Canine LSA Past Paper PDF

Canine Lymphoma Corey Saba, DVM, DACVIM (Oncology)  Objectives Know the biologic behavior of lymphoma in dogs Know common presenting clinical signs Formulate staging (diagnostic) and a general therapeutic plan Educate clients about lymphoma  Lym...

Canine Lymphoma Corey Saba, DVM, DACVIM (Oncology)  Objectives Know the biologic behavior of lymphoma in dogs Know common presenting clinical signs Formulate staging (diagnostic) and a general therapeutic plan Educate clients about lymphoma  Lymphoma Round cell tumor – Lymphoma – Transmissible venereal tumor – Mast cell tumor – Plasma cell tumor – Histiocytoma COMMON!! – 83% of all hematopoeitic tumors  Lymphoma Malignant cell originates from lymphoreticular cells – Lymph nodes** – Spleen – Bone marrow – GALT (gastrointestinal tract) – Skin – Others Systemic disease  Canine lymphoma classification Histologic grade/size of cells – Grade based on MC/hpf (400x) Low: 0-5/hpf Intermediate: 6-10/hpf High: >10/hpf = most common Immunophenotype (B vs. T cell) – Diffuse large cell B cell lymphoma (DLCBL) = most common Valli VE, et al. Vet Pathol, 2013;50:738-748  Canine lymphoma classification Anatomic form – Multicentric form = most common Stage/substage – Stage 3-5 = most common  History Questions to ask – When did you first notice the lumps? – Any change in their size? – Are they bothering the dog? – V/D/C/S/PU/PD, etc. – Meds? Travel history?  Physical examination Which peripheral LN should you always be able to feel? Which are only palpable if abnormal? prescapular mandibular inguinal popliteal axillary  Clinical signs “Happy dog with lumps” “Happy dog with lumps” +/- hepatosplenomegaly +/- hepatosplenomegaly +/- PU/PD +/- PU/PD +/- uveitis +/- uveitis +/- GI signs +/- GI signs +/- respiratory signs +/- respiratory signs Clinical signs FNA equipment FNA Slide Preparation  Lymph node cytology How do you ensure you have a diagnostic slide? How do you ensure you hit LN? How do you tell normal versus abnormal? What is abnormal? Should you send slides to a commercial lab? Broken cells = NON-DIAGNOSTIC! Lymphoglandular bodies  Lymph node cytology Normal – 90-95% mature lymphocytes – 5-10% lymphoblasts, other Lymphoma – >50-90% lymphoblasts – Use neutrophil as micrometer for size Reactive – Up to 50% lymphoblasts – Small lymphocytes – Plasma cells – Neutrophils, eosinophils, etc. Normal lymph node Lymphoma Lymphoma  Now that you’ve dx’d LSA… What will you tell the client about the diagnosis? What about staging? What will you tell the client about the treatment? Goal(s) of treatment? What will you tell the client about the prognosis?  About the diagnosis… Common cancer especially in some breeds – Golden retrievers – Boxers Systemic disease, so chemotherapy is treatment of choice Treatable but rarely curable (MST ~ 1 year) Similar to non-Hodgkin’s lymphoma in people  Clinical staging Cytology or excisional biopsy of affected lymph node CBC, chemistry panel, urinalysis Thoracic radiographs Abdominal imaging Bone marrow aspirate Immunophenotyping  Clinical staging I. Involvement of single node II. Involvement of multiple nodes in a regional area (i.e. on one side of the diaphragm) III. Generalized lymph node involvement IV. Liver and/or spleen involvement V. Blood and/or bone marrow involvement OR extra nodal sites Substage a: Without systemic signs (i.e. not sick) Substage b: With systemic signs (i.e. sick)  CBC & serum chemistry Why would you do these tests? What might you find? – Often normal – Anemia – Leukocytosis—Stress leukogram – Thrombocytopenia – Pancytopenia – Hypercalcemia! – Increased liver enzymes – Monoclonal gammopathy  Imaging Thoracic radiographs – Lymphadenopathy – Diffuse interstitial pattern – Rarely nodular pattern Abdominal radiographs Abdominal ultrasound Bone marrow aspirate Immunophenotyping  Immunophenotyping Identification of lymphoid lineage T cell vs. B cell – Immunohistochemical staining of tissue samples – Immunocytochemical staining of air-dried cytology slides – Flow cytometry T cell marker: CD3, CD4, CD8… B cell marker: CD79a, CD20, CD21… Commercially available “B is Better. T is Tougher.” Immunophenotyping  Staging bottom line! Be able to justify what tests you perform! Don’t spend all of the owner’s money on staging and leave none for treatment!  Treatment Chemotherapy—lots of options! – Side effects of chemo? – Multi-drug protocols preferred – Prednisone alone Define your goal – Clinical remission Why don’t we cure dogs? – Multi-drug resistance Side effects of chemo…  Side effects of chemo… Before chemo After chemo  Side effects of chemo… Before chemo After chemo  15 week CHOP 12 treatments delivered over 15 weeks Multiple agents that are rotated sequentially – Week: 1 vincristine, pred, +/-L-asp prednisone tapers over 3-4 weeks – Week 2: cyclophosphamide – Week 3: doxorubicin – Week 4: rest – Weeks 5-15: repeat – if in remission, hold on treatment, monitor q 30 d  Remission Is lymphoma responsive to chemotherapy? – 85-90% will go into remission with CHOP – Some go into remission with pred alone How will we know if treatment is working? How do we define remission? – Resolution of clinical signs – Decrease in LN size – Normalization of calcium  Remission How quickly will we know if our treatment is working? – Sometimes within days of first treatment! At what point in the protocol would we conclude that treatment is NOT working? – After treatment with doxorubicin – After all drugs in protocol have been tried  Treatment What should we do if the LN are enlarging during the protocol? – Change protocols! How can you explain why the LN STOP responding to chemotherapy? – Drug resistance!  Multidrug resistance Cause of treatment failure Expected sequelae of chronic chemotherapy Numerous mechanisms P-glycoprotein P-glycoprotein  Rescue chemotherapy LOTS OF OPTIONS! CCNU (lomustine) – 60-70 mg/m2 PO q 3-4 wks – Myelosuppressive Thrombocytopenia can be persistent and dose limiting – Hepatotoxic – Nephrotoxic – Otherwise, well-tolerated  Prognosis Median survival time (MST) for multicentric LSA: – Combination chemotherapy including Adriamycin® = ~1 year (B cell > T cell) – Single agent Adriamycin® = 6-9 months – Prednisone alone = 2-3 months – No treatment = 4-6 weeks  Prognosis Worse prognosis if T cell immunophenotype substage b Stage 5? Pretreatment with prednisone GI, hepatic, mediastinal location Presenting Complaint: Lumps under chin “Fynnigan” a 10 year old FS MBD  History Lumps noted last week; no change in size One episode of vomiting after drinking too much water; occasional cough Meds = HW and flea preventatives No travel history PPH = HBC at 2 yrs of age; repaired R femur fracture  Physical Examination BAR; T: 101.0*F; P: 120; R: panting; mm: pink/hydrated Integument—healed scar over R lateral thigh Musculoskeletal—normal EENT—normal Circulatory—normal Respiratory—normal Digestive—hepatomegaly vs. splenomegaly vs. both? GU—normal Lymphatic—enlarged mandibular, prescapular, L axillary, inguinal, and L popliteal LN Neuro—normal  Problem List 1. Generalized enlarged peripheral LN 2. Enlarged spleen/liver or both DDx for non-painful, enlarged peripheral LN + cranial organomegaly in an otherwise healthy dog?  Fynn’s Cytology CBC/chem = WNL Interpretation Started CHOP chemotherapy—Oct 19, 2017 Completed protocol and began monitoring—Mar 7, 2018 Relapsed—Aug 15, 2018 (10 months RD) Re-started CHOP chemotherapy Completed protocol and began monitoring—Dec 20, 2018 Relapsed—Mar 19, 2019 (7 months RD) Re-started CHOP chemotherapy Progressive disease—Apr 11, 2019 (1 month RD) Protocol changed to rabacfosadine—Apr 11, 2019 Completed protocol Jul 1, 2019 Relapsed—Aug 12, 2019 (4 months RD) Protocol changed to lomustine—Aug 12, 2019 Progressive disease—Oct 13, 2019 (2 month RD) Euthanized Nov 25, 2019 RD = remission duration  In conclusion… Lymphoma is an easily diagnosed cancer Its treatment offers the potential for extending life with excellent quality Develop long-term positive client relations