Oncology Flashcards
Medulloblastoma fast facts
Most common malignant brain tumour Embryonal neuroepithelial tumour M>F Small round blue cell tumour Associated syndromes: gorlin, Li-Fraumeni, Turcot, Gardner, Cowden Arise from cerebellum, typically vermis. ONLY occurs in the posterior fossa. Spreads along the neuroaxis: metastatic disease 1/3 at presentation Prognosis WNT1: good SHH: intermediate MYC, p52: bad
ATRT (Atypical teratoid/ rhabdoid tumour)
Embryonal malignancy Highly malignant Usually in children <3yrs Short clinical history 90% show loss of INI1 nuclear staining (SMARCB1) Can occur ANYWHERE in the brain or spine Poor prognosis, survival ~ 12 months even with complete resection Check for germline mutation- at risk for renal + soft tissue tumours
Ependymoma fast facts
Tumour originating from the wall of the ventricle or spinal cord composed of neoplastic ependymal cells Slow growing Increased in NF2 Surgery + radiation main treatment. Not usually chemosensitive.
In what tumour do you find rosenthal fibres?
Low grade glioma: astrocytoma
Low grade glioma fast facts
Largest group of CNS tumours- mostly juvenile pilocytic astrocytoma 2/3 occur in posterior fossa Almost ALL tumours involving the optic pathway are juvenile astrocytomas Generally good outcomes
Types of transplants
Autologous = patient receives own cells Syngeneic = use of cells from identical twin Allogenic= cells collected from a relative or unrelated donor
Types of transplant matches
HLA identical Haploidentical: half match Mismatch Matching based on HLA typing. Tested in 2 ways: 1) serologic testing (use antibody assay for HLA antigens) 2) molecular typing (looks at underlying alleles on chromosome)
Preferred characteristics of a transplant donor
Matched sibling= ideal donor CMV negative Males + non-parous women (women may have antibody to Y antigen) ABO + Rh status compatibility NOT required
Graft preparation: What is the purpose of T cell depletion of a transplant recipient / donor
Reduces the risk of GVHD BUT this also increases the risk of recurrence + infection
Describe the graft vs leukaemia effect
In addition to stem cells, the graft contains mature blood cells of donor origin, including T cells, B cells, natural killer cells, and dendritic cells. These cells repopulate the recipient’s lymphohematopoietic system and give rise to a new immune system, which helps eliminate residual leukemia cells that survive the conditioning regimen.
Describe graft vs host disease
Donor alloreactive cytotoxic CD8+ effector T cells may attack recipient tissues, particularly the skin, gastrointestinal (GI) tract, and liver
Who does HLA-A, HLA-B, and HLA-C major histocompatibility complex (MHC) class I molecules, present peptides to?
CD8+ T cells
Who does HLA-DR, HLA-DQ, and HLA-DP MHC class II molecules present peptides to?
CD4+ T cells
Acute vs chronic GVHD
GVHD is caused by engraftment of immunocompetent donor T lymphocytes in an immunologically compromised host who shows histocompatibility differences with the donor. These differences between the donor and the host may result in donor T-cell activation against either recipient major histocompatibility complex (MHC) antigens or minor histocompatibility antigens. Acute: within 3 months of transplant Chronic develops OR persists > 3 months post transplant
Grades of GVHD
Grade I: skin rash (maculopapular) only < 25% BSA Grade II: mod severe multiorgan disease. Rash 25-50% BSA, elevated bili, diarrhoea Grade III: severe multiorgan disease. Rash >50% BSA, elevated bili, diarrhoea (survival 25%) Grade IV: life threatening (survival 5%)
Pharmacological prophylaxis of GVHD
Immunosupression - Cyclosporine or tacrolimus - Methotrexate, prednisolone, MMF Prednisolone remains the most effective 1st line treatment (response ~55%)
What 2 factors have increased the rates of chronic GVHD
Use of MUD Use of peripheral blood as stem cell source
Clinical manifestations + biopsy findings in acute GVHD
SKIN - Maculopapular rash, pain, blisering - Biopsy: apoptotic bodies in the basal layer of epithelium LIVER - Jaundice + deranged LFTs - Biopsy: bile duct destruction with apoptotic bodies GIT: - N+V, diarrhoea, abdo pain, bleeding. - Biopsy: apoptotic bodies in the base of crypts
Primary vs secondary graft failure
Primary graft failure - Failure to achieve a neutrophil count of 0.5 × 109/L after transplantation. Secondary graft failure - Loss of peripheral blood counts following initial transient engraftment of donor cells.
Causes of graft failure
- Inadequate stem cell dose - Viral infections (e.g. CMV, HHV6) which are often associated with activation of recipient macrophages - Immunologically mediated rejection by residual recipient T cells that survive conditioning
Describe veno-occlusive disease (VOD)
AKA sinusoidal obstruction syndrome Injury to hepatic venous endothelium leads to dilation + RBC congestion = obstruction of the sinusoidal blood flow. Venous occlusion –> necrosis of liver –> multi-organ failure Onset usually within 30 days
Risk factors for VOD
- Previous hepatic disease - CXT induction agents: cyclophosphamide, busulphan, MTX - Allogenic graft > autologous graft - Young age - Abdominal radiation - Repeated transplants - HLH
Clinical features of VOD
Weight gain Ascities Tender hepatomegaly Elevated bilirubin (jaundice) Thrombocytopenia Hepatosplenomegaly
Treatment of VOD
Defibrotide Ursodeoxycholic acid
What cancer has the highest rate of secondary malignancy?
Hereditary retinoblastoma (~50% at 50yrs)
Ectopic production of what hormone may cause precocious puberty in males with hepatoblastoma
bHCG Approximately 10% of hepatoblastomas secrete ectopic b-hCG. hCG, through its LH-like action, causes Leydig cell stimulation in the testes. In turn, testosterone levels reach those of a normal adult, and secondary sexual characteristics develop together with premature skeletal maturity. The testes usually do not significantly enlarge – as Leydig cells only constitute about 25% of testicular volume; Sertoli cell hyperplasia or spermatogenesis is dependent on FSH.
Is development of inhibitors more common in haemophilia A or B?
Haemophilia A (FVIII deficiency) The inhibitors are antibodies (primarily IgG) directed against the specific deficient factor. This occurs in: 25-30% of patients with severe haemophilia A; and 3-5% of patients with severe haemophilia B. Development of an inhibitor, usually occurs early in treatment, shortly after replacement therapy has been initiated (within first 50 exposure days of factor given). Inhibitors are more likely in severe disease. The presence of an inhibitor does not lead to a marked increase in bleeding events, but inhibitors can make bleeding episodes more difficult to control. Inhibitor activity is measured by the Bethesda assay (diagnoses inhibitor presence and quantifies the antibody titre) Management is with factor VIII replacement therapy, with minimal change in the factor VIII dose.. Inhibitor eradication (immune tolerance induction), requires routine administration of the deficient factor to reset the patient’s immune system.
Difference in clinical presentation of radiation vs. anthracycline induced cardiotoxicity
Patients who present with cardiac toxicity due to radiation therapy alone generally present with pericardial effusions or constrictive pericarditis. Radiation can also lead to premature coronary artery disease. Patients with anthracycline-induced cardiomyopathy usually present with symptoms of congestive heart failure (CHF), which may develop spontaneously or be initiated by stressors such as extreme exertion, as in weight lifting or difficult labor. Pericarditis may also be present, further compromising cardiac function. Additionally, ventricular arrhythmias may occur.
