Clinical Pathological Clinical Pathological ConferenceConference

Shrujal Baxi, M.D.Shrujal Baxi, M.D.Chief Resident Chief Resident

Department of MedicineDepartment of MedicineNovember 9, 2007November 9, 2007

Chief ComplaintChief Complaint

An 83 year-old man presents with An 83 year-old man presents with three days of intermittent chest pain three days of intermittent chest pain

History of Present IllnessHistory of Present Illness Six months prior to admission when he noted decreased Six months prior to admission when he noted decreased

exercise tolerance and was found to have a normocytic exercise tolerance and was found to have a normocytic

anemiaanemia thought to be Myelodysplastic syndrome, but no thought to be Myelodysplastic syndrome, but no work up done at that timework up done at that time

About five months prior to admission, pt noted a About five months prior to admission, pt noted a nonproductive, chronic cough that was worse in nonproductive, chronic cough that was worse in

evenings and relieved with prn albuterol therapyevenings and relieved with prn albuterol therapy

One month prior to admission, the patient again started One month prior to admission, the patient again started experiencing increasing shortness of breath.experiencing increasing shortness of breath.

5-10lb weight loss over last few months, night sweats, 5-10lb weight loss over last few months, night sweats, subjective feverssubjective fevers

History of Present IllnessHistory of Present Illness

On day of admission, pt presented with three days On day of admission, pt presented with three days of intermittent chest pain that was substernal and of intermittent chest pain that was substernal and radiated to his left arm and shoulder. It was radiated to his left arm and shoulder. It was sharp and stabbing in nature and worse with sharp and stabbing in nature and worse with inspiration. The episodes would last hours and inspiration. The episodes would last hours and were variably relieved with sublingual were variably relieved with sublingual

nitroglycerin.nitroglycerin.

Past Medical History:Past Medical History: Hypertension ≥ 20 yearsHypertension ≥ 20 yearsDiabetes ≥ 10 yearsDiabetes ≥ 10 yearsHypercholesterolemia ≥ 10 yearsHypercholesterolemia ≥ 10 years

Past Surgical HistoryPast Surgical History::

Appendectomy Appendectomy

Medications:Medications: (outpatient) (outpatient)

GlyburideGlyburide

RamiprilRamipril

AtenololAtenolol

Erythropoietin and ironErythropoietin and iron

albuterol prnalbuterol prn

Allergies:Allergies: nonenone

Family HistoryFamily History:: Brother died at 55 of MI. No family history of Brother died at 55 of MI. No family history of

malignancy, inflammatory conditionsmalignancy, inflammatory conditions

Social History:Social History: Born in the United States, patient fought in East Born in the United States, patient fought in East

Asia during World War II. He has no recent Asia during World War II. He has no recent travel. travel.

50 pack year tobacco history, quit 35 years ago. No 50 pack year tobacco history, quit 35 years ago. No alcohol use. No illicit drug use. Pt lives with wife alcohol use. No illicit drug use. Pt lives with wife in upstate New York. Pt worked in construction in upstate New York. Pt worked in construction prior to retiring at the age of 69. prior to retiring at the age of 69.

ROS:ROS: otherwise noncontributoryotherwise noncontributory

General: General: Well developed male with evidence of Well developed male with evidence of respiratory distress who appears younger than respiratory distress who appears younger than stated agestated age

Vital SignsVital Signs: BP 105/68 HR 120, regular, RR 20, Temp : BP 105/68 HR 120, regular, RR 20, Temp 98.2, SpO2 92% room air98.2, SpO2 92% room air

HEENTHEENT: Oropharynx clear and dry: Oropharynx clear and dry

Lymph Nodes: Lymph Nodes: No cervical, axillary or inguinal No cervical, axillary or inguinal lymphadenopathy lymphadenopathy

NeckNeck: Supple, jugular venous distention difficult to : Supple, jugular venous distention difficult to assessassess

Physical ExamPhysical Exam

PulmonaryPulmonary: Decreased breath sounds at bases, 1/3 : Decreased breath sounds at bases, 1/3 up bilaterally. Dull to percussionup bilaterally. Dull to percussion

HeartHeart: Decreased heart sounds, tachycardic, : Decreased heart sounds, tachycardic, regular rhythm, pulsus paradoxus of 22regular rhythm, pulsus paradoxus of 22

AbdominalAbdominal: Soft, nontender, nondistended, normal : Soft, nontender, nondistended, normal bowel sounds, with liver span of 14cm and dullness bowel sounds, with liver span of 14cm and dullness in Traube’s space in Traube’s space

ExtremitiesExtremities: No peripheral edema, 2+ peripheral : No peripheral edema, 2+ peripheral pulsespulses

SkinSkin: No rashes, no purpura, no petechia: No rashes, no purpura, no petechia

Physical ExamPhysical Exam

Admission LabsAdmission LabsLaboratoryLaboratory On AdmissionOn Admission Reference RangeReference Range

Hemoglobin (g/dl)Hemoglobin (g/dl) 10.110.1 13-1813-18

HematocritHematocrit (%)(%) 29.529.5 40-5240-52

White Cell Count (per mm3)White Cell Count (per mm3) 7,2007,200 4,500-11,0004,500-11,000

Differential Count (%) Differential Count (%)

NeutrophilsNeutrophils 5353 42-75%42-75%

LymphocytesLymphocytes 2222 20-50%20-50%

MonocytesMonocytes 77 2-12%2-12%

EosinophilsEosinophils 1818 0-7%0-7%

Mean Corpuscular VolumeMean Corpuscular Volume 83.283.2 80-9580-95

Platelet Count (per mm3)Platelet Count (per mm3) 195,000195,000 150-450,000150-450,000

MVPMVP 7.37.3 7.5-10.57.5-10.5

Partial-thromboplastin time, activated (sec)Partial-thromboplastin time, activated (sec) 33.6 33.6 23.3-35.623.3-35.6

Prothrombin time (sec) Prothrombin time (sec) 18.218.2 10.0-13.810.0-13.8

INRINR 1.51.5 .9-1.2.9-1.2

Lactate Dehydrogenase/LDHLactate Dehydrogenase/LDH 348348 110-225110-225

Admission LabsAdmission Labs

LaboratoryLaboratory On AdmissionOn Admission Reference RangeReference Range

Sodium (mmol/liter)Sodium (mmol/liter) 141141 135-145 135-145

Potassium (mmol/liter)Potassium (mmol/liter) 4.14.1 3.5-5.03.5-5.0

Chloride (mmol/liter)Chloride (mmol/liter) 104104 100-110100-110

Carbon dioxide (mmol/liter)Carbon dioxide (mmol/liter) 2828 24-3224-32

Urea nitrogen (mg/dl)Urea nitrogen (mg/dl) 2121 6-226-22

Creatinine (mg/dl)Creatinine (mg/dl) .7.7 .4-1.2.4-1.2

GlucoseGlucose 9595 65-11565-115

Calcium (mg/dl)Calcium (mg/dl) 8.58.5 8.5-10.58.5-10.5

Magnesium (mmol/liter)Magnesium (mmol/liter) 0.80.8 0.7-1.00.7-1.0

Phosphorus (mmol/liter)Phosphorus (mmol/liter) 2.92.9 2.6-4.52.6-4.5

Aspartate aminotransferase (U/liter)Aspartate aminotransferase (U/liter) 2525 10-4210-42

Alanine aminotransferase (U/liter)Alanine aminotransferase (U/liter) 1818 10-4210-42

Total Bilirubin (g/dl)Total Bilirubin (g/dl) 2.62.6 0.1-1.20.1-1.2

Alk PhosAlk Phos 109109 42-12142-121

Total Protein (g/dl)Total Protein (g/dl) 6.16.1 6.4-8.26.4-8.2

Albumin (g/dl)Albumin (g/dl) 4.24.2 3.8-5.13.8-5.1

EKGEKG

Upon AdmissionUpon Admission

A prompt cardiac evaluation revealed a moderate to A prompt cardiac evaluation revealed a moderate to large pericardial effusion with right atrial collapse large pericardial effusion with right atrial collapse with a question of a right atrial mass. Pt was with a question of a right atrial mass. Pt was admitted to CCU for further evaluation. A admitted to CCU for further evaluation. A diagnostic procedure was performed…diagnostic procedure was performed…

T1 T2 STIR

PATHOLOGY

Dr. Hui TsouClinical Assistant Professor Department of Pathology  

Final DiagnosisFinal Diagnosis

Diffuse Large B-Cell Lymphoma Diffuse Large B-Cell Lymphoma (DLBCL) with primary cardiac (DLBCL) with primary cardiac involvementinvolvement

- CD45+, CD20+ - CD45+, CD20+

- CD3-, CD15-, CD30-, CD10-- CD3-, CD15-, CD30-, CD10-

Primary Cardiac TumorsPrimary Cardiac Tumors

Prevalence-.002-.025% at autopsyPrevalence-.002-.025% at autopsy 75% benign in nature75% benign in nature Systemic embolization is presenting Systemic embolization is presenting

symptom in 25-50% of casessymptom in 25-50% of cases Metastatic tumors 10-40X more likely Metastatic tumors 10-40X more likely

than primary tumor than primary tumor

Primary Cardiac TumorsPrimary Cardiac Tumors

Benign (75% of all cases)Benign (75% of all cases) MyxomaMyxoma RhabdomyomaRhabdomyoma FibromaFibroma TeratomaTeratoma

Malignant (25% of all cases)Malignant (25% of all cases) Sarcoma (majority)Sarcoma (majority)

• AngiosarcomaAngiosarcoma• RhabdomyosarcomaRhabdomyosarcoma

LymphomaLymphoma HistiocytomaHistiocytoma

Malignant (25 of all cases)Malignant (25 of all cases)SarcomaSarcoma

AngiosarcomaAngiosarcomaRhabdomyosarcomaRhabdomyosarcomaFibrosarcomaFibrosarcomaLeiomyosarcomaLeiomyosarcoma

OtherOtherLymphomaLymphomaHistiocytomaHistiocytoma

Primary Cardiac Lymphoma (PCL)Primary Cardiac Lymphoma (PCL) Defined as presence of Non-Hodgkin’s Defined as presence of Non-Hodgkin’s

Lymphoma confined to the heart or Lymphoma confined to the heart or pericardiumpericardium

PCL represents <2.0% of 1° cardiac tumors PCL represents <2.0% of 1° cardiac tumors

and 0.5% of extranodal lymphomasand 0.5% of extranodal lymphomas

More common in immunocompromisedMore common in immunocompromised

Increased incidence due to AIDS and Increased incidence due to AIDS and

improved imaging techniquesimproved imaging techniques

LymphomaLymphoma

Now the 5Now the 5thth most common cancer most common cancer diagnosed in both men and womendiagnosed in both men and women

Represent 4% of all cancersRepresent 4% of all cancers Approximately 63,000 cases diagnosed Approximately 63,000 cases diagnosed

annuallyannually Age at diagnosis is 60 with more than 50% Age at diagnosis is 60 with more than 50%

over the age of 65over the age of 65 5 year survival is 63% and 10 year survival 5 year survival is 63% and 10 year survival

is 49%is 49%

PathophysiologyPathophysiology

PathophysiologyPathophysiology

Kuppers R et al. N Engl J Med 1999;341:1520-1529

Assignment of Human B-Cell Lymphomas to Their Normal B-Cell Counterparts

PathophysiologyPathophysiology

PCLPCL

Common presentations of this uncommon Common presentations of this uncommon diagnosis are based on location of tumordiagnosis are based on location of tumor

Right-sided heart failureRight-sided heart failure Precordial chest painPrecordial chest pain Pericardial effusionPericardial effusion Superior vena cava syndromeSuperior vena cava syndrome ArrhythmiaArrhythmia CHFCHF Constitutional SymptomsConstitutional Symptoms

Pathogenesis of DiseasePathogenesis of Disease

Environmental Factors

Mutation to Oncogene

of Lymphoid Cell

Tumor Mass fromreplicating atypical

lymphoma cells

Release of Cytokines (TNF, IL-6)

Pericardial Effusion

Tissue invasion of right atriumand septal wall

Atrial Fibrillation

Pleural effusions

cough dyspnea chest pain

Anemia of Chronic Disease

WeightLoss

fatigue

Night Sweats

Diagnostic StudiesDiagnostic Studies

Labs: Labs: LDH, LDH, IL-2, IL-2, ESR ESR ECG: AV block, RBBB, Inverted T waves, ECG: AV block, RBBB, Inverted T waves,

Low voltageLow voltage CXR: Pleural Effusion and/or CardiomegalyCXR: Pleural Effusion and/or Cardiomegaly Echocardiography: Echocardiography:

• Hypoechoic masses in the R atrium with pericardial Hypoechoic masses in the R atrium with pericardial effusioneffusion

• TTE: difficulty visualizing pulmonary vessels, SVC, R TTE: difficulty visualizing pulmonary vessels, SVC, R atriumatrium

Diagnostic StudiesDiagnostic Studies CTCT

• Appears hypodense or isodense relative to adjacent Appears hypodense or isodense relative to adjacent myocardium myocardium

• + Contrast: heterogenous enhancement+ Contrast: heterogenous enhancement MRIMRI

• T1 images: Hypointense and Dark T1 images: Hypointense and Dark • T2 images: Hyperintense and BrightT2 images: Hyperintense and Bright• + Gadolinium: Heterogenous enhancement+ Gadolinium: Heterogenous enhancement• Useful in making diagnosis and assessing response to RXUseful in making diagnosis and assessing response to RX

Nuclear medicine techniquesNuclear medicine techniques• Gallium 67Gallium 67• Technetium-99m hexakis-2-methoxyisobutyl isonitrileTechnetium-99m hexakis-2-methoxyisobutyl isonitrile• Thallium-201Thallium-201

Diagnostic StudiesDiagnostic Studies

Tissue is the Issue…Tissue is the Issue… Pericardial fluid Pericardial fluid

• Diagnostic in 67 % of casesDiagnostic in 67 % of cases

Tissue biopsyTissue biopsy• MediastinoscopyMediastinoscopy• Thoracoscopic biopsyThoracoscopic biopsy• TEE guided biopsyTEE guided biopsy• Endomyocardial transvenous biopsyEndomyocardial transvenous biopsy• Exploratory thoracotomyExploratory thoracotomy

TreatmentTreatment

Treatment for DLBCL is the chemotherapy Treatment for DLBCL is the chemotherapy regimen of R-CHOPregimen of R-CHOP

R=RituximabR=Rituximab C=CyclophosphamideC=Cyclophosphamide H=AdriamycinH=Adriamycin O=VincristineO=Vincristine P=PrednisoneP=Prednisone

Alternative regimens include: Alternative regimens include: COPCOP CHOPCHOP Bone Marrow TransplantBone Marrow Transplant

Follow-UpFollow-Up

Upon admission, pt had pleural and Upon admission, pt had pleural and pericardial drains placedpericardial drains placed

While work-up continuing, patient While work-up continuing, patient developed rapid afib controlled with low-developed rapid afib controlled with low-dose b-blockerdose b-blocker

Due to concern of significant atrial wall Due to concern of significant atrial wall involvement of disease, first 2 cycles of R-involvement of disease, first 2 cycles of R-CHOP given in CCU setting with continuous CHOP given in CCU setting with continuous cardiac monitoringcardiac monitoring

Patient is currently disease free after Patient is currently disease free after receiving a complete course of R-CHOPreceiving a complete course of R-CHOP

Thank you…Thank you…

Dr. Srichai-ParsiaDr. Srichai-Parsia Dr. KahnDr. Kahn Dr. Hui TsouDr. Hui Tsou Dr. BlaserDr. Blaser Dr. GriecoDr. Grieco Dr. BallardDr. Ballard Dr. Mark FischDr. Mark Fisch