Posttransplant Lymphoproliferative Disorder Case Presentation

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Post-transplant Lymphoproliferative Disorder -
Case Presentation -

• Alison Jazwinski, MD
• Flinders Medical Center
• Adelaide, South Australia

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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

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Patient

• PMH
• Protein C deficiency
• Budd-Chiari Syndrome resulting in liver
  transplant 11/2007
• Medications
• Tacrolimus 7mg bid
• Clonidine 100mg bid
• Propanolol 40mg bid
• Warfarin

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Physical Exam

• 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

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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 lt10
• Tacrolimus 7.7

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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

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Head CT
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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.

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Brain MRI
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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.

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Differential Diagnosis

• Infection
• Bacterial abscess
• Cryptococcus
• Toxoplasma
• Malignancy
• Lymphoma
• Primary CNS tumor
• Metastatic disease

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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

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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

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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 200681888 Transplantation
1990491080
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Putative Checkpoints in the EBV Life Cycle That
Might Give Rise to Lymphoma
N Engl J Med 3501328, March 25, 2004
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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 133173
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Areas of Involvement

• Gastrointestinal tract
• Lungs
• Skin
• Liver
• CNS (20-25)
• Allograft lesions (20-25)

Transplantation 1995 59240
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Treatment Approaches

• Reduction in immunosuppression
• Antiviral agents
• Chemotherapy
• Immune globulin
• Surgical resection
• Radiation
• Interferon-alpha

Pediat Transplant 2001 5198
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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
  (7.5-10mg) and stop other agents
• Could reduce Cyclosporine or Tacrolimus by 50
  and discontinue Azathioprine or MMF
• Risk is allograft rejection

Transplantation 1999 681517
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Other methods of treatment

• Only case reports at this time
• Largely dependent on severity of disease and
  treatment center

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Thanks!