AIDSAIDS--related related LymphomaLymphoma

Modupe TeniolaModupe TeniolaVisiting Medical StudentVisiting Medical Student

Morehouse School of Medicine MS4Morehouse School of Medicine MS4Dr LiebermanDr Lieberman

Advanced Radiology Beth Israel Deaconess Hospital

AgendaAgenda

Definition of Lymphoma and the different Definition of Lymphoma and the different categories associated with AIDScategories associated with AIDSBrief explanation of AIDS associated Brief explanation of AIDS associated lymphomas lymphomas Patient PresentationPatient PresentationImaging modalities in the diagnosis of NonImaging modalities in the diagnosis of Non--Hodgkin's LymphomasHodgkin's LymphomasPrognosis of lymphoma patientsPrognosis of lymphoma patients

Definition of a LymphomaDefinition of a Lymphoma

Lymphomas are neoplasm that originate from Lymphomas are neoplasm that originate from malignant transformation of lymphoid cells malignant transformation of lymphoid cells

Originate from lymph nodes and presents as an enlargement Originate from lymph nodes and presents as an enlargement of the nodeof the node

Thomas Hodgkins published the first description of Thomas Hodgkins published the first description of lymphomas in 1832lymphomas in 1832

Categories of LymphomasCategories of Lymphomas

There are different classifications of lymphomas There are different classifications of lymphomas and the WHO (2001) classified 43 types into and the WHO (2001) classified 43 types into four categoriesfour categories

Mature B cell neoplasmMature B cell neoplasmMature T cell and Natural Killer NeoplasmMature T cell and Natural Killer NeoplasmHodgkin LymphomaHodgkin LymphomaImmunodeficiency associated lymphoproliferative Immunodeficiency associated lymphoproliferative disordersdisorders

http://http://en.wikipedia.orgen.wikipedia.org/wiki/Lymphoma./wiki/Lymphoma.

Immune deficiency associated Immune deficiency associated LymphomasLymphomas

In the immunodefiencyIn the immunodefiency--associated disorders associated disorders category there are lymphomas:category there are lymphomas:

Associated with a primary immune disorderAssociated with a primary immune disorderAssociated with the Human Immunodeficiency Associated with the Human Immunodeficiency Virus (Virus (HIVHIV))PostPost--transplant transplant Associated with Methotrexate therapy Associated with Methotrexate therapy

Lymphomas and HIV Lymphomas and HIV

An immuneAn immune--compromised state, such as compromised state, such as Acquired Immunodeficiency Syndrome, Acquired Immunodeficiency Syndrome, increases the incidence of neoplastic increases the incidence of neoplastic transformationtransformationLymphomas develop in HIVLymphomas develop in HIV--infected patients at infected patients at the same frequency as in other the same frequency as in other immunosuppressive disorders immunosuppressive disorders

AIDS defining malignanciesAIDS defining malignancies

2525--40% of HIV40% of HIV--1 seropositive patients 1 seropositive patients eventually develop a malignancy eventually develop a malignancy There are four AIDs defining malignancies of There are four AIDs defining malignancies of which two are lymphomaswhich two are lymphomas

Kaposi’s sarcomaKaposi’s sarcomaNonNon--Hodgkin’s lymphomaHodgkin’s lymphomaPrimary CNS lymphomaPrimary CNS lymphomaInvasive Cervical carcinomaInvasive Cervical carcinoma

Fig. 1: Picture of a man with Kaposi Sarcoma. upload.wikimedia.org/wikipedia/commons/c/c2/K..

AIDs related lymphomasAIDs related lymphomas

AIDs related lymphomas are mostly categorized AIDs related lymphomas are mostly categorized into three:into three:

Systemic nonSystemic non--Hodgkin's lymphoma Hodgkin's lymphoma Primary CNS lymphoma Primary CNS lymphoma Primary effusion ("body cavity") lymphomas Primary effusion ("body cavity") lymphomas

Non Hodgkin’s lymphomaNon Hodgkin’s lymphoma

Systemic nonSystemic non--hogkins lymphoma hogkins lymphoma accounts for the majority of AIDS accounts for the majority of AIDS associated lymphomasassociated lymphomasPrimarily encountered in patients Primarily encountered in patients with more advanced disease:with more advanced disease:

CD4 <100/ulCD4 <100/ulPoorly controlled HIVPoorly controlled HIVIt can develop with It can develop with undetectable HIV viral loadundetectable HIV viral load

7070--90% of the lymphomas are high 90% of the lymphomas are high grade and almost exclusively grade and almost exclusively diffuse large B cell and Burkitt’s diffuse large B cell and Burkitt’s lymphomalymphoma

Images from: www.uhrad.com/ctarc/ct086.htm

Fig 3: Soft tissue attenuation demonstrating lymphoma infiltration

Fig 2: Non-Hodgkins

Lymphoma causing a mass effect on bowel loops and peripheral displacement of the bowel

Primary CNS lymphomaPrimary CNS lymphoma

Incidence in HIV infected Incidence in HIV infected patients is 2patients is 2--6%6%Pathogenesis is strongly related Pathogenesis is strongly related to Epsteinto Epstein--Barr virus infectionBarr virus infection

EBV DNA sequences can be EBV DNA sequences can be detected in the CSF of patientsdetected in the CSF of patients

Increased incidence with Increased incidence with prolonged survival of HIVprolonged survival of HIV--11Found in patient with a CD4 Found in patient with a CD4 count usually <50/ulcount usually <50/ul

Fig 4: This is an MRI/T1 weighted image obtained after intravenous contrast.

Shows a ring enhancing lesion in the medial left temporal lobe

aidscience.org/.../Imaging/Figures/figure9.jpg

Primary effusion lymphomaPrimary effusion lymphoma

Predilection for body cavities such as peritoneal, pleural, and Predilection for body cavities such as peritoneal, pleural, and pericardial spaces without an identifiable tumor masspericardial spaces without an identifiable tumor massMalignant cells are monoclomal BMalignant cells are monoclomal B--cellscellsContain genomic material from HHVContain genomic material from HHV--8, kaposi sarcoma 8, kaposi sarcoma associated herpesvirus and EBV associated herpesvirus and EBV Those with prior history of Kaposi’s sarcoma, have an increased Those with prior history of Kaposi’s sarcoma, have an increased risk of developing this type of lymphomarisk of developing this type of lymphomaRadiographic images in primary effusion lymphoma reveals Radiographic images in primary effusion lymphoma reveals evidence of the local effusions. Chest radiographs and CT evidence of the local effusions. Chest radiographs and CT reveals pleural and/or pericardial effusion, slight serosal (plereveals pleural and/or pericardial effusion, slight serosal (pleural, ural, pericardial) thickening, and the absence of parenchymal pericardial) thickening, and the absence of parenchymal abnormalities, solid masses, or mediastinal enlargement abnormalities, solid masses, or mediastinal enlargement

Mr. B.PMr. B.P

Mr. B.P is a 69y/o male from Cape Verde with HIV, Mr. B.P is a 69y/o male from Cape Verde with HIV, CD4 156, VL 489,000 copies/mlCD4 156, VL 489,000 copies/mlIn Cape Verde, 4/2008, he had cough, dyspnea, and In Cape Verde, 4/2008, he had cough, dyspnea, and weight loss (10kg)weight loss (10kg)Diagnosis: TuberculosisDiagnosis: TuberculosisPresented to ID clinic at BIMDC 9/18/2008 for Presented to ID clinic at BIMDC 9/18/2008 for followfollow--up up

CXR CXR ––

PA/LateralPA/Lateral

PACS BIDMC

Image 1: CXR PA/Lateral: Showing an apical cavity (purple arrow)

with reticular and nodular opacities (blue arrow). An anterior mediastinal mass can also be seen on the lateral view

Review of systemsReview of systems

Since the last visit, Mr. BP reports that he continues to Since the last visit, Mr. BP reports that he continues to feelfeel fairly well. fairly well. He denies fevers, chills, night sweats, weightHe denies fevers, chills, night sweats, weightloss, cough, or hemoptysis. loss, cough, or hemoptysis. He alsoHe also complains of epigastric abdominal pain. The complains of epigastric abdominal pain. The pain is of an achypain is of an achy quality and it also keeps him awake at quality and it also keeps him awake at night. He has had thenight. He has had the pain off and on previously but it pain off and on previously but it has gotten worse over the past fewhas gotten worse over the past few days. days. He denies nausea, vomiting, or diarrhea.He denies nausea, vomiting, or diarrhea.He has mildHe has mild constipation.constipation.

Fig 6: http://www.sghhealth4u.com.sg/Health4U/respiratory/rccm_content_frameset.html?tuberculosis.htm~preview

ExtrapulmonaryExtrapulmonary

TuberculosisTuberculosis

Tuberculosis canAffect different parts of the body and it could be the source of the patient’s abdominal pain

CHEST CT/ABDCHEST CT/ABD

PACS BIDMC : Image 2: Scout Image of the chest CT and abdomen showing an anterior mediastinal mass

PACS BIDMC

Image 3: Axial and coronal chest CT of patient’s B.P. Showing the characteristic tree in bud pattern, which consists of small centrilobular nodules of soft-tissue attenuation connected to multiple branching linear structures of similar caliber that originate from a single stalk

CHEST CT of Pt. B.PCHEST CT of Pt. B.P

PACS BIDMC

Anterior Mediastinal MassAnterior Mediastinal Mass

Image 3: Sagittal

view of Patient’s B.P. CT, showing an anterior mediastinal mass.

Tumor mass in the anterior mediatinum

Differential Differential DxDx. of Anterior . of Anterior Mediastinal MassMediastinal Mass

THYMOMATHYMOMATERATOMATERATOMATHYROIDTHYROIDLYMPHOMALYMPHOMA

PACS BIDMC

Abdomen CTAbdomen CT

Stomach

Spleen

Soft tissue Mass

Superior Mesenteric artery

Liver

Image 4: Coronal view of Pt. B.P’s

abdomen showing a soft tissue mass encapsulating the major vessel and peripheral displacement of the bowel loops

PACS BIDMC

SagittalSagittal

viewview

Small intestine

Soft tissue mass in the lower abdomen

Stomach

Liver

Image 5: Sagittal

view of the abdominal mass and lymphadenopathy

PACS BIDMC

Abdomen CTAbdomen CT

Soft tissue mass

Stomach

Spleen

Kidney

Celiac Trunk

Liver

Image 6: a) Axial Image of the Abdomen CT of the patient showing the soft tissue mass encircling the celiac trunk and b) soft tissue mass in the lower abdomen

A B

CT FindingsCT Findings

Bilateral diffuse tree in bud densities which are Bilateral diffuse tree in bud densities which are compatible with patient’s diagnosis of TBcompatible with patient’s diagnosis of TB

Anterior mediastinal, mesenteric and pelvic Anterior mediastinal, mesenteric and pelvic nodal masses compatible with high grade nodal masses compatible with high grade lymphomalymphoma

Mr. B.P Mr. B.P

WHAT IS THE DIAGNOISWHAT IS THE DIAGNOISAfter an exploratory laparatomy, he underwent a After an exploratory laparatomy, he underwent a mesenteric lymph node biopsy mesenteric lymph node biopsy

PLASMABLASTIC LYMPHOMAPLASMABLASTIC LYMPHOMA

Plasmablastic lymphomaPlasmablastic lymphoma

It is a type of AIDsIt is a type of AIDs--related nonrelated non--Hodgkin’s lymphoma, Hodgkin’s lymphoma, usually presenting in the oral cavity and jawusually presenting in the oral cavity and jaw

Extension of lymphoma presents at a later stageExtension of lymphoma presents at a later stageRarely presents as cutaneous disease without systemic Rarely presents as cutaneous disease without systemic involvementinvolvementRapidly progressive and found Rapidly progressive and found in those with advanced diseasein those with advanced diseaseTumor cells are derived from Tumor cells are derived from B cells and are plasmablasts B cells and are plasmablasts that shares features with that shares features with diffuse B cell lymphomadiffuse B cell lymphoma

Fig 6: www.scielo.br/.../rsbmt/v40n5/a17fig01.jpg

Imaging techniques for the diagnosis Imaging techniques for the diagnosis of Lymphomasof Lymphomas

Chest RadiographsChest RadiographsMost lymph nodes can be affectedMost lymph nodes can be affectedCan affect adjacent organs causing superior vena Can affect adjacent organs causing superior vena cava syndrome, phrenic nerve compression and the cava syndrome, phrenic nerve compression and the compromise of the airway and esophaguscompromise of the airway and esophagus

Other radiological findingsOther radiological findingsConsolidation, masses, or nodules and peribronchial Consolidation, masses, or nodules and peribronchial diseasesdiseasesChest wall, pleural, and pericardial involvementChest wall, pleural, and pericardial involvement

Imaging TechniquesImaging Techniques

Abdomen and Pelvis Abdomen and Pelvis CT has replaced lymphagiography and CT has replaced lymphagiography and ultrasonography for initial evaluationultrasonography for initial evaluationLiver/spleen : fine needle aspiration biopsy under Liver/spleen : fine needle aspiration biopsy under radiologic guidance may lead to needed diagnosisradiologic guidance may lead to needed diagnosisGenitourinary: Involvement is detected by CT Genitourinary: Involvement is detected by CT scanning in 10% of patients at initial diagnosis scanning in 10% of patients at initial diagnosis Kidney, testis, ovary are the most affected. Testicular Kidney, testis, ovary are the most affected. Testicular involvement is best evaluated by ultrasound.involvement is best evaluated by ultrasound.

Imaging TechniquesImaging Techniques

Abdomen and PelvisAbdomen and PelvisGastrointestinal tract Gastrointestinal tract involvement is seen in 10involvement is seen in 10--60% 60% of patients with NHLof patients with NHLBarium contrast studies or CT Barium contrast studies or CT scanning are both useful for scanning are both useful for evaluating mucosal lesions, evaluating mucosal lesions, although CT assesses although CT assesses extraluminal extent of lesions extraluminal extent of lesions and associated adenopathyand associated adenopathyEndoscopic procedures are Endoscopic procedures are extremely helpful in tumor extremely helpful in tumor localization and staging.localization and staging.

www.medcyclopaedia.com/.../nic_k221_126.jpg

www.eusimaging.com/.../images/eusgi1b_md.jpg

Fig 7: Barium contrast studies showing mucosal lesion in the bowel wall

Fig 8: Picture of endoscopic ultrasound

Imaging TechniquesImaging TechniquesCNSCNS

Magnetic Resonance Imaging is indicated in patients Magnetic Resonance Imaging is indicated in patients with neurologic symptoms or signswith neurologic symptoms or signs

Skeletal ImagingSkeletal ImagingNot routinely performed but is indicated in the Not routinely performed but is indicated in the presence of bony pain and or suspicion of a presence of bony pain and or suspicion of a pathologic fracturepathologic fractureBone lesions are mostly osteolytic in NonBone lesions are mostly osteolytic in Non--Hodgkin's Hodgkin's compared to osteoblastic in hodgkin’s lymphomacompared to osteoblastic in hodgkin’s lymphomaUrgent MRI if suspicion of spinal cord compressionUrgent MRI if suspicion of spinal cord compression

Imaging TechniquesImaging Techniques

PET scanningPET scanning1818--fluorodeoxyglucose (18fluorodeoxyglucose (18--FDG) appears to be FDG) appears to be highly sensitive and specific for detecting NHL in highly sensitive and specific for detecting NHL in nodal and extra nodal sitesnodal and extra nodal sitesIn a study by Schoder et al, intensity appears to In a study by Schoder et al, intensity appears to correlate directly with tumor aggressiveness in NHLcorrelate directly with tumor aggressiveness in NHLEarly reports indicates that, for patients with Early reports indicates that, for patients with lymphoma, PET/CT results in more accurate initial lymphoma, PET/CT results in more accurate initial staging compared to PET or CT alone staging compared to PET or CT alone

Ann Harbor stagingAnn Harbor staging

Fig 9: Lymph nodeswww.uptodate.com/.../Lymph_nodes_body.jpg

Fig 10: Ann Harbor Staging for Non-Hodgkin’s Lymphoma.www.dartmouth.edu/~nlevy/staging2.jpeg

PrognosisPrognosis

Survival in patients is related in part to the Survival in patients is related in part to the severity of AIDS and to the response to severity of AIDS and to the response to chemotherapychemotherapyAdverse factorsAdverse factors

Age>35 yearsAge>35 yearsIntravenous drug abuseIntravenous drug abuseStage III or IV diseaseStage III or IV diseaseCD4 cell count <100/microLCD4 cell count <100/microL

SummarySummary

There are different types of lymphomas but there are a There are different types of lymphomas but there are a certain few that is more predominant in the AIDS certain few that is more predominant in the AIDS populationpopulationImmunocompromised states such as AIDS predisposes Immunocompromised states such as AIDS predisposes to the development of lymphomasto the development of lymphomasThere are different imaging modalities in the diagnosis There are different imaging modalities in the diagnosis of Nonof Non--Hodgkin's LymphomasHodgkin's LymphomasPrognosis of patients with AIDS and Non Hodgkin’s Prognosis of patients with AIDS and Non Hodgkin’s Lymphoma is dependent on a lot of factorsLymphoma is dependent on a lot of factors

AcknowledgementsAcknowledgements

Dr. LiebermanDr. LiebermanMaria LevantakisMaria LevantakisDr Fargol BooyaDr Fargol BooyaDr Martin SmithDr Martin Smith

ReferencesReferences

http://en.wikipedia.org/wiki/Lymphoma.http://en.wikipedia.org/wiki/Lymphoma. Assessed on October 17th, 2008Doweiko, J. MD, Groopman, J. MD. Doweiko, J. MD, Groopman, J. MD. AIDsAIDs--related lymphomasrelated lymphomas. Uptodate.com. Date viewed . Uptodate.com. Date viewed

10/17/200810/17/2008Doweiko, J. MD, Groopman, J. MD. Doweiko, J. MD, Groopman, J. MD. AIDsAIDs--related lymphomas: Primary Effusionrelated lymphomas: Primary Effusion LymphomaLymphoma . . Uptodate.com. Date viewed 10/17/2008Uptodate.com. Date viewed 10/17/2008Freedman, A. MD, Friedberg, J MD. Freedman, A. MD, Friedberg, J MD. Approach to the diagnosis of NonApproach to the diagnosis of Non--Hodgkin's Lymphomas.Hodgkin's Lymphomas.Uptodate.com. Date viewed 10/17/2008.Uptodate.com. Date viewed 10/17/2008.Santiago Enrique Rossi, MD et al. Santiago Enrique Rossi, MD et al. TreeTree--inin--Bud pattern at Thin section of CT of the lungs: Bud pattern at Thin section of CT of the lungs: RadiologyRadiology--Pathologic overviewPathologic overview. Education Exhibit. Radiological Society of North America. 2005. Education Exhibit. Radiological Society of North America. 2005Schoder et al. Schoder et al. Intensity of 18fluorodeoxyglucose uptake in positron emission toIntensity of 18fluorodeoxyglucose uptake in positron emission tomography mography distinguishes between indolent and aggressive nondistinguishes between indolent and aggressive non--Hodgkin's lymphomaHodgkin's lymphoma. Journal of Clinical . Journal of Clinical Oncology, 07/20/2005. Oncology, 07/20/2005. 46434643--51 51