Lecture Three Flashcards
What are the adverse effects of immune cell neoplasia?
- Immunodeficiency
- Local effects - due to disruption of physiological function
- Distant/systemic effects - paraneoplastic syndromes - examples include hypercalcaemia, hypoglycemia etc.
What is lymphoma and what stage of development can it arise from?
Lymphoma is the clonal proliferation of neoplastic lymphocytes. It can rise from any stage in the development/maturation of lymphocytes. Precursor (B or T lymphocytes), mature lymphoid cells (B or T cells) or NK cells
What are three ways that lymphoma can be classified?
- Based on anatomical classification
- B cell versus T cell
- WHO classification
Briefly describe the progression of lymphoma on a scale of I to V:
I = single lymph node II = Regional lymphadenopathy (one side of diaphragm) III = generalised lymphadenopathy IV = Liver and/or spleen involvement V = blood, bone marrow or other organ involvement
What is the difference between substage a and b?
a = without systemic signs (clinically healthy) b = with systemic signs
What are the clinical signs of immune cell neoplasia?
- Lymphadenomegaly or mass (cutaneous or on diagnostic imaging)
- Systemic signs reflecting organ system affected
- Clinical signs of paraneoplastic syndrome
What lymph nodes are normally palpable and what lymph nodes become palpable with lymphadenomegaly?
The LN’s normally palpable in a dog are:
- submandibular
- prescapular
- popliteal
A dog with lymphoma will also have the following palpable:
- axillary
- superficial inguinal
What are some differential diagnosis for lymphadenomegaly?
- Metastatic neoplasia
2. Regional or systemic inflammation
Explain the mechanism of hypercalcaemia of malignancy:
Neoplastic cell (CD4+) produce parathyroid-hormone-related peptide (PTH-rp). The PTH-rp has the same effects in the body as the PTH causing increased calcium re-absorption in kidneys and increased calcium reabsorption in the bone. As a result this leads to a state of hypercalcaemia. The hypercalcaemia blocks ADH action on renal collecting ducts. As a result this leads to nephrogenic diabetes insipidus and polyuria with secondary polydispsia
Explain the pathophysiology mechanism of hypoglycaemia:
Neoplastic cells (esp. lymphoma cells) autonomously produce insulin like peptides. The high insulin concentrations moves glucose intracellularly while simultaneously suppressing glycogenolysis and hepatic glucose production. This causes hypoglycaemia that then causes neuroglycopenia which then causes weakness, trembling and behavioural changes ultimately causing seizures (fatal)
Provide an example of a condition that could lead to paraneoplastic anaemia:
Microangiopathic haemolytic anaemia - this is more common with histiocytic sarcoma than lymphoma. RBC’s are injured as they travel through capillary beds infiltrated by neoplastic cells resulting in the premature removal of RBCs from circulation
Briefly describe the clinical tests and process that would be taken in lymphoma diagnosis and staging:
- Cytology - a fine needle aspirate allows differentiation of neoplasm from reactive LN. The lymphoma typically tends to aspirate quite well
- Histopathology - Routine H and E and immuno-histochemistry (allows us to differentiate between B-cell and T-cell leukaemia which is useful as they are treated differently)
- PARR - PCR for clonal antigen receptor re-arrangement - can be done if cytology or histopathology is inconclusive
What is leukaemia and what other condition can if be difficult to differentiate from?
Leukemia = neoplastic leukocyte in the peripheral blood. It is quite a rare condition and can be difficult to distinguish from stage V lymphoma
What are the two main types of leukaemia?
Lymphoid leukaemia (more common of the two) = Acute lymphoblastic leukaemia and chronic lymphocytic leukaemia
Myeloid leukaemia (less common of the two)
What are the two main types of lymphoid leukaemia?
Acute lymphoblastic leukaemia (ALL) = poorly differentiated lymphoblasts in circulation and bone marrow, concurrent cytopenias common, treatment is via multi-agent chemotherapy. This is a very aggressive type of cancer typically with poor prognosis
Chronic lymphocytic leukaemia (CLL) = well differentiated, small mature lymphocytes in circulation and BM. It is mostly T-cell (although B-cell origin reported). The treatment is with less aggressive chemotherapy although long survival times are expected.
What is meant by the term multiple myeloma?
Systemic proliferation of malignant plasma cells within the bone marrow.
What is an extramedullary plasmacytoma?
Plasma cell neoplasm outside of the bone marrow
Describe the pathophysiology of multiple myeloma?
Local disease causes osteopenia and cortical lysis leading to bone pain and fractures.
This also leads to systemic disease and paraneoplastic syndromes. This causes hypercalcaemia of malignancy and monoclonal gammopathy meaning hyperviscosity syndrome.
Briefly describe some of the clinical signs that may be observed with multiple myeloma:
Bone pain and lameness, PU?PD (hypercalcaemia) , behaviour/neurologic abnormalities (if hyperviscosity)
What are some tests that can be used in the diagnosis of multiple myeloma?
Serum protein electrophoresis - Monoclonal gammopathy
Radiographs or CT
- allows us to see if we have lytic lesions in the bone (usually multiple)
Bone marrow cytology - aids in the identification of neoplastic plasma cells
Briefly describe the three different clinically recognised syndromes in the histiocytic disease complex:
- Canine cutaneous histiocytoma complex (benign neoplasia) - common benign skin masses in dogs can regress spontaneously
- Canine reactive histiocytosis (not neoplastic) - cutaneous versus systemic forms of it
- Histiocytic sarcoma complex (malignant neoplastic) - disseminated neoplastic transformation of APC’s
What are the two main conditions found in the canine histiocytic sarcoma complex?
- Histiocytic sarcoma - mainly large breeds and of interstitial dendritic origin. Localised HS - affects a single tissue or organ (with multiple disseminated foci). Systemic HS = disseminated histiocytosis - spread and involving multiple organs
- Haemophagocytuc histocytic sarcoma - originates in the splenic red pulp and bone marrow macrophages - diffuse splenomegaly is seen. The neoplastic histiocytes phagocytose RBCs and platelets . The erythrophagocytosis results in severe cytopenias. This has the worst prognosis typically only about 4 weeks.
