managing lymphoma in small animal practice wendy blount, dvm

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Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

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Page 1: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Managing Lymphoma in Small Animal Practice

Wendy Blount, DVM

Page 2: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Lymphoma

• aka lymphosarcoma (LSA)• Other than euthanasia in shelters, cancer is

the #1 killer of dogs• most common cancer in dogs and cats• Most common cause of hypercalcemia in

dogs and cats• 30% of cats with cancer have lymphoma• 24% of dogs with cancer have lymphoma

• Most common spinal cord tumor in the cat• Most common brain tumor in the cat• Most common nasal tumor in the cat• Most common liver tumor in the cat

Page 3: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Etiology

• GI lymphoma can be preceded by IBD in cats• Helicobacter spp increase risk of GI

adenocarcinoma in people, and are often present in gastric LSA histopath in cats

• FeLV predisposes to LSA in cats• Lymphoma respects age less than other

tumors

Page 4: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsVary tremendously by tumor location

Multicentric lymphoma most common• Multiple painless enlarged lymph nodes,

hepatomegaly, splenomegaly in dogs• Enlarged mesenteric lymph node, hepatomegaly,

splenomegaly in cats• Fever• Other locations

Ocular lymphoma• Third eyelid or conjunctival mass in cats

• rapidly enlarges• Anterior or posterior uveal infiltrates and/or uveitis

Page 5: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 6: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 7: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 8: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 9: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 10: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 11: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 12: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsFred Holt – Tioga TX

Gregory Wood – Katy TX

Holly Hoffman – Wichita Falls TX

Page 13: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsVary tremendously by tumor location• GI lymphoma (focal or diffuse)

• Vomiting, diarrhea, steatorrhea, melena• Hematochezia, mucoid feces, tenesmus• Mass on rectal palpation• Anorexia, weight loss, lethargy• Abdominal pain or effusion• Palpable abdominal mass, thickened loops of

bowel• Pallor, anemia if GI bleeding• Icterus if obstruction of bile duct

Page 14: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Nasal lymphoma• Unilateral or bilateral nasal discharge• Epistaxis, Sneezing• Dyspnea, stertor, nasal stridor• Facial distortion and ocular discharge• Intermediate to large cells

Clinical Signs

Page 15: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Nasal lymphoma• Unilateral or bilateral nasal discharge• Epistaxis, Sneezing• Dyspnea, stertor, nasal stridor• Facial distortion and ocular discharge• Intermediate to large cells

Page 16: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Nasal lymphoma• Unilateral or bilateral nasal discharge• Epistaxis, Sneezing• Dyspnea, stertor, nasal stridor• Facial distortion and ocular discharge• Intermediate to large cells• Neurologic signs if invasion of the cribriform plate

– anterior forebrain• Seizures• Behavioral changes, obtunded, head pressing• Blindness, circling• CP deficits worst in rear

Page 17: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsSpinal cord lymphoma• Extramedullary tumor• Onset chronic or acute• More common in cats than dogs• Localized severe spinal pain

• Extramedullary tumors seem to be more painful than medullary

• More pain receptors in these areas• LMN signs (flaccid weakness) 2 vertebrae caudal

to the area of spinal pain• UMN signs (spastic paresis) caudal to that• Usually part of multifocal disease• Younger cats, up to 2 years of age• Difficult to diagnose, CSF often not diagnostic

Page 18: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsBrain lymphoma• Symptoms caused by

• Displacement of brain tissue• Disruption of blood brain barrier• Disruption of CSF and blood flow

• Seizures the most common symptom in dogs (cerebral)• Lethargy, weight loss, obtunded• Circling, behavior changes, head pressing• Contralateral CP deficits worse in rear

• Head tilt and ataxia in cats (caudal brain stem)• Brain herniation in the late stages

• Coma, dilated pupils, death

Page 19: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsAcute Lymphoblastic Leukemia (ALL)• Usually non-specific signs• May have coagulopathy of thrombocytopenia

• Petechiae• Epistaxis, bleeding from the gums• Primary hemostasis disorder

• Often part of multicentric disease• Usually atypical cells in circulating but not

always• “Aleukemic leukemia”• Cytopenias prompt bone marrow sample

Page 20: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsLymphomatoid granulomatosis

• aka eosinophilic pulmonary granulomatosis • aka lymphoid granulomatosis• aka lymphoproliferative angitis• aka granulomatosis

• Destructive angitis in the lungs• Atypical T-cell lymphoma• History of treated heartworm disease• May progress to lymphoma• Symptoms of pneumonitis

Page 21: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsRenal lymphoma (feline)• Bilateral large, bumpy kidneys• The many signs of renal failure

Mediastinal lymphoma (feline)• Dyspnea, coughing• Regurgitation• Horner’s Syndrome

Hepatic lymphoma• Marked hepatomegaly, liver failure• Large cell in dogs, small cell in cats

Page 22: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical SignsCutaneous lymphoma• Usually diffuse in the dog

• Intense pruritis, resistant to treatment• Two forms in cats

• Epitheliotropic – diffuse• “Mycosis fungoides”• Intradermal nests of 5-10 cells• Usually large but sometimes small T

cells• Non-epitheliotropic

• Large B cells deeper in the dermis

Page 23: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

CBC• Neutrophilia• Lymphocytosis

• atypical lymphocytes if ALL• May not have atypia with CLL

• Anemia• Anemia of chronic inflammatory disease

• Mild nonregenerative anemia• Iron deficiency anemia if GI bleeding

• Regenerative or non-regenerative• Pancytopenia if leukemia is present

Page 24: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Panel • Hypercalcemia• Elevated ALT, SAP, GGT if hepatic LSA• Icterus – GI, hepatic, pancreatic LSA• Low albumin

• PLE due to intestinal LSA• GI bleeding due to GI LSA

• High globulins – B cell lymphoma• Low globulins – GI bleeding due to GI LSA• High BUN

• Pre-renal• GI bleeding due to GI LSA• Feline renal LSA

Page 25: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clint Duncan – Spring TXJohn Wood – Lufkin TX

Kevin Acuna – Nacogdoches TX

Page 26: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Panel - icterus with normal liver enzymes• A unique presentation in the cat • Differential diagnosis:

• Pancreatitis – elevated fPLI• Lymphoma – cytology or histopathology• FIP – histopathology or diagnostic trifecta

• Lymphopenia <1500/ul• Titer 1:160 or greater• Globulins >5.1 g/dl• Positive predictive value 89%• Negative predictive value 99%• Histopath and fluid analysis supportive• Fluid analysis chart

Page 27: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Abdominal Imaging (rads)• Abdominal mass – gut or lymph node• Hepatomegaly, splenomegaly• Gut obstruction• Abdominal effusion

• Chyle or modified transudate• Thickened gut wall (muscularis)• Pneumoperitoneum if GI perforation• Mucosal craters• Soft tissue calcification if hypercalcemia• Bilateral renomegaly in cats

Page 28: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Bilateral renomegaly in cats

Page 29: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Cat with mid-abdominal mass and ascites

Page 30: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Hepatosplenomegaly due to multicentric lymphoma in a dog

Page 31: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Abdominal Imaging (US)• Enlarged mediastinal lymph node• Hepatomegaly

• Hypoechoic focal to multifocal lesions• Generalized hypo- or hyper-echogenicity• Normal hepatic sonogram

• Splenomegaly• Nodular to diffuse• hyper or hypoechoic

Page 32: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Lila• 1.5 year old female Rottweiler• Acute onset of abdominal pain and tachypnea• Has not eaten for 2 days, no vomiting, mucus

in the stool• Abdominal splinting on palpation• Fever – 103.8F• CBC, panel – NSAF• cPLI – abnormal (>400)• Fecal float negative• No response to treatment with IV fluids and

antibiotics for 2 days (began vomiting)

Page 33: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 34: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Ileus and abdominal effusion

Page 35: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Lila• Abd US declined due to financial limitations• Elected diagnostic surgery• Generalized peritonitis, serosanguinous

abdominal fluid• No obstruction or foreign body• Fluid analysis

• Modified transudate• Neoplastic very large lymphoid cells

• Responded to chemo within a few days• Remission 6 months• End – recurrence of initial clinical signs

Page 36: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Abdominal Imaging (US)• Abdominal effusion• Soft tissue calcification if hypercalcemia• GI lesions

• Gut obstruction – dilated fluid filled bowel• Thickened gut wall (muscularis)• Obliteration of gut layers• Pneumoperitoneum if GI perforation• Mucosal craters• Decreased motility

Page 37: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Renal lymphoma in a cat

Page 38: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Renal lymphoma in a cat

Page 39: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

gastric lymphoma in a cat with ascites

Page 40: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Abdominal effusion and infiltrated omentum in a cat

Page 41: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Hypoechoic liver - lymphoma

Page 42: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Hyperechroic liver - lymphoma

Page 43: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Stomach & duodenum in a dog with lymphoma

Page 44: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Doug AshburnLufkin TX

Andre MichaelTyler TX

Elizabeth Beck Luling TX

Page 45: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Thoracic Imaging (rads)• Enlarged perihilar lymph nodes• Interstitial nodular pattern• Enlarged sternal lymph node• Mediastinal mass• Pleural effusion• Soft tissue calcification if hypercalcemia• Lymphoid granulomatosis

• Soft tissue masses in the lungs• Interstitial to alveolar pattern• Enlarged lymph nodes• Pleural effusion

Page 46: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 47: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Enlarged

mediastinal lymph

nodes and

chylothorax

in a cat with LSA

Page 48: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Enlarged mediastinal, sternal and perihilar lymph nodes in a dog with LSA

Page 49: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Page 50: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Interstitial pulmonary nodules in a dog with lymphoma, enlarged lymph nodes

Page 51: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

Pleural effusion in a dog with lymphoma

Page 52: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Clinical Signs

ECG • VPCs if splenic mass• Possible arrhythmia if hypercalcemia

• Prolonged PR interval (>0.14sec)• 1st degree AV block

• 2nd degree AV block• P wave not followed by QRS

• Ventricular fibrillation if severe• Calcium (>18)

Page 53: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy

aka Pseudohyperparathyroidism

aka HHM (humoral hypercalcemia of malignancy)

• HHM is most common cause of hypercalcemia in the dog and cat• 67% of dogs with hyperCa have cancer• 33% of cats with hyperCa have cancer

• Dogs with HHM most often have• Anal sac adenocarcinoma• LSA • multiple myeloma

• Cats with HHM most often have LSA or SCC

Page 54: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy• 90% of dogs with anal sac tumors have HHM

• >50% are hypercalcemic at diagnosis• 10-35% of dogs with LSA have HHM• 15-20% of dogs with multiple myeloma have

HHM• Cats with LSA and HHM are most likely to

have cranial mediastinal lymphoma• >90% of dogs with LSA and HHM have

enlarged lymph nodes

Page 55: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy• Some tumors release PTH-rp

• Parathyroid hormone related protein • Stimulates osteoclastic bone resorption • Increases renal tubular reabsorption of

calcium • Made in low amounts by normal tissues

• Thought to regulate calcium transport during gestation and lactation

• Other humoral factors are involved in HHM• Bony invasion can contribute to HHM

Page 56: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy• Clinical Signs of HHM

• PU-PD• Weakness, lethargy• Anorexia, weight loss• Vomiting, diarrhea

Page 57: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy

Diagnosis

1. Rule out lab artifact• Fasting prevents lipemia• No hemolysis

2. Confirm hypercalcemia is real• Ionized calcium• Follow reference lab handling guidelines• Altered by temperature, pH and CO2

3. Look for tumors• Rectal exam, LN palpation, imaging, CBC• Sample bone marrow if cytopenias

4. Send PTH, PTHrp and iCa++ to Michigan

Page 58: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy

Diagnosis• If concurrent azotemia, it can be difficult to

distinguish HHM from renal hypercalcemia• Hypercalcemia can cause nephrotoxicity

• Marked azotemia and mild hypercalcemia is more consistent with renal disease

• Marked hypercalcemia with mild azotemia is consistent with HHM

• Phosphorus often high with renal disease• Phosphorus often low with HHM• iCa++ high with HHM• iCa++ normal to low with renal failure

Page 59: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy

Differential Diagnosis Hypercalcemia• H = Hyperparathyroidism (1°, 3°, hyperplasia), HHM,

houseplants, hyperthyroid (cats)• A = Addison's disease, aluminum toxicity, vitamin A• R = Renal disease, raisins/grapes (dogs)• D = Vitamin D toxicosis (granulomatous dz), drugs,

Dovonex, dehydration, diet• I = Idiopathic (cats), infectious, inflammatory• O = Osteolytic (osteomyelitis, immobilization, local

osteolytic hypercalcemia, bone infarct)• N = Neoplasia (HHM and LOH), nutritional• S = Spurious, schistosomiasis, salts of calcium,

supplements

Page 60: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Hypercalcemia of Malignancy

Differential Diagnosis Hypercalcemia

Diagnostic Chart • 16 conditions and 10 blood parameters

Treatment Algorhythm• Clinically ill with high iCa++• Chronic hypercalcemia without illness• Idiopathic hypercalcemia in cats

Page 61: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisCytology• Avoid sampling the submandibular lymph

nodes, as they are most prone to inflammation

• Use “core technique” – needle only with no attached syringe for aspiration, then attach 10-12cc syringe full of air to squirt onto slide

• Vertical pull apart, as lymphoid cells are fragile

• Horizontal smears destroy the cells (“smudge cells”)

Page 62: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisCytology• Normal lymph node

• Mostly small lymphocytes• Smooth chromatin, scant cytoplasm, no

prominent nucleoli• 1-1.5x size of RBC

• Fewer intermediate & large lymphocytes• Occasional neutrophil, macrophage, plasma

cell, mast cell• But pyramid of maturation is conserved

• Reactive lymph node• Can have many blasts• Many cell types present

Page 63: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisCytology• >80% lymphoblasts = large cell lymphoma

• 3-5x size of RBC• More abundant cytoplasm, round to

slightly cleaved nucleus, pale chromatin, prominent nucleoli

• Small cell lymphoma• Other cells are largely missing• Not many intermediate or large

lymphocytes• Difficult cytologic diagnosis (need

histopath)

Page 64: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisCytology - cats• Immunoblastic lymphoid hyperplasia• Aka atypical follicular lymphoid hyperplasia

• Peripheral LN hyperplasia in a young cat is more likely to be this than lymphoma

• Associated with FIV or FeLV positive• Pyramid of maturation preserved• Very large immunoblastic lymphoid cells

are present• Prognosis after treatment with

corticosteroids is excellent in retroviral negative cats (beware of latent infection)

Page 65: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

CR Schilling

Lufkin TX

Robert Conces

Huntsville TX

Conces Compadre

Hunstville TX

Page 66: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisNormal lymph node

Page 67: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisReactive lymph node

Page 68: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisFeline large cell lymphoma

Page 69: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosislarge cell lymphoma

Page 70: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisSI biopsy touch prep

Small cell lymphoma on histopath

Page 71: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisSI biopsy touch prep

Large cell granular lymphoma (feline)

Azurophilic granules

Page 72: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisFNA enlarged kidney diffusely hyperechoic

Large cell lymphoma (feline)

Page 73: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisChylothorax – mediastinal mass

Thymoma

Page 74: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisChylothorax – mediastinal mass

Mediastinal Lymphoma – large cell

Page 75: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisLiver aspirate

Hepatic Lymphoma

Page 76: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisLiver aspirate

Hepatic Lymphoma & fatty liver

Page 77: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

DiagnosisIs histopathology necessary?• Lymph nodes cytology by boarded oncologist

or pathologist is often sufficient• Some circumstances might require biopsy

• Low grade lymphoma resembling mature lymphocytes• Feline lymphomas• Small cell lymphomas in dogs

• Severe inflammation and necrosis• GI lymphoma (full thickness biopsies)• Hepatic lymphoma

Page 78: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosis

Cell Size – Degree of anaplasia• Most dogs have large cell lymphomas• Most cats have large or intermediate cell

lymphomas• Small cell lymphomas are more common in

the cat than in the dog• Small cell more common in old cats• Large cell more common in young cats

Page 79: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosis

Special tests for atypical sites• Nasal rads in cats

• Open mouth, DV, frontal sinus skyline• Soft tissue opacities• Turbinate lysis

• Nasal biopsy in cats• Anterograde and retroflexed behind soft palate• blind biopsy yields diagnosis more often than

rhinoscopy guided• Use radiographs as a guide

• Rhinoscopy – low yield

Page 80: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosis

Right nasal lymphoma in a cat

Page 81: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosis

posterior nares – small mass on the left

Page 82: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosis

posterior nares – small mass on the left

Page 83: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosis

Nasal biopsy• Platelet count and BMBT• Anesthetize and intubate the dog• Count 4x4 gauze use to pack off the

pharyngeal area• Elevate the shoulders above the nares• Absorbent pad on the floor

Page 84: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Mary Marble – Frankston TXThomas Dunn – Orange TX

Celeste Hill – Sweetwater TX

Page 85: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Diagnosis

Nasal biopsy• Platelet count and BMBT• Anesthetize and intubate the dog• Count 4x4 gauze use to pack off the

pharyngeal area• Elevate the shoulders above the nares• Absorbent pad on the floor• Wait 10 minutes prior to beginning anesthetic

recovery• Hospitalize overnight – they sneeze blood

Page 86: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

LSA - Stage

• Stage I – Single node or site involved• No evidence of distant metastasis

• Stage II - Two or more lymph node regions both on the same side of the diaphragm

• Stage III - Two or more lymph node regions on different sides of the diaphragm

• Stage IV - Any lymph nodes PLUS liver or spleen involvement

• Stage V - Involvement of extranodal tissue

Page 87: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

LSA - Stage

Substage – added to any stage• Substage A – no clinical signs• Substage B – illness caused by tumor

Histopathologic grade – MI• Little effect on prognosis

Staging of limited prognostic value EXCEPT• Stage V worse prognosis than others• Substage B negatively impacts prognosis

Page 88: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Classification

Location• 80% of dogs with LSA have multicentric• Cat lymphomas not as likely to be multicentric

as in dogs• GI most common in cats• mediastinal 2nd most common

• Cats with multicentric LSA are less likely to have peripheral lymphadenopathy than dogs

• Skin Lymphoma – different behavior than the typical multicentric lymphoma in dogs• T cell in dogs – resistant to treatment• Both T and B cell in cats – variable

response to treatment

Page 89: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Classification

Immunophenotyping – immunohistochemistry, flow cytometry, PCR

• B (CD79) or T (CD3) cell?• Also null cell lymphomas• Dog LSA – >70% B cell, <30% T cell• Cat LSA – B cell more common than T cell• More of a prognostic indicator in dogs as

compared to cats• High grade B lymphomas have better

response and longer survival than high grade T cell lymphomas

Page 90: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Many protocols, and most have similar prognosis and outcome

• CHOP – cyclophosphamide, doxorubicin, Oncovin (vincristine), prednisone

• COPA – cyclophosphamide, Oncovin, prednisone, Adriamycin (doxorubicin)

• VELCAP – vincristine, Elspar, cyclophosphamide, Adriamycin, prednisone

Other induction protocols are out there, but those including these 4 drugs are thought to be most effective

Elspar is added for high tumor burden

Page 91: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Examples of CHOP Protocols• Wisconsin 19 Week Protocol (4)• Wisconsin 25 Week Protocol (4)

• Same as above with 6 weeks off• TAMU Canine Large Cell Protocol (2)• TAMU Feline Large Cell Protocol (7)• Tufts VELCAP-L (6)

• Final “L” distinguishes from another shorter intermittent Tufts protocol

• Ohio State 3 Week Cycle (max)

Page 92: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Ohio State 3 Week Cycle• Week 1 - doxorubicin 30 mg/m2 IV

• 1 mg/kg in dogs under 15 kg• Dispense prednisone 20 mg/m2 PO EOD

• Week 2, day 1 - vincristine 0.7 mg/m2 IV• Week 2, day 3 - Cyclophosphamide 200

mg/m2 PO • Week 3 – vincristine 0.7 mg/m2 IV

Repeat for 20-25 weeks (7-9 cycles), or until out of remission

Doxorubicin reaches maximum lifetime dose

Page 93: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Other protocols – with prednisone

See Rescue Handout for details• Doxorubicin q3 weeks• Doxorubicin + cyclophosphamide• Lomustine q3-4 weeks

Oral Chemotherapy• Chlorambucil 6-8 mg/m2 QOD• Prednisone 40 mg/m2 PO SID, then QOD• CBC every 2-3 weeks

Page 94: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

• Most protocols last about 5-6 months (20-25 weeks)

• Older protocols continued chemo until the patient came out of remission• “Maintenance Therapy”

• Current thinking is that chemo beyond 25 weeks is not beneficial when in remission• Maintenance chemo may increase drug

resistance at relapse• If relapse occurs more than 2-3 months after

chemo stopped, 60-70% will respond again to CHOP

• Maintenance chemo increases cost of chemo and increases side effects

Page 95: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

• Maintenance therapy beyond 25 weeks indicated only for indolent low grade tumors

Typical response to chemo for large cell lymphoma in dogs:• In remission within 4-8 weeks• 5-6 months chemo• 2-3 months remission after chemo• Variable response to rescue therapy• Minimal illness• Each successive remission lasts as about

half as long as the last• More than 3 remissions is unusual

Page 96: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Common misconceptions• My pet will lose his hair• My pet will likely be ill as a trade off for

attempting a longer life• It would be better for my pet to die of

cancer than to die of chemo treatment

Page 97: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Things important to say• You will likely think your dog is cured

• The probability of this is just about zero • I can give you the averages, but whatever

happens to you is 100% for you• If at any time you want to stop chemo, all

you have to do is say the word• You know your pet best, and what is best for

your pet. Our job is to give you information and help you manage your pet’s cancer as you think best. You are in the driver’s seat and we are here to help.

Page 98: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Rescue Therapy• Drugs used at the time of relapse are no

longer effective and should not be used• Repeat CHOP if not being used at relapse• Then maximize doxorubicin dose• Then try either CCNU and MOPP, in either

order• Then try various other rescue protocols

Page 99: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

Low Grade, small cell tumors• GI lymphomas in cats• CLL in dogs• Chlorambucil 15 mg/m2 PO SID x 4d

• Repeat every 3 weeks • Prednisone 40 mg/m2 PO SID• 70-75% remission• Median remission 19 months

Page 100: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Treatment - Chemotherapy

ALL• Can try large cell protocol, but expect more

myelosuppression• Or Cytosine arabinoside 400 mg/m2 over 6-8

hours• Administer weekly

• Monitor for sepsis and treat accordingly• Blood transfusions as needed for RBC• Platelet rich plasma for platelets• Whole fresh blood for depleted factors

Page 101: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Other Treatments

• Intestinal resection and anastomosis for obstructive GI LSA

• Whole body radiation • Nasal cavity radiation• Monoclonal antibodies• Cerebral lesions

• Mannitol, furosemide, diazepam acutely• Chemo long term• Anticonvulsants (zonisamide or

phenobarbital)• Natural alternatives

Page 102: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Other Treatments

Treatment of Hypercalcemia Handout• Treat if >15-16 or symptoms• IV 0.9% NaCl

• Increased GFR and calciuresis• Decreases renal calcium reabsorption

• Furosemide 1-4 mg PO BID • inhibits Ca++ reabsorption in ascending

loop of Henle• Prednisone 1-2 mg/kg PO BID

• Inhibits VitD and GI calcium absorption• Cytotoxic effect on LSA and myeloma

Page 103: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Other Treatments

Treatment of Hypercalcemia Handout• >18 is a medical emergency

• Salmon calcitonin 4-8 U/kg BID-TID• Pamidronate 1-2 mg/kg IV in 0.9% NaCl

over 2–4 hrs; repeat in 2-4 weeks)• Zoledronate 0.25 mg/kg IV over 15

minutes q 4-5 weeks

Page 104: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

AJ ClemmonsLiberty Hill TX

Thomas Hembree Wells TX

Bethany MooreAustin TX

Page 105: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

Response to chemotherapy – canine large cell multicentric lymphomas

• 70-80% achieve full remission• 20-25% are partial or non-responders• Average length of remission is 10 months• Median survival 12 months• 20-25% survive 2 years or longer• Each remission is shorter lived and more

difficult to achieve• Every tumor is expected to eventually

become responsive to all treatment

Page 106: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

Response to chemotherapy – canine large cell multicentric lymphomas

• Short term prognosis usually good, long term prognosis is invariably dismal

• Staging doesn’t matter, except V is worse• Grade doesn’t matter• Things that worsen prognosis

• systemically ill (substage B)• Hypercalcemia• dyspnea on presentation• Bone marrow involvement, especially if

cytopenias• T cell is worse than B cell

Page 107: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

GI lymphoma is more often T cell in dogs• Median survival 13 days for SI LSA• Colorectal LSA can have prolonged survival• There can be a histopathologic gray area

between IBD and LSA• Some Dx LSA behave as IBD• Some Dx IBD behave as lymphoma• Perhaps misdiagnosed?

Lymphoid granulomatosis in dogs is highly variable

• 6 days to 4 years

Page 108: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

ALL has grave prognosis• Days to weeks common• Occasionally a few months• Chemo may not prolong life• ALL distinguished from Stage V LSA (bone

marrow) by immunohistochemistry• The latter does not carry grave prognosis,

though not as good as lower stages• Death usually by hemorrhage

Page 109: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

Prognostic indicators in cats• Retroviral status• Anatomic location• Initial response to therapy• Stage & grade do not matter• immunophenotyping matters less in cats as

compared to dogs

Some of the indolent low grade tumors can have long survivals (2-3 years+)

• GI small Lymphoma in cats• chronic lymphocytic leukemias in dogs

Page 110: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

Nasal lymphoma in cats• increased risk for kidney lymphoma• Presence of anorexia worsens prognosis if

not treated with chemo or radiation• Median survival 135 days if anorectic• Median survival 320 days if eating

• Same prognosis for chemo alone, radiation alone, or both together• Median survival 536 days• Much shorter MST if cribriform breach

(76 days)

Page 111: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

Mediastinal lymphoma in cats• Associated more with FeLV+ than GI • Younger cats than GI LSA

Feline Hodgins-like lymphoma• Not common• Affect lymph nodes in head and neck• Cells are of mixed phenotype• Long term prognosis is good

Page 112: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Prognosis

Hepatic lymphoma in cats• Associated more with FeLV+ than GI • Younger cats than GI LSA

Cutaneous Lymphoma• Better prognosis in cats - B cell • 50% remission in dogs – T cell• Average remission 4-6 months in dogs• CCNU + Elspar in dogs• Treated as multicentric in cats

• CHOP for large cell• Chlorambucil + pred for small cell

Page 113: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Client Handouts

• Lymphoma in Dogs• Lymphoma in Cats• Skin Lymphoma• Acute Lymphoid Leukemia

• Nutritional Alternatives for Cancer

• Drug Handouts discussed under chemotherapy (Sunday)

Page 114: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Acknowledgements

• Philip J. Bergman, DVM, MS, PhD, DACVIM (Oncology)VIN, BrightHeart Veterinary Centers

• Louis-Philippe de Lorimier, DVM, ACVIM (Oncology)VIN, U Illinois Urbana-Champaign

• Karri A. Meleo, DVM, ACVIM (Oncology), ACVRVIN, Veterinary Oncology Services, Edmonds, WA

Page 115: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Acknowledgements

• Mark Rishniw, BVSc, MS, ACVIM (SAIM), ACVIM (Cardiology)VIN, Clinical Research CoordinatorIthaca, NY

• Kurt R. Verkest, BVSc, BVBiol, MACVSc (Small Animal)VIN, Univ Queensland, Australia

• Kari Rothrock, DVM, Tennessee

Page 116: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Acknowledgements

Linda Shell, DVM, DACVIM (Neurology)• VIN Consultant

Nancy Johnstone McLean, DVM, DACVO • U of Tennessee CVM

Amanda Podles, DVM• Massachussets

Page 117: Managing Lymphoma in Small Animal Practice Wendy Blount, DVM

Acknowledgements

• Robert J. Vasilopulos DVM, DACVIM (Internal Medicine)

VIN Consultant, Vet Spec Ctr of Tucson

• Dennis J. Chew, DVM, ACVIM (Internal Medicine)The OSU CVM, Columbus, OH

• Patricia A. Schenck, DVM, PhD

Mich State U, East Lansing, MI, USA