Lymph Nodes

What are the 3 common causes of lymphadenopathy

• reactive hyperplasia

• Inflammation (lymphadenitis)

• Neoplasia

Two key functions of lymph nodes

• filtering lymph

• Initiating immune responses

Why does lymphadenomegaly occur

Lymph Flows through node → macrophages that line the sinuses remove foreign material → antigen recognition by dendritic cells/macrophages/sensitized B cells → helper T lymphocytes (Th1 = cytotoxic, Th2 = humoral (Ab) response) → B cells in follicles proliferate → germinal center hyperplasia

What is required for determining the underlying cause of lymphadenomegaly?

Diagnostic sampling → FNA, cytology or biopsy

What is a baseline FNA of a normal lymph node?

• 75-85% small, well differentiated lymphocytes

• <10-15% intermediate to large lymphocytes (lymphoblasts)

• less than 3% plasma cells

• Less than 1% macrophages, neutrophils, eosinophils, mast cells

Cell ID (blue, black & green arrow)

• blue arrow = plasma cell

• Black arrow = small lymphocytes

• Green arrow = lymphoblasts

What is reactive lymphadenopathy + example

• Benign & common response to lymph nodes to antigenic stimulation in their drainage area. Not considered true inflammation - no significant neutrophilia infiltration, edema, and normal LN architecture is preserved

• Can also occur in response to tumor antigens from a neoplasm located outside the node

• No systemic illness, nonpainful lymph node, firm but not hard

• Example: abscess in the sole of a cow foot results in an enlarged popliteal lymph node.

Mechanism of sole abscess to enlarged popliteal lymph node in reactive lymphadenomegaly

Sole abscess forms → antigens from abscess enter the lymphatic circulation → travel to the draining lymph node in reactive→ lymph node responds by proliferating lymphocytes

What is lymphadenitis

• inflammation of a lymph node, often resulting from an infection in the area that the lymph node drains

• Typically painful upon palpation, especially during acute stages of the disease

How can the predominant type of inflammatory cells within an inflamed lymph node (neutrophils, eosinophils/mast cells, macrophages) provide clues to its origin?

• neutrophils → predominant in suppurative lymphadenitis, often indicates a bacterial infection

• Eosinophils/mast cells → parasitic infection

• Macrophages → granulomatous lymphadenitis, commonly present in chronic stages of various disease

What are two common differential diagnoses of this type of necrosis?

certain bacterial infections

• Mycobacterium bovis (bovine tuberculosis)

• Corynebacterium pseudotuberculosis (cause of caseous lymphadenitis in sheep & goats)

How is CLA characterized?

• Chronic suppurative lymphadenitis caused by Corynebacterium pseudotuberculosis

• Primarily affects sheep & goats

• Characterized by abscess formation in superficial lymph nodes & internal organs

• Results in decreased milk & wool production, reduced growth rates, carcass condemnation

What are the features of Corynebacterium pseudotuberculosis?

• Gram positive, Non motile, Facultative intracellular bacterial rod

• Persists in soil contaminated with feces or exudates

• Resistant to desiccation & sunlight

Pathogenesis of CLA

transmission (tail docking, castration, shearing or infected discharges or inhalation from infected animal→ invasion to local lymph node → suppurative lymphadenitis → lymphogenous & hematogenous dissemination in older animals → organ abscess → bacteria lives intracellularly, eventually killing host cell → releases more bacteria into surrounding tissue → macrophages arrive to site → chronic infection leads to formation of capsule of connective tissue

Clinical findings of CLA

• enlargement of one or more superficial lymph node (parotid, submandibular, prescapular)

• Lesions may have whitish/creamy pus

• Weight loss

• Reduced milk production

• Discomfort on palpation

• Progression to visceral disease → slow, occurs in older animals; affects lungs, liver, kidneys, or mediatstinal lymph nodes

Gross findings of CLA

• Enlarged LN with central core of thick creamy necrotic material, greenish-white & gritty

• Older lesions = onion skin formed due to concentrically lamellated layers of fibrous connective tissue with alternating zones of caseous friable material

How would you confirm a diagnosis of CLA & what lab test would be used?

• Collect pus samples from abscess using sterile techniques → submit lab sample for bacterial culture & identification (gold standard for confirming C. Pseudotuberculosis)

• FNA from deeper or non ruptured lymph nodes

• Blood samples for CBC or serological testing (need to determine if it is worth cost)

• Cytology (cannot specifically ID Corynebacterium pseudotuberculosis)

What is effective prevention of CLA?

• Good Biosecurity practices (isolating affected animals, limiting introduction of new animals without testing)

• Regular herd screening through serology

• Careful monitoring of wounds for signs of infection

• Prompt tx of abscesses with drainage or surgical intervention can help reduce spread

• Vaccination in areas where CLA is endemic

Pathogenesis of bovine tuberculosis

inhalation of infected aerosol droplets → respiratory tract infection → spread to regional lymph nodes (bronchial or mediastinal LN) → mycobacteria are phagocytosed by macrophages → some macrophages may clear the infection but others may allow bacteria to proliferate → granuloma formation

What constitutes the primary complex of bovine tuberculosis?

granulomas in the lungs & their draining lymph nodes

Bacteria can also spread through the blood stream & lymphatics and can lead to generalized disease

Gross lesions of bovine tuberculosis

• appearance of affected LN varies based off of species, degree of immunity, type of mycobacteria involved - many animals show no clinical signs

• Cattle

  • Multiple pale, caseous granulomas that may become calcified, indicating chronic granulomatous lymphadenitis

• Deer & Possums

  • LN lesions are more suppurative

Clinical signs of bovine tuberculosis

• enlarged lymph nodes in throat latch region

• Chronic cough, occasional nasal discharge

• Weight loss

• Mild respiratory effort

What is lymphoma

Malignant lymphoid neoplasia arising in solid tissues (lymph nodes, spleen, gut associated lymphoid tissue)

Usually occurs without circulating neoplastic cells

Usually sporadic, but some are associated with viral infections

Classification of lymphoma - anatomic classification

1. Multi centric → multiple LN (dogs)

2. Alimentary → GI tract & mesenteric LN (cats)

3. Mediastinal → thymus or mediastinal LN

4. Cutaneous → skin

5. Extranodal → CNS, eye, kidney

Classification of lymphoma - cell type + prognosis

• B cell → better prognosis

• T cell → aggressive

Classification of lymphoma → how aggressive is it → cell size, mitosis index, nuclear figures

• High grade → rapid growth, more responsive to chemo

• Low grade → slower progression, harder to detect early

Classification of lymphoma - clinical staging

• Stage l → single LN or single organ affected

• Stage ll → multiple LN in a regional area

• Stage lll → generalized lymphadenopathy

• Stage IV → involvement of liver and/or spleen, with or without LN involvement

• Stage V → involvement of bone marrow, blood, or other extra nodal sites (CNS, eye, lungs)

Diagnostic approach in lymphoma cases

1. FNA + cytology → first line diagnostic test to assess cells in the affective tissue, only okay for presumptive dx

2. Biopsy → confirms dx & allows grading & structural assessment

3. Immunohistochemistry → ID T-cells vs B cell origin in tissue samples, useful for prognosis & tx plan

4. Flow cytometry from FNA or blood

5. CBC & blood smear examination → assesses for leukemic phase or cytopenias

6. Thoracic/abdominal imaging → assess internal organ involvement & staging

7. Bone marrow aspiration → cases with cytopenias or suspicion of leukemic spread

8. PARR → confirms clinal lymphoid population

What is the most common presentation of lymphoma in dogs?

• Multicentric (multiple LN affected), with generalized lymphadenopathy

• May involve liver, spleen, & bone marrow

• Dogs are usually clinically well despite large LN

Common lab findings of lymphoma in dogs

• Non-regenerative anemia & thrombocytopenia with chronic disease or bone marrow involvement

• Leukocytosis, lymphocytosis, or neoplastic lymphocytes in peripheral blood (usually seen in Stage V)

• Paraneoplastic hypercalcemia → 10-20% of cases, most often associated with T-cell lymphoma

• Always consider paraneoplastic hypercalcemia → elevated blood Ca levels caused by a tumor - hypercalcemia can lead to secondary complications (PU/PD + renal dysfunction)

Types of lymphoma in cattle

bovine leukemia virus (Enzootic bovine leukosis)

• adult cattle 4-5 years

• BLV infects B cells in cattle

• Most infected animals are asymptomatic carriers

• Multicentric lymphadenopathy

• Common lymphoma sites → heart (R atrium), abomasum, uterus, LN, spinal canal

Sporadic lymphoma

• juvenile form

  • Birth-7 months

  • Multicentric, involving LN, bone marrow, liver, kidneys

  • May cause dystocia

  • Often presents with leukemia

• Thymic form

  • 6-24 months

  • Massive thymic enlargement, causes ventral neck swelling (cranial thoracic mass)

  • Leukemia uncommon

• Cutaneous form (rare)

  • 1-3 years

  • Presence of skin nodules that may ulcerate or regress

  • Internal organ infiltration occurs later

  • Leukemia rare

How does lymphoma present in horses?

• visceral organs involved → LN, spleen, GIT, liver, kidneys

• Leukemia rare

Types of lymphoma in cats

LYMPHOMA IS MOST COMMON MALIGNANT NEOPLASM IN CATS! Can affect virtually any organ system, ALWAYS CONSIDER IN DDX FOR CHONIC ILLNESS IN OLDER CATS w/ VAGUE SIGNS/LYMPHADENOPATHY!

Sporadic (FeLV-negative) lymphoma

• Middle aged to older cats (>10 years)

• Chronic inflammation, genetic mutation, & environmental exposures may contribute

• Common organs affected → GIT, mesenteric LN, liver, spleen, kidneys

Retrovirus-associated lymphoma

• Feline leukemia virus (FeLV) associated lymphoma

  • Younger cats (<4 years)

  • Thymus is more commonly affected, Multicentric form common

  • Gamma retrovirus that can cause direct cell transformation by insertional mutagenesis

  • 1/3 of cats may develop lymphoma or leukemia

• Feline immunodeficiency virus (FIV) associated lymphoma

  • Characterized by increased susceptibility to opportunistic infections, neurological disease, tumors

  • Acquired immunodeficiency syndrome

Clinical signs of FeLV

• dyspnea, coughing

• Muffled heart sounds

• Pleural effusion

• Rads - cranial mediastinal mass may displace lungs & heart

• Cats can have a thymic lymphoma & be FeLV negative

Clinical signs of alimentary or gastrointestinal lymphoma in cats

• most common presentation (esp older, FeLV negative cats)

• Weight loss

• V/D

• Anorexia

• Thickening of intestinal wall with loss of normal layering

• Mesenteric lymphadenopathy

A young dog presents for vaccination. The only abnormal finding is mild submandibular lymph node enlargement. Cytology shows a mixed population of lymphocytes, some plasma cells, and macrophages. What is the most likely diagnosis?

Lymphoma

Lymph node metastasis

Reactive lymph node hyperplasia

Suppurative lymphadenitis

Reactive LN hyperplasia

A ewe has firm swellings around the head and neck. Post-mortem shows laminated abscesses in lymph nodes.
What is the most likely cause?

Corynebacterium pseudotuberculosis

Mycobacterium bovis

Mannheimia haemolytica

Trueperella pyogenes

Corynebacterium pseudotuberculosis → causes caseous lymphadenitis with characteristic onion ring abscesses

A cow shows weight loss and chronic cough. Retropharyngeal lymph nodes are enlarged and gritty on sectioning.
Most likely diagnosis?

Enzootic bovine leukosis

Sporadic bovine lymphoma

Tuberculous lymphadenitis

Suppurative lymphadenitis

Tuberculous lymphadenitis → granulomatous inflammation with caseous necrosis & mineralization is typical of TB

A 6-year-old dog has generalised lymphadenomegaly. Cytology shows large, monomorphic lymphocytes with frequent mitoses. What is the most likely diagnosis?

Lymphoma → presence of large, monomorphic & presence of mitotic figures + generalized lymphadenopathy is consistent with lymphoma

A cat presents with vomiting and an abdominal mass. Imaging shows thickened intestines and enlarged mesenteric lymph nodes. What is you most likely diagnosis? Include the correct terminology according to the anatomic location.

Alimentary lymphoma → most common form of lymphoma in older cats, affects GI tract & mesenteric nodes

A 2-year-old beef steer presents with progressive weight loss, dullness, and firm enlargement of the prescapular and mesenteric lymph nodes. The remainder of the herd appears unaffected. BLV serology is negative. Based on the signalment and findings, which form of lymphoma is most likely?

Adult sporadic lymphoma

• BLV negative, affects young adult, presents with peripheral lymphadenopathy without herd involvement

Cytology of a cat's lymph node is inconclusive. PARR testing is recommended. What is the main purpose of this test?

ID clonal lymphocyte population

• Helps distinguish lymphoma from reactive processes