Neoplasia 1

What is the cell of origin for lymphoma?

Lymphocyte

What is the most common form of hematopoietic neoplasia in the dog and cat?

Lymphoma/lymphosarcoma (same thing)

True or False: Lymphoma arises from lymphoid organs most commonly and is considered a liquid tumor, meaning it can arise from any tissue.

True!

True or False: Lymphoma is usually a locally invasive disease that should be treated locally rather than systemically.

False! Lymphoma is a SYSTEMIC disease and therefore is best treated systemically.

What are the two major "types" of lymphoma?

B or T cell lymphoma

What age and breeds are most susceptible to canine lymphoma?

Age: middle to older

Breed: Boxers and Goldens

(Bull Mastiff, Basset, Scottie, Pittie also)

True or False: The etiology of canine lymphoma is multifactorial and largely unknown, but genetics play a role.

True!

What are the FOUR major methods of classification for canine lymphoma?

1. Anatomic location

2. Histo/cytologic criteria

3. Immunophenotype

4. Stage

What is the most common anatomic location of canine lymphoma, making up 85%?

Multicentric nodal

True or False: Dogs with multicentric nodal LSA often have systemic disease affecting multiple lymph nodes, liver/spleen, or other organs (GI, rectal, skin, eye, anywhere).

True!

Do dogs with multicentric nodal LSA usually present sick?

No, usually happy dogs with "lumps" under jaw" or "swollen glands" per owner

(can also be sick though- less common)

What are some PE findings in terms of palpation, mucus membranes, and ocular exam with canine LSA?

Palp: enlarged lymph nodes (mandibular, superficial cervical, popliteal, +/- axillary and inguinal)

MM: anemia/pallor, icterus, petechiae, ulceration

Ocular: uveitis or hyphema

What THREE respiratory findings are consistent with LSA?

1. Mediastinal mass

2. Pulmonary infiltrates

3. Pleural effusion

What are the THREE progressive forms of dermatologic disease consistent with canine LSA?

scaling/alopecia/pruritis -> erythema/thickening/ulcer/exudate ->

plaques/nodules

What are THREE abdominal findings consistent with LSA?

1. Hepatosplenomegaly

2. Intestinal thickening

3. Fluid wave

What are THREE rectal findings consistent with LSA?

1. Enlarged sublumbar LNs

2. Rectal mucosa involvement

3. Diarrhea/melena/hematochezia

What are the FOUR ways cells can be histologically and cytologically classified?

Cell type, cell size, grade, architecture

What are the most common cell type, size, and grade of canine LSA?

Cell type: B-cell

Cell size: Large (intermediate to large)

Grade: High (intermediate to high)

True or False: Grade often correlates with cell size, but not always. For example, a small cell is usually indolent while a large cell is more aggressive.

True!

What are the two different architecture options of cells?

Diffuse or follicular/nodular

What often yields diagnosis of an intermediate to large cell canine LSA?

FNA and cytology

What often yields diagnosis of a small cell canine LSA? Why is this different than intermediate to large cell?

Histopathology and molecular (PARR or flow cytometry)

Hard to differentiate normal vs abnormal small cells

What is still considered "gold standard" for classifying lymphoma?

Name TWO issues with this.

Histopathology (biopsy)

1. GA and sx required

2. Often FNA is enough

Small lymphocytes are smaller, intermediate lymphocytes are similar to, and large lymphocytes are larger than what cell used for comparison?

Neutrophil

True or False: >80-90% monomorphic large lymphocytes define an LSA.

True!

Name THREE tips for best performing a lymph node cytology.

1. Avoid cell lysis, especially large

2. Do not make too thick

3. Avoid reactive lymph nodes (hard to tell reactive cells from neoplastic)

What are FOUR major advantages of cytology?

1. Non-invasive

2. Cheap

3. Fast results (1-2 days)

4. Diagnostic in most int-large cases

What are TWO major disadvantages of cytology?

1. No histologic classification

2. Inconclusive (emerging/early lymphoma, small cell variants)

True or False: Lymphoma histologic classification requires lymph node biopsy with histopathology and immunohistochemistry staining interpreted by a pathologist trained in lymphoma classification.

True!

True or False: Subclassification of lymphoma is commonly pursued in vet med.

False! Subclassification of lymphoma is NOT commonly pursued in vet med.

What histologic difference is there in a low grade vs high grade lymphoma?

Low: expanded nodal architecture

High: effaced nodal architecture

A patient is more likely to have a T-cell lymphoma under what THREE unique circumstances?

1. Boxer

2. Hypercalcemic

3. Mediastinal mass

True or False: In the case of high-grade lymphomas, T -cell has a better prognosis than B-cell.

False! In the cases of high-grade lymphomas, B-CELL has a better prognosis than T-CELL.

What is the one major caviat to the B cell is better than T cell rule?

Most common low-grade canine LSA is T ZONE lymphoma

(T-cell, but better than any HIGH grade lymphoma)

What diagnostic provides cell size and cell markers, which can help determine prognosis?

Flow cytometry

What diagnostic uses special stains on histo samples to determine cell lineage (B vs T-cell), also known as immunophenotype?

Immunohistochemistry

What TWO things are used to determine WHO subtype classification?

Immunohistochemistry and lymph node architecture

Which diagnostic explicitly requires the cells to be living?

Flow cytometry

True or False: Flow cytometry stains with antibodies to look at surface markers, which helps differentiate reactive vs neoplastic and the immunophenotype.

True!

How can you make flow buffer?

1 mL saline + 0.1 mL patient serum

Flow cytometry should be --- when shipped overnight and results come back usually in --- days.

Chilled (not frozen)

3-5 days

What diagnostic test isolates and amplifies the unique lymphocyte DNA to rule in or out lymphoid neoplasia based on clonality (is it clonal or not)?

PARR (PCR for Antigen Receptor Rearrangement)

True or False: PARR can be performed on cytology, fluid, and histo samples and does NOT require live cells.

True!

True or False: PARR is a reliable test for immunophenotyping.

False! FLOW CYTOMETRY and IMMUNOHISTOCHEMISTRY are best for immunophenotyping.

What diagnostic is used when cytology or histo shows lymphocyte proliferation, but definitive answers on whether it is neoplasia or not is still needed?

PARR

How would neoplasia show up on PARR?

Monoclonal (all express same region)

What FOUR things are false positive PARRs related to?

1. Ehrlichiosis

2. Leishamiasis

3. FeLV/FIV

4. Myeloid cancer

When does a PARR result come back?

5-7 days

True or False: >80% are stage III or higher at diagnosis.

True!

What are the FIVE WHO stages of canine lymphoma?

I: single node

II: >1 node on 1 side of diaphragm

III: generalized lymphadenopathy

IV: liver/spleen

V: blood, bone marrow, non-lymphoid

What are the TWO WHO substages of canine lymphoma?

a: without systemic signs (not sick)

b: with systemic signs (sick)

What labwork is recommended for lymphoma workup?

Minimum database

What THREE imaging components are included in a lymphoma workup?

1. Thorax rads

2. Abdominal u/s with spleen/liver aspirates for cytology

3. Bone marrow aspirate/biopsy

What is the most important lymphoma-specific diagnostic in a workup?

Immunophenotyping (flow cytometry)

True or False: Stage of disease impacts treatment more than immunophenotype.

False! Stage of disease does NOT change treatment, but IMMUNOPHENOTYPING (B vs T) may.

Name FOUR reasons why labwork is important in lymphoma workup.

1. Impact chemo treatment

2. Help stage/prognostics

3. Concurrent disease screen

4. Labwork changes daily

Name TWO ways labwork can impact chemo initiation.

1. Cytopenias- avoid drugs causing myelosuppression

2. Liver malfunction- avoid drugs with liver metabolism/function

Name TWO examples of findings that help with staging and prognostic info.

1. Cytopenias or circulating neoplastic cells raise suspicion for Stage V

2. Hypercalcemia seen with T cell

What is classic for lymphoma on splenic u/s?

Lacy spleen

What are the THREE major staging tests?

1. Thorax rads

2. Abdominal u/s

3. Bone marrow sampling

What are the FOUR minimum initial diagnostics of canine lymphoma?

1. Lymph node cytology

2. CBC

3. Chem

4. UA

What TWO things should be done if cytology confirms lymphoma and clinically fits with a high-grade lymphoma?

1. Recommend flow cytometry for immunophenotyping

2. Discuss staging tests (not required)

What TWO things should be done if cytology does NOT confirm lymphoma or clinically does NOT fit with high-grade lymphoma?

1. Recommend LN biopsy and molecular test (flow cytometry/PARR)

2. Consider staging tests

True or False: Treatment for canine lymphoma is usually a multi-agent chemotherapy protocol, and 90% of dogs achieve remission with CHOP-based chemo.

True!

What is the median survival time for multicentric lymphoma in the following categories:

Pred alone

CHOP for B cell

CHOP or LOPP for T cell

Pred alone: 50 days

CHOP for B cell: 1 year

CHOP/LOPP for T cell: 8-9 months

True or False: Remission is curative.

False! Remission means it is NOT DETECTABLE clinically or molecularly (PARR).

Some people like to use --- for T cell lymphoma.

LOPP

What drug is a commonly used drug during induction phase for sick patients, like a "gateway drug?"

L-asparaginase (Elspar)

Why is pred used?

Induce apoptosis of neoplastic lymphocytes

True or False: It is best to put a patient on pred until you get a definitive diagnosis of lymphoma to mitigate side effects.

False! DO NOT use steroids until diagnosis is reached- it will kill the neoplastic lymphocytes and make diagnosis challenging and resistant to chemo

What are the EIGHT negative prognostic factors for canine LSA?

1. Stage V disease

2. Substage b

3. T cell immunophenotypes (except T zone)

4. High grade

5. GI involvement

6. Hypercalcemia

7. Pretreatment with steroids (resistance to chemo)

8. Poor response to treatment

What is considered the most important prognostic indicator of canine LSA?

Poor response to treatment

What is the most common type of indolent lymphoma in the dog?

T Zone lymphoma

What TWO ways can a T zone lymphoma be diagnosed?

1. Flow cytometry

2. Histopathology

What is the treatment for T zone lymphoma?

Prednisone and chlorambucil (oral chemo)

True or False: Because T zone lymphoma is indolent, treatment is more chronic/conservative, where there is an initial response with treatment followed with plateau/stabilization.

True!

What is the prognosis of T zone lymphoma?

Excellent (many years and may not require tx at diagnosis)