution: Bimodal age distribution: 30 & 7030 & 70
NonNon--Hodgkin’sHodgkin’sHeterogeneous groupHeterogeneous group60% originate in lymph 60% originate in lymph nodesnodes85% from B cells; 15% 85% from B cells; 15% from T cellsfrom T cellsOccurs in all age groups Occurs in all age groups (mean age 50 years)(mean age 50 years)Increased incidence in Increased incidence in patients with altered patients with altered immune statusimmune status
1414
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
MediastinalMediastinal Mass BiopsyMass Biopsy
www.mrcmedical.it/ aemedical.htm
•Median sternotomy procedure
•3-4 cm incision through the skin and subcutaneous tissue
•To the right of the sternum, between the first and second ribs
1515
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Tissue HistologyTissue Histology
Uniform, small Uniform, small undifferentiated cells undifferentiated cells with basophilic with basophilic cytoplasmcytoplasm
TingibleTingible--body body macrophages: starrymacrophages: starry--sky patternsky pattern
Diagnosis: Burkitt’s LymphomaImage, http://individual.uptodateonline.com/application/topic/print.asp?file=lymphoma/14479&type=A&selectedTitle=1~17
1616
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
http://individual.uptodateonline.com/application/topic/print.asp?file=lymphoma/6348
1717
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Burkitt’sBurkitt’s LymphomaLymphoma
•Endemic (African) and non-endemic (American) forms•Most often in children and immunocompromised hosts•Tumors originate from EBV-infected B cells•t(8,14) translocation and activation of c-myc
Patient 5: Endemic Burkitt’s Patient 6: Non-endemic Burkitt’s
http://individual.uptodateonline.com/application/topic/print.asp?file=lymphoma/14479&type=A&selectedTitle=1~17
1818
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
NHL: Epidemiology & Risk Factors NHL: Epidemiology & Risk Factors
EpidemiologyEpidemiology**
–– Incidence: 15.1 per 100,000 persons per year in U.S.Incidence: 15.1 per 100,000 persons per year in U.S.–– 73% increase since 1970’s73% increase since 1970’s–– Steady increase due in part to AIDS pandemicSteady increase due in part to AIDS pandemic–– Subtypes differ in frequency between age groupsSubtypes differ in frequency between age groups
Risk FactorsRisk Factors–– Transplant patientsTransplant patients–– AIDSAIDS–– Congenital immunodeficiencyCongenital immunodeficiency–– Collagen vascular diseases: RA, SLECollagen vascular diseases: RA, SLE–– Infectious agents: EBV, Infectious agents: EBV, H. pyloriH. pylori
*Grainger, p. 1401
1919
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Staging NonStaging Non--Hodgkin’s LymphomaHodgkin’s Lymphoma
StageStage Site of InvolvementSite of Involvement
II Single lymph node region (I) or single Single lymph node region (I) or single extralymphaticextralymphatic organ or site (IE)organ or site (IE)
IIII Two or more lymph node regions on the Two or more lymph node regions on the same side of the diaphragm (II) or one or same side of the diaphragm (II) or one or more lymph node regions plus and more lymph node regions plus and extralymphaticextralymphatic site (IIE) site (IIE)
IIIIII Lymph nodes of both sides of the diaphragmLymph nodes of both sides of the diaphragm
IVIV One or more One or more extralymphaticextralymphatic organs with or organs with or without lymph node involvementwithout lymph node involvement
2020
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Imaging Modalities: LymphomaImaging Modalities: Lymphoma
Plain filmPlain filmCTCTMRIMRIUltrasoundUltrasoundNuclear Medicine (Gallium Scanning & Nuclear Medicine (Gallium Scanning & FDGFDG--PET)PET)Fusion Imaging (PETFusion Imaging (PET--CT)CT)
2121
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Plain FilmPlain Film
2525--40% of NHL patients present with thoracic 40% of NHL patients present with thoracic node involvementnode involvement
Pulmonary Pulmonary parenchymalparenchymal abnormalities: alveolar abnormalities: alveolar opacities & opacities & peribronchialperibronchial diseasedisease
Skeletal imaging indicated for bony pain or if Skeletal imaging indicated for bony pain or if pathological fracture is suspectedpathological fracture is suspected
Bony lesions are mostly Bony lesions are mostly osteolyticosteolytic
2222
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Computed TomographyComputed Tomography
Modality of choice for staging and followModality of choice for staging and follow--upup
Ability to demonstrate enlarged lymph nodes Ability to demonstrate enlarged lymph nodes throughout the bodythroughout the body
Detection of soft tissue pathologyDetection of soft tissue pathology
Limitation: distinguishing active tumor from Limitation: distinguishing active tumor from fibrotic massfibrotic mass
2323
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Computed TomographyComputed Tomography
Scout view of Ms. M
PACS, BIDMC
Kidneys
Spleen
Liver
AortaPancreas
Ms. M’s Abdomen
No evidence of abdominal lymphoma
2424
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Metastasis to Liver & SpleenMetastasis to Liver & Spleen
•Note the size of liver and spleen•Nodular low-density mass in spleen•B-cell lymphoma
•Nodular infiltration of liver•Diffuse large B-cell NHL
http://individual.uptodateonline.com/application/topic/print.asp?file=lymphoma/13075&type=A&selectedTitle=1~203
Patient 7 Patient 8
2525
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Magnetic Resonance ImagingMagnetic Resonance Imaging
Modality of choice to evaluate CNS Modality of choice to evaluate CNS involvementinvolvement
Extremely sensitive in detecting bone Extremely sensitive in detecting bone marrow involvementmarrow involvement
Lymph nodes are lowLymph nodes are low--intermediate intermediate attenuation on T1 and intermediateattenuation on T1 and intermediate--high high on T2on T2
2626
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Ms. M’s Brain MRIMs. M’s Brain MRI
PACS, BIDMC
Sagittal T1 MRI Axial T2 MRI
Arachnoid Cyst
Typical site ofprimary CNSlymphoma
Leptomeninges: common siteof metastatic CNS lymphoma
No CNS lymphoma was detected in Ms. M.
2727
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
UltrasoundUltrasoundConfirming that a palpable mass is fact nodalConfirming that a palpable mass is fact nodal
Lymph node enlargement readily seen in celiac region, Lymph node enlargement readily seen in celiac region, splenicsplenic hilumhilum and and portaporta hepatishepatis
Feature: uniform Feature: uniform hypoechoichypoechoic lobulatedlobulated massesmasses
Detection of tumor involvement in liver, kidney, spleen Detection of tumor involvement in liver, kidney, spleen or testesor testes
Limitations: entire Limitations: entire retroperitoneumretroperitoneum cannot be shown, cannot be shown, findings are nonspecificfindings are nonspecific
2828
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Patient 9: Testicular UltrasoundPatient 9: Testicular Ultrasound
Large anechoic mass
http://individual.uptodateonline.com/application/topic/print.asp?file=lymphoma/13075&type=A&selectedTitle=1~203
Arrows outline edge of testis
Biopsy proved to be lymphoma
2929
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Gallium ScanningGallium Scanning
Adjunctive for stagingAdjunctive for stagingDetection of residual disease or relapse Detection of residual disease or relapse after treatmentafter treatmentSites of involvement take up Gallium and Sites of involvement take up Gallium and appear as bright “gallium avid” areasappear as bright “gallium avid” areasCaveat: Gallium uptake nonspecific, scan Caveat: Gallium uptake nonspecific, scan must be done before treatment, not useful must be done before treatment, not useful in in nonavidnonavid tumorstumors
3030
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Ms. M: Gallium ScanningMs. M: Gallium Scanning
Gallium avid area
•Initial whole body scan after presentation•Five days after intravenous injection of tracer•Intense uptake in mediastium & mildly in liver
•Three months into treatment•Three days after injection of tracer•Disappearance of gallium-avid
disease in the thorax
Images: PACS, BIDMC
3131
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
FDGFDG--PETPET
22--FluorineFluorine--18 Fluoro18 Fluoro--22--Deoxy DDeoxy D--GlucoseGlucoseAccumulates in highly metabolic cells via Accumulates in highly metabolic cells via glycolyticglycolytic pathwaypathwayEvaluation of residual mass during and Evaluation of residual mass during and after treatmentafter treatmentSensitivity (86%) and specificity (100%) Sensitivity (86%) and specificity (100%) higher than CT (86% & 67% respectively)higher than CT (86% & 67% respectively)
3232
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Fusion Imaging: PETFusion Imaging: PET--CTCT
Integration of both biological and Integration of both biological and anatomical information during a single anatomical information during a single examinationexamination
Role: staging, response to treatment, Role: staging, response to treatment, followfollow--upup
3333
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Patient 10: PETPatient 10: PET--CTCT
Axial CT PET Scan PET-CT
•Tonsillar lymphoma in a 20-year-old male•Secondary to Burkitt lymphoma in the abdomen•Asymmetric signal uptake suggestive of lymphoma•PET-CT helps localize uptake to palatine tonsils•Physiologic uptake in tonsils difficult to distinguish from extranodal lymphoma
Images: Radiographics 2004; 24:1418.
3434
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Back to Ms. MBack to Ms. M
Treated with StanfordTreated with Stanford--based regimen with based regimen with highhigh--dose CHOPdose CHOP
Also given Also given allopurinolallopurinol and and LupronLupron ((GnRHGnRHanalog)analog)
Responded well without major Responded well without major complicationscomplications
3535
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Ms. M: CXR Status Post TherapyMs. M: CXR Status Post Therapy
PACS, BIDMC
PA Chest X-ray on admission Six months later
3636
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Ms. M 20 Months Later…Ms. M 20 Months Later…
Axial CT with contrast, 20 months laterAxial CT with contrast, on admission
PACS, BIDMC
3737
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Ms. M’s Prognosis…Ms. M’s Prognosis…
International Prognostic IndexInternational Prognostic Index–– Age > 60Age > 60–– Serum LDH > normalSerum LDH > normal–– ECOG performance status > 2ECOG performance status > 2
(non(non--ambulatory)ambulatory)
–– Ann Arbor Stage III or IVAnn Arbor Stage III or IV–– Number of Number of extranodalextranodal sites > 1sites > 1
• One point for each of the above• Ms. M has a score of zero
3838
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Cure RatesCure Rates**
ScoreScore RiskRisk 55--year Overallyear OverallSurvival (percent)Survival (percent)
0 to 10 to 1 LowLow 7373
22 LowLow-- intermediateintermediate
5151
33 HighHigh-- intermediateintermediate
4343
4 to 54 to 5 HighHigh 2626
*UpUp--ToTo--DateDate 20042004
Ms. M
3939
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
Take Home PointsTake Home Points
LymphomaLymphoma-- neoplasticneoplastic proliferation of proliferation of lymphoid cellslymphoid cellsPresents as homogenous softPresents as homogenous soft--tissue mass tissue mass most commonly in the thorax and GImost commonly in the thorax and GICT is modality of choice, critical for CT is modality of choice, critical for staging and monitoringstaging and monitoringNuclear medicine: evaluation of residual Nuclear medicine: evaluation of residual masses and fibrotic tissuemasses and fibrotic tissue
4040
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
ReferencesReferencesClemente, CD. Anatomy: A Regional Atlas of the Human Body, 3rd Ed. Co 1987 by Urban & Schwarzenberg, Figs. 152 & 187.Freedman AS. Approach to the diagnosis; staging; and prognosis oFreedman AS. Approach to the diagnosis; staging; and prognosis of nonf non--Hodgkin’s lymphoma. Hodgkin’s lymphoma. UpUp--ToTo--DateDate 2004.2004.Freedman AS. Freedman AS. PathobiologyPathobiology of nonof non--Hodgkin’s lymphoma. Hodgkin’s lymphoma. UpUp--ToTo--DatDate 2004.e 2004.Freedman AS, Friedberg JW. Treatment of aggressive and highly agFreedman AS, Friedberg JW. Treatment of aggressive and highly aggressive gressive nonnon--Hodgkin’s lymphoma. Hodgkin’s lymphoma. UpUp--ToTo--DateDate 2004.2004.Freedman AS, Harris NL. Clinical and pathologic features of Freedman AS, Harris NL. Clinical and pathologic features of Burkitt’sBurkitt’s lymphoma. lymphoma. UpUp--ToTo--DateDate 2004.2004.Grainger RG, Allison DJ, Adam A, Dixon AK, eds. Diagnostic RadioGrainger RG, Allison DJ, Adam A, Dixon AK, eds. Diagnostic Radiology: A logy: A Textbook of Medical Imaging, 4Textbook of Medical Imaging, 4thth Edition. Co 2001 by Harcourt Publishers Ltd. Edition. Co 2001 by Harcourt Publishers Ltd. VolVol 2, pp. 14012, pp. 1401--1432.1432.KostakogluKostakoglu L, L, HardoffHardoff R, R, MirtchevaMirtcheva R, Goldsmith SF. PETR, Goldsmith SF. PET--CT fusion imaging in CT fusion imaging in differentiating physiologic from pathologic FDG uptake. differentiating physiologic from pathologic FDG uptake. RadiographicsRadiographics 2004; 2004; 24: 141124: 1411--1430.1430.NovellineNovelline RA. Fundamentals of Radiology, 6RA. Fundamentals of Radiology, 6thth Edition. Co 2004 by Harvard Edition. Co 2004 by Harvard University Press, 600University Press, 600--601.601.RehmRehm PK. Radionuclide evaluation of patients with lymphoma. PK. Radionuclide evaluation of patients with lymphoma. The Radiologic The Radiologic Clinics of North AmericaClinics of North America 2001; 39:9572001; 39:957--978.978.WeisslederWeissleder R, R, RieumontRieumont MJ, Wittenberg J. Primer of Diagnostic Imaging, 2MJ, Wittenberg J. Primer of Diagnostic Imaging, 2ndnd
Edition. Co 1997 by Mosby, Inc., pp. 71Edition. Co 1997 by Mosby, Inc., pp. 71--75.75.
4141
September 2004Guibenson Hyppolite, HMS IIIGillian Lieberman, MD
AcknowledgmentsAcknowledgments
Nicole Nelson, MDNicole Nelson, MDFabio Fabio KomlosKomlos, MD, MDMichael Schuster, MDMichael Schuster, MDGillian Lieberman, MDGillian Lieberman, MDPamela Pamela LepkowskiLepkowskiLarry BarbarasLarry Barbaras