ISSN 2398-2969      

Lymphoma

icanis

Synonym(s): Malignant lymphoma, Lymphosarcoma, LSA


Introduction

  • Definition: neoplasm arising from lymphoid tissues, in any area of the body. 
  • Most common hemopoietic neoplasm, 7-24% of all canine malignant neoplasms, 83% of all canine hematopoietic malignancies.
  • Forms: multicentric, thymic, alimentary, cutaneous, CNS, hepatic, renal and others. Can be intermediate/high grade or indolent.
  • Signs: depend on form, eg malaise, polydipsia, polyuria, respiratory distress, vomiting, diarrhea, constipation. Multicentric usually presents feeling well and owners notice 'lumps under jaw'.
  • Diagnosis: fine needle aspirate and cytology. Biopsy can be used to better define histologic variants and guide therapy and prognosis. Flow cytometry and PARR can help further with definitive diagnosis. 
  • Treatment: cytotoxic drugs, surgery or radiation therapy can be used to treat localized problematic masses. Radiation therapy can be used for consolidation of tumor following chemotherapy (eg half body radiation therapy). Bone marrow transplantation. Immunotherapy is under development. 
  • Prognosis: poor if no treatment for intermediate/high grade. Fair for indolent lymphomas. 
    Print off the owner factsheet on Canine lymphoma to give to your client.

Pathogenesis

Etiology

  • Unknown.
  • Genetic and molecular factors: gain of canine chromosomes 13 and 31, loss of chromosome 14, increase in in duration of first remission and overall survival time in dogs with trisomy 13, germline and somatic genetic mutations as well as altered oncogene/tumor suppressor gene expression have been reported in dogs. 
  • Environmental factors (none definitively proven): herbicides (2,4-D), use of chemicals (paint or solvents), use of pesticides, exposure to strong magnetic fields, exposure to tobacco smoke, proximity to environmental waste. 
  • Impaired immune function is associated with higher risk of developing lymphoma.

Pathophysiology

  • Malignant proliferation of lymphoid cells arising in any area containing lymphoid tissue → focal or diffuse masses in intestine, skin, thymus or lymph nodes → may progress to extranodal sites, eg liver, spleen, bone marrow.
  • Most common anatomic form, in order of decreasing prevalence: multicentric (80% of dogs with lymphoma), gastrointestinal, mediastinal, cutaneous. Rarer extranodal forms include for example renal, CNS, ocular, hepatosplenic, intravascular.
  • Can be due to malignant proliferation of B, T cell lines, or NK cells.
  • 60-80% are B cell origin, 10-38% T cell, 22% mixed B and T cell, < 5% null cel.
  • T cell tumors have a worse prognosis and poorer survival than B cell tumors.
  • All large cell T cell tumors should be treated as highly malignant and carry a poor prognosis. Small cell T-cell tumors can be very indolent with long term survival.
  • Paraneoplastic effects Neoplasia: paraneoplastic disease, eg hypercalcemia Hypercalcemia: overview (reported in 10-40% of dogs with lymphoma, most common with mediastinal form and T immunophenotype), immune-mediated thrombocytopenia Immune-mediated thrombocytopenia, anemia.

Timecourse

  • Rapidly fatal (4-6 weeks) without treatment for intermediate/high grade. 
  • Months to years of survival for indolent lymphomas (with the exception of nodal marginal zone lymphoma) sometimes even without treatment.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Aresu L, Agnoli C, Nicoletti A, Fanelli A, Martini V (2021) Phenotypical Characterization and Clinical Outcome of Canine Burkitt-Like Lymphoma. Front Vet Sci 8, 647009 PubMed
  • Benjamin S E, Sorenmo K U, Krick E L, Salah P, Walsh K A et al (2021) Response-based modification of CHOP chemotherapy for canine B-cell lymphoma. Vet Comp Oncol PubMed.   
  • Henriques J, Felisberto R, Constantino-Casas F, Cabeçadas J, Dobson J (2021) Peripheral blood cell ratios as prognostic factors in canine diffuse large B-cell lymphoma treated with CHOP protocol. Vet Comp Oncol 19(2), 242-252 PubMed
  • Hughes K L, Ehrhart E J, Rout E D, Harris L J, Fernandez M (2021) Diffuse Small B-Cell Lymphoma: A High-Grade Malignancy. Vet Pathol PubMed
  • Stein L, Bacmeister C, Kiupel M (2021) Immunophenotypic Characterization of Canine Nodal T-Zone Lymphoma. Vet Pathol 58(2), 288-292 PubMed.
  • Cawley J R, Wright Z M, Meleo K, Post G S, Clifford C A (2020) Concurrent use of rabacfosadine and L-asparaginase for relapsed or refractory multicentric lymphoma in dogs. J Vet Intern Med 34(2), 882-889 PubMed
  • Harris L J, Rout E D, Labadie J D, Avery P R, Fernandez M et al (2020) Clinical features of canine nodal T-cell lymphomas classified as CD8+ or CD4-CD8- by flow cytometry. Vet Comp Oncol 18(3), 416-427 PubMed.
  • Purzycka K, Peters L M, Desmas I, Davies O, Chang Y M, Lara-Garcia A (2020) Clinicopathological characteristics and prognostic factors for canine multicentric non-indolent T-cell lymphoma: 107 cases. Vet Comp Oncol 18(4), 656-663 PubMed
  • Saba C F, Clifford C, Burgess K, Phillips B, Vail D (2020) Rabacfosadine for naïve canine intermediate to large cell lymphoma: Efficacy and adverse event profile across three prospective clinical trials. Vet Comp Oncol 18(4), 763-769 PubMed
  • Wolf-Ringwall A, Lopez L, Elmslie R, Fowler B, Lori J (2020) Prospective evaluation of flow cytometric characteristics, histopathologic diagnosis and clinical outcome in dogs with naïve B-cell lymphoma treated with a 19-week CHOP protocol. Vet Comp Oncol 18(3), 342-352 PubMed.
  • Boyé P, Floch F, Serres F, Geeraert K, Clerson P (2019) Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma. J Vet Intern Med 33(4), 1728-1739 PubMed.  
  • Chalfon C, Martini V, Comazzi S, Aresu L, Stefanello D et al (2019) Minimal residual disease in lymph nodes after achievement of complete remission predicts time to relapse in dogs with large B-cell lymphoma. Vet Comp Oncol 17(2), 139-146 PubMed.
  • Chan C M, Frimberger A E, Moore A S (2018) Clinical outcome and prognosis of dogs with histopathological features consistent with epitheliotropic lymphoma: a retrospective study of 148 cases (2003-2015). Vet Dermatol 29(2),154-e59 PubMed.
  • Deveau M A, Sutton M, Baetge C, Diesel A B (2019) A case report of total skin photon radiation therapy for cutaneous epitheliotropic lymphoma in a dog. BMC Vet Res 15(1),407 PubMed
  • Elliott J, Baines S (2019) A Retrospective Study of Multi-agent Chemotherapy including either Cyclophosphamide or Lomustine as Initial Therapy for Canine High-grade T-cell Lymphoma (2011-2017). Aust Vet J 97(9), 308-315 PubMed
  • Intile J L, Rassnick K M, Al-Sarraf R, Chretin J D (2019) Evaluation of the Tolerability of Combination Chemotherapy with Mitoxantrone and Dacarbazine in Dogs with Lymphoma. J Am Anim Hosp Assoc 55(2), 101-109 PubMed
  • Marconato L, Aresu L, Stefanello D, Comazzi S, Martini V (2019) Opportunities and challenges of active immunotherapy in dogs with B-cell lymphoma: a 5-year experience in two veterinary oncology centers. J Immunother Cancer 7(1),146 PubMed
  • Marconato L, Comazzi S, Aresu L, Riondato F, Stefanello D et al (2019) Prognostic significance of peripheral blood and bone marrow infiltration in newly-diagnosed canine nodal marginal zone lymphoma. Vet J 246, 78-84 PubMed.
  • Smallwood K, Tanis J B, Grant I A, Blackwood L, Killick D R (2019) Evaluation of a multi-agent chemotherapy protocol combining dexamethasone, melphalan, actinomycin D, and cytarabine for the treatment of resistant canine non-Hodgkin high-grade lymphomas: a single centre's experience. Vet Comp Oncol 17(2), 165-173 PubMed
  • Taylor A, Finotello A, Vilar-Saavedra P, Couto C G, Benigni L et al (2019) Clinical characteristics and outcome of dogs with presumed primary renal lymphoma. J Small Anim Pract 60(11), 663-670 PubMed
  • Thamm D H (2019) Novel Treatments for Lymphoma. Vet Clin North Am Small Anim Pract 49(5), 903-915 PubMed.
  • Vos N, Pellin M, Vail D M (2019) A comparison of 12- and 19-week CHOP protocols using non-randomized, contemporaneous controls. Vet Comp Oncol 17(3), 276-284 PubMed.
  • Al-Nadaf S, Rebhun R B, Curran K M, Venable R O, Skorupski K A (2018) Retrospective analysis of doxorubicin and prednisone as first-line therapy for canine B-cell lymphoma. BMC Vet Res  14(1), 356 PubMed
  • Batschinski K, Dervisis N, Kitchell B, Newman R, Erfourth T (2018) Combination of Bleomycin and Cytosine Arabinoside Chemotherapy for Relapsed Canine Lymphoma. J Am Anim Hosp Assoc 54(3), 150-155 PubMed.
  • Brown P M, Tzannes S, Nguyen S, White J, Langova V (2018) LOPP chemotherapy as a first-line treatment for dogs with T-cell lymphoma. Vet Comp Oncol 16(1), 108-113 PubMed
  • Childress M O, Ramos-Vara J A, Ruple A (2018) Retrospective analysis of factors affecting clinical outcome following CHOP-based chemotherapy in dogs with primary nodal diffuse large B-cell lymphoma. Vet Comp Oncol 16(1), E159-E168 PubMed
  • Comazzi S, Marelli S, Cozzi M, Rizzi R, Finotello R (2018) Breed-associated risks for developing canine lymphoma differ among countries: an European canine lymphoma network study. BMC Vet Res 14(1), 232 PubMed
  • Couto K M, Moore P F, Zwingenberger A L, Willcox J L , Skorupski K A (2018) Clinical characteristics and outcome in dogs with small cell T-cell intestinal lymphoma. Vet Comp Oncol 16(3), 337-343 PubMed.
  • Fournier Q, Serra J-C, Handel I, Lawrence J (2018) Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy. J Vet Intern Med 32(1), 384-393 PubMed
  • Lane J, Price J, Moore A, Dandrieux J R S, Clifford C (2018) Low-grade gastrointestinal lymphoma in dogs: 20 cases (2010 to 2016). J Small Anim Pract 59(3), 147-153 PubMed
  • Lanza M R, Musciano A R, Dubielzig R D, Durham A C (2018) Clinical and pathological classification of canine intraocular lymphoma. Vet Ophthalmol 21(2), 167-173 PubMed.
  • LaRue M K, Taylor A R, Back A R, Lindley S E, Boudreaux B L (2018) Central nervous system lymphoma in 18 dogs (2001 to 2015). J Small Anim Pract 59(9), 547-552 PubMed
  • Moore E L, Vernau W, Rebhun R B, Skorupski K A, Burton J H (2018) Patient characteristics, prognostic factors and outcome of dogs with high-grade primary mediastinal lymphoma. Vet Comp Oncol 16(1), E45-E51 PubMed
  • Morgan E, O'Connell K, Thomson M, Griffin A (2018) Canine T cell lymphoma treated with lomustine, vincristine, procarbazine, and prednisolone chemotherapy in 35 dogs. Vet Comp Oncol 16(4), 622-629 PubMed
  • Saba C F, Vickery K R, Clifford C A, Burgess K E, Phillips B et al (2018) Rabacfosadine for relapsed canine B-cell lymphoma: Efficacy and adverse event profiles of 2 different doses. Vet Comp Oncol16(1), E76-E82 PubMed
  • Sadowski A R, Gardner H L, Borgatti A, Wilson H, Vail D M (2018) Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma. BMC Vet Res 14(1), 250 PubMed.
  • Sierra Matiz O R, Santilli J, Anai L A, Da Silva M C L, Sueiro F A (2018) Prognostic significance of Ki67 and its correlation with mitotic index in dogs with diffuse large B-cell lymphoma treated with 19-week CHOP-based protocol. J Vet Diagn Invest 30(2), 263-267 PubMed
  • Sogame N, Risbon R, Burgess K E (2018) Intestinal lymphoma in dogs: 84 cases (1997-2012). J Am Vet Med Assoc 252(4), 440-447 PubMed.
  • Tanis J-B, Mason S L, Maddox T W, Blackwood L, Killick D R et al (2018) Evaluation of a multi-agent chemotherapy protocol combining lomustine, procarbazine and prednisolone (LPP) for the treatment of relapsed canine non-Hodgkin high-grade lymphomas. Vet Comp Oncol 16(3), 361-369 PubMed
  • Treggiari E, Elliott J W, Baines S J, Blackwood L (2018) Temozolomide alone or in combination with doxorubicin as a rescue agent in 37 cases of canine multicentric lymphoma. Vet Comp Oncol 16(2), 194-201 PubMed
  • Gillem J, Giuffrida M , Krick E (2017) Efficacy and toxicity of carboplatin and cytarabine chemotherapy for dogs with relapsed or refractory lymphoma (2000-2013). Vet Comp Oncol 15(2), 400-410 PubMed.
  • Lautscham E M, Kessler M, Ernst T, Willimzig L, Neiger R (2017) Comparison of a CHOP-LAsp-based protocol with and without maintenance for canine multicentric lymphoma. Vet Rec 180(12), 303 PubMed
  • Santoro D, Kubicek L, Lu B, Craft W, Conway J (2017) Total skin electron therapy as treatment for epitheliotropic lymphoma in a dog. Vet Dermatol 28(2), 246-e65 PubMed
  • Thamm D H, Vail D M, Post G S, Fan T M, Phillips B S et al (2017) Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Naïve Canine Multicentric Lymphoma. J Vet Intern Med 31(3), 872-878 PubMed
  • Childress M O, Ramos-Vara J A, Ruple A (2016) A randomized controlled trial of the effect of prednisone omission from a multidrug chemotherapy protocol on treatment outcome in dogs with peripheral nodal lymphomas. J Am Vet Med Assoc 249(9), 1067-1078 PubMed
  • Desmas I, Burton J H, Post G, Kristal O, Gauthier M et al (2017) Clinical presentation, treatment and outcome in 31 dogs with presumed primary colorectal lymphoma (2001-2013). Vet Comp Oncol 15(2), 504-517 PubMed.
  • George R, Smith A, Schleis S, Brawner W, Almond G et al (2016) Outcome of dogs with intranasal lymphoma treated with various radiation and chemotherapy protocols: 24 cases. Vet Radiol Ultrasound 57(3), 306-312 PubMed
  • Wang S L , Lee J J, Liao A T (2016) Chemotherapy-induced neutropenia is associated with prolonged remission duration and survival time in canine lymphoma. Vet J 205(1), 69-73 PubMed.  
  • Marconato L, Stefanello D , Sabattini S , Comazzi S , Riondato F et al (2015) Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma. Vaccine 33(39), 5080-5086 PubMed
  • Parsons-Doherty M, Poirier V J, Monteith G (2014) The efficacy and adverse event profile of dexamethasone, melphalan, actinomycin D, and cytosine arabinoside (DMAC) chemotherapy in relapsed canine lymphoma. Can Vet J 55(2), 175-180 PubMed
  • Seelig D M, Avery P, Webb T, Yoshimoto J, Bromberek J et al (2014) Canine T-zone lymphoma: unique immunophenotypic features, outcome, and population characteristics. J Vet Intern Med 28(3), 878-886 PubMed.
  • O'Brien D, Moore P F, Vernau W, Peauroi J R, Rebhun R B (2013) Clinical characteristics and outcome in dogs with splenic marginal zone lymphoma. J Vet Intern Med 27(4), 949-954 PubMed
  • Van den Steen N, Berlato D, Polton G, Dobson J, Stewart J, Maglennon G, Hayes A M et al (2012) Rectal lymphoma in 11 dogs: a retrospective study. J Small Anim Pract 53(10), 586-591 PubMed.  
  • Berlato D, Schrempp D, Van Den Steen N, Murphy S (2012) Radiotherapy in the management of localized mucocutaneous oral lymphoma in dogs: 14 cases. Vet Comp Oncol 10(1, 16-23 PubMed
  • Dank G, Rassnick K M, Kristal O, Rodriguez C O, Clifford C A (2011) Clinical characteristics, treatment, and outcome of dogs with presumed primary hepatic lymphoma: 18 cases (1992-2008). J Am Vet Med Assoc 239(7), 966-971 PubMed.
  • Gustafson N R, Lana S E, Mayer M N & LaRue S M (2004) A preliminary assessment of whole-body radiotherapy interposed within a chemotherapy protocol for canine lymphomaVet Comp Oncol (3), 125-31 PubMed.
  • Dhaliwal R S, Reed A L & Kitchell B E (2001) Multicentric lymphosarcoma in a dog with multiple-site skeletal involvement. Vet Rad Ultra 42 (1), 38-41 PubMed.
  • Thomas J S & Rogers K S (1999) Platelet aggregation and adenosine triphosphate secretion in dogs with untreated multicentric lymphoma. JVIM 13 (4), 319-322 PubMed.
  • Vail D M et al (1997) Application of rapid CD3 immunophenotype analysis and argyrophilic nucleolar organizer region (AgNOR) frequency to fine needle aspirate specimens from dogs with lymphoma. Vet Clin Path 26 (2), 66-69 PubMed.
  • Valerius K D et al (1997) Doxorubicin alone or in combination with asparaginase, followed by cyclophosphamide, vincristine, and prednisone for treatment of multicentric lymphoma in dogs - 121 cases (1987-1995). JAVMA 210 (4), 512-516 PubMed.
  • Teske E, van Heerde P (1996) Diagnostic value and reproducibility of fine-needle aspiration cytology in canine malignant lymphoma. Vet Q 18 (3), 112-115 PubMed.
  • Moore A S et al (1995) The expression of P-glysoprotein in canine lymphoma and its association with multidrug resistance. Cancer Invest 13 (5), 475-479 PubMed.
  • Grindem C B et al (1994) Thrombocytopenia associated with neoplasia in dogs. J Vet Intern Med 8 (6), 400-405 PubMed.
  • Moore A S et al (1994) Evaluation of mitoxantrone for the treatment of lymphoma in dogs. JAVMA 204 (12), 1903-1905 PubMed.
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Other sources of information

  • Vail D M, Pinkerton M, Young K M (2020) Hematopoietic tumours. In: Withrow & MacEwen’s Small Animal Clinical Oncology. 6th edn. Saunders pp 688-711.
  • Kansas State University modified UW-Madison lymphoma protocol for dogs Lymphoma: chemotherapy protocols.

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