HHaemopoeaemopoetticic neopneopllasmsasms andand spspllenenicic disdisrroorrdedersrs ooff DDogsogs andand CCaatsts

Peter Vajdovich

Szent István University, Faculty of Veterinary Science, Department of Internal Medicine and Clinics Tumorgenesis Oncogene

1910. Rous–filtrableagent–avianleukosisvirus(retrovirus) „viraloncogen” (v-onc).

Inthecells-„cellularoncogens” (c-onc).

Theseare„proto-oncogens”-theyarechangablegenomsandcan be transformedtobe oncogenic.

Protooncogen Oncogen The tumorgenesis is passive accumulation of genetic impairments.

Normal gene dysregulation – proto-oncogenes (signal transduction /cell signaling/, proliferation, differentiation)

The proto-oncogenes key genoms, they control the cellular proliferation, differentiation and apoptosis.

The major funcfunctions are: Growth factors Growth factor receptors Protein kinases Signal transducers NuNucclear proteins and transcription factors Life of the cells

Birth

Proliferation

Arrest in growing

Differentiation

Death (apoptosis) M Mitosis and cytokinesis

Prophase

Metaphase

Anaphase

Telophase Rb Cell cycle G1 willstart, when phosph. M thechromosomas mitosis and cytokinesis areseparatedto the Meta- mitoticspindle Pro- Ana- Telo- phase phase phasepahes

M-delaying factors disappear, DNA-replik. block, G1 Chromos. condens. G0 Intermediate phase G2 Resting Biosynth.: prot, RNS Premitotic phase phase Restriction point 8 h-1 year Rb dephosph . S DNA-synth. Apoptosis (double starnd DNA-production, two identic chromatid) www2.nano.physik.uni-muenchen.de/research/rep03/ Cyklin/CDK INK, KIP HHaemaemopoopoeetticic ttuummoorsrs ooff ddogsogs CaCaninninee llyymmphophomama

Causes: in humans herbicide (2,4 diclorphenoxyacetate) lawn defence Ebstein-Barr virus (EBV) Immundeficiency Familiar pre dysposition

Forms: Ø Multicentric Ø Cranial mediastinal Ø Alimentary (gastrointestinal) Ø Skin Ø Other (kidney, spleen, CNS etc.) Multicentric form

Lymphoblastic infiltration

most common Nodular (N) and Extranodular (EN) forms N: nodes – submandibular, retropharingeal, prescapular etc. EN: eye, nervous system, bone, testicules, nasal cavity etc. Clinical signs: in20-40% badgen. cond., bw¯, appet. ¯, fever, pu/pd in27% diff. pulm. infiltr. in50% spleen•, liver• in60% chestx-ray+ (enlargedsternal, mediast. ln., orthymus) in20% cran. mediast. lnswell.® oftenT-lyorigin in10-40% totCa• (fromitin43% mediastln•) oftenT-lyorig.

Alimentary form amongalllymphomasin5-7% thickerintest. walls(enlargedmesenterialln., spleen, liver) canbe mixed upwithLymphocyticPlasmacyticEnteritis

Clinicalsigns: bw¯, appet. ¯, TP ¯ (malabs.), pu/pd Mesenteriallnswelling

Hepatomegaly Mediastinal form in5% amonglymphomas

Cranialmediastinalln •, (swellingof thymus)

Clinicalsigns: bw¯, appet. ¯ respiratorydistress (tachypn., dyspnoe, oed. pulm.) precavalsyndrome (v. cavaconstriction– edemaonthehead, forelimbs, fluid inthechest) Sternallnswelling Skin form rare solitarytumors(evenmouthormucousmembr.), generallyB-cells generalized: mycosisfungoides (epitheliotropicform) ® T-cell Clinicalsigns: I. peeling, alopecia, pruritus!, erythema, II. thickeningof skin, III. placks, nodules, exudation, ulceration Other form i.e. ocularform irisswelling, anterioruveitis(frequentinstageV), hypopyon, posterior synechia, glaucoma Differential diagnosis

Generalized lymphadenopathia Disseminated infections: · Bacteria–streptococcosis, Lyme-disease, mycoplasma, mycobact. · Viruses–adenovirus, distemperetc., · Rickettsias–bartonellosis,leishmaniasis, ehrlichiosis · Parasites–toxoplasmosis, demodicosis, · Fungi–aspergylosis, candidiasis,histoplasmosis, blastomyc. (can be hypercalcaemia) Immunmediated disorders Other haemopoietic neoplasms: · leukemias, · myeloma, · systemichistiocytosis, Tumor metastases Benign ln hyperpasia in cats Alimentary Intestines: · Infiltrativeenteritis -lymphcytic, plasmacytic, eosinophilicforms · Intestinal neoplasms, · Granulomatousenteritis, · Gastrointestinal mastocytoma(cat) Liver: · Hyperaemia, · Lipoticinfiltration(starv., hyperadrenocorticism, DM etc.) · Inflamm.-bacterial(cholangiohepatitis), viral(Rubarth-disease), parasitic(toxocariosis–larvaemigration, incatsflukesi.e.: Opistorchisfelineus), · Extramedullaryhaematopoiesis, · Cirrhosis, · Metastasesof otherneoplasmsinliver Spleen · Hyperemia, · Hematoma, · Chronicinflammation–hyperplasia, · Extramedullary haematopoiesis, · Haemolyticdiseases, · Sepsis, · Haemangiosarcoma, · Metastasesof otherneoplasmsinspleen Skin · Pyoderma · Immunemediateddermatitis (i.e.pemphigus), · Skintumors Mediastinum · Thymoma, · Heartbasetumor(chemodectoma), · Ectopicthyroidtumor, · Lymphomatoidgranulomatosisinlungs, · Granulomatosis(i.e.blastomycosis) Paraneoplastic syndromes non regenerativeanemia, maybehaemolyticanemia Ne•, Ly • (20%), Tcyt ¯ (30-50%), monoclongammopath, Ca • (PTHrp) and duetoit ® appet. ¯, pu/pd, kidneyfailure.

Staging (TNM Classificationof TumorsinDomesticAnimals, Geneva, 1980) I.: onelninvolvement, II.: manyln-sbelongingtooneregion, III.: generalizedlnenlargement, IV.: splenicand/orliverinvolvement(stageIII. yes, orno), V.: bonemarrowinvolvement, appearanceof neoplasticcellsinblood, and/orinvolvementof a byln. Substae: „a”-no badcond.:bw ¯, appet ¯, dyspnoe, anemiaetc. „b”-ifthesesignsarevsible 80% in stage III.-IV ! Major diagnosticpointsof view inhaemopoieticneoplasms

Frequent common signs: • decreased body weight, anorexia, matted fur, anemia • ln enlargement, abd cavity: hepato- és splenomegaly • paraneoplastic disorders (hypercalcaemia, fever) • metastases in other organs (lung, heart muscle, brain) Diagnosis of lymphoma

•bloodtests •x-rayexamination(CT) •ultrasonography(abdomenand heart–doxorubicincaused cardiotoxicity) •ultrasoundguidedsplenic, liver, intestinalaspirationcytol. •bonemarrowaspiration, orbiopsy(corebiopsy)

(from53 only28% had beenleukemic, butin57% therewere lymphoblastsingreaternumber) •cerebrospinalfluid (iftherewereCNS signs)

Forfirmdiagnosis totallnexcisionis needed!! Histopathology

follicular center diffuse large B-cell cell lymphoma lymphoma

Immunfenotype

B-cell marker: CD 79a

T-cell marker: CD3 Proliferation markers

Ki-67 % nuclear antigen (in all cell in cycle)

PCNA % (prolifeartive cell nuclear antigen)

AgNOR frequency and square (silver colloid method to stain nucleolar organizing regions)

cytology follicular center histology cell lymphoma Basic principlesinthetherapyof haemopoietictumors

Cytostatic therapy (and prognosis) according to the tumor type! •different combinations of pharmacons (doses are calculated in square meters2 or bw) •danger of side effects •human health •prize of drugs •multidrug resistance (MDR) •Glucocorticoid-therapy?! •Symptomatic therapy: vitamins, alternative drugs

Therapy of lymphoma

Points: prize, period, combination, effect, toxicity, experience

Monotherapy: doxorubicin: 50-70% completeremission(CR), life span(L): 6-8 month Combination: 1, COP (cyclo, vincr., pred.): 60-70% CR L: 6-7 m, 10-19%>1 year 2, CHOP: 80-90% CR L: 11,5 m, 27%>1 year, 13%>2 year(H=doxo) 3, L-VCA (UW-Madison): 94% CR L: 13,2 m, 50%>1year, 24%>2year (L=asparag)

Surgery –stageI. (and spleniclymphoma) Radiotherapy –stageI. and palliative (submand., rectal, bone, mediast.) Beforetreatment

After induction Beforetreatment

After induction PPrrognoognossisis:: bad: Ø stageIV. b, V. Ø histology(high, lowgrade) Ø mediastlnenlargement Ø highgrade(ki67 pos. high%) Ø highAgNORfrequency, square Ø T-cellorigin Ø totCa• Ø previoussteroidtreatment Ø P-glycoprotein

Notallhavebad prognosis! CCaaninenine lleeuukemkemicic didiseasesseases There are neoplastic white cells present in bone marrow. Ifthereis no increased(neopl.) whitecellcountinblood, itis not an exclusion!

Acuteleukemicdisorders:

Poorlydiffereniatedblast-cells willbe presentinperiphericblood.

Sometimesneoplasticcellsarenotpresentinblood, onlyanemia, leukopenia, thrombocytopenia is detected. Bone marrow aspirationorhistologyis needed.

•Acutelymphoblasticleukemia(ALL) •Acutemyeloidleukemia(AML) Chronicleukemicdisorders:

Maturedifferentiatedcells arepresentinblood. •Chronicsmalllymphocyticleukemia(CLL) •Chronicmyeloid(neutrophilgranulocytic, eosinophilic, basophilic, monocyticleukemia, polycytaemiaabsolutavera (overgrowthof matureRBCs),essentialthrombocytosis(overgrowth of maturethrombocytes). Lymphoid leukemia

Acute lymphoblastic leukemia (ALL) lybl-sinbm, spleen, liver, intest., mesent. ln-s, CNS lyblinfilt. from9: 4 null cell, 3 T-ly, 2 B-ly, (1 typeB-cell, 1 typeT-cell) Clinicalsigns: appet.¯, bw¯, pu/pd, spleen•, liver•, peteches,bleeding non reg. an., Ne ¯, Tcyt ¯, WBC > 14x109/l (v. WBC ¯)

Diagnosis: Ly>15x109/l generally., lybl-sinbm(itis difficultto differentiatefromotherblastcellsof bm-cyto-, histochemistry)

Stage: I. Ly • + ln • II. Ly • + spleen •, liver • III. Ly • + anemiaHb<7g% IV.Ly • + Tcyt ¯ (Tcyt<100 x 109/l) Therapy: adequatefeeding, maybewholebloodtransfusionis needed, broadspectr. ab-s, fluid therapy

Prenisolone Vincristine L-asparaginase Doxorubicin

Prognosis: average.: 120 day(in1 case: 19 month) Chronic small lymphocytic leukemia (CLL) differenciatedmatureLy-sinthebm, too from12, 8 T-ly (2 typesB-cell, 4 typesT -cell)

Before treatment

After 2 monthof treatment Clinicalsigns: Ly •, spleen •, ln • , Ht<35, Tcyt: 110-190 x 109/l glob • (60%), monoclonalgammopathy(68%)

Therapy: Chlorambucil Prenisolone Vincristine splenectomyis recommended(especially, ifNe¯, Tcyt¯)

Prognosis: L: 12 month >2 year(30%) MMyeyeloploprroliolifferaerattiiveve lleeuukkememiiasas (M(ML)L)

1/10 of thecaninelymphoproliferativedisorders

ALL>CLL >ML Acute myeloid leukemia – myeloblastic (10 types!) most common: myelomonocytic leukemia Chronic myeloid leukemia neutrophil granulocytic, eosinophil granulocytic, basophil granulocytic, monocytic, megakaryotic myelosis / essential thrombocytosis polycythemia rubra vera Acute myeloid leukemia poorlydifferenciatedmyeloidcells inbm, and blood

Clinicalsigns: anemia, Ne¯, Tcyt¯, infections, peteches, bleeding WBC• or ¯, canbe even150x109/l, spleen•, liver•, ln•, tonsill.•, kidney•, inheartand inCNS canbe manifested

Therapy: citosinearabinose doxorubicin orCOAP protokol, or: citosinarabinose 6-tioguanine doxorubicin Spleen ln Chronic myeloid leukemia

General signs: bw ¯ , appet. ¯ ,fever, palor, spleen•, liver•, ln•, vomiting, diarrhea, lamness, ocularsigns, CNS signs, non reg. anemia, Tcyt¯, DIC, Tcyt-pathia, Tcyto- morfol. abnorm. Polycythemia absoluta vera (PV) generallyinmiddleageddogs causes: damageof thestemcellclon, IGF-1 •(hum), Clinicalsigns: Ht>65-80%, mm erythema, hyperviscosity– ataxy, seizures, bm–M:E canbe normal, buthyperplastic!, erythropoetincc. norm.! Therapy: bloodrelease(20 mlg/kgbw) –instead: colloid, cristalloid hydroxiurea Chonic myeloid (granulocytic) leukemia (CML)

Clinicalsigns: WBC >100x109/l, granulocyte(Eo, Ne, Ba)•, leftshift., orhypersegm. (canbe), anemia, Tcyt ¯, spleen•, liver•, ln• bmhyperplasia, extramedullaryhaematopoiesis(spleen, liver) (ifEo-, orBa-CML: typicalcellspresentingreatnumberin organs)

Cave: leukemoidreaction!! (ifEo-type, cave: parasitic, allergic, osteomyelitis, mastocytoma, myositiseosinoph. etc.) causesof death: infection, bleding, orblasticcrisis

Therapy: hidroxiurea, prednisolon Megakaryocytic myelosis / Essential thrombocytosis

Clinicalsigns: Tcyt. >600-1000 x109/l, thrombosis, bleeding(DIC), splenic enlargement, MCV fals ¯, K+ •, bizarreTcytforms

Cave: Tcyt • -inflam., P.abs.V., haemolyt. an., bloodlossan., inITP reboundaftertreatment, vincristinetreatment

Therapy: see. CML Myelofibrosis

Cause: radiation, estrogene, cephalosporine, ehrlichiosis megakaryoblastbreakdown • -fibroblastprolif. •

Clinicalsigns: anemia, Tcyt • , spleen • , extramed. myelopoiesis,

Myelodysplastic syndroma

2 v. 3 cellline ¯, Ne ¯, an., Tcyt ¯, bmhyperplasia

Therapy: EPO IL, interferon etc. Plasmacytic tumors

Myeloma multiplex (MM) Waldenstormmakroglobulinaemia(ha IgM-originatedMM) lightchane–Bence-Jones prot. prod. heavychane–HeavyChainDisease Solitary plasmacytoma (evenbone) onribs, zygomaticarch, skin-mouth, intetstines

IgA, IgG, IgMorigincanbe, cryolobulins (on37 oCprecip. –apearsinclotorattachmentof RBCs) plasmacell. tum. <1% of othermalign. tumors 3,6% of hemopoet. tumors Germanshepherdbreedpredilection Plasmacytic tumors

Clinicalsigns: bleeding(epistaxis, retina-bleed.), coagulopathia, Tcyt ¯ -pathia, spleen•, liver•, kidney•,renalfailure., CNS signs, pathological bonebreaks, glucose ¯, totCa•, pu/pd(duetototCa• ), non reg. anem, pancytopenia, hyperviscositysyndrome

Diagnosis: inbmplasmacellNo•, Ig • inblood(myelomaprotein), kidneyfailure., totCa•, hyperviscosity, ELFO (immune-ELFO), bonebiopsy, ecision

Therapy: solitarytumor: surgery, radiotherapy, hypervisc. syndr.- plasmapheresis!, Melphalane, Prednisolone rescueprotokol: VAD–vincristine, doxorubicin, dexametasone Haemopoietic tumors of the cat haemop. tumorsare1/3 of ohertumors fromhaemop. tumors50-90% is lymphoma generally4-6 yers, FeLV(FIV) pos. (FeLV, retrovirus, Oncornavirinae)

Lymphoma

Types: mediastinal, alimentary, multicentric, leukemia, extranodal inyoung: FeLVpos. –mediast, multicentr. inspinalchordextranod. lymphomas85-90% catsareFeLVpos., generallyB-cell(B-Ly), oftenaliment. + nod. and mediast. + nod. type Alimentary form Clinicalsigns: in70-80% abdominalresistance, thickintestinalwallsor mesenterialln • in50-80% intestinalchange, in25% changeinstomach, incolon often, -tenesmus(41% of colontumorsis lymphoma, othersareadenocarc.) bw ¯, appet. ¯, spleen •, Tcyt ¯, TP ¯ Mediastinal form

Clinicalsigns: thymus •, mediast. ln •, stern.ln •, pleur. fluid accum., edema- pulm., and forelims, neck, tachypnoe, dyspnoe, cran. chest pressing ¯, dullheartsoundsand resp. sounds, Hornersyndr. (duetothesympatheticnervcompressioninthechest) Horner’ssyndrome

Small pupil size (miosis) Protrusion of the third eyelid Drooping of the upper eyelid (ptosis) Sunken appearance to the eye (enophthalmos) Dilation of blood vessels on affected side of the face, which makes the area feel warmer to the touch Hornersyndr. (duetothesympatheticnerv compressioninthechest) Multicentic form Clinicalsigns: ln •, spleen •, liver •, 1/3 of catsareFeLVpos., frequentlyT-celldisorders, Cave: perif. non neopl. lymphadenopathy(frequent) –histology!! 2-3x more ln-s, fever, polyclon. gammopathia, FeLVneg. Benignlymphoidhyperplasia

Extranodal form kidneyform–bilat. •, irregul., renalfailure primaryCNS form–peracute, quiclyprogrediating, spinalchord thoracolumb. part (T2-L4), frequentlyextraduralforms nasalform–olderFeLVneg. cats: nasaldyscharge, epistaxsis, headdeformity, exophtalmus., appet. ¯ skinform–FeLVneg. cats: alopecia, erythemacrustedpapula Extranodalforms

PL36b.tif EExxttrranodalanodal foforrmsms Therapy:

COP Cyclophospahmide Vincristine Prednisolone

VCM Vincristine Cyclophospahmide Vincristine Methorexate Prednisolone FFeelineline lleeuukemkemiiasas Myeloid leukemias

ØGranulocytic–rare ØMyelomonocytic Ne and Momalign. prolif. –more frequent ØMonocytic–rare ØEosinophilgraulocytic Eo>15x109/l, bm: manyEo, Eoprecurs.-M:E • hyepeosinophilicsyindr., Eoinfiltr. inmanyorgans ØBasophilic–rare ØErythroidmyelosis erythroidcell–erythroblasticpredominance ØErythroleukemia(Reticuloendotheliosis) generallyacute, many„blast”cells ØPrimaryerythrocytosis Ht>65-80%, hypervisc., CNS signs, visiondisorders ØMegakaryocyticleukemia abnormal„dwarf”megakaryocytesincirculation ØPrimarythrombocythemia Tcyta>1000x109/l, giantTcyt-s ØMalignanthistiocytosis spleen •, liver •, haemolyt. anem. (Coomb’spoz.) Tcyt ¯, erythrophagocytosis(Cave: imm. hemol. anem.) ØMyelofibrosis, Myeloidmetaplasia abnorm. prolif. erythrocyt., megakaryocyt., garnulocyt., anemia, WBC¯, Tcyt ¯, FeLVpos.

Therapy: myel. leuk., primeryth.: hidroxiurea megak. leuk: citosinearabinose, cyclophosphamide+ transfusions! Lymphoid leukemias

25% of catswithlymphomawillgetleukemia, too

Acutelymphoblastic inbmmany„blast”cell, WBC ¯ , anemia, catswithALL 60-80% FeLVpos. and T-Ly Therapy: COP –27% CR

Chronicsmalllymhocytic WBC >50x109/l, catsareFeLVnegingeneral Therapy: chlorambucil, prednisolone

Increasingappetite: diazepam, ciproheptadine, megestroleacetate SSpplleennicic ddiissoordrdeersrs

•Causes of splenic enlargement

haematoma, hyperaemia (passive, active), hyperplasia (infl.), extramedullary haematopoiesis

•Splenic torsion (torsio lienis) - (gastric dil. volv.) Subcapsular splenic haematoma in dog •Splenic neoplasms

•Primary (frequent) * ~sarcoma, haemangiosarcoma, malignant fibrosis, nodular hyperplesia, lymphoma, (carcinoma - rare) * frequently metastasis: peritoneum/lung/liver/heart/kidney

•Secondary (rare): leiomyosarcoma, haemopieticus tumor (lymphoma), osteosarcoma, fibrosarcoma, liposarcoma, mesenchymoma, non differenciated sarcoma, histiocytoma Haemangiosarcoma (HSA) Frequentindogs(in0,3-2%, withoutskintumorsin5%) inmales, olderdogs(8-13 years), GS, goldenand labradorretriever

Primary localisation is generallythespleen otherlocation: right atrium, skin, pericardium, liver, lung, kidney, oralcavity, bone, urinebladder, peritoneum (splenicdisease: tumorsarein2/3, 2/3 of tumorsis HSA) Haemangiosarcoma (HSA)

Splenic form

Outlook: changeable-greyish, darkred, nodular, soft includebleeding, necrosis, notvellcircumscribed, notbound, oftenconnectedtootherorgans, oftenbroken, bleeding

Haemangiosarcoma (HSA) Skintype inskin(goodprog.), orinsubcutaneoustissue(badprog.), most commonlyatventralabd., oratpreputialskin, wherehairis rare Haemangiosarcoma (HSA) Right atrium 3rd most frequentappearanceof HSA, most commonheartbase tumor, oftensolitary, butcanbe multiplicated, haemopericardium, ortamponadecandevelop Haemangiosarcoma (HSA) Metast. hematogenous, ortransabdominalimplantation(liver, omentum, mesenterium, lung, kidney, /abdom.-/ muscle, peritoneum, ln-s, adrenalgland, brain–in14% of HSA) 25% of thosewhohas splenic-HSA, right atrialinvolvement

HSA incat oftenintraabdom. (liver, omentum, diaphragmpancreas, spleen, mesenterium, intestines, abd. muscle) –biggermetast. rate, otherspaces: lung, skin Haemangiosarcoma (HSA) Clinicalsigns most dramatic: suddendeathduetoacutebleeding, or tamponade gen. weakness, anorexia, abd. enlargement, fluid accum., palor, frequentweakpulse, dyspnoe, frequentbreathing., bw¯,

AbdominalenlarPgLlepemd3tifent Haemangiosarcoma (HSA) dullheartsounds(pericard. fluid), arrhytmias, right sided heartfailure, inskindarkredtumor, orsubcut. bleeding mass, lamenes(muscleform), swellingof limbs, often microangiopathichaemolysis, reg. anaemia, WBC•, Ne•,

PL25A.tif TP: 25.2 g/l, Alb: 16.2 g/l, Crea: 81 mmol/l Haemangiosarcoma (HSA) Diagnosis Haemangiosarcoma (HSA) in80% of diagnosismetats. is present! x-ray., US, fluid inbody cavities (cytol. pos. onlyin25%), histologysampling must be takenfrommanyparts!! immunhistochemistry(von Willebr. factorAg)

Splenichematoma

Nodulesinspleen Haemangiosarcoma (HSA)

Rupturedsplenictumor, haemangiosarcoma

Haemangiosarcoma (HSA) Haemangiosarcoma

Bloody exsudate

2303.tif PL14.ti f Citology: chromnicreactiveprocess and inflammation Staging Haemangiosarcoma (HSA) T primarytumor Haemangiosarcoma (HSA)

T0: no visibletumor, T1: tumor <5 cm (dermis), T2: tumor >5 cm (subcutis), T3: tumor reachessurrundingtissues, i.e. muscle

N regionallymphnodes

N0: no reg. lnmetast., N1: reg. ln. involv., N2: distantln. metast.

M distantmetastasis

M0: no visiblemetast., M1: distantmetast.

Staging:

I.: T0, orT1, N0, M0 –i.e. non rupturedspleen II.: T1 orT2, N0, orN1, M0 –i.e.rupturedspleen III.: T2 orT3, N0, N1 orN2, M1

Cave: intraoperativeinvasiveHSA canbe mixed upwithsplenichematoma and metastaticnodulesinlivercanbe mixed upwithregenerativenodules, or extramed. haematopoiesis!! spleen macroscopicallyand cytologicallycanshow similarpatternin: IHA, Babesiosis!! Intraoperativeeuthanasia, onlyincaseof firmdiagnosis!! Haemangiosarcoma (HSA) Therapy surgical–beforecheckhaemostasis(DIC!) i.e. totalexcision: spleen, pericardium chemotherapy(onlyadjuvant), 4-5 cyvlerecommended: VAC Doxorubicine Vincristine Cyclophosphamide

Prognosis onlysurgical: 19-86 dayexp. life, more then1 year < 10% surgical+ chemotherapy.: 141-179 days non rupt. spleen (stageI.) better, thanrupt. spleen (StageII., III.) skinformbetter(dermis: 780 days, subcutis:172 days, muscle: 307 days) right atrium(badprog.): 2 days-8 month incats: splenectomy+ chemo.: 6-35 weeks, skinform–60-80% recrr. Splenicfibrosarcoma (dog) Splenicfibrosarcoma (dog)

vku91uh.tif vku91mu.tif