Transcript Post-transplant Lymphoproliferative Disorder

Post-transplant
Lymphoproliferative Disorder
- Case Presentation -
Alison Jazwinski, MD
Flinders Medical Center
Adelaide, South Australia
Patient
• 43 yo male
• HPI:
• Sent to FMC with persistently elevated liver enzymes
on routine lab check (ALT 971, AST 521)
• On admission reported taking 2 Paracetamol tablets
every 2 hours for a headache
• Denied abdominal pain, melena/hematemesis,
vomiting, diarrhea
• Also denied numbness, weakness, difficultly
swallowing or speaking
Patient
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PMH:
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Protein C deficiency
Budd-Chiari Syndrome resulting in liver
transplant 11/2007
Medications
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Tacrolimus 7mg bid
Clonidine 100mg bid
Propanolol 40mg bid
Warfarin
Physical Exam
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Vitals: BP 130/78, HR 80, RR 16, temp 36.8
Gen: well appearing male in NAD
HEENT: no scleral icterus, MMM
Neck: no lymphadenopathy
CV: RRR no M/R/G
Lungs; CTAB no W/R/R
Abdomen: soft, mildly TTP RUQ, no rebound/guarding,
NABS
• Extrem: no edema
• Neuro: CN II-XII intact, strength 5/5 all muscle groups,
reflexes 2+ throughout, gait normal, sensation intact to
light touch, pinprick, vibration
Admission Labs
Na 141
K 4.0
Cl 105
Bicarb 25
Urea 6.2 (WNL)
Cr 103 (WNL)
Hb 127g/L
Hct 37
WBC 5.6
Platelets 108
Total prot 76g/L (WNL)
Albumin 43g/L (WNL)
Alk phos 165U/L
ALT 332U/L
AST 58U/L
Bili 14umol/L (WNL)
Paracetamol <10
Tacrolimus 7.7
Patient
• LFT abnormalities thought to be related to
Paracetamol over-use.
• He was using it for a headache… why did
he have a headache?
• Further evaluation revealed…
Head CT
Head CT
28mm ring enhancing mass in right temporal
lobe with moderate surrounding vasogenic
edema. There is 6mm midline shift and
effacement of overlying cerebral sulci.
Brain MRI
Brain MRI
Solitary, thick walled ring enhancing lesion in right
temporal lobe measuring 2.8cm x 2.3 cm x 1.8cm
associated with extensive vasogenic edema and
adjacent mass effect. Appearances are
indeterminate, could represent a cerebral abscess
however a high-grade glioma or solitary
metastasis may also give this appearance.
When spectroscopy was added, the findings were
keeping with a high grade primary cerebral
neoplasm such as a GBM.
Differential Diagnosis
• Infection
• Bacterial abscess
• Cryptococcus
• Toxoplasma
• Malignancy
• Lymphoma
• Primary CNS tumor
• Metastatic disease
Further steps
• Patient was initiated on dexamethasone and
loaded with phenytoin for seizure proph
• CT chest/abdomen/pelvis negative for
source of primary malignancy
• On to surgery with resection
• Cultures sent for AFB, cryptococcus,
toxoplasma, and bacterial culture, all
returned negative
Histology
• Features most in keeping with an EBV
driven post-transplant lymphoproliferative
disorder with no convincing monoclonality
identified on immunoperoxidase stains and
associated with considerable tissue necrosis
PTLD
• Mostly large cell lymphomas
• Most B cell type
• Extranodal involvement in 30-70%
• Appears to be related to EBV inducing B
cell proliferation in setting of chronic
immunosuppression
• PTLD cells are of host origin in the majority
of cases
Transplantation 2006;81:888
Transplantation 1990;49:1080
Putative Checkpoints in the EBV Life Cycle
That Might Give Rise to Lymphoma
N Engl J Med 350:1328, March 25, 2004
Forms of Disease
• Benign polyclonal lymphoproliferation (55%)
• Infectious mono-type illness
• Develops 2-8 weeks after immunosuppression initiated
• Polyclonal B cell proliferation with normal cytogenetics
• Polyclonal lymphoproliferation with early
malignant transformation (30%)
• Localized solid tumors (15%)
• Monoclonal B cell proliferation with malignant
cytogenetic abnormalities
Am J Pathol 1988; 133:173
Areas of Involvement
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Gastrointestinal tract
Lungs
Skin
Liver
CNS (20-25%)
Allograft lesions (20-25%)
Transplantation 1995; 59:240
Treatment Approaches
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Reduction in immunosuppression
Antiviral agents
Chemotherapy
Immune globulin
Surgical resection
Radiation
Interferon-alpha
Pediat Transplant 2001; 5:198
Reduction of Immunosuppression
• Most will resolve with this
• Best response among those with early disease
where immunosuppression is a major contributing
factor
• Depends on severity of disease
• Could reduce Prednisone to maintenance doses (7.510mg) and stop other agents
• Could reduce Cyclosporine or Tacrolimus by 50% and
discontinue Azathioprine or MMF
• Risk is allograft rejection
Transplantation 1999; 68:1517
Other methods of treatment
• Only case reports at this time
• Largely dependent on severity of disease
and treatment center
Thanks!