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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Malignant, neoplastic disorder of lymphoid tissue.

Pathophysiology!!navigator!!

  • Neoplastic cells in equine lymphoid tumors are primarily of B or T cells
  • Equine lymphoid tumors have been classified as T-cell-rich large B-cell lymphoma (most common), peripheral T-cell lymphoma, diffuse large B-cell lymphoma, cutaneous T-cell lymphoma, and anaplastic T-cell lymphoma

Systems Affected!!navigator!!

  • 4 forms of equine lymphosarcoma described based on location of tumors—multicentric (generalized); intestinal (alimentary); mediastinal (thymic); and cutaneous
  • Lymphocytic leukemia secondary to lymphosarcoma is rare and characterized by presence of mild to moderate numbers of atypical lymphocytes in blood
  • Most common sites for tumors include peripheral and internal lymph nodes, skin/subcutis, spleen, liver, intestine, kidneys, mediastinum, heart, and lungs
  • More rarely nervous, ocular, and reproductive

Genetics!!navigator!!

N/A

Incidence/Prevalence!!navigator!!

Most common tumor of equine hemolymphatic system, but prevalence is <5%.

Geographic Distribution!!navigator!!

Worldwide

Signalment!!navigator!!

  • Most common in horses 5–10 years of age, with range from aborted fetus to 25 years
  • No sex predilections, but cutaneous lymphosarcoma more common in Thoroughbreds

Signs!!navigator!!

General Comments

  • Clinical signs may be caused by—organ and tissue dysfunction due to infiltration of tumor lymphocytes; physical obstruction from tumor masses; or cytokines released by tumor cells
  • Space-occupying masses may cause compression and impairment of venous and lymphatic circulation, causing edema or intracavitary fluid collection
  • Clinical signs are variable; depend on organ or system affected by neoplastic infiltrate; may have gradual or sudden onset, but often progress slowly over weeks to months
  • Some horses with lymphosarcoma have compromised humoral or cellular immunity, which may predispose to secondary infection

Historical Findings

  • Chief complaints include signs of dullness, weight loss, inappetence, and decreased performance
  • History of weight loss in intestinal (alimentary) form due to poor absorption, loss of protein, colic, or diarrhea

Physical Examination Findings

  • Most common findings include fever, poor body condition, pallor of mucous membranes, ventral edema, and enlarged lymph nodes, which may be internal, external, regional, or generalized
  • Alimentary form may see ventral edema
  • Mediastinal (thymic) form may cause tachypnea, dyspnea, dysphagia/esophageal reflux, distended jugular/pulse, and pleural effusion
  • Cutaneous form may present with single or multiple dermal or subcutaneous nodules (1–20 cm diameter) covered with hair, not painful or warm to touch
  • Nodules may appear suddenly, grow slowly, remain static, or regress and recur
  • Local lymph nodes often enlarged, but metastasis to internal organs is rare

Causes!!navigator!!

Viral association has been proposed, but cause and effect not been confirmed.

Risk Factors!!navigator!!

Infection with viruses (e.g. equine herpesvirus) may predispose to lymphosarcoma.

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Chronic inflammatory diseases may present with signs of dullness, inappetence, weight loss, fever, pallor, and ventral edema
  • Clinical presentation of inflammatory bowel disease is similar to intestinal lymphosarcoma due to loss of absorption and protein-losing enteropathy; histologic distinction between lymphocytic–plasmacytic enteritis and lymphosarcoma can be challenging
  • Infectious diseases including equine infectious anemia and babesiosis (piroplasmosis) can cause fever, pallor, and weight loss
  • Immune-mediated hemolytic anemia and immune-mediated thrombocytopenia may be associated with lymphosarcoma
  • Borrelia-associated cutaneous pseudolymphoma resembles histologically cutaneous lymphosarcoma or lymphoid hyperplasia

CBC/Biochemistry/Urinalysis!!navigator!!

  • Laboratory findings are variable, often nonspecific, and usually indicate a chronic inflammatory condition
  • CBC reveals neutrophilic leukocytosis, hyperfibrinogenemia, and anemia
  • Lymphocyte counts are normal or mildly decreased; reactive lymphocytes on a peripheral blood smear are common, but lymphocytic leukemia with atypical and/or increased lymphocyte counts is rare
  • Biochemistry reveals hypoalbuminemia and hyperglobulinemia; either inflammatory globulins, polyclonal gammopathy (common), or a monoclonal gammopathy (rare)
  • Hypercalcemia associated with pseudohyperparathyroidism of malignancy occurs occasionally
  • Low serum levels of immunoglobulin M reported, but in <50% of horses, and positive predictive value for lymphosarcoma is low
  • Increased activities of liver-derived enzymes may be caused by neoplastic infiltration of liver

Other Laboratory Tests!!navigator!!

  • In cases of concomitant leukemia, aspiration of bone marrow may reveal myelophthisis characterized by decreased red and white blood cell precursors and infiltration by neoplastic lymphocytes
  • Oral glucose or xylose absorption tests may be abnormal due to neoplastic infiltration of small intestine
  • Coombs test verifies immune-mediated hemolytic anemia and platelet factor 3 test is an indirect test for immune-mediated thrombocytopenia

Imaging!!navigator!!

  • Thoracic US examination for pleural effusion and enlargement of lymph nodes; thoracic radiographs may reveal metastasis but false-negative results are possible
  • Abdominal US examination for ascites, enlargement/infiltration of lymph nodes, spleen, liver, and kidneys, and increased intestinal wall thickness

Other Diagnostic Procedures!!navigator!!

  • Rectal palpation and thoracic radiographs may reveal intracavitary masses and enlarged lymph nodes
  • Definitive diagnosis of lymphosarcoma based on observation of neoplastic lymphocytes in aspirate or biopsies from a lymph node or fluid collected from the thoracic or abdominal cavity, cerebrospinal fluid, or aqueous humor
  • For intestinal lymphosarcoma, mucosal samples can be collected via duodenoscopy and rectal biopsies; chances of achieving a diagnosis increases in diffuse disease
  • Histologic examination of biopsies is preferred as it may be difficult to differentiate neoplastic versus reactive lymphocytes in cytologic evaluation of aspirates; imprint smears of biopsies directly on glass slides improves diagnosis
  • Immunophenotyping can be performed in cytologic and histologic samples in order to characterize type of tumor (e.g. B or T cell); these data can be used to determine tumor severity, progression, treatment choices, and prognosis
  • Laparoscopy, exploratory laparotomy, or postmortem examination may be required to make a definitive diagnosis

Pathologic Findings!!navigator!!

  • Gross lesions include lymphadenomegaly and neoplastic masses in the spleen, liver, kidney, intestine, heart, lung, thymus, and/or skin
  • Affected lymph nodes are white-gray and glisten on cut surface
  • Cytologic and histologic findings reveal variably sized lymphocytes that are larger and darker staining (cytoplasmic basophilia) than normal, contain a variable nucleus to cytoplasm ratio, prominent or multiple nucleoli, clumping of nuclear chromatin, indented or binucleate nuclei, and mitotic figures
  • Histologically, the neoplastic cellular morphology varies, but destruction of normal tissue architecture by a population of lymphoid cells aids diagnosis

Treatment ⬆ ⬇

Outline

TREATMENT

Aims!!navigator!!

To reduce the size of neoplastic tissue while minimizing normal tissue damage, systemic effects, toxicity, and acquired drug resistance of tumor cells.

Appropriate Health Care!!navigator!!

Combination therapy, such as surgical removal, chemotherapy, and/or radiation therapy, has been increasingly used for lymphosarcoma in horses.

Nursing Care!!navigator!!

In-house care may be required for horses undergoing chemotherapy and/or radiation therapy.

Activity!!navigator!!

N/A

Diet!!navigator!!

N/A

Client Education!!navigator!!

Caution owners about poor prognosis.

Surgical Considerations!!navigator!!

Surgical removal of a solitary masses (e.g. cutaneous, intestinal, or splenic mass) may prolong life of horses without evidence of metastasis.

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Drug choice or treatment protocols based on type of tumor (phenotype) not yet available for horses
  • Chemotherapeutic agents including cytarabine, cyclophosphamide, vincristine, doxorubicin, l-asparaginase, and lomustine, used in various combination protocols, and in conjunction with prednisolone administered orally daily
  • Cutaneous form of lymphosarcoma is responsive to oral administration of dexamethasone or prednisolone, but cutaneous or subcutaneous masses may recur (potentially more aggressive and rapidly progressive) in horses treated with systemic glucocorticoids for inadequate periods
  • Response to progestin (altrenogest) or progestogen (megestrol) treatment has shown variable results
  • Intralesional cisplatin suspended in sesame oil has been used successfully to treat solitary cutaneous masses
  • Glucocorticoids used to treat concomitant immune-mediated hemolytic anemia or immune-mediated thrombocytopenia

Contraindications!!navigator!!

N/A

Precautions!!navigator!!

  • Prolonged glucocorticoid and/or combination chemotherapy may cause adverse reactions
  • Horses should be monitored to assess side effects, such as infections, gastrointestinal ulcers, kidney disease, cardiotoxicity, bone marrow suppression, and other organ dysfunction

Possible Interactions!!navigator!!

N/A

Alternative Drugs!!navigator!!

N/A

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

Reduction in size of lymph node(s) or mass(es) and improved attitude, appetite, and weight gain can indicate positive response to treatment.

Prevention/Avoidance!!navigator!!

N/A

Possible Complications!!navigator!!

Infections due to immunosuppression, side effects, and organ failure due to drug toxicity, and resistance of tumoral cells to drugs (recurrence).

Expected Course and Prognosis!!navigator!!

  • Prognosis for a horse with multicentric, intestinal, or mediastinal forms of lymphosarcoma is poor; most untreated horses do not live beyond 6 months after diagnosis
  • Treatment of horses with these forms using combination chemotherapy may prolong the life by a few months
  • Horses with the cutaneous form of lymphosarcoma have a better prognosis and a longer clinical course; lesions may regress spontaneously or with treatment and patients can survive beyond 6 months post diagnosis

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Lymphocytic–plasmacytic inflammatory bowel disease
  • Lymphadenopathy
  • Immune-mediated hemolytic anemia
  • Immune-mediated thrombocytopenia
  • Immunosuppression

Age-Related Factors!!navigator!!

Alimentary form more common in younger horses.

Zoonotic Potential!!navigator!!

None

Pregnancy/Fertility/Breeding!!navigator!!

  • Combination chemotherapy may pose a risk to the fetus, especially when administered during the first trimester
  • Combination chemotherapy administered during months 6–11 of pregnancy and discontinued 1 week prior to foaling had no adverse effects on foal

Synonyms!!navigator!!

Malignant lymphoma, lymphoma, lymphoid tumor.

Abbreviations!!navigator!!

US = ultrasonography, ultrasound

Suggested Reading ⬆ ⬇

Ness SA. Lymphoma. In: Felippe MJB, ed. Equine Clinical Immunology. Ames, IA: Wiley Blackwell, 2016:181–191.

Author(s) ⬆

Author: M. Julia B. Felippe

Consulting Editors: David Hodgson, Harold C. McKenzie, and Jennifer L. Hodgson

Acknowledgment: The author and editors acknowledge the prior contribution of W. Kent Scarratt.