NAVLE Hemic and Lymphatic

Equine Lymphoma Study Guide

📅 March 28, 2026 ⏱ 25 min read

Overview and Clinical Importance

Lymphoma (also called lymphosarcoma) is the most common hematopoietic neoplasm in horses, accounting for 1.3% to 14% of all equine tumors. It is a malignant cancer arising from lymphocytes that can affect virtually any organ system. Unlike many other species, equine lymphoma presents with significant clinical heterogeneity, making early diagnosis challenging. The disease is typically diagnosed at an advanced stage, which significantly impacts prognosis and treatment options.

Lymphoma affects horses of all ages, breeds, and sexes, with horses aged 5-10 years showing increased predisposition. The median age at diagnosis ranges from 10-13 years. There is no apparent breed or sex predilection, though American Quarter Horses, Thoroughbreds, and Standardbreds are frequently represented in case studies, likely reflecting population demographics.

High-YieldOn the NAVLE, remember that lymphoma is the most common malignant tumor of the equine gastrointestinal tract and thorax. The multicentric form is most common, followed by cutaneous and alimentary forms. T-cell rich large B-cell lymphoma (TCRLBCL) is the most frequently diagnosed histologic subtype.

Form	Prevalence and Location	Key Features
Multicentric	Most common (41%); involves multiple lymph nodes and organs	Generalized lymphadenopathy; can progress to leukemia
Cutaneous	Second most common (19%); skin and subcutis	Best prognosis; nodules wax and wane; TCRLBCL most common
Alimentary	Third most common (11%); GI tract, especially small intestine	T-cell type predominates; called juvenile lymphosarcoma in young horses
Mediastinal/Thymic	Less common; mediastinal lymph nodes and thymus	T-cell type more common; respiratory signs predominate
Solitary/Extranodal	Rare; single organ (spleen, eye, CNS, nasopharynx)	Signs depend on organ affected; may be surgically resectable

Etiology and Pathogenesis

The exact cause of equine lymphoma remains poorly understood. Unlike in cattle where bovine leukemia virus (BLV) causes lymphoma, no definitive viral etiology has been established in horses, though associations have been suggested. Recent research has identified Equine Herpesvirus-5 (EHV-5) in some equine lymphoma cases, particularly in TCRLBCL, multicentric, and cutaneous forms. However, a direct causal relationship has not been definitively established.

Lymphoma arises from lymphoid tissues including lymph nodes, spleen, and gut-associated lymphoid tissue (GALT). The disease can develop from two main cell lineages: B-cells or T-cells, with some tumors showing mixed populations. The WHO classification system categorizes equine lymphoma based on morphology, immunophenotype, and anatomic location.

Form	Key Clinical Findings
Multicentric	Weight loss, ventral edema, generalized lymphadenopathy, fever, lethargy, neurologic signs possible
Alimentary	Weight loss, recurrent colic, chronic diarrhea, protein-losing enteropathy, palpable masses
Mediastinal	Dyspnea, coughing, jugular distension, pleural effusion, muffled heart sounds
Cutaneous	Multiple firm subcutaneous nodules, waxing/waning lesions, alopecia, best prognosis
Solitary	Signs depend on location: ocular signs (third eyelid), neurologic (CNS), splenic rupture

Anatomic Classification of Equine Lymphoma

Equine lymphoma is classified into five main anatomic forms based on the primary site of involvement:

Parameter	Finding	Frequency
Fibrinogen	Hyperfibrinogenemia	70% of cases
Albumin	Hypoalbuminemia	51% of cases
Globulins	Hyperglobulinemia	35% of cases
PCV	Anemia (usually normocytic, normochromic)	51% of cases
Platelets	Thrombocytopenia	35% of cases
LDH	Elevated	Common finding
WBC	Leukemia rare; neutrophilia common	Variable

Clinical Signs by Anatomic Form

General Clinical Signs (All Forms)

The most common clinical signs are nonspecific and reflect systemic disease:

Weight loss - most common presenting complaint (67% of cases)
Ventral edema - due to hypoalbuminemia or vascular obstruction
Lethargy and depression
Recurrent fever
Inappetence
Lymphadenopathy - palpable in superficial lymph nodes

Multicentric Lymphoma

In addition to general signs, multicentric lymphoma may present with:

Generalized peripheral lymphadenopathy (submandibular, prescapular, prefemoral)
Abdominal distension
Icterus (hepatic involvement)
Malabsorption syndrome
Neurological signs: ataxia, cranial nerve deficits, Horner syndrome, seizures
Polyuria and polydipsia (hypercalcemia)

Alimentary Lymphoma

Alimentary lymphoma primarily affects the gastrointestinal tract, with the small intestine most commonly involved:

Recurrent colic
Chronic diarrhea
Protein-losing enteropathy
Malabsorption
Palpable abdominal masses on rectal examination

NAVLE TipWhen presented with a young horse (less than 5 years) with chronic weight loss, diarrhea, and protein-losing enteropathy, alimentary lymphoma (historically called "juvenile lymphosarcoma") should be high on the differential list. T-cell lymphoma predominates at intestinal sites.

Mediastinal/Thymic Lymphoma

Respiratory distress and dyspnea
Coughing
Jugular vein distension (cranial vena cava syndrome)
Muffled heart sounds
Pleural effusion
Head and neck edema

Cutaneous Lymphoma

Cutaneous lymphoma has distinct features and carries the best prognosis among all forms:

Multiple subcutaneous nodules (1-20 cm diameter)
Nodules are firm, non-painful, and scattered over the body
Waxing and waning of lesions (influenced by hormones, season, steroid therapy)
Alopecia over nodules
Ulceration and exudation in advanced cases
Rarely involves lymph nodes or spreads systemically

Clinical Signs Summary by Anatomic Form

Marker	Cell Type	Clinical Significance
CD3	T-lymphocytes	T-cell lymphomas generally more aggressive
CD20	B-lymphocytes	Preferred B-cell marker in horses (better than CD79)
CD79alpha	B-lymphocytes	Alternative B-cell marker

Diagnosis

Laboratory Findings

Laboratory abnormalities are common but nonspecific. CBC and serum chemistry often show:

High-YieldHyperglobulinemia (greater than 4.4 g/dL) is associated with significantly shorter survival time (median 4 days) compared to horses with normal or low globulin concentrations. This is a poor prognostic indicator on the NAVLE.

Diagnostic Imaging

Ultrasound is the most valuable imaging modality for equine lymphoma:

Thoracic ultrasound: pleural effusion, mediastinal masses, enlarged lymph nodes
Abdominal ultrasound: hepatosplenomegaly, mesenteric lymphadenopathy, intestinal wall thickening
Guides fine-needle aspiration and biopsy
Infiltrated organs show altered echogenicity

Cytology and Histopathology

Definitive diagnosis requires cytologic or histopathologic confirmation of neoplastic lymphocytes:

Fine-needle aspiration (FNA): Quick, minimally invasive; useful for accessible masses and effusions
Biopsy: Gold standard; allows immunophenotyping and grading
Cytology of effusions: Pleural fluid often diagnostic; abdominal fluid less reliable (21-50% positive)
Bone marrow aspiration: To detect leukemia or bone marrow infiltration

Key Histopathologic Features

Effacement of normal tissue architecture by neoplastic lymphocytes
Heterogeneous tumor cell morphology
Histiocytic and multinucleated giant cell infiltrates common
Mitotic count determines grade: 0-1 (indolent), 2-5 (low), 6-10 (mid), greater than 10 (high)

Immunophenotyping

Immunohistochemistry (IHC) classifies lymphoma by cell origin and provides prognostic information:

NAVLE TipT-cell rich large B-cell lymphoma (TCRLBCL) is the most common histologic subtype in horses! It contains few neoplastic B-cells surrounded by numerous non-neoplastic T-cells. Quarter Horses almost exclusively develop TCRLBCL for cutaneous lymphoma. TCRLBCL has a better prognosis than pure T-cell lymphomas.

Syndrome	Clinical Features
Hypercalcemia	PU/PD, depression, anorexia, cardiac arrhythmias; caused by PTHrP production
Anemia	Anemia of chronic disease; rarely immune-mediated hemolytic anemia
Cachexia	Severe weight loss despite adequate nutrition; cytokine-mediated
Pruritus/Alopecia	Generalized hair loss without primary skin lesions
Monoclonal Gammopathy	Hyperglobulinemia due to IgG1 or IgG4/7 production by B-cell lymphomas
Hypoglycemia	Rare; due to excessive glucose consumption by tumor cells

Paraneoplastic Syndromes

Paraneoplastic manifestations are common in equine lymphoma and may precede the diagnosis of the underlying neoplasia:

Treatment	Protocol/Dosage	Notes
Corticosteroids	Prednisolone 0.5-1 mg/kg PO q12-24h; Dexamethasone 0.05-0.1 mg/kg IV/PO q24h	First-line palliative; cutaneous form often responsive
Cyclophosphamide	150-800 mg/m2 IV	Used in multi-drug protocols; risk of hemorrhagic cystitis
Doxorubicin	35-70 mg/m2 IV q3 weeks	Cardiotoxic (cumulative); hypersensitivity risk
L-Asparaginase	10,000 U/m2 SC	Often combined with other agents
Vincristine	0.5-0.7 mg/m2 IV	Part of multi-drug protocols
Lomustine (CCNU)	65 mg/m2 PO	Effective for cutaneous lymphoma
Surgical Excision	Complete removal of localized masses	Best for solitary, well-circumscribed tumors
Radiotherapy	External beam or brachytherapy	Limited availability; good for localized disease

Treatment Options

Treatment for equine lymphoma is typically palliative rather than curative. Options include:

High-YieldHorses receiving 4-5 drug chemotherapy protocols tend to have longer survival times than those on single-agent therapy. Overall response rate to chemotherapy is approximately 93%, with 33% achieving complete remission. Median survival time with treatment is approximately 8 months (range 1-46 months).

Form	Median Survival	Prognostic Factors
Cutaneous	34 months with treatment; may survive years	Best prognosis; surgery may be curative for TCRLBCL
Multicentric	7 months with chemotherapy	Stage of disease; response to initial treatment
Alimentary	25-90 days (EATL)	Poor prognosis; EATL grade 1 better than grade 2
Mediastinal	Generally poor; months	T-cell type; extent of pleural effusion
Untreated	4 days median	Rapid deterioration without intervention

Prognosis

Prognosis for equine lymphoma is generally poor, but varies significantly by anatomic form and treatment approach:

Differential Diagnosis

Consider these differentials based on presentation:

Cutaneous masses: Equine sarcoids, melanoma, squamous cell carcinoma, granulomatous disease, abscess
Weight loss and lymphadenopathy: Strangles, pigeon fever, systemic fungal infection, EIA
Chronic GI signs: Inflammatory bowel disease, intestinal adenocarcinoma, parasitism, sand enteropathy
Pleural effusion: Pleuropneumonia, hemangiosarcoma, mesothelioma

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