Lecture Three

Question 1

What are the adverse effects of immune cell neoplasia?

Answer 1

1. Immunodeficiency
2. Local effects - due to disruption of physiological function
3. Distant/systemic effects - paraneoplastic syndromes - examples include hypercalcaemia, hypoglycemia etc.

Question 2

What is lymphoma and what stage of development can it arise from?

Answer 2

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

Question 3

What are three ways that lymphoma can be classified?

Answer 3

1. Based on anatomical classification
2. B cell versus T cell
3. WHO classification

Question 4

Briefly describe the progression of lymphoma on a scale of I to V:

Answer 4

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

Question 5

What is the difference between substage a and b?

Answer 5

a = without systemic signs (clinically healthy) 
b = with systemic signs

Question 6

What are the clinical signs of immune cell neoplasia?

Answer 6

1. Lymphadenomegaly or mass (cutaneous or on diagnostic imaging)
2. Systemic signs reflecting organ system affected
3. Clinical signs of paraneoplastic syndrome

Question 7

What lymph nodes are normally palpable and what lymph nodes become palpable with lymphadenomegaly?

Answer 7

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

Question 8

What are some differential diagnosis for lymphadenomegaly?

Answer 8

1. Metastatic neoplasia

2. Regional or systemic inflammation

Question 9

Explain the mechanism of hypercalcaemia of malignancy:

Answer 9

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

Question 10

Explain the pathophysiology mechanism of hypoglycaemia:

Answer 10

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)

Question 11

Provide an example of a condition that could lead to paraneoplastic anaemia:

Answer 11

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

Question 12

Briefly describe the clinical tests and process that would be taken in lymphoma diagnosis and staging:

Answer 12

1. Cytology - a fine needle aspirate allows differentiation of neoplasm from reactive LN. The lymphoma typically tends to aspirate quite well
2. 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)
3. PARR - PCR for clonal antigen receptor re-arrangement - can be done if cytology or histopathology is inconclusive

Question 13

What is leukaemia and what other condition can if be difficult to differentiate from?

Answer 13

Leukemia = neoplastic leukocyte in the peripheral blood. It is quite a rare condition and can be difficult to distinguish from stage V lymphoma

Question 14

What are the two main types of leukaemia?

Answer 14

Lymphoid leukaemia (more common of the two) = Acute lymphoblastic leukaemia and chronic lymphocytic leukaemia

Myeloid leukaemia (less common of the two)

Question 15

What are the two main types of lymphoid leukaemia?

Answer 15

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.

Question 16

What is meant by the term multiple myeloma?

Answer 16

Systemic proliferation of malignant plasma cells within the bone marrow.

Question 17

What is an extramedullary plasmacytoma?

Answer 17

Plasma cell neoplasm outside of the bone marrow

Question 18

Describe the pathophysiology of multiple myeloma?

Answer 18

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.

Question 19

Briefly describe some of the clinical signs that may be observed with multiple myeloma:

Answer 19

Bone pain and lameness, PU?PD (hypercalcaemia) , behaviour/neurologic abnormalities (if hyperviscosity)

Question 20

What are some tests that can be used in the diagnosis of multiple myeloma?

Answer 20

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

Question 21

Briefly describe the three different clinically recognised syndromes in the histiocytic disease complex:

Answer 21

1. Canine cutaneous histiocytoma complex (benign neoplasia) - common benign skin masses in dogs can regress spontaneously
2. Canine reactive histiocytosis (not neoplastic) - cutaneous versus systemic forms of it
3. Histiocytic sarcoma complex (malignant neoplastic) - disseminated neoplastic transformation of APC’s

Question 22

What are the two main conditions found in the canine histiocytic sarcoma complex?

Answer 22

1. 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
2. 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.