HOLS diagnosis of lymphoproliferative disorders Flashcards

1
Q

What is lymphoma

A

Neoplastic proliferation of lymphocytes; centre of population is lymph nodes
So see lymphadenopathy +/- organomegaly due to cell infiltration

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2
Q

What is leukaemia

A

Neoplastic proliferation of haematopoetic stem cells or leukocytes in BONE MARROW
- We notice spill out of abnormal cells into circulation

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3
Q

Are large of small cell lymphomas more agressive

A

Large = more aggressive and shorter survivial times

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4
Q

Haematology/biochem results from lymphoma

A

See mild non-regenerative anaemia (called anaemia of inflammatory/neoplastic disease)
In stage 5 lymphoma can have cytopenias due to crowding out of bone marrow (thrombocytopenia first)

Hypercalcaemia seen in 15% of cases due to production of PTHrP by neoplastic lymphoctes

+ If liver infiltrated: elevated ALT/AST mark damage
+ If SI infiltrated: reduction in serum albumin as less absorption

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5
Q

Considerations when taking FNA from lymph nodes in suspected lymphoma

A

Avoid submandibular: affected by dental disaese
Take 2+
- Avoid centre of the node as may be necrotic

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6
Q

What are the 4 differential diagnoses for lymphadenopathy

A

Reactive lymphoid hyperplasia from immune stimulation

Lymphadenitis; increased inflammatory cells in node

Lymphoma: infiltration by neoplastic lymphocytes

Metastatic neoplasia: infiltration by neoplastic cells via lymphatic spread

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7
Q

Normal lymph node cytology

A

> 90% SMALL lymphocytes (i.e smaller than neutrophil)
+ some low numbers of intermediate/large lymphocytes

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8
Q

Cytology findings with reactive lymphoid hyperplasia

A

Still >50% small lymphocytes (<neutrophil size)
BUT now have increase in numbers of intermediate/large lymphocytes as these are immature (10-50%)

+ more plasma cells; differentiated to produce Abs; incuding Mott cells

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9
Q

Cytology findings of lymphadenitis

A

Neutrophilic: >5% neutrophils
Eosinophilic: >3% eosinophils
May see histiocytic or granulomatous lymphadenitis with fungal/protozoal infections

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10
Q

Cytology of large cell lymphoma

A

> 50% of lymphocytes are LARGE sized BUT usually >80% like this
May see increased mitotic figures
no/few plasma cells unlike in reactive hyperplasia

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11
Q

Cytology of small cell lymphoma

A

Hard to differentiate
Suspect with enlarged nodes full of small lymphocytes and with no inflammatory signs

> May see ‘hand mirror’ shape

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12
Q

Cytology of lymph nodes with metastatic neoplasia

A

See cells that SHOULDN’T be there
e.g epithelial cells with criteria of malignancy
(take care not to confuse epithelioid macrophages with this)

Clusters of mast cells

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13
Q

What has happened if we try and aspirate submandibular and get pink background with windrowing of red cells and no lymphocytes

A

Salivary gland has been sampled

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14
Q

Is immunophenotyping lymphoma better with immunohistochemistry or flow cytometry

A

Flow cytometry

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15
Q

What can we do to confirm lymphoma if suspected from FNA

A

Lymph node biopsy and histopath
PCR for antigen receptor rearrangements (PARR)

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16
Q

Once lymphoma diagnosis confirmed what additional tests might be useful

A

Flow cytometry: to differentiate B/T cells and work out what subclass of T cells
Immunohistochem

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17
Q

What is PARR useful for

A

Clonality test; to check if neoplastic or just reactive
- Quite easy as can be done on cytology preparation c/f biopsy

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18
Q

What key information does flow cytometry/immunophenotyping NOT give us about lymphoma

A

Whether or not cells are neoplastic; so must have already got confirmatinon via cytology or histopath first

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19
Q

What do we use for flow cytometry of lymphoma

A

Aspirate from lymph node
> Sample must be <48 hours old

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20
Q

What prognostic importance can immunophenotyping of lymphoma tell us

A

High grade B cells have better prognosis than high grade T cells

CD8+ large T cells have better prognosis than CD4+ large T cells

High MHC classs II expression more favourable

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21
Q

Clinical signs and findings with leukaemia

A

Vague: lethargy, weight loss and anorexia
> On bloods: lymphocytosis or increased circulating atypical cells; other cytopenias due to crowding out of BM

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22
Q

Specific levels of lymphocytosis or circulating atypical cells consistent with leukaemia

A

MARKED
i.e >40x10^9 lymphocyte cells/L

> 40x10^9 atypical cells/:

23
Q

How can we differentiate between leukaemia and stage V lymphoma

A

Lymphoma would have lymphadenopathy

24
Q

What are other causes of lymphocytosis apart from leukaemia

A

Excitement, young animals, hypoadrenocorticism: up to 2X RI increase
Chronic inflammation: <40x10^9/L
FeLV in cats

BUT remember that leukaemia can be ANY degree of lymphocytosis; rule other causes out

25
Q

Characteristics of acute leukaemia

A

Neoplastic proliferation of immature leukocytes
* See >20-30% of large sized round cells = blasts

OR see presence of CD34+ cells in circulation on flow cytometry (should be just in BM as these are stem cells)

Often see multiple cytopenias due to myelophthesis

26
Q

Characteristics of chronic leukaemia

A

Neoplastic proliferation of mature lymphocytes
* Cells are small/intermediate (so = or < neutrophil)
Mild signs
Often no or very mild haematological abnormalities

27
Q

What is chronic myeloid leukaemia

A

Clonal proliferation of mature neutrophils
- Must differentiate from inflammatory causes of high neutrophil counts

28
Q

What is an ‘increased lymphocyte count’ i.e worth investigating

A

> 10x10^9/L

29
Q

What is plasmacytoma

A

Mature B cell tumours in the skin

30
Q

What viruses are associated with lymphoma in cats and cattle

A

Cats: FeLV
Cattle; BLV

31
Q

What antibody is used to detect B cells and which T cells

A

B cells: CD79a antibody
T cells: CD3

32
Q

Do B or T cell tumours in multicentric lymphoma give better prognosis

A

B cells (and this is the more common type)

33
Q

Stages of multicentric lymphoma by WHO

A

Stage 1: involvement limited to a single node or lymphoid tissue in single organ
Stage 2: involvement of nodes in regionnal area +/- tonsils
Stage 3: generalised lymph node involvement
Stage 4: hepatic/splenic involvment
Stage 5: manifestation in the blood, involvement of bone marrows +/- other organs

34
Q

Substages a and b of lymphoma

A

substage a = without clinical signs
substage B = with clinical signs

35
Q

What are the first and second most common types of lymphoma in dogs

A

1) Multicentric lymphoma
2) Mediastinal (thymic) lymphoma

36
Q

characteristics of mediastinal (thymic) lymphoma

A

Anterior mediastinal mass
SO: present with resp distress, facial swelling (due to impedence of lymph drainage), hypercalcaemia related complications i.e PU/PD

generally T cell phenotype
Historically cats were FeLV +ve

37
Q

What is most common type of malignant lymphoma seen in dogs

A

Diffuse large B cell lymphoma

38
Q

Which species is alimentary lymphoma important

A

Cats; symptoms relate to location of lymphoma

39
Q

How to work out if a lymphoma is B or T cell

A

immunophenotype
> CD79a for B cell
> CD3 for T cell

40
Q

3 major categories of lymphoma that we can divide tumours into based on cytology

A

1) Diffuse large B cell lymphoma (most common form)
2) High grade, lymphoblastic peripheral T cell lymphoma = poor prognosis
3) Low grade, small cell, T zone lymphomas = longest survival

41
Q

What tests are essential in staging lymphoma once the diagnosis has been made

A

Physical exam
Haematology
Biochemistry (for evidence of hypercalcaemia, check kidney function to decide if you can give cyclopsosphamide)
Urinalysis

42
Q

What is the standard palliative care treatment for lymphoma

A

Prednisolone

43
Q

Effect of steroid pre-treatment of subsequent chemotherapy

A

REDUCES efficacy; do don’t put animal on preds while decision is made if you might do chemo

44
Q

What is the COP chemotherapy protocol and what two options are there

A

Cyclophosphamide, vincristine, prednisolone
Choose this in cats

1) Continuous/low dose: induce for 8 weeks
= Daily cyclophosphamide (oral)
+ weekly vincristine
+ prednisolone dairy high dose for first week; then lower dose
IF IN REMISSION AFTER 8 WEEKS: reduce to treatment every other week

2) high dose/pulse therapy
= High dose cyclophosphamie every 3 weeks
+ Vincristine weekly for 4 weeks; then every 3 weeks
+ prednisolone daily for 4 weeks; then every other day
THEN STOP

45
Q

What is added in the CHOP protocol c/f COP

A

Doxorubicin
= gold standard (for high grade B cell tumour in dogs)

46
Q

3 drugs in the COP protocol

A

Cyclophosphamide, vincristine, prednisolone
NB: MOST lymphomas in dogs/cats respond well to this (+/- doxorubicin i.e CHOP)

47
Q

What is added to CHOP in the VLCAP/UW-Madison protocol

A

L-asparaginase

48
Q

What is different in the LOP protocol

A

Lomustine not cyclophosphamide

49
Q

How do cyclic combination chemotherapy protocols work

A

Get different drugs each week
+ have prednisolone at a reducing dose rate the whole time
Do for 19 weeks and then if in remission STOP
NB: must do haematology before every treatment to check for neutropenia (only must do every month in continuous low dose)

50
Q

Which two prognostic factors are key in lymphoma

A

Immunophenotype
Substage i.e substage b (symptoms seen) much worse

51
Q

What chemo protocol usually chosen from large cell B cell lymphoma

A

CHOP/COP

52
Q

What chemo protocol usually chosen for high grade lymphoblastic T cell lymphoma

A

LOP/LOPP
(because don’t respond so well to doxorubicin)

53
Q

What chemo protocol is chosen for low grade, small cell, T zone lymphoma

A

Chlorambucil