CO5 Hemolymphatic

Question 1

is lymphoma common in animals? is it benign or malignant?

Answer 1

• Lymphoma in animals is a common cancer.
• Although the term “lymphoma” implies a benign cancer, all lymphomas are malignant and will kill the patient if left untreated.

Question 2

are lymphomas often treatable?

Answer 2

lymphomas are very variable in their disease course, and often are amenable to successful treatment

Question 3

nodal vs extranodal lymphoma, and typical sites?

Answer 3

• Lymphoma most often arises from within the lymph nodes, and is termed “nodal” (or sometimes “multicentric”) lymphoma. These lymphomas affect the spleen, the thymus, and the thoracic, abdominal and superficial lymph nodes.
• Lymphoma can also occur in almost any other tissue, and is then termed “extranodal”. Typical sites for extranodal lymphoma are the intestine, kidney, eye, skin, or central nervous system.

Question 4

are cells of a lymphoma similar, and why?

Answer 4

Lymphomas are clonal proliferations of lymphocytes and often resemble the cell of origin in appearance and function.

Question 5

What causes lymphocytes to become neoplastic?

Answer 5

It is known from human medicine that most lymphomas have specific mutations in genes involved in the production of immunoglobulin, in proto-oncogenes, or in cytokine genes, and that persistent immune stimulation increases the risk of lymphoma. Thus, a potential scenario involves the accumulation of “chromosomal accidents” during the rearrangement of genes for the formation of B or T cell antigen receptors. Lymphocytes are relatively unique in how frequently they have organized “gene shuffling events”, meaning that they normally break their chromosomes into specific pieces, and then stitch them back together in a different order. Therefore, if lymphocytes become prone to errors in the repair of chromosomes, clones with genetic errors may evolve. Once a gene rearrangement has taken place that imparts faster cell division, or less reliance on other factors that normally regulate cell division, a malignant clone may arise with the potential to keep growing.
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Other factors that may contribute to lymphoma are exposure to genotoxic substances such as herbicides, immunodeficiency through poor regulation of antigen-induced proliferation, and viruses that infect lymphocytes and produce factors to enhance cell proliferation.

Question 6

do nodal lymphomas affect one or multiple sites? extranodal?

Answer 6

Since lymphocytes normally travel between lymph nodes, it is typical for nodal lymphomas to involve multiple lymph nodes, and for extranodal lymphomas to be more restricted to a specific site.

Question 7

most common type of lymphoma in dogs?

Answer 7

Lymphoma is a very common cancer of dogs. Nodal lymphomas are most common, and more often of B- than T-cell origin. Most nodal lymphomas in dogs are high grade, meaning that they will kill the animal fairly quickly without treatment.
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Diffuse lymphoma – most common in dogs
Nodular (follicular) lymphoma – very uncommon in dogs
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* typical onset middle-aged
* multiple enlarged lymph nodes, non-painful
* most dog lymphomas are high grade, ie. aggressive
* nevertheless, can get good response to chemotherapy
* 20 to 40% of nodal lymphomas and all mediastinal lymphomas are of T cell origin

Question 8

high grade lymphoma in dogs prognosis with treatment

Answer 8

remission times in excess of 1 year can be achieved in many high-grade lymphomas with chemotherapy

Question 9

which type of lymphomas in dogs are typically of T-cell origin? response to chemotherapy?

Answer 9

About 20 to 30 % of nodal lymphomas, and almost all mediastinal lymphomas in dogs, are of T-cell origin, and some of these respond less well to chemotherapy.

Question 10

hypercalcemia is seen with what type of lymphoma? why? should we treat?

Answer 10

Hypercalcemia is common with helper T- cell lymphomas, and is due to a PTH-like factor produced by the neoplastic T lymphocytes. Persistent hypercalcemia has numerous deleterious systemic effects, such as induction of renal disease and soft tissue calcification. Therefore, hypercalcemia should never be left untreated!

Question 11

what age dog is most affected by lymphoma?

Answer 11

middle age

Question 12

What is the best diagnostic approach to lymphoma?

Answer 12

Aspirate several enlarged lymph nodes.
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* Aspirate one or several enlarged lymph nodes and make 5 to 10 “good” (thin) smears
* Submit unstained slides to a veterinary laboratory
* In dogs, 80-90% of the time a diagnosis can be
established on cytology
* Not as easy to diagnose lymphoma with cytology in cats and horses
* May need an incisional or excisional biopsy of an enlarged lymph node in these cases
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- Prepare 3 to 5 good quality “feather edge” or “pull-apart” smears from at least 2 enlarged nodes.
- In 80 to 90% of cases those slides will be sufficient for a diagnosis of lymphoma by an experienced cytopathologist. If it is a very early lymphoma, or a “small cell” type (rare), than a cytological diagnosis may not be possible. In these cases, a lymph node needs to be biopsied or excised, fixed, and examined histologically. Abdominal and thoracic lymph nodes may be accessible for aspiration with the aid of ultrasound, and here again it is important to submit several good smears for diagnosis.

Question 13

what lymph node is it best to avoid aspirating for a lymphoma diagnosis?

Answer 13

It is best to avoid the submandibular lymph node since that node is exposed to many antigens from the mouth, and may have increased reactivity that makes it more difficult to identify lymphoma.

Question 14

type of lymphoma more common in cats? locations? cell origins?

Answer 14

• Lymphoma in cats is more frequently extranodal than nodal.
• The most common sites are the intestine, kidney, liver/mesentery, and CNS.
• B cell origin is most common except for Feline leukemia virus (FeLV)-associated lymphoma and mediastinal lymphomas, which are of T cell origin.
• Intestinal lymphomas are common in older cats, and typically occur as a solitary but invasive mass in the small intestine.

Question 15

How does FeLV cause lymphoma?

Answer 15

As a retrovirus, FeLV makes a DNA copy of its RNA genome, and then inserts that double-stranded DNA into the cat’s chromosomes. This “gene cutting and inserting” process may involve cellular proto-oncogenes, which may then be over- expressed when the virus replicates. This, in turn, may cause persistent production of proteins favoring cell growth and division, which may lead to cancer.
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The incidence of FeLV infection has decreased in the past decade, and infection is now more commonly associated with degenerative diseases and not lymphoma.

Question 16

FIV is associated with what type of lymphomas?

Answer 16

Infection with the feline immunodeficiency virus (FIV) is associated with aggressive extranodal B cell lymphomas

Question 17

How is FIV responsible for indirect viral carcinogenesis?

Answer 17

FIV, too, is a retrovirus, and causes immunodeficiency from lack of T helper (CD4+) cell production after many years of infection. The lack of T helper cells results in inadequate suppressor T cell function. This, in turn, contributes to persistent antigenic stimulation, which favors the clonal expansion of lymphocytes that have acquired growth advantages through gene lesions. The tumor lymphocytes do not contain FIV, thus, this is indirect viral carcinogenesis.

Question 18

age for lymphoma in large animals?

Answer 18

Lymphoma in large animals may occur at all ages, including neonates to geriatric animals.

Question 19

what cell origin are most horse lymphomas? why can some be difficult to distinguish cytologically? how can we diagnose in these cases?

Answer 19

• Most horse lymphomas are of T-cell origin,
• and some T- and many B-cell lymphomas produce cytokines that result in massive tumor infiltration with non-malignant small lymphocytes (i.e. “T-cell rich B-cell lymphoma”).
• Therefore, some horse lymphomas consist of multiple lymphocyte types, and may be difficult to diagnose cytologically.
• Partial or complete excision of a lymph node and histological examination is then required for the diagnosis.

Question 20

what lymph-node property in horses can complicate the diagnosis of lymphoma?

Answer 20

Complicating the diagnosis of lymphoma in horse is that palpable lymph nodes (submandibular, prescapular) are rarely enlarged.

Question 21

often, horses with lymphoma have what other blood-related conditions? why?

Answer 21

• often horses with lymphoma have immune hemolytic anemia or thrombocytopenia.
• In these cases, the tumor cells produce a paraprotein that cross-reacts with red blood cells or platelets, and causes agglutination and anemia or thrombocytopenia through reduced life span.

Question 22

lymphomas in cattle are mostly caused by what? how commonly? what cells are mostly affected?

Answer 22

• Lymphomas in cattle are mostly caused by infection with the bovine leukemia virus (BLV).
• This retrovirus is common in Ontario herds, infects B-lymphocytes, and causes persistent lymphocytosis in ~30% of infected cows, but lymphoma or leukemia in only 3 to 5% of infected cows.

Question 23

at what age do dairy cows generally get lymphoma? where do these tumors start and how do they progress?

Answer 23

Lymphoma in dairy cows typically occurs in middle-aged to older cows. These tumors generally start in the lymph nodes and progress to involve organs such as the heart, uterus, and CNS.

Question 24

lymphoma of young cattle is not associated with what virus?

Answer 24

Lymphoma of young cattle (cutaneous, multicentric, or mediastinal) is not associated with BLV infection.

Question 25

is lymphoma common in sheep and goats? what may be a cause in sheep?

Answer 25

Lymphoma is among the more common neoplasms in sheep and goats, and may be associated with inadvertent infection of sheep with BLV.

Question 26

what anatomical structures are usually affected in ferret lymphoma? how rapidly do ferret lymphomas progress?

Answer 26

• Ferrets get lymphoma, too, and it involves most often the abdominal organs and not the peripheral lymph nodes.
• Some ferret lymphomas are very slowly progressive and very chemosensitive.
• Mediastinal lymphomas in ferrets occur in young animals and are rapidly fatal.

Question 27

What is needed for a diagnosis of lymphoma? in various species?

Answer 27

• In most dog lymphomas, a cytology preparation from a lymph node or tumor aspirate is sufficient for a cytopathologist to make a diagnosis.
• In horses and cats the malignant lymphocytes are often mixed with benign lymphocytes, therefore, making a diagnosis of lymphoma is possible in only ~50-70% of cases.
• In the remaining cases histological assessment of an excised or biopsied node or tumor is necessary.
• In cattle, cytological assessment is generally sufficient to establish a diagnosis of lymphoma.

Question 28

are additional diagnostic efforts beyond cytology and histology warranted for lymphoma?

Answer 28

Yes, though they available to a limited extent in veterinary medicine. A diagnosis of lymphoma in human medicine is typically refined into a more precise category according to the expression of numerous cluster of differentiation (CD) markers on the neoplastic lymphocytes by flow cytometry or immunohistochemistry, and by the the presence of typical gene changes identified with molecular diagnostics. Each subcategory of lymphoma has a specific treatment protocol and a unique prognosis. This kind of information is only starting to be available for dogs and cats, and beyond T and B cell immunophenotyping we know little about different treatments and prognoses. However, even determination of T or B cell origin can make a difference with respect to prognosis, and will allow accumulation of statistical information. Hence, for an owner who is considering treatment of a cost of $2,000 to $3,000 for their dog’s lymphoma, knowing whether it is a T or B cell lymphoma at a price of $100 may be a worthwhile investment.

Question 29

How is the immunophenotype of a lymphoma determined?

Answer 29

Monoclonal antibodies specific for T or B cells are incubated with unstained cytology samples, neoplastic lymphocytes in suspension, or fixed tissue sections, and a color label on the antibody assesses the degree of binding. Thus, this can be done on any sample submitted for interpretation by a pathologist, though usually at an additional cost.

Question 30

The spleen in health has multiple functions:

Answer 30

• Blood storage in the sinuses of the red pulp, - blood surveillance through macrophages lining the sinusoids of the red pulp,
• and immune responses through B and T lymphocytes in the white pulp.

Question 31

what effects does of the spleen in adult animals have?

Answer 31

has slight effects on the removal of aged and abnormal blood cells, but no appreciable effect on immune responses.

Question 32

Lesions of the spleen most commonly manifest as

Answer 32

splenomegaly
> There may be solitary masses on the spleen, or diffuse enlargement.

Question 33

Processes affecting either the red or white pulp may result in splenomegaly:

Answer 33

• hemolytic anemia
• congestion / engorgement
• extramedullary hematopoiesis
• siderotic nodules
• systemic infections
• hemangiosarcoma
• lymphoma
• leukemia
• mast cell tumour

Question 34

what systemic infections can result in splenomegaly?

Answer 34

Many systemic infections such as ehrlichiosis, histoplasmosis, cytauxzoonosis, mycobacterial infections, and leishmaniasis cause
splenomegaly and lymphadenopathy.

Question 35

what is hemangiosarcoma and how does it result in splenomegaly?
- diagnosis difficulties?

Answer 35

A malignant neoplasm of endothelial cells that frequently affects the spleen. The tumor consists of abnormal blood vessels filled with blood,
and involves either part or all of the spleen. This is a difficult tumor to diagnose definitively antemortem, and usually a diagnosis is derived from typical hematological changes, detection of splenomegaly, and recurrent hemoabdomen. The neoplastic cells are highly diluted among the blood within the tumor, and thus percutaneous aspiration of the spleen usually is not diagnostically useful.

Question 36

what drug can cause congestion of the spleen? what injury in vivo?

Answer 36

This is a typical post mortem finding following barbiturate injections. In vivo engorgement may occur with splenic torsion.

Question 37

what type of stress can result in an enlarged spleen and how?

Answer 37

During hematopoietic stress (persistent anemia, chronic inflammation, myelofibrosis) the spleen may become enlarged due to
active hematopoiesis.

Question 38

what are siderotic nodules

Answer 38

Siderotic nodules - Small plaques that contain heme pigments and fibrous tissue.

Question 39

lymphoma presentation on the spleen? Dx?

Answer 39

Nodal lymphomas typically involve the spleen, and may either cause nodular lesions or diffuse enlargement. Aspiration of a “solid” area of the spleen with the aid of ultrasound may yield diagnostically useful information.

Question 40

what type of splenomegaly is typical of leukemia?

Answer 40

Leukemia typically involves the bone marrow and the spleen, and may arise in the spleen (chronic lymphocytic leukemia in the dog). The splenomegaly associated with leukemia is generally diffuse.

Question 41

mast cell tumours in the spleen
- in what species are they primary? metastatic? difference in pattern between species? Dx?

Answer 41

Mast cell tumors may occur in the spleen as the primary site (common in the cat, and uncommon in the dog), or involve the spleen during metastasis. Focal lesions are typical in the dog, while diffuse tumor involvement is more typical of splenic mast cell tumors in the cat. Since mast cells readily exfoliate and are easy to recognize cytologically, this tumor may be diagnosed from well-placed splenic aspirates.

Question 42

causes of splenomegaly in ferrets?

Answer 42

Splenomegaly is a common clinical finding in ferrets. Causes include:
1. Extramedullary hematopoiesis.
2. Lymphoma.
3. Chronic infection.
4. Histiocyte proliferation.

Question 43

Dx of splenomegaly in ferrets - methods? what conditions can be diagnosed? considerations?

Answer 43

• Due to the small size of ferrets, aspiration of the spleen is fairly readily possible. If the sample is very hemorrhagic, it is necessary to prepare slides rapidly (before the sample clots), or to quickly anti-coagulate the sample (put it into an EDTA [purple top] tube)
• Lymphoma and extramedullary hematopoiesis can be diagnosed in most cases; however, the cause for the extramedullary hematopoiesis is not always apparent. If extramedullary hematopoiesis is extensive, it is important to closely examine findings in the circulating blood and to investigate why bone marrow hematopoiesis is inadequate.