The Management of Lymphoma in a Dog or Cat V. E. Valli DVM

An Introduction to Lymphoid Neoplasms  The

lymphoid neoplasms of animals are characterized by two phenoptypic presentations (about 10 each) that share huge variations in presentation and progression.  These variations in clinical behavior have resulted in the subtypes of lymphoma being given specific names to facilitate recognition and then clinical care. 2

The Classification of Lymphomas in Animals  Few

areas of human and veterinary medicine have been characterized by the marked numbers of systems for naming lymphoid neoplasms.  Most recent of these are the Kiel classification used largely in Europe and the Working Formulation used in NA.  Progress in Clinical Oncology was delayed due to geographic differences in nomenclature.

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The International Lymphoma Study Group  This

group of Oncologists and Pathologists devised a system that included ALL information about each type of lymphoma (REAL)  The REAL was adopted by the WHO and clinically tested in1997.  The WHO system was found to be applicable to dogs by European and NA Veterinary Pathologists in 201l. 4

Leukemia or Lymphoma?  The

WHO system defined this question to be determined on the basis of the location of the greatest volume of tumor.  If the tumor predominated in the bone marrow it was Leukemia, and if in the peripheral tissues Lymphoma.

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Cytology and Histology  Cytology

is an efficient and rapid means of determining if inflammation, hyperplasia or lymphoma is present  Histology is required for a specific subtype of lymphoma  Phenotype is essential for lymphomas not of follicular type 6

Criteria Essential for Diagnosis of Lymphoma for Therapy  Topography

and extent of tumor (Staging)  Tissue architecture, nodular or diffuse  Tumor cell size and shape as compared to a red cell (small 1, int.1.5, large 2.0 rbc  Chromatin, aggregated or dispersed  Nucleolar size, number and location  Mitotic rate and presence of macrophages 7

Essentials of a Good Histologic Diagnosis  Diffuse

or Follicular architecture  Phenotype B or T-cell type  Cell size and nuclear type  Grade in terms of Low, Intermediate or High on basis of number of mitoses /400X field. (0-5 low. 6-10 Int. >10 Hi.) 8

Applying the WHO Classification to the dog and cat  ACVP

initiated study on Lymphomas 2004  Study designed to mimic the human test of efficacy of the WHO system applied to dogs  1000 cases of lymphoma examined by histology with phenotyping and follow-up on 497 cases. 9

Overall survival of all subtypes of canine lymphoma

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Impact of Small and Large Breed on survival of Dogs with lymphoma

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Impact of Gender on survival of Dogs treated for lymphoma

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Impact of Stage of Disease on survival of dogs with Lymphoma

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Impact of Lymphoma Subtype on Survival of treated Dogs

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Impact of treatment protocol on survival of Dogs with Lymphoma  Lymphomas

in Dogs mirror those in Humans in rate of progression and response to chemotherapy  Adriamycin prolongs survival in high grade lymphomas  Chemotherapy is detrimental to survival in T-Zone Lymphoma 15

Cytology/Histology Correlations  Case:

7 year old American Eskimo Dog. Presents with mild generalized lymphadenopathy  Dog retains appetite and activity  A fine needle aspirate is taken from the right popliteal node with lymphoma diagnosed  A Tru-cut biopsy is taken of the same node 16

FNA with Wright /Giemsa Stain

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Cytology detail

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TruTru-cut Biopsy of Node

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TruTru-cut Biopsy of Node Detail

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Phenotype, High grade diffuse BBcell Lymphoma of BurkittBurkitt-like type B-cell CD79 TT-cell CD3

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Cytology/Histology Correlations  Case:

7year Std Poodle. Presents with mild depression, hypercalcemia and mild generalized lymphadenopathy  A fine needle aspirate is taken from the right submandibular node  A Tru-cut biopsy is taken from the same lymph node 22

FNA with Wright /Giemsa Stain

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TruTru-cut Biopsy of Node

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TruTru-cut Biopsy of Node Detail

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Phenotype, High grade diffuse TT-cell Lymphoma, Lymphoblastic type B-cell CD79 TT-cell CD3

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Cytology/Histology Correlations  Case:

4year old Domestic Short Hair MC cat presents with I month of weight loss and has very large submandibular node and a mass anterior to heart  No response to Baytril  A FNA was taken of the node and a Trucut biopsy was taken from the thoracic mass 27

FNA with Wright /Giemsa Stain

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FNA with Wright /Giemsa Stain

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TruTru-cut Biopsy of Thoracic Mass

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TruTru-cut Biopsy of Thoracic Mass Detail

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TruTru-cut Biopsy of Thoracic Mass Detail

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TruTru-cut Biopsy of Thoracic Mass Detail

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Phenotype, TT-cell Rich Large BB-cell Lymphoma B-cell CD79 TT-cell CD3

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Cytology/Histology Correlations  Case:

15 year old MC Domestic Short Hair cat presents with a history of vomiting after eating. On examination a mediastinal mass was identified.  A fine needle aspirate was taken with small lymphocytes identified and the mass was removed and sectioned with PCR for clonality carried out. 35

FNA with Wright /Giemsa Stain

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Mediastinal mass H&E Stain

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Ciliated lining of thymic cyst

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Epithelial cuff around vein in thymoma

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Remnant of Hassall’ Hassall’s Corpuscle in outer margin of thymoma

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Cortical epithelial cells of Thymoma

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Conclusions re diagnosis and management of lymphoid neoplasms in animals  The

WHO system of human lymphoma classification is readily applicable to domestic animals  Animal lymphomas like those in humans vary widely in their rates of progression and response to chemotherapy  Effective management of animal lymphoma requires a specific diagnosis and grade of tumor

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Conclusions Cont’ Cont’d  To

determine the specific subtype of lymphoma it is necessary to obtain a tissue biopsy and carryout phenotypic staining for B and T-cell type  Treatment must be calibrated for the specific type and grade of lymphoma  For some indolent types of lymphoma chemotherapeutic treatment is detrimental to survival 43