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Hematopoietic Neoplasias - Coggle Diagram

- - - - 24% of all canine neoplasia
      - 83% of all canine hmpt neoplasia
    - - genetic pre-disp in dogs
      - viral in cats and cows
    - - affects any organ sys
        
        anorexia and wt loss
        
        vom and diarrhea
        
        dyspnea
        
        fever
        
        PU/PD
      - PE findings
        
        enlg (non-painful) LN
        
        hepato-splenomegaly
    - - Hx and PE
      - clin path
        
        CBC, serum biochem, UA
        
        evidence of organ invovlement and paraneoplastic synd
      - find neoplastic c
        
        microscopic techniques
        
        direct visual detection/charac of c
        
        molecular techniques
        
        charac c based on prot expr or genetic data
        
        best used TOGETHER
      - aspir cytology (FNAC)
        
        commonly used, easyish, inexpensive, rapid
        
        one flavor = diffuse lg c lymphoma
        
        1.25-2 X sm lympho/neutro
        
        inc cytoplasmic vol
        
        round nucleus, clumped chromatin, and 1-3 nucleoli
        
        *> 50% of lg c (in LN) = lymphoma
        
        most common form of canine nodal lymphoma
        
        pitfalls: reactive/hyperplastic LNs, sm c lymphomas, does not provide architec info, splenic lymphoma --> ALL REQ CONFIRM TEST
        
        loc, sp, and dz matter in usefulness
        
        canine B c lymphoma = cytology is highly specific
        
        feline mesenteric LN = 90% false neg rate for T cell lymphoma
      - biopsy + histopath
        
        currently gold std for diag of lymphoma
        
        advant
        
        more tis archtec
        
        allows for adv classif
        
        overcomes cytology shortcomings
        
        disadvant
        
        more invasive
        
        more expensive
        
        longer turnaround time (TAT)
      - molecular techniques
        
        tests that rely on non-morph cellu properties (DNA/prot)
        
        IHC, clonality assays, flow cytometry (FC)
        
        IHC
        
        Ab based - directed against CDs
        
        used to diag and immunopheno: all T or all B
        
        provide prog info and confirm monoclonality
        
        IHC and ICC use Ab to demo lineage-specific Ag on c = immunophenotyping
        
        clonality assay
        
        all lymphos carry unique DNA seq
        
        B c = Ig recep
        
        T c = TCR
        
        seq are unique b/c DNA is perma rearranged
        
        in a popu of lymphos, PCR can reveal
        
        single gene product (monoclonal)
        
        many gene products (polyclonal)
        
        inflamm lymphos are polyclonal and neoplastic lympho expansion is monoclonal
        
        PARR
        
        PCR for Ag recep rearrangement
        
        detects T and B c lymphoma
        
        2 more items...
        
        any smpl w/ stable DNA
        
        useful in ambiguous cases
        
        specialty labs + expensive
        
        flow cytometry
        
        quant charac of c in suspension
        
        forward scatter = cell size
        
        side scatter = nuclear shape and cytoplasmic granularity
        
        Ab bound to fluor
        
        3 more items...
        
        benefits
        
        quant data on millions of c
        
        quick
        
        can be performed on many smpls
        
        1 more item...
        
        specialty labs, expensive and req fresh smpl
        
        diag/charac hmpt neoplasia
        
        neoplastic c
        
        2 more items...
        
        quant other charac
        
        1 more item...
        
        can be used as diag
        
        lymphoma vs not lymphoma
        
        also provide addl info
        
        immunophenotype (T or B)
        
        other prognostic info
        
        many are useful beyond lymphoid malig
    - - any symptom of cancer tat is NOT direct result of tumor mass
        
        often 1st sign of malig
        
        unexplained anemia
        
        inc water consump and urination
        
        wt loss
      - may be hallmark of certain malig
      - mediated by produc of cyk and horm by neoplastic popu
      - Ex: hypercalcemia, hyperglobulinemia
    - - why? b/c not all lymphomas are the same
        
        30+ forms of lymphoma in vet med
        
        definite prognostic diff
        
        inc recog of trtmt diff
      - how?
        
        diag + histopath/IHC
        
        diag + FC
        
        FC alone?
      - objective
        
        use diag data to ID single dz type that has predictable bio charac
        
        clin benefit = inform trtmt and prognosis
        
        research benefit = detect dz specific outcomes
      - indolent dz
        
        gen accepted in dog that T = terrible and worse prog than B c
        
        B c = 9-12 mo and T c = 6 mo
        
        WHO 4 types
        
        T zone lymphoma
        
        prolonged survival time (MST = 33.5 mo)
        
        trtmt w/ aggressive chemotherapy
    - - common canine neoplasm (7-24% of all neoplasms) and single most common hmpt variant (83%)
      - dz in any age but highest incid in 10-11 yo
      - breed inc risks
        
        B c = bassett hounds, cocker spaniels
        
        T c = irish wolfhounds, shih tzus, cavalier king charles spaniels, yorkies, huskies
      - NO infec etiology
    - - incid rate unk but believed to be more common feline malig
      - infec agent (FeLV) is impt cause
      - post FeLV era (mid-1980s to present) = shift in dz
        
        FeLV era = 80% of cats w/ lymphoma were FeLV+, median age was 3-4 yo, lymphomas were T c and gen/thymic
        
        post-FeLV era (>1983) = 13% of cats w/ lymphoma are FeLV+, median age is >11 yo, lymphomas are either B or T c and intes or renal
    - - 2 forms
        
        enzootic
        
        assoc w/ bov leuk virus (BLV)
        
        <5% of BLV infec cattle dev lymphoma
        
        dz of adult cattle
        
        horiz spread by exposure to infec blood
        
        anat loc: heart, spinal cord, uterus, abomasum
        
        sporadic
        
        non-viral assoc dz
        
        3 types
        
        calf
        
        ani < 6 mo
        
        LN, kidney, spleen
        
        thymic
        
        < 2 yo
        
        cutaneous
        
        2-3 yo
        
        eventual sys involvement
    - - classif by distrib of dz (stage I-IV) and whether ptx is "sick" (substage a or b)
      - prog and trtmt info
      - req: rads, US, clin path
      - maj of dogs stage III-IV at time of diag
  - - - lineage
        
        lymphoid or myeloid
      - differen
        
        acute leuk = undifferen c
        
        chronic leuk = differen c
      - conc of neoplastic c in blood
        
        leukemic leuk
        
        neoplastic c can be readily detec in blood or BM
        
        aleukemia leuk
        
        neoplastic c cannot be easily detec in blood
        
        subleukemic leuk
        
        neoplastic c are present in blood but in insuffic #s to inc total WBC
      - 4 maj categories: ALL or CLL and AML or CML
    - - req ID of > 20% lymphoblasts in blood or BM
      - poor prognosis - d to wks
      - hepatosplenomegaly in 50% of cases
      - periph cytopenias common
    - - inc # of lymphocytes in blood or BM
        
        up to 300,000/uL
      - c appear like norm lymphos
      - better prognosis than ALL
      - often an incidental finding
      - fewer periph cytopenias
      - canine
        
        older ani (7-10 yo)
        
        lethargy, vom, anorexia
        
        CLL more common than ALL
        
        up to 50% of CLL dogs are asymp
        
        organomegaly (spleen 70% and liver 50%) are most common PE finding
      - feline
        
        rare
        
        dz of older cats (12.5 yo)
        
        50% asymp at presentation
        
        wt loss, organomegaly, anemia
    - - inc # of lymphos or atyp lymphos
        
        CBC and blood film eval
      - lg atyp lymphoid c in the blood
        
        ALWAYS abnorm
      - matur c lymphocytosis
        
        often (not always) neoplastic = they live
      - FC can provide diag/prog info
        
        gold std for diag of leuk
        
        CD34 expr = extremely poor prog indicator
        
        B c CLL = size is prog
        
        sm c MST >1000 d
        
        lg c MST = 129 d
        
        T c CLL = # is prog
        
        *>30K c MST = 131 d
        
        <30K MST = 1068 d
      - in dog, ddx = chronic ehrlichiosis, thymoma, addison's dz, leuk
  - - - extramedullary plasmacytoma
        
        any site other than bone
        
        cutaneous EMPs
        
        skin (86%) is most common site in dog
        
        gen benign
        
        non-cutaneous EMPs
        
        GI tract in dog: oral cavity, rectum
        
        sim beh to cuta EMP
        
        gen non-Ig producing
      - multiple myeloma
        
        malig plasma c neoplasm
        
        8% of canine hematopoietic neoplasia
        
        clin dz
        
        bone lysis
        
        renal dysfunc
        
        anemia, bleeding, hypercalcemia
        
        hyperviscosity
        
        monoclonal Ig (M-spike) secre is hallmark of nearly all cases of MM
        
        feline plasma c neoplasia (myeloma rela disorder)
        
        liver/spleen involvement is common
        
        often w/ concurrent BM involvement
        
        cut dz is more aggressive
      - solitary osseous plasmacytoma
        
        rare tumor in dogs and cats
        
        may progress to MM
    - - ID of clonal popu of plasma c in suspect lesion
        
        cytology/histo
        
        suffic for EMP and MRD
        
        abund blue cytoplasm, perinuclear clear zone, eccetnric round nucleus, clumped nuclear chromatin
      - diag of MM req more data (2-3)
        
        bone lysis
        
        inc # / clonal plasma c in BM
        
        detec of M-prot
        
        prot product of neoplastic plasma c
        
        serum or urine
        
        prot sep based on size and charge
        
        directly stained + tracing = prot electrophoresis (SPE)
        
        M prot ddx
        
        lymphoprolif dz (plasma c/lymphoma)
        
        Ehrlichia canis
        
        other inflamm dz (rare)
        
        apply Ab against all hvy and lite chain classes and look for single, dom sp = prot immunofixation
        
        M prot
        
        all B c prod unique Ig
        
        ea Ig molec = 1 hvy and 1 lite chain
        
        polyclonal plasma c popu has many Ig molec
        
        monoclonal plasma c popu has 1 (M prot)
        
        can be
        
        intact Ig (usually)
        
        hvy chain only (rarely)
        
        lite chain only (infreq) - Bence-Jones prot
        
        typ indicates plasma c neoplasia
  - - - WHO considers to be diff presentation of same dz
  - - - abnorm c/inc #s
    - - ALL = poor outcome
      - T-CLL = # matters
      - B-CLL = size matters
- - - - evidence of unsuccessful matur and release
    - - lg erythrocytes, lg neutro precurosr, or abnorm nucelated forms
- - - - no charac age of affec ani
      - varied WBC count (typ >100,000 c/uL) and >2 cytopenias
        
        aleukemic and subleukemic forms can be seen
      - fulminant, rapidly fatal dz
        
        MST = 20 d
      - involvement of visceral organs (spleen and liver) is common
      - cat: assoc w/ FeLV infec
    - - REQ ID of > 20% myeloblasts in either blood or BM
      - myeloblasts ID by
        
        CBC and blood film examin
        
        cyto/histo of BM
        
        b/c lymphoblasts and myeloblasts are indisting, addl tools are needed to disting them
        
        IHC/ICC
        
        FC
        
        gen approach for determ cellu lineage (same as for LPD)
    - - detec of cytogenetic abnorm is hallmark in diag and workup of leuk in hu
        
        been shown to provide better prog and trtmt data than morph classif
      - use and role in vet med is still in infancy