Any tumour with distant metastasis, blood or BM involvement Flashcards
Lymphoma
Malignant proliferation of peripheral lymphoid tissues (eg lymph nodes) but can sometimes infiltrate bone marrow (stage V)
Complex disease /group of diseases – over 40 different subtypes based on – histology, anatomical location immunophenotype!
Lymphoma – clinical signs
Asymptomatic / clinically well – but palpable mass/lymph node
Non-specific (general malaise, lethargy, inappetance, fever, weight loss)
Paraneoplastic disease
Hypercalcaemia (dogs>cats) – more T cell related, especially mediastinal mass
Hyperviscosity (rare) – more B cell (Ig) related
Organ specific signs - related to Anatomical classification
What is the most common type of lymphoma in dogs
Multicentric
What is multicentric lymphoma
Lymphadenomegaly – non-painful very enlarged LNs, usually generalised
What is the most common type of lymphoma in cats
Alimentary / gastro-intestinal
Outline alimentary/GI lymphoma
Usually in small intestine (focal or diffuse, ± LN enlargement), possibly stomach, colon rare
Vomiting, diarrhoea, weight loss, anorexia
Palpable abdominal mass, thickened loops intestine
Difference in pathology grade of alimentary lymphoma
High grade (poor px) – large/intermediate cells, often B cell, usually palpable abdominal mass - focal, ± LN enlargement, but can be diffuse too
Low grade (good px) - small cell - mature lymphocytes, often T cell
thickened intestine – more diffuse but can appear grossly normal (Ddx is IBD)
What do you expect to see of an ultrasonography of GI lymphoma
Mass, lymphadenomegaly
Thickening of gut wall
Loss of layering
Regional/segmental hypomotility – no peristalsis
Outline Mediastinal (thymic) lymphoma
Common in younger cats (FeLV positive) – poor px
Better prognosis in FeLV negative cats
Common in dogs (often hypercalcaemic)
Often T cell (thymus derived)
Clinical signs of Mediastinal (thymic) cancers
Cough, dyspnoea
Pleural effusion
Dull heart /lung sounds
Difference between primary and secondary skin lymphoma
Primary skin lymphoma starts in skin as the primary site while Secondary skin lymphoma spreads to the skin from another site eg lymph nodes and is part of multicentric disease
Primary skin lymphoma is always B cell derived (T/F)
False! Always T cell derived
What is extranodal lymphoma
More common in cats than dogs
Sites other than LNs eg eyes, nose, brain, spine, kidney
Prognosis varies (nasal good, CNS poor)
Outline the diagnosis of Lymphoma
Sample a representative lesion (mass) or LN
Examine representative fluid (eg pleural)
FNA for cytology is diagnostic in many cases
Biopsy is needed if any doubt from FNA or for more precise subclassifications /grade of lymphoma- Remove whole node to examine LN architecture
What do you expect to see from a FNA of a patient with lymphoma
Large/intermediate size immature lymphoblasts
Is High grade/large cell lymphoma common in both dogs and cats?
Most common canine multicentric presentation
Most common feline GI presentation
Summarise high grade lymphoma
Immature, undifferentiated lymphoblasts, rapidly dividing
Needs aggressive chemotherapy
What diagnostic test can i run from fluid gathered from FNA to test for lymphoma
Slides- Cytology
Fluid medium- Flow cytometry
DNA/PARR
What is PARR
PARR (Polymerase Chain Reaction for Antigen Receptor Rearrangement) is a molecular diagnostic technique to detect clonal rearrangements in the genes encoding the antigen receptor in lymphocytes. This method helps diagnose and characterize lymphoid malignancies, such as lymphoma and leukemia, in animals. By amplifying specific regions of immunoglobulin or T-cell receptor genes, PARR identifies clonal expansions indicative of malignancy, providing valuable diagnostic information when conventional methods may be inconclusive.
Summarise how flow cytometry is used to diagnose lymphoma
Sample Collection: A sample of cells, usually obtained from peripheral blood, bone marrow, lymph nodes, or other tissues suspected to be involved, is collected from the patient.
Cell Staining: The cells in the sample are stained with fluorescently labeled antibodies that specifically bind to cell surface markers characteristic of lymphocytes and their subpopulations.
Flow Cytometric Analysis: The stained cells are passed through a flow cytometer, a specialized instrument that can analyze the cells based on their fluorescence and light-scattering properties as they pass through a laser beam.
Cell Characterization: By measuring the intensity of fluorescence emitted by the labeled antibodies and analyzing light scatter properties, flow cytometry can identify and characterize different types of lymphocytes and detect abnormalities in their distribution and expression of cell surface markers.
Diagnosis of Lymphoma: In cases of lymphoma, flow cytometry can detect abnormal populations of lymphoid cells with atypical immunophenotypes, such as aberrant expression or loss of specific surface markers, altered cell size, or abnormal DNA content. These findings can help differentiate between different types of lymphoma (e.g., B-cell vs. T-cell lymphoma) and subclassify them based on their immunophenotypic profiles.
Summarise PCR for Ag rearrangement
Purpose: PCR for antigen receptor rearrangement is used to identify clonal expansions of lymphocytes, indicative of lymphoid malignancies like lymphoma and leukemia.
Principle: The technique amplifies specific regions of antigen receptor genes using PCR, targeting conserved sequences within variable regions that undergo rearrangement during lymphocyte development.
Procedure: DNA is extracted from lymphoid tissue or cells, and PCR is performed using primers specific to the variable regions of immunoglobulin or T-cell receptor genes. This amplifies rearranged gene segments, allowing detection of clonal lymphocyte populations.
Detection: Amplified PCR products are analyzed using gel electrophoresis or other methods to visualize DNA bands. A monoclonal band indicates clonal expansion, suggestive of lymphoid malignancy.
Outline staging of lymphoma
Bloods- Haematology reflects bone marrow cells as baseline prior to chemo and may see circulating LSA cells in blood
Biochemistry indicates organ involvement & PNSyndromes
FeLV and FIV status for cats
Diagnostic imaging of chest and abdomen and other sites
Urinalysis – baseline data
Bone marrow – stage V
Summarise treatment of lymphoma
1st – Stabilise paraneoplastic syndromes if present
2nd - Treat the lymphoma ( Steriods-Pallative/Chemotherapy)
What is the most common paraneoplastic syndrome of lymphoma
Hypercalcaemia
Treatment of hypercalcaemia
Need to reduce the level of ionised Ca in blood by Correcting fluid deficit
Restore circulating volume and support kidneys
0.9% saline diuresis at 2-3 x maintenance
Loop diuretics (frusemide) optional once rehydrated
Refractory hypercalcaemia
Condition where blood calcium levels remain persistently elevated despite treatment attempts
Drugs used to treat refractory hypercalcaemia
Glucocorticoids (IV or oral)
Decrease bone & intestinal absorption, promote renal excretion
Toxic to lymphocytes (do not give prior to diagnosis of LSA)
Calcitonin (SC)
Decreases serum calcium
Bisphosphonates (IV Pamidronate, Zoledronate or possibly oral alendronate)
Decrease osteoclast activity
Some antitumour activity (bone tumours)
Potentially analgesic
Renal toxicity possible with pamidronate (give lots of fluids)
Indications of a good prognosis for lymphoma
Well patients (substage a)
Low clinical stage (I or II)
Low histological grade
B cell immunophenotype (dogs - not yet shown in cats)
Nasal site (cats and probably dogs)
Complete remission (CR) to treatment (cats)
Using Doxorubicin in protocol (cats)
Indications of a bad prognosis for lymphoma
Sick patients (substage b)
High clinical stage (V) – bone marrow
T cell immunophenotype (dogs, not done in cats)
Certain anatomical locations eg skin, CNS, ocular
FeLV /FIV positive (cats)
Low body weight at presentation (cats) – often GI
Not achieving complete remission (cats)
Prior steroid use (multidrug resistance)
What is leukaemia
Haemopoietic malignancy that usually ORIGINATES in bone marrow – transformation of bone marrow cells and cell proliferation
Usually results in increased numbers of specific circulating blood cells
Can spread to peripheral lymphoid/haemopoietic organs
How is leukaemia classified
LYMPHOID (most common) or MYELOID
ACUTE or CHRONIC (myeloproliferative neoplasms)
Summarise difference between lymphoid and myeloid leukaemia
Origin:
Lymphoid Leukemia: Lymphoid leukemia originates from abnormal lymphoid stem cells, leading to the overproduction of immature lymphocytes (white blood cells) in the bone marrow and blood.
Myeloid Leukemia: Myeloid leukemia originates from abnormal myeloid stem cells, resulting in the overproduction of immature myeloid cells, including red blood cells, white blood cells, and platelets.
Cell Types Affected:
Lymphoid Leukemia: Lymphoid leukemia primarily affects lymphoid cells, including B-cells, T-cells, and natural killer (NK) cells.
Myeloid Leukemia: Myeloid leukemia affects myeloid cells, which give rise to red blood cells, white blood cells (other than lymphocytes), and platelets.
Summarise difference between acute and chronic leukemia
Acute: Neoplastic transformation early in the cell lineage (proliferation of blasts)
Chronic (myeloproliferative neoplasm (MPN)) :Neoplastic transformation late in the cell lineage (proliferation of mature differentiated cells)
Summarise pathogenesis of leukaemia
Leukemia arises from genetic mutations in blood-forming stem cells, leading to uncontrolled proliferation and impaired differentiation of immature cells called blasts. These abnormal cells infiltrate the bone marrow, disrupt normal blood cell production, and may spread to other organs. Genetic mutations often confer resistance to apoptosis, allowing leukemic cells to survive and proliferate.
Differentiate appearance of a patient with chronic and acute leukaemia
Chronic: Generally well
Acute: Often sick
Differentiate results of a clinical exam of a patient with chronic and acute leukaemia
Chronic: Clinically normal/ Mild lymphadenomegaly/ Big spleen/liver
Acute: Big spleen/liver/ Mild lymphadenomegaly/ Pale mucous mbs
Differentiate results of Haematology of a patient with chronic and acute leukaemia
Chronic: High white cell counts/ Mild cytopenias of other lines
Acute: High /low WBC/ Immature circulating cells/ Cytopenias common
Differentiate results of Biochemistry of a patient with chronic and acute leukaemia
Chronic: PNS may be present
Acute: PNS less likely
Differentiate results of Bone marrow of a patient with chronic and acute leukaemia
Chronic: Increased nos of well diff cells
Possibly other lines decreased
Acute: Increased nos of blasts
Other lines decreased
Leukaemia-Diagnosis
Haematology is suggestive –large numbers of malignant / aberrant cells on blood smear, cytopenias, etc
Bone marrow sample is usually diagnostic – altered cell maturation, malignant cells etc
Flow cytometry (blood or marrow) helps to differentiate cell lineage and precursors using specific abs to cell surface proteins
Acute lymphoid leukemia vs Lymphoma
Both characterised by proliferation of large blast cells
Lymphoma
Malignant neoplasms of peripheral lymphoid tissues
Can affect bone marrow (stage V)
Prognosis is reasonable with chemotherapy
Acute lymphoid leukaemia
Originates within bone marrow
Can spread to peripheral tissues
Prognosis is poor even with chemotherapy
How to differentiate between acute lymphoid leukaemia and lymphoma
Lymphoma
Often well
Massive lymphadenopathy
< 30% blasts in the bone marrow
CD34 –ve on flow cytometry
Acute leukaemia
Usually sick
Mild lymphadenopathy
Splenomegaly
Usually severe haematological abnormalities
> 30-40% blasts in bone marrow
CD34 +ve on flow cytometry
Multiple myeloma
Multiple myeloma is a type of cancer that affects plasma cells, a type of white blood cell that produces antibodies.
Origin: Multiple myeloma originates in the bone marrow, where abnormal plasma cells proliferate uncontrollably.
Pathogenesis: The exact cause of multiple myeloma is not fully understood, but it is believed to involve genetic mutations in plasma cells that lead to their uncontrolled growth and survival.
Clinical Features: Multiple myeloma can cause various symptoms, including bone pain (due to bone destruction), weakness, fatigue, recurrent infections, anemia, kidney damage, and increased susceptibility to fractures.
Diagnosis of multiple myeloma
Plasma cells in BM sample (>10%)
Osteolytic bone lesions on radiographs
Myeloma proteins in blood
Myeloma proteins in urine
how does multiple myeloma cause hypervisocity
Increased Production of Abnormal Proteins: In multiple myeloma, cancerous plasma cells produce abnormal monoclonal immunoglobulins, also known as M proteins or monoclonal gammopathies. These abnormal proteins can accumulate in the blood, leading to increased serum viscosity.
Elevated Serum Protein Levels: As the concentration of abnormal proteins increases in the blood, the overall serum protein levels rise. This increase in protein concentration contributes to elevated blood viscosity.
Signs of hyperviscosity
Heart: cardiomyopathy
Ocular: retinal lesions/detachment
Neurological: lethargy, seizures
Kidney: azotemia
Coagulopathy
Lethargy, seizures, blindness, bleeding
