Onco 4 Lymphoma

sihirlifil's version from 2018-05-01 20:48

Feline & Canine

Question Answer
Ddx for Lympadenopathy/megalyNeoplasia (1ry lymphoma, metastatic)
Infxn: fungal (Blasto), Rickettsial (Ehrlichia)
Reactive (periodontal dz)
Hge, infarction, edema
Etiology of lymphomaMalignant transformation of lymphocytes
Incidence of lymphoma7-24% of all canine cancers (24-100 / 100,000 dogs!); incidence is 2/3 that seen in cats
Increases with age (commonly middle-aged, 6-9 years)
Can appear in any age, breed, or sex (lower expected in females)
Signalment/clinical featuresIndolent or aggressive presentation
Solitary, node-based, or associated with any organ in the body
Non-painful lymphadenomegaly = MOST COMMON!
Risk factors for lymphoma2,4-D herbicide exposure (lawn care, golf courses)
Industrial living
Chemical use
Genetically heritable
Genomic loss of methylation of cytosine bases
High-risk breedsBoxers
Scotties, St. Bernards, Airedales, Bulldogs (bassetts)
(Low-risk breeds)(Pomeranians, Daschudns, GSD?)
Classification of lymphomaAnatomic site
Histologic/cytologic type (large cell, high-grade)
Immunophenotype: 70-80% are B-cell (B = better, T = terrible)
Forms of lymphomaMulticentric
Alimentary (may be solitary or diffuse)
Cutaneous/mycoses fungoides
Mediastinal (+/- pleural effusion)
Extranodal: ocular, cardiac, CNS
MOST COMMON form of lymphomaMulticentric 80-85% (generalized: LN all over body)
Histologic forms of lymphomaLymphoblastic: large, immature
Lymphocytic (small, mature)
TUMOR STAGE: I1 LN affected
TUMOR STAGE: II>1 LN affected, same side of diaphragm
TUMOR STAGE: IIIMultiple nodes, both sides of diaphragm
TUMOR STAGE: IVLiver or spleen involvement (+/- Stages I-III)
TUMOR STAGE: VMarrow or extranodal involvement (+/- Stages I-III)
What are the substages?A: no clinical signs
B: clinical signs
Which staging tests are available? for what purpose? (chart)
**Which staging test is most important?Usu only does FNA (rapid dx). All other more academic/just for the parents (spend so much money on dx, now cant afford tx, and don’t need to know stage in order to tx)
Which test is this?
Immunocytochemistry: T-cell =CD3
Immunocytochemistry: B-cell =CD79
Immunocytochemistry: what is flow cytometry for?Only if you cant get your answer from cytology. Distinguishes neoplastic vs. inflammatory/reactive lymphocytes. NOT SCREENING OR INITIAL DX TEST (can do blood sample, don’t need LN biopsy)
Immunocytochemistry: what is PARR?PCR for antigen receptor rearrangement
Assay to determine if a population of cells is the result of clonal expansion of B or T cells (usually implies lymphoid neoplasia)
What does PARR tell you?1) If the sample is from a cancerous condition of lymphocytes; 2) If it is of a B-lymphocyte or a T-lymphocyte origin
Biologic behavior: most common?Systemic illness (most common presentation for multicentric)
Majority of patients have B-cell lymphoma
CS attributable to location
Alimentary lymphoma occurs how?Less frequent that multicentric!
Associated w/ hypoproteinemia, chronic enteritis may proceed development
Must be ddx from lympocytic/plasmacytic enteritis
CS of lymphomaVague, related to site
Weight loss, lethargy, fever, V+/D+, cough
PU/PD (incr Ca2+)
What paraneoplastic syndromes associated w/ lymphoma?Hypercalcemia (PU/PD)
Cachexia (ddx heart dz! weight loss despite good appetite)
What’s this? sign of what?
Forelimb edema: caval syndrome. Also muzzle swelling! (obstruction of submandibular, mediastinal LN)
Type of lymphoma? STAGE?
Epitheliotropic = STAGE 5! (mucocutaneous: T-cell)
Pulmonary LSA (stage 5!) Diffuse interstitial
Dx by FNA! doesn’t look like lymphoma on rads
What is complete remission?No symptoms, no signs indicate presence of cancer. 100% reduction in LN size
90% of patients :) and can happen 6h after starting tx!
What is partial remission?Large percentage of signs & symptoms are gone. 50-75% reduction in LN size
What is stable dz?Doesn’t respond to tx
What is progressive dz?Other organs develop lymphoma in spite of tx
Prognosis for remissionStage III: 80-90%
Stage IV: 60-80%
Stage V: 50%
Treatment approachTeam, compassionate care (supportive, not usually painful)
Human-animal bond
Considerations: owner (time, cost, goals), patient (health, location), vet (comfort lvl with drugs & potential complications)
Survival time: no tx4-6 week average (succumb to obstruction etc)
Survival time: Pred alone2-3 month, w/ SEffx (panting, PU/PD, behavior)
**What’s the approach for steroid use?Don’t do before chemo! (Generally no longer than 3-4 weeks pre-chemo) Increases multidrug resistance: doesn’t get in, or gets pumped right out
Need to get dx first! As long as you’ve retrieved your sample, go for it (interfere w/ getting diagnostic tests beforehand)
What’s P-glycoprotein? why do we care?Multidrug resistance associated protein! Decreases drug uptake, increases drug efflux, activates detoxifying systems & DNA repair mechanisms, evasion of drug-induced apoptosis
TX: Which drugs available?COP (Cyclophosphamide, vincristine, prednisone)
Adriamycin +/- L-Asparaginase
TX: what is COP?Cyclophosphamide, vincristine, prednisone (Sterile hge cystitis, peripheral neuropathy)
Survival time: COP and adriamycin +/- L-Asparaginase6-9 month, less QOL
Adriamycin +/- L-Aspariginase: benefits of +1 drugsGets to all points of cell cycle where cancer is
Adriamycin +/- L-Asparaginase: SEffxDogs: cardiotoxicity
Cats: nephrotoxicity, anorexia
What’s the modified U of Wisconsin-Madison protocol?
Survival time: U of W-M protocol12-18 month
MOST AGGRESSIVE! weekly, for 6m, $$$
What’s the idea behind no maintenance therapy?Want to be able to continue using the same drugs the patient responded to before (done in 6m, get into remission; when finish protocol, check for big LN, PU/PD, etc). If keep treating continuously, can’t create a clean slate, LN get enlarged again
Other treatment options besides chemoSurgery (solitary site): splenectomy (?), GI perforation
Ratiation: half body irradiation, solitary extranodal
Rescue chemo protocols: what happens w/ 2nd, 3rd, 4th remissions?Harder to achieve, last half as long
Reasons for relapse during chemo (3)Inadequate dosing & frequency of admin
Development of multidrug resistance
Failure to achieve high concentrations of chemo drugs in certain sites e.g. CNS
Why not give additional chemo to induce more remissions?Undesirable SEffx, financial concerns
As long as we’re doing no harm & the patient is still responding, there is no reason to not at least try! (fly by the seat of our pants protocol lol)
What is Tanovea?(it sux don’t use it) Vax being developed. Stimulates immune system to create antibodies to CD20 protein that is found on B cells, leading to cell destruction
(Begin 2-4w after completing chemo, initially given q2w for 4 doses, then booster q6m)
Not longer survival time than another round of chemo, more $$$
New way to monitor remission status?cLBT blood test! (Multiple serum biomarker test)
How does cLBT work?(Canine lymphoma blood test) Looks for D-reactive protein & haptoglobin. Should see higher lvls in lymphoma patients
Use as screening test, capable of detecting relapse up to 8 weeks before CS. Assists monitoring for remission & early detection of dz recurrence
Greatest benefit as a standard test in all patients (guide to tx success)
cLBT: low score means? high?Low = Objective indicator of good clinical remission, signing patient off w/ successful response (owners get nervous not visiting you anymore lol)
High = prognostic indicator: animal not in full clinical remission, and you could expect shorter remission duration. Further monitoring should be run, +/- further tx


Question Answer
Incidence of lymphomaHematopoietic neoplasia accounts for 1/3 to 1/2 of all feline neoplasia (most common, 50-80% or 200/100,000 cats)
What age of cats get lymphoma?Bimodal age distribution
2 years, then 10-12 years
Biggest prognostic indicator for feline lymphomaVIREMIC STATUS
Incidence of feline lymphomaIncreased risk Manx & Burmese
Lower risk in intact females
Retroviral causes: FeLV = 62x higher risk, FIV = 6x higher, concurrent FeLV/FIV = 77-fold increased risk
How do cats w/ lymphoma present?2 groups! Young cats positive for FeLV-associated dz (respiratory b/c mediastinal node enlargement & pleural effusion, hypercalcemia) & OLDER cats negative for FeLV w/ GI dz
Causes of lymphadenopathy(Same in dogs!)
Lymphadenopathy (solitary node, regional group, all LN); reactive hyperplasia (proliferation of lymphocytes & plasma cells from antigenic stimulation); lymphadenitis (influx of inflamm cells due to local infxn); neoplastic infiltration (1ry lymphoid neoplasia or from metastatic neoplastic dz)
Diagnosis & staging: how is it, compared to dogs?Same except FeLV/FIV status. WHO stages are not as useful to describe prognosis
Which samples are taken for testing?Mediastinal: cytological exam (node or pleural fluid)
GI: endoscopically or sx-collected
Nasal: requires biopsy
Multicentric & extranodal: FNA or biopsy
How is feline lymphoma diagnosed?Thorough PE!
CSF tap
Thoracic & abdominal rads
Abdominal US
FeLV/FIV test!
LN biopsy, BM aspirate
FeLV status: if positive?50-70%! especially young cats
Older cats are usually…?FeLV negative
FeLV trends: MediastinalFeLV+
FeLV trends: AlimentaryFeLV- (ELISA), FeLV+ (PCR)
FeLV trends: SpinalFeLV+
How has the FeLV vax affected FeLV+ case #?Less FeLV+ since vax! But lymphoma increased incidence despite FeLV (Oriental breeds w/ mediastinal)
Biological behavior of feline lymphomaSame! (But generally the Hodgkin’s form…?)
FeLV-related lymphomas tend to be _-cell lineageT
(Mediastinum, generalized, CNS, ocular)
FIV-related lymphomas tend to be _-cell lineageB
(Extranodal locations, nasopharyngeal)
Any environmental links to lymphoma?Cigarette smoke! 2nd-hand increases risk 2-3x depending on duration of exposure (1+ packs a day > 3x risk than nonsmoking)
How are vaccine-site sarcomas related to lymphoma?Cats developing vax-site sarcomas have much higher subsequent risk of developing lymphoma (predisposition or trigger e.g. chronic inflammation)
How is IBD related to lymphoma?Frequently arise in organs/sites affected by chronic inflammation. Linkage to alimentary lymphoma has been suggested
Lymphocytic-plasmacytic, low-grade intraepithelial T-cell malignant lymphoma and not a reactive T-cell proliferation
Prednisone & chlorambucil
Most common anatomic siteAlimentary 50-70%
(Multicentric 10-25%, mediastinal 10-20%, nasal 10%, renal 5-10%) (don’t really stage cats)
Where does mediastinal happen?(T-cell) Thymus, mediastinal LN, +/- BM infiltration
Where does alimentary happen?(T-cell) Solitary, diffuse, or multifocal GI tract infiltration
Intestine, mesenteric LN liver, spleen, *renal
Miscellaneous sites of lymphomaNasal (B-cell)
*Renal, BM involvement
CS: CNSAnisocoria, Horner’s, posterior paresis
CS: Body cavityPleural: dyspnea, coughing, regurgitation, effusion, noncompressible cranial mediastinum
Peritoneal: abdominal distention, effusion
CS: alimentaryV+, D+, weight loss, anorexia
CS: NasalFaciall swelling, nasal d/c
CS: RenalPU/PD
CS: HematologicAnemia, atypical lymphocytes, hypercalcemia, BM involvement (50%)
MAINSTAY chemotherapy optionsVincristine
*Cytosine arabinoside
Prognosis: Multicentric/alimentary50-60% achieve complete or partial remission (compare to 90% in dogs :( )
Prognosis: Mediastinal70% achieve remission
When can you use radiation therapy?Mediastinal
Nasal 1 time can CURE! :D
Tx medical emergency (like caval syndrome. right pic is 8h after)
When is surgery an option?Easily resectable (not usually)
No significant risk to patient
Obstructive dz (if GI --> perforation or obstruction, then FOLLOW UP w/ chemo)
Prognostic factorsResponse to therapy
FeLV/FIV status
Survival time: Untreated4-8 weeks
Survival time: if 50-60% remission6-9 months
Survival time: how many last >2y?10-15%
Survival time: if FeLV+WORSE! 3-4 months… usually weeks

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