Imaging Non-Hodgkin’s Lymphoma Guibenson …eradiology.bidmc.harvard.edu/LearningLab/respiratory/Hyppolite.pdfImaging Non-Hodgkin’s Lymphoma Guibenson . Guibenson Hyppolite Harvard

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

http://www.hms.harvard.edu/

http://images.google.com/imgres?imgurl=http://research.bidmc.harvard.edu/HemThromb/images/Logos/logo_hands2.gif&imgrefurl=http://research.bidmc.harvard.edu/HemThromb/DHT_furie.htm&h=64&w=70&sz=2&tbnid=Zt6AG8uoTIoJ:&tbnh=60&tbnw=65&start=5&prev=/images%3Fq%3Dha

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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

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Chest XChest X--ray Findingsray FindingsLateralPA Trachea

Silhouetting out of right heart border Soft-tissue density inretrosternal areaPACS, BIDMC

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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

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Anterior Anterior MediastinalMediastinal AnatomyAnatomy

Clemente CD. Anatomy: A Regional Atlas of the Human Body. Fig. 152.

Thymus

Thyroid

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MediastinalMediastinal Lymph NodesLymph Nodes

Clemente CD. Anatomy: A Regional Atlas of the Human Body. Fig. 187.

Superior AnteriorMediastinal Lymph Nodes: 34% involvement in NHL

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Differential DiagnosisDifferential Diagnosis

ThymomaThymoma

Thyroid MassThyroid Mass

TeratomaTeratoma

LymphomaLymphoma

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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

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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

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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

http://www.medscape.com/content/2003/00/44/91/449156/449156_fig.html

1111


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

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Patient 4: Patient 4: TeratomaTeratoma

Courtesy of Fabio Komlos, MD, BIDMC

Thoracic CT

Calcific density

Fat & soft-tissuedensities

Notice the size!

1313


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

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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

http://www.mrcmedical.it/aemedical.htm

1515


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

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http://individual.uptodateonline.com/application/topic/print.asp?file=lymphoma/6348

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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

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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

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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


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)

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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


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


Computed TomographyComputed Tomography

Scout view of Ms. M

PACS, BIDMC

Kidneys

Spleen

Liver

AortaPancreas

Ms. M’s Abdomen

No evidence of abdominal lymphoma

2424


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


Patient 7 Patient 8

2525


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


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


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


Patient 9: Testicular UltrasoundPatient 9: Testicular Ultrasound

Large anechoic mass


Arrows outline edge of testis

Biopsy proved to be lymphoma

2929


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


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


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)

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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


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.

http://radiographics.rsnajnls.org/cgi/content/full/24/5/1411/F10A

http://radiographics.rsnajnls.org/cgi/content/full/24/5/1411/F10B

http://radiographics.rsnajnls.org/cgi/content/full/24/5/1411/F10C

3434


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


Ms. M: CXR Status Post TherapyMs. M: CXR Status Post Therapy

PACS, BIDMC

PA Chest X-ray on admission Six months later

3636


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


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


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


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


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.

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AcknowledgmentsAcknowledgments

Nicole Nelson, MDNicole Nelson, MDFabio Fabio KomlosKomlos, MD, MDMichael Schuster, MDMichael Schuster, MDGillian Lieberman, MDGillian Lieberman, MDPamela Pamela LepkowskiLepkowskiLarry BarbarasLarry Barbaras

Documents

Imaging Non-Hodgkin’s Lymphoma Guibenson …eradiology.bidmc.harvard.edu/LearningLab/respiratory/Hyppolite.pdfImaging Non-Hodgkin’s Lymphoma Guibenson . Guibenson Hyppolite Harvard