Managing the canine lymphosarcoma patient in general practice
#{ O?|5c ]%]9q0I diographs，abdominal ultrasonography，a bone I m砸ar眦row。。afsp。ihraetehvaenr danbdi0。止psye,n，ulatnradsoeu如nd叩-a。giu。inde。df the left popliteal lymph node for the purpose of immunophenotypin9．Neoplastic lymphoid cell infiltrates were found in the bone marrow and liv- er specimens and the results of immunophenotyp—— ing revealed T—cell origin of the tumor cells．Ac— cording to the World Health Organization (WHO)clinical staging system for canine lym— phosarcoma(Table l)，the patient was classified as Stage Va． A modifed University of Wisconsin——M霉dison chemotherapy protocol(Table 2)was started at the WCVM．A CBC was performed before ini— tialing chemotherapy．The recommended mini— mum baseline cell counts prior to initiating treat—— ment are at least l．5×109／L neutrophils and 75 X 1 012／L platelets．The blood cell counts in this case were adequate on all occasions．Side effects in this patient had been minimal，including mild weight loss and l incident of hemorrhagic enteritis at week 4，following doxorubicin administration that resolved with supportive medical therapy by the referring veterinarian．Currently，the patient is clinically doing very well with a good appetite， adequate weight gain，increased activity level，de— creased lymph node size，and retum to normal at— titude． Lymphosarcoma is the most common canine hematopoietic neoplasm．The 4 anatomic forms of lymphosarcoma comprise the followin9：multicen—— tric lymphosarcoma，which represents 80％t0 85％ of cases；alimentary(5％t0 7％)；cranial mediastinal (5％)；and cutaneous forms that combine to make`
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TabIe l．Wor ld HeaIth Organization cl inicaI stages of can i ne I ymphoma tacn stage can De turther subcIassitied int0： 一Substage a：without systemic signs —Substage b：systemic signs up the rest of the cases．Extranodal sites，such as the eye，nasal cavity，testis，central nervous system， and bone，are much less common．This discussion will foCUS on the multicentric forrn of the disease． The most common presenting clinical sign is gen—— eralized painless lymphadenopathy(Figure l)，but other nonspecific signs，such as anorexia，weight loss，vomiting diarrhea，emaciation，ascites，dysp— nea，polyuria，polydypsia，and fever，are often the only signs of illness．Differential diagnoses for gen— eralized lymphadenophthy include the followin9： infectious causes(such as fungal or rickettsial dis— ease)，other cancers(acute and chronic leukemia)， and immune mediated disease(moderate increase in lymph node size)． There are several paraneoplastic syndromes that can be associated with lymphosarcoma．The most common of these is an anemia of chronic disease Figure l．Marked bi I ateraI mandibuIar Iymphadenopathy commonIY seen in a dog with muIticentr ic Iymphosarcoma． 。中国宠物医师网B"YJ8Cr
/].JI(g xi!Q:H0(mild， nonregenerative， normochromic， norm0— cytic)．Other CBC abnormalities include leukocy— tosis(25％t0 40％of cases)，lymphocytosis(20％of cases)，and thrombocytopenia (30％t0 50％of cases)．Thrombocytopenia as a consequence of paraneoplastic effects of lymphosarcoma rarely re—— sults in clinical hemorrhage．Hypercalcemia is a common paraneoplastic event that Occurs sec—— ondary to the production of parathy7roid hor—— mone—related peptide by tumor cells，resulting in an increase in serum free calcium．In cases of lymphosarcoma，hypercalcemia of mafignancy is most often associated with tumors of T-cell ori- 百n．Associated clinical signs of hypercalcemia in— clude polyuria，polydypsia，muscle weakeness， lethargy，weight loss，and central nervous system depression．Less common paraneoplastic condi— tions include monoclonal gammopathies，neu— ropathies，and cancer cachexia are observed． Diagnosis can be made via a fine neele aspirate of a peripheral lymph node(Figure 2)．This tech— nique can be performed easily at any clinic and the aspirate then submitted to a pathologist for definitive diagnosis．Many practitioners opt to save 1 0f the smears such that“in—house’’microscopic evaluation of the slide can be performed as well9I:e"@.U
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uP9bC)T qY`6C0____。——this helps to ensure that an adequate diagnostic yield has been obtained oarge number of intact lymphoid cells with adequate smear preparation) and provides an opportunity for the referring clin—— ician to become familiar with microscopic appear—— ance of lymph node cytologic smears． Complete staging involves thoracic radiographs， abdominal radiography and／or ultrasonography， liver，spleen，and bone marrow aspirates and im— munophenotyping of the tumor population，based on either immunohistochemical staining of biopsy specimens or immunocytochemical staining of prior unstained cytologic smears．The tumor is then classified by using the WHo system fTable 1)．Most dogs(>80％)will be presented in ad— vanced stages(111 to V)．Keep in mind that while it is important to do complete staging in pa—— tients，it is also not mandatory．If a chent had to choose between staging tests and treatment，treat— ment would be the better option，since at this time in veterinary medicine，stage and type of lymphosarcoma do not change the type of treat—— ment offered．However，staging does help the medical oncologist give a more specific prognosis to the client．The more information that can be obtained from each patient，the more likely clini二 cians are to improve their understanding of cancer biology，further their ability to characterize mali9—中国宠物医师网Sl`TIco T {
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F I gure 2．Lymph node asp i rate． Smear cons i sts of a monotonous popuIation of Iarge， neopI astic Iymphoid ceI I s that measure approximateIY l—1．5×the diameter of a nearby segmented neutroph i I (artowhead)．The tumor ceI I s are characteri zed by high nucIeus： cytopIasm rati0． a smaI I amount of deep basophi I ic cytopIasm．and round nucIei with fiRe chromatin and prominent nucIeoI i． Ruptured cytopIasmic debr i s i s present in the background． Bar=25 um． (Cyto I ogy i mage courtesy of KR Fr i edr i chs，DVM．DACVP) nancies，and hopefully one day，establish treat— ments tailored to the molecular fingerprint of the disease，thus leading to the development of new therapeutic modalities． Treatment of lymphosarcoma in the dog is often rewardin9，as appropriate chemotherapy can signif- icantly increase survival time．Treatment of multi— centfic lymphosarcoma is gratifying because of the high percentage of clinical remissions(clinical dis— ease is not present and the clinical signs that prompted initial treatment have resolved)．There are 2 main goals of chemotherapy：1)to induce a durable clinical remission (>6 mo)，and 2)to reinduce or rescue a remission after l or more re- lapses．There are many chemotherapeutic choices available for the treatment of lymphosarcoma． Dogs that respond to chemotherapy and achieve a clinical remission usually retum to a good quality of life．Concurrent medical problems，paraneoplas— tic syndromes like hypercalcemia，severe weight loss，or fiver insufficiency，are all factors that may decrease the patient’s overall quality of life．Pr0— tocols based on CHOP(cyclophosphamide，dox— orubicin，vincristine，prednisone，+／一L—asparagi— nase)have been shown to induce clinical remis— sion in 80％t0 90％of cases．The University of Wisconsin—Madison protocol fUM—M short)has a median survival time of l3 m0．Approximately 25％of dogs survive 2 Y or longer with CHOP—— based protocols．Other choices for treatment in— clude single agent doxorubicin，which has a clini— cal remission rate of 60％t0 85％and a median survival time of 6 t0 9 m0．Prednisone can induce a short—rived remission of l t0 2 m0，but it in— creases the risk of multi——drag resistance if the client decides to pursue more aggressive treatment at a later date．Most dogs will die within 4 t0 6 wk of diagnosis without treatment． Clients are continually becoming more open to the idea that a diagnosis of cancer in their pet does not always have to lead to immediate eu—— thanasia．Clinical cure of lymphosarcoma is rare(< 1 0％of cases)，but the ability to give clients 6 to 24 mo of quality time with their pets is possible if clinicians stay informed as to the treatment op—— tions available．Multicentric lymphosarcoma is a disease that can be managed by the general practi—— tioner；it does not require referral to a specialized practice．It is，however，important to remember that there are valuable resources available to the practitioner for the development of a chemothera—— PY protocol for a patient．Continuing education， journal articles，and，most importantly，colleagues with special interest or advanced training in the area of medical oncology can all be consulted be—— fore beginning therapy．However，it may be most1Sv#J#f2Yf,I/^-N'J0
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