Lymphoma Flashcards
Lymphoma, Chemo and Tumour Lysis Syndrome - Example Question
A 44 year old female patient is admitted to the oncology ward to undergo chemotherapy for Diffuse Large B-Cell lymphoma stage IVb. She had originlly presented to her GP with intermittent abdominal bloating and constipation and occasional shortness of breath. She also reported having to often get up in the middle of the night to change the bed clothes due to drenching sweats. Her GP had been concerned by these symptoms and had organised an immediate chest X-ray to be undertaken at the nearby hospital.
Chest X-ray
large mediastinal mass with clear lung fields.
On receiving this report the GP arranged an urgent appointment with a local haematologist as he suspected that the patient was suffering from lymphoma. She was seen only 4 days later. Given the clinical history the team at the hospital arranged some urgent investigations.
Hb 9.5 g/dl
Platelets 140 * 109/l
WBC 36.5 * 109/l
Lactate Dehydrogenase 2540IU/l
CT-guided Lymph node biopsy
cells are large, with prominent nucleoli and abundant cytoplasm and many mitoses expressing CD19 and CD20 markers
PET scan
large extra-nodal disease bulks most notable in the ileo-caecal area and in the mediastinum. Overall bulky disease in keeping with the diagnosis of advanced stage lymphoma.
The patient is admitted to receive cycle one of R-CHOP chemotherapy under close monitoring.
What electrolyte abnormalities would suggest tumour lysis syndrome?
High Potassium, high Calcium, low Phosphate Low Potassium, high Calcium, low Phosphate > High Potassium, low Calcium, high Phosphate Low Potassium, low Calcium, high Phosphate Low Potassium, low Calcium, low Phosphate
Tumour Lysis Syndrome
Tumour lysis syndrome
Tumour lysis syndrome (TLS) is a potentially deadly condition related to the treatment of high grade lymphomas and leukaemias. It can occur in the absence of chemotherapy but is usually triggered by the introduction of combination chemotherapy. On occasion it can occur with steroid treatment alone. Awareness of the condition is critical as prophylactic medication can be given to prevent the potentially deadly effects of tumour cell lysis.
Patients at high risk of TLS should be given IV allopurinol or IV rasburicase immediately prior to and during the first days of chemotherapy. Rasburicase is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. Patients in lower risk groups should be given oral allopurinol during chemotherapy cycles in an attempt to avoid the condition.
TLS occurs from the breakdown of the tumour cells and the subsequent release of chemicals from the cell. It leads to a high potassium and high phosphate level in the presence of a low calcium. It should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level.
From 2004 TLS has been graded using the Cairo-Bishop scoring system -
Laboratory tumor lysis syndrome: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy.
uric acid > 475umol/l or 25% increase
potassium > 6 mmol/l or 25% increase
phosphate > 1.125mmol/l or 25% increase
calcium < 1.75mmol/l or 25% decrease
Clinical tumor lysis syndrome: laboratory tumor lysis syndrome plus one or more of the following:
increased serum creatinine (1.5 times upper limit of normal)
cardiac arrhythmia or sudden death
seizure
Burkitt’s Lymphoma
Burkitt’s lymphoma is a high-grade B-cell neoplasm. There are two major forms:
endemic (African) form: typically involves maxilla or mandible
sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV
Burkitt’s Lymphoma - Genetics
Burkitt’s lymphoma is associated with the c-myc gene translocation, usually t(8:14). The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt’s lymphoma and to a lesser extent the sporadic form.
Burkitt’s Lymphoma - Microscopy Findings
Microscopy findings
‘starry sky’ appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
Burkitt’s Lymphoma - Mx
Management is with chemotherapy. This tends to produce a rapid response which may cause 'tumour lysis syndrome'. Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*) is often given before the chemotherapy to reduce the risk of this occurring. Complications of tumour lysis syndrome include: hyperkalaemia hyperphosphataemia hypocalcaemia hyperuricaemia acute renal failure
*allantoin is 5-10 times more soluble than uric acid, so renal excretion is more effective
Pt with HIV and Lymphoma - Example Question
A 29-year-old man who is known to be HIV positive is reviewed. He has been taking anti-retroviral therapy for the past 2 years and has remained relatively well. Over the past few weeks however he has developed abdominal distension with some discomfort in the right iliac fossa. On examination a mass can be felt in the right lower quadrant. A biopsy shows a B cell lymphoma. Sheets of a medium sized lymphoid cells with high proliferative activity, forming a ‘starry sky’ appearance, are noted. What cytogenic abnormality is most likely to be found?
t(11;14) t(14;18) > t(8;14) t(9;22) t(11;18)
This patient has an immunodeficiency-associated Burkitt lymphoma.
Hodgkin’s Lymphoma - Histological Classification
NB Bimodal age distributions - 30s and 70s
NODULAR SCLEROSING = Most common (70%) > Good prognosis, more common in F, assoc with Lacunar cells
MIXED CELLULARITY = 20% > Good prognosis, assoc with large number of Reed Sternberg cells
LYMPHOCUTE PREDOMINANT = 5% > Best prognosis
LYMPHOCYTE DEPLETED = Rare > Worst prognosis
Hodgkin’s Lymphoma - Prognosis
Apart from histology above
- B symptoms imply poor prognosis (weight loss > 10% in 6m, fevers > 38, night sweats)
Other factors identified in 1998 NEJM paper:
- age >45
- stage IV disease
- Hb < 10.5g/dl
- Lymphocyte count < 600/microL or < 8%
- male
- albumin < 40g/L
- WBC > 15,000/microL
Hodgkin’s Lymphoma - Staging
= malignant proliferation of lymphocytes characterised by presence of the Reed-Sternberg cell
Bimodal age distribution - 30s and 70s
ANN-ARBOR STAGING OF HODGKIN'S LYMPHOMA I - Single lymph node II - 2 or more lymph nodes/regions on same sides of diaphragm III - Nodes on both sides diaphragm IV - Spread beyond lymph nodes
Each stage may be subdivided into A or B
A = No systemic Sx other than pruritus
B = weight loss > 10% in last 6m, fever >38, night sweats (poor prognosis) (B Symptoms)
Complications of Tumour Lysis Syndrome
Complications of tumour lysis syndrome include: hyperkalaemia hyperphosphataemia hypocalcaemia hyperuricaemia acute renal failure
Diffuse Large B Cell Lymphoma - Genetics
BCL2 and TP53 mutations are seen in diffuse large B cell lymphoma.
